Patel et al., 1

Supplemental Material

Materials and Methods

Immunohistochemistry

Primary antibodies used for validation studies include: mouse anti-desmoglein-3 (Cat. #

32-6300, Invitrogen, CA, USA; 1:25), rabbit anti-cytokeratin 4 (Cat. # ab11215, Abcam,

Cambridge, MA, USA; 1:100), mouse anti-cytokeratin 16 (Cat. # ab8741, Abcam; 1:25), rabbit

anti-desmoplakin antibody (Cat. # ab14418, Abcam; 1:200), mouse anti-vimentin (Cat. # M7020,

Dako, Carpinteria, CA, USA; 1:100). Secondary antibodies conjugated with biotin (Vector,

Burlingame, CA, USA) were used, diluted to 1:400. Tissues slides containing archival FFPE

sections, or tissue micro arrays (TMA) consisting of 508 HNSCC and controls, were dewaxed in

SafeClear II (Fisher Scientific, Pittsburgh, PA, USA) hydrated through graded alcohols,

immersed in 3% hydrogen peroxide in PBS for 30 min to quench the endogenous peroxidase, and

processed for antigen retrieval and immunostaining with the appropriate primary antibodies and

biotinylated secondary antibodies as described (1), followed by the avidin-biotin complex

method (Vector Stain Elite, ABC kit; Vector). Slides were washed and developed in 3,3'-

diaminobenzidine (Sigma FASTDAB tablet; Sigma Chemical) under microscopic control, and

counterstained with Mayer's hematoxylin. For each stained TMA the number of positive cells in

each core was visually evaluated and the results expressed as a percentage of stained cells/ total

number of cells. According to their immunoreactivity the tissues array cores were divided

according to tumor differentiation, where the percentage of stained cells in the three tumor

classes were scored as more than 5% and less than 25% of the cells stained, 26 to 50%, 51 to

75% or, 75 to 100%.

Patel et al., 2

Laser Capture Microdissection (LCM)

FFPE oral cancer tissue sections were deparaffinized in SafeClear II and hydrated

through graded alcohols to 70% ethanol. Slides were briefly washed in water and stained in

Mayer’s hematoxylin (10-15 sec) followed by dehydration through graded ethanol (70-100%)

and SafeClear II. For LCM, stained uncovered slides were air dried, and cells of interest captured

using a PIXCELL IIe (Molecular Devices Corporation, Sunnyvale, CA, USA) as described (2).

Approximately 20,000 cells were capture from a single or consecutive tissue sections using up to

4 CapSure LCM Caps (Molecular Devices Corporation), which were transferred to a 0.5 ml

sterile Eppendorf tube for protein extraction (see below).

Protein Extraction

Protein extraction was carried out using the Liquid Tissue MS Protein Prep kit according

to manufacturer’s protocol (Expression Pathology Inc., Gaithersburg, MD, USA). Briefly, the

films from the underside of the caps for each sample were removed, transferred to low binding

reaction tubes, and incubated with 20 µl of Liquid Tissue extraction buffer at 950C for 1.5 h,

with intermittent mixing followed by a quickspin, to consolidate the material. Samples were

centrifuged at 10,000 rpm for 1 min, cooled on ice, followed by digestion with 1 µl of trypsin

(15-20 U/µl) for 1 h at 370C with intermittent mix and spin. The samples were centrifuged one

final time at 10,000 rpm for 1 min prior to reduction with 2 µl of 100 mM DTT (10 mM final

concentration) at 950C for 5 min, followed by centrifugation and storage at –80 0C until ready for

analysis.

Patel et al., 3

Tandem Mass Spectrometry and Bioinformatic Analysis

FFPE extracted samples were acidified with 0.1% trifluoroacetic acid (TFA) and desalted

with C-18 ZipTip microcolumns (Millipore, Billerica, MA, USA), lyophilized to dryness,

resuspended in 0.1% TFA, and quantified by the BCA protein assay (Pierce, Rockford, IL,

USA). Nanoflow reversed-phase liquid chromatography (RPLC) was performed using an

Agilent 1100 capillary LC system (Agilent Technologies, Palo Alto, CA, USA) coupled online to

a linear ion trap (LIT) mass spectrometer (LTQ, Thermo Electron, San Jose, CA, USA).

Separations were performed using 75 µm i.d. x 360 o.d. x 10 cm long fused silica capillary

columns (Polymicro Technologies, Phoenix, AZ, USA) that were slurry packed in house with 3

µm, 300 Å pore size C-18 silica-bonded stationary phase (Vydac, Hysperia, CA, USA). After

injecting 2 µL of sample (approximately 200 ng protein), the column was washed for 30 min

with 98% mobile phase A (0.1% formic acid in water) at a flow rate of 0.5 µL/min. Peptides

were eluted using a linear gradient of 2% mobile phase B (0.1% formic acid in acetonitrile) to

40% solvent B in 110 minutes, then to 98% B in an additional 30 min, all at a constant flow rate

of 0.25 µL/min.

The LIT-MS was operated in a data dependent MS/MS mode in which each full MS scan

is followed by five MS/MS scans where the five most abundant peptide molecular ions are

selected for collision-induced dissociation (CID), using a normalized collision energy of 35%.

Dynamic exclusion was utilized to minimize redundant selection of peptides previously selected

for CID. The heated capillary temperature and electrospray voltage were set at 160 ºC and 1.6

kV, respectively. Data were collected over a broad mass to charge (m/z) precursor ion selection

scan range of 400-2000, followed by four segmented precursor selection scan ranges (e.g. gas

Patel et al., 4

phase fractionation in the m/z dimension, GPFm/z) using the following overlapping m/z intervals:

400-605, 595-805, 795-1205, and 1195-2000.

Tandem mass spectra were searched against the UniProt human protein database

(06/2005 release) from the European Bioinformatics Institute (http://www.ebi.ac.uk/integr8)

using SEQUEST (Thermo Electron). For a fully tryptic peptide to be considered legitimately

identified, it had to achieve stringent charge state and proteolytic cleavage-dependent cross

correlation (Xcorr) scores of 1.9 for [M+H]1+, 2.2 for [M+2H]2+ and 3.5 for [M+3H]3+, and a

minimum delta correlation ∆Cn) of 0.08. Results were further filtered using software developed

in-house to determine unique peptides and proteins. Based on criteria followed in previous work,

the error in protein identification was <1.5% (3). To facilitate biological interpretation of the

protein lists derived from this experiment, data was subjected to EASE analysis (Expression

Analysis Systematic Explorer) to identify Gene Ontology (GO) categories and terms that might

indicate over-representation in the tissues analyzed.

References

1. Amornphimoltham P, Patel V, Sodhi A, et al. Mammalian target of rapamycin, a molecular target in squamous cell carcinomas of the head and neck. Cancer Res 2005;65:9953-61.

2. Baker H, Patel V, Molinolo AA, et al. Proteome-wide analysis of head and neck squamous cell carcinomas using laser-capture microdissection and tandem mass spectrometry. Oral Oncol 2005;41:183-99.

3. Hood BL, Darfler MM, Guiel TG, et al. Proteomic analysis of formalin-fixed prostate cancer tissue. Mol Cell Proteomics 2005;4:1741-53.

Supplemental Table 1: Proteins identified in only in normal squamous epithelium

PeptidesAccession Protein (number)

Q12756 Kinesin-like protein KIF1A (Axonal transporter of synaptic vesicles) 6P35813 Protein phosphatase 2C alpha isoform (EC 3.1.3.16) (PP2C-alpha) (IA) (Protein phosphatase 1A) 3Q9Y561 Low-density lipoprotein receptor-related protein 12 precursor (Suppressor of tumorigenicity protein 7) 3Q6ZN03 Hypothetical protein FLJ16545 3O94916 Nuclear factor of activated T cells 5 (T cell transcription factor NFAT5) (NF-AT5) (Tonicity-responsive 2P23458 Tyrosine-protein kinase JAK1 (EC 2.7.1.112) (Janus kinase 1) (JAK-1) 2P13611 Versican core protein precursor (Large fibroblast proteoglycan) (Chondroitin sulfate proteoglycan core 2P16455 Methylated-DNA--protein-cysteine methyltransferase (EC 2.1.1.63) (6-O-methylguanine-DNA methyltra 2Q9H0M3 Hypothetical protein DKFZp434O0710 (Hypothetical protein KIAA1549) 2Q9UGU5 High-mobility group protein 2-like 1 (HMGBCG protein) 2Q6ZWK7 Hypothetical protein FLJ16045 2Q7Z7J3 Hypothetical protein 2Q6UXX9 QFRL9384 2Q96BY6 Dedicator of cytokinesis protein 10 (Protein zizimin 3) 2O43693 Zinc-finger protein (Fragment) 1P68106 FK506-binding protein 1B (EC 5.2.1.8) (Peptidyl-prolyl cis-trans isomerase 1B) (PPIase 1B) (Rotamase 1B) 1P68402 Platelet-activating factor acetylhydrolase IB beta subunit (EC 3.1.1.47) (PAF acetylhydrolase 30 kDa sub 1P78318 Immunoglobulin-binding protein 1 (CD79a-binding protein 1) (B cell signal transduction molecule alpha 4) 1O15537 Retinoschisin precursor (X-linked juvenile retinoschisis protein) 1P57082 T-box transcription factor TBX4 (T-box protein 4) 1O43300 Leucine rich repeat neuronal protein 2 precursor (Leucine-rich repeat transmembrane neuronal 2 protein 1P62906 60S ribosomal protein L10a (CSA-19) 1P62690 HERV-K_22q11.23 provirus ancestral Gag polyprotein (Gag polyprotein) [Contains: Matrix protein; Capsid 1P51813 Cytoplasmic tyrosine-protein kinase BMX (EC 2.7.1.112) (Bone marrow kinase BMX) (Epithelial and endoth 1O60235 Airway trypsin-like protease precursor (EC 3.4.21.-) 1P52961 GPI-linked NAD(P)(+)--arginine ADP-ribosyltransferase 1 precursor (EC 2.4.2.31) (Mono(ADP-ribosyl)tra 1Q13445 Putative T1/ST2 receptor binding protein (Interleukin 1 receptor-like 1 ligand,) 1P05937 Calbindin (Vitamin D-dependent calcium-binding protein, avian-type) (Calbindin D28) (D-28K) 1Q14674 Separin (EC 3.4.22.49) (Separase) (Caspase-like protein ESPL1) (Extra spindle poles-like 1 protein) 1Q13945 3',5'-cyclic AMP phosphodiesterase (Fragment) 1Q13591 Semaphorin 5A precursor (Semaphorin F) (Sema F) 1Q14202 Zinc finger protein 261 (DXS6673E protein) 1P82650 Mitochondrial 28S ribosomal protein S22 (S22mt) (MRP-S22) (GK002) 1O15234 Cancer susceptibility candidate gene 3 protein (Metastatic lymph node protein 51) (MLN 51 protein) (Bar 1Q07001 Acetylcholine receptor protein, delta chain precursor 1O15013 Rho guanine nucleotide exchange factor 10 1O95602 DNA-directed RNA polymerase I largest subunit (EC 2.7.7.6) (RNA polymerase I 194 kDa subunit) (RPA1 1P22455 Fibroblast growth factor receptor 4 precursor (EC 2.7.1.112) (FGFR-4) 1P20711 Aromatic-L-amino-acid decarboxylase (EC 4.1.1.28) (AADC) (DOPA decarboxylase) (DDC) 1P23141 Liver carboxylesterase 1 precursor (EC 3.1.1.1) (Acyl coenzyme A:cholesterol acyltransferase) (ACAT) (M 1P25054 Adenomatous polyposis coli protein (APC protein) 1O95361 Tripartite motif protein 16 (Estrogen-responsive B box protein) 1P13798 Acylamino-acid-releasing enzyme (EC 3.4.19.1) (AARE) (Acyl-peptide hydrolase) (APH) (Acylaminoacyl-pe 1P12882 Myosin heavy chain, skeletal muscle, adult 1 (Myosin heavy chain IIx/d) (MyHC-IIx/d) 1P11940 Polyadenylate-binding protein 1 (Poly(A)-binding protein 1) (PABP 1) 1P02649 Apolipoprotein E precursor (Apo-E) 1P19878 Neutrophil cytosol factor 2 (NCF-2) (Neutrophil NADPH oxidase factor 2) (67 kDa neutrophil oxidase f 1P00966 Argininosuccinate synthase (EC 6.3.4.5) (Citrulline--aspartate ligase) 1P40394 Alcohol dehydrogenase class IV mu/sigma chain (EC 1.1.1.1) (Retinol dehydrogenase) (Gastric alcohol dehy 1O75206 Hypothetical protein A-152E5.9 1P46100 Transcriptional regulator ATRX (X-linked helicase II) (X-linked nuclear protein) (XNP) (Znf-HX) 1P48167 Glycine receptor beta chain precursor (Glycine receptor 58 kDa subunit) 1P48506 Glutamate--cysteine ligase catalytic subunit (EC 6.3.2.2) (Gamma-glutamylcysteine synthetase) (Gamma- 1O75128 KIAA0633 protein (Fragment) 1P09529 Inhibin beta B chain precursor (Activin beta-B chain) 1O75122 KIAA0627 protein (Fragment) 1P43403 Tyrosine-protein kinase ZAP-70 (EC 2.7.1.112) (70 kDa zeta-associated protein) (Syk-related tyrosine ki 1O75909 Cyclin K 1P35080 Profilin-2 (Profilin II) 1

O75691 DRIM protein 1Q9H1S9 DNA sequence from clone RP11-271B5 on chromosome 13 Contains the FGF9 fibroblast growth factor 9 1Q9H0E7 Ubiquitin carboxyl-terminal hydrolase 44 (EC 3.1.2.15) (Ubiquitin thiolesterase 44) (Ubiquitin-specific pr 1Q9BXG0 P231 1Q9H4A3 Serine/threonine-protein kinase WNK1 (EC 2.7.1.37) (Protein kinase with no lysine 1) (Protein kinase, lys 1Q9BYM8 Ubiquitin conjugating enzyme 7 interacting protein 3 (Hepatitis B virus X-associated protein 4) (HBV ass 1Q9H501 Hypothetical protein C20orf6 1Q9H552 OTTHUMP00000021786 1Q9H5T4 Hypothetical protein FLJ23059 1Q96MQ1 Hypothetical protein FLJ32062 1Q96NR3 Hypothetical protein FLJ30296 1Q96HI0 Sentrin-specific protease 5 (EC 3.4.22.-) (Sentrin/SUMO-specific protease SENP5) (Protease FKSG45 1Q96K08 Hypothetical protein FLJ14855 1Q9BQ48 39S ribosomal protein L34, mitochondrial precursor (L34mt) (MRP-L34) 1Q96RB7 Olfactory receptor 5M11 1Q96RT8 Gamma-tubulin complex component 5 (GCP-5) 1Q96RW7 Hemicentin 1Q99704 Docking protein 1 (p62(dok)) (Downstream of tyrosine kinase 1) (pp62) 1Q9UN73 Protocadherin alpha 6 precursor (PCDH-alpha6) 1Q9UPA5 Bassoon protein (Zinc-finger protein 231) 1Q9UQE7 Structural maintenance of chromosome 3 (Chondroitin sulfate proteoglycan 6) (Chromosome-associated 1Q9UQP3 Tenascin N precursor 1Q9UQR0 Sex comb on midleg-like protein 2 1Q9UKR3 Kallikrein 13 precursor (EC 3.4.21.-) (Kallikrein-like protein 4) (KLK-L4) 1Q9UKU9 Angiopoietin-related protein 2 precursor (Angiopoietin-like 2) (UNQ170/PRO196) 1Q9UKV8 Eukaryotic translation initiation factor 2C 2 (eIF2C 2) (eIF-2C 2) 1Q9UKX3 Myosin heavy chain, skeletal muscle, extraocular (MyHC-eo) 1Q9UN33 Epstein-Barr virus-induced zinc finger protein (ZNF-EB) (CT-ZFP48) (Zinc finger protein dp) (ZNF-dp 1Q9Y277 Voltage-dependent anion-selective channel protein 3 (VDAC-3) (hVDAC3) (Outer mitochondrial membran 1Q9Y592 NY-REN-58 antigen 1Q9Y2I0 KIAA0974 protein (Fragment) 1Q9Y3T9 UPF0120 protein DKFZp564C186 1Q9NXS3 BTB/POZ domain containing protein 5 1Q9NVR7 Hypothetical protein FLJ10560 1Q9NW08 DNA-directed RNA polymerase III subunit 127.6 kDa polypeptide (EC 2.7.7.6) (RNA polymerase III sub 1Q9NYU1 UDP-glucose:glycoprotein glucosyltransferase 2 precursor (EC 2.4.1.-) (UDP--Glc:glycoprotein glucosyltra 1Q9NRA8 Eukaryotic translation initiation factor 4E transporter (eIF4E transporter) (4E-T) (Eukaryotic translati 1Q9NTK5 Putative GTP-binding protein PTD004 (PRO2455) 1Q9NV79 Protein C20orf36 1Q9UBW7 Zinc finger protein 198 (Fused in myeloproliferative disorders protein) (Rearranged in atypical myelopro 1Q9UBX1 Cathepsin F precursor (EC 3.4.22.41) (CATSF) 1Q9UFE4 Hypothetical protein DKFZp434A128 1Q9UID3 ANG2 (Chromosome 11 open reading frame2) 1Q9UH92 Transcription factor-like protein 4 (Max-like bHLHZip protein) (BigMax protein) (Mlx) 1Q9P1Z3 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 1Q6ZU42 Hypothetical protein FLJ44010 1Q6ZTQ0 Hypothetical protein FLJ44384 1Q6ZW19 Hypothetical protein FLJ41761 1Q6ZW52 Hypothetical protein FLJ41598 1Q6ZTQ1 Hypothetical protein FLJ44382 1Q6ZS91 Hypothetical protein FLJ45725 1Q6ZSG2 Hypothetical protein FLJ45557 1Q86UD0 Chromosome 9 open reading frame 140 (OTTHUMP00000064739) 1Q86T65 Disheveled associated activator of morphogenesis 2 1Q86UC4 RNA binding protein 1Q86WW8 Hypothetical protein 1Q7M4M4 Phosphorylation regulatory protein HP-10 1Q7Z353 Hypothetical protein DKFZp686K21156 1Q7Z4A1 MGC45780 1Q6ZNE1 Hypothetical protein FLJ16186 1Q5U5K5 CASC1 protein (Fragment) 1Q5VTB9 Novel protein 1

Q5W0S6 Novel SPANX protein 1Q15436 Protein transport protein Sec23A (SEC23-related protein A) 1Q68DG2 Hypothetical protein DKFZp781J069 1Q16164 G1 phase-specific gene protein (Fragment) 1Q6P5U1 Hypothetical protein 1Q6PN88 Hematopoietic stem/progenitor cell induced protein 2 (Fragment) 1Q86XX4 Extracellular matrix protein FRAS1 precursor 1Q6JEL2 Kelch-like protein 10 1Q6P0M0 Hypothetical protein 1Q8TEK3 Histone-lysine N-methyltransferase, H3 lysine-79 specific (EC 2.1.1.43) (Histone H3-K79 methyltransfe 1Q8TF01 SR rich protein 1Q8WUA4 General transcription factor 3C polypeptide 2 (Transcription factor IIIC-beta subunit) (TF3C-beta) (TF 1Q8WWF3 LOC136263 (Hypothetical protein FLJ40316) 1Q8WWL2 Spir-2 protein (Fragment) 1Q8NI84 OK/SW-CL.10 1Q8TBY9 Hypothetical protein MGC33630 1Q8TDD2 Transcription factor Sp7 (Zinc finger protein osterix) 1Q8TDM0 Breast carcinoma amplified sequence 4 1Q96C67 COL14A1 protein 1Q92914 Fibroblast growth factor-11 (FGF-11) (Fibroblast growth factor homologous factor 3) (FHF-3) 1Q8NGS5 Olfactory receptor 13C4 1Q8N1N1 Hypothetical protein FLJ39107 1Q8N338 Hypothetical protein (Fragment) 1Q8IUA7 ATP-binding cassette sub-family A member 9 1Q8IVF9 KIAA2012 protein (Fragment) 1Q8NC19 Hypothetical protein FLJ90595 1Q8NDC3 Hypothetical protein DKFZp547N1615 (Fragment) 1Q8NDZ4 Hypothetical protein MGC33365 1Q8NF91 Nesprin 1 (Nuclear envelope spectrin repeat protein 1) (Synaptic nuclear envelope protein 1) (Syne-1) (M 1Q8N986 Hypothetical protein FLJ38225 1Q8N7C3 Hypothetical protein FLJ25801 1Q8N7S3 Hypothetical protein FLJ40411 1Q8N8C9 Hypothetical protein FLJ39654 1Q8N5D1 MRPL47 protein 1

Supplemental Table 2: Proteins identified only in well differentiated HNSCC

PeptidesAccession Protein (number)

Q13561 Dynactin complex 50 kDa subunit (50 kDa dynein-associated polypeptide) (p50 dynamitin) (DCT 5Q9UKX2 Myosin heavy chain, skeletal muscle, adult 2 (Myosin heavy chain IIa) (MyHC-IIa) 4P12883 Myosin heavy chain, cardiac muscle beta isoform (MyHC-beta) 4Q9BR76 Coronin-1B (Coronin-2) 3P30049 ATP synthase delta chain, mitochondrial precursor (EC 3.6.3.14) 3Q96E11 Mitochondrial ribosome recycling factor, isoform 1 3P11216 Glycogen phosphorylase, brain form (EC 2.4.1.1) 3Q08380 Galectin-3 binding protein precursor (Lectin galactoside-binding soluble 3 binding protein) (Ma 3P11137 Microtubule-associated protein 2 (MAP 2) (MAP-2) 3P31025 Von Ebner's gland protein precursor (VEG protein) (Tear prealbumin) (TP) (Tear lipocalin) (Lipo 3Q9HCF8 KIAA1614 protein (Fragment) 3Q6NUR7 Villin 2 3Q96PE1 Probable G protein-coupled receptor 124 precursor (Tumor endothelial marker 5) 2P06732 Creatine kinase, M chain (EC 2.7.3.2) (M-CK) 2Q96I25 Splicing factor 45 (45kDa splicing factor) (RNA binding motif protein 17) 2P11678 Eosinophil peroxidase precursor (EC 1.11.1.7) (EPO) 2Q9BVL4 Selenoprotein O 2P12429 Annexin A3 (Annexin III) (Lipocortin III) (Placental anticoagulant protein III) (PAP-III) (35- 2Q00587 CDC42 effector protein 1 (Serum protein MSE55) 2Q14315 Filamin C (Gamma-filamin) (Filamin 2) (Protein FLNc) (Actin-binding like protein) (ABP-L) (ABP- 2P60866 40S ribosomal protein S20 2Q9NS91 Postreplication repair protein RAD18 (hRAD18) (hHR18) (RING finger protein 73) 2O15074 KIAA0368 protein (Fragment) 2O60447 EVI-5 homolog 2P04196 Histidine-rich glycoprotein precursor (Histidine-proline rich glycoprotein) (HPRG) 2P58546 Myotrophin (V-1 protein) 2P62805 Histone H4 2P50416 Carnitine O-palmitoyltransferase I, mitochondrial liver isoform (EC 2.3.1.21) (CPT I) (CPTI-L) ( 2P52292 Importin alpha-2 subunit (Karyopherin alpha-2 subunit) (SRP1-alpha) (RAG cohort protein 1) 2P42261 Glutamate receptor 1 precursor (GluR-1) (GluR-A) (GluR-K1) (Glutamate receptor ionotropic, AM 2P35998 26S protease regulatory subunit 7 (MSS1 protein) 2Q9H7W7 Hypothetical protein FLJ14183 2Q9Y6K5 2'-5'-oligoadenylate synthetase 3 (EC 2.7.7.-) ((2-5')oligo(A) synthetase 3) (2-5A synthetase 2Q9Y6L6 Solute carrier organic anion transporter family member 1B1 (Solute carrier family 21 member 2Q9NQS5 Inflammation-related G protein-coupled receptor EX33 (Putative G-protein coupled receptor) 2Q9NZH7 Interleukin 1 family member 8 (IL-1F8) (Interleukin-1 eta) (IL-1 eta) (FIL1 eta) (Interleukin-1 2Q6ZNX0 Hypothetical protein FLJ26965 2Q86W64 TPM1 protein (Fragment) 2Q63HQ8 Hypothetical protein DKFZp686M21196 2Q15485 Ficolin 2 precursor (Collagen/fibrinogen domain-containing protein 2) (Ficolin-B) (Ficolin B) (Se 2Q15582 Transforming growth factor-beta induced protein IG-H3 precursor (Beta IG-H3) (Kerato-epit 2Q8IYW7 Hypothetical protein (Fragment) 2Q8IW93 Rho guanine nucleotide exchange factor (GEF) 19 (Novel protein) 2Q8NE71 ATP-binding cassette, sub-family F, member 1 (ATP-binding cassette 50) (TNF-alpha stimulate 2Q8N9S5 Hypothetical protein FLJ36608 2Q96EP5 DAZ-associated protein 1 (Deleted in azoospermia-associated protein 1) 1Q96F86 Hypothetical protein FLJ21128 (Hypothetical protein PP844) 1Q8TDS5 G-protein coupled receptor TG1019 1Q96I71 Zinc finger protein 42, isoform 1 1Q96G74 Hypothetical protein DKFZp761A052 1Q8WYH7 Hypothetical protein PP1009 1Q96C19 EF-hand domain-containing protein 2 (Swiprosin 1) 1Q96A55 Hypothetical protein MGC10485 1P31415 Calsequestrin, skeletal muscle isoform precursor (Calsequestrin 1) (Calmitin) 1Q9BS14 G2AN protein (Fragment) 1Q9BTX7 Protein C20orf121 1P08590 Myosin light polypeptide 3 (Myosin light chain 1, slow-twitch muscle B/ventricular isoform) (ML 1P07602 Proactivator polypeptide precursor [Contains: Saposin A (Protein A); Saposin B (Sphingolipid ac 1Q8TDG7 CLL-associated antigen KW-6 (Fragment) 1

Q96L12 Calreticulin 3 precursor (Calreticulin 2) 1P20042 Eukaryotic translation initiation factor 2 subunit 2 (Eukaryotic translation initiation factor 2 b 1Q96NJ6 Hypothetical protein FLJ30726 1Q6ZQW7 Hypothetical protein FLJ46843 1Q01650 Large neutral amino acids transporter small subunit 1 (L-type amino acid transporter 1) (4F2 lig 1Q01831 DNA-repair protein complementing XP-C cells (Xeroderma pigmentosum group C complementing 1Q6ZU46 Hypothetical protein FLJ44004 1P36543 Vacuolar ATP synthase subunit E (EC 3.6.3.14) (V-ATPase E subunit) (Vacuolar proton pump E s 1Q6ZW16 Hypothetical protein FLJ41795 1Q6ZUF0 Hypothetical protein FLJ43766 1Q07325 Small inducible cytokine B9 precursor (CXCL9) (Gamma interferon induced monokine) (MIG) 1Q6ZU30 Hypothetical protein FLJ44035 1P84095 Rho-related GTP-binding protein RhoG 1Q15738 NAD(P)-dependent steroid dehydrogenase (EC 1.1.1.-) (H105e3 protein) 1Q5U651 Ras-interacting protein 1 1Q15466 Nuclear receptor 0B2 (Orphan nuclear receptor SHP) (Small heterodimer partner) 1Q15181 Inorganic pyrophosphatase (EC 3.6.1.1) (Pyrophosphate phospho-hydrolase) (PPase) 1Q75VX8 KIAA2038 protein (Fragment) 1Q6NVV8 LOC285148 protein (Fragment) 1Q6N061 Hypothetical protein DKFZp686B2197 1Q13402 Myosin VIIa 1Q12972 Nuclear inhibitor of protein phosphatase-1 (NIPP-1) (Protein phosphatase 1, regulatory inhibito 1Q69YW3 Hypothetical protein DKFZp434L2430 1P42696 Probable RNA-binding protein KIAA0117 (HAL845) 1Q8N9Y4 Hypothetical protein FLJ36068 1Q8NBR8 Hypothetical protein FLJ90835 1Q8N7Z5 Hypothetical protein FLJ40191 1Q8N7J2 Hypothetical protein FLJ25477 1P46721 Solute carrier organic anion transporter family member 1A2 (Solute carrier family 21 member 1Q8TBG4 Alanine-glyoxylate aminotransferase 2-like 1 (Hypothetical protein FLJ34569) 1P41236 Protein phosphatase inhibitor 2 (IPP-2) 1Q8N3Y1 F-box/WD-repeat protein 8 (F-box and WD-40 domain protein 8) (F-box only protein 29) 1P38159 Heterogeneous nuclear ribonucleoprotein G (hnRNP G) (RNA binding motif protein, X chromoso 1Q8NCI1 Hypothetical protein FLJ90238 1Q86VU5 Catechol-O-methyltransferase domain containing 1 (Methyltransferase) 1Q86SQ9 Dehydrodolichyl diphosphate synthase (EC 2.5.1.-) (Dedol-PP synthase) 1P59768 Guanine nucleotide-binding protein G(I)/G(S)/G(O) gamma-2 subunit (G gamma-I) 1Q8IVG6 KIAA2004 protein (Fragment) 1P62333 26S protease regulatory subunit S10B (Proteasome subunit p42) (Proteasome 26S subunit ATP 1Q8N2K3 Hypothetical protein FLJ90162 1O95239 Chromosome-associated kinesin KIF4A (Chromokinesin) 1Q9HC99 P47ING3 protein (Hypothetical protein ING3) 1Q9UDY2 Tight junction protein ZO-2 (Zonula occludens 2 protein) (Zona occludens 2 protein) (Tight jun 1O75173 ADAMTS-4 precursor (EC 3.4.24.82) (A disintegrin and metalloproteinase with thrombospondi 1O75163 KIAA0676 protein (Fragment) 1P00973 2'-5'-oligoadenylate synthetase 1 (EC 2.7.7.-) ((2-5')oligo(A) synthetase 1) (2-5A synthetase 1 1Q9HCK8 Chromodomain-helicase-DNA-binding protein 8 (CHD-8) (Helicase with SNF2 domain 1) (Fragm 1P02585 Troponin C, skeletal muscle 1Q9NR61 Delta-like protein 4 precursor (Drosophila Delta homolog 4) (UNQ1895/PRO4341) 1Q9NVX2 WD-repeat protein HUSSY-07 1Q9NRA0 Sphingosine kinase 2 (EC 2.7.1.-) (SK 2) (SPK 2) 1O00548 Delta-like protein 1 precursor (Drosophila Delta homolog 1) (Delta1) (H-Delta-1) (UNQ146/PRO 1Q9Y3E5 Peptidyl-tRNA hydrolase 2, mitochondrial precursor (EC 3.1.1.29) (PTH 2) (Bcl-2 inhibitor of tr 1O15093 KIAA0393 protein (Fragment) 1O15119 T-box transcription factor TBX3 (T-box protein 3) 1Q9Y566 SH3 and multiple ankyrin repeat domains protein 1 (Shank1) (Somatostatin receptor interactin 1O00462 Beta-mannosidase precursor (EC 3.2.1.25) (Mannanase) (Mannase) 1O00230 Cortistatin precursor [Contains: Cortistatin-29; Cortistatin-17] 1Q9Y4H2 Insulin receptor substrate-2 (IRS-2) 1Q9ULX5 Zinc finger protein 179 (Brain finger protein) (RING finger protein 112) 1Q9UHU3 PRO1659 1Q9UKB5 Hypothetical protein MOT8 (Transmembrane protein SHREW1) 1Q9UL15 BAG-family molecular chaperone regulator-5 (BAG-5) 1

Q9UHI8 ADAMTS-1 precursor (EC 3.4.24.-) (A disintegrin and metalloproteinase with thrombospondin 1O43405 Cochlin precursor (COCH-5B2) (UNQ257/PRO294) 1O43168 KIAA0443 protein (Fragment) 1Q9Y224 Protein C14orf166 (CGI-99) 1O15143 ARP2/3 complex 41 kDa subunit (P41-ARC) (Actin-related protein 2/3 complex subunit 1B) 1O60341 Amine oxidase flavin containing domain protein 2 (AOF2 protein) (BRAF-HDAC complex protein 1Q9H8D6 Hypothetical protein FLJ13729 1Q9H5W3 Hypothetical protein FLJ22944 1Q9H816 Hypothetical protein FLJ13998 (DNA cross-link repair 1B) (PSO2 homolog, S. cerevisiae) (OTT 1P04114 Apolipoprotein B-100 precursor (Apo B-100) [Contains: Apolipoprotein B-48 (Apo B-48)] 1P06340 HLA class II histocompatibility antigen, DO alpha chain precursor (MHC class II antigen DOA 1Q9HB48 Hypothetical protein 1Q9H8K6 Hypothetical protein FLJ13491 1P59533 Taste receptor type 2 member 38 (T2R38) (T2R61) (PTC bitter taste receptor) 1P61289 Proteasome activator complex subunit 3 (Proteasome activator 28-gamma subunit) (PA28gamm 1O43663 Protein regulating cytokinesis 1 (Protein regulator of cytokinesis 1, isoform 1) 1P67809 Nuclease sensitive element binding protein 1 (Y box binding protein-1) (Y-box transcription fac 1O43303 Centrosomal protein of 110 kDa (CP110 protein) 1O43304 KIAA0420 protein (Fragment) 1P62266 40S ribosomal protein S23 1O60266 Adenylate cyclase type III (EC 4.6.1.1) (Adenylate cyclase, olfactive type) (ATP pyrophosphate 1O60268 Protein KIAA0513 1O60320 Hypothetical protein KIAA0574 (Fragment) 1P51784 Ubiquitin carboxyl-terminal hydrolase 11 (EC 3.1.2.15) (Ubiquitin thiolesterase 11) (Ubiquitin-sp 1P09110 3-ketoacyl-CoA thiolase, peroxisomal precursor (EC 2.3.1.16) (Beta-ketothiolase) (Acetyl-CoA 1P50748 Kinetochore-associated protein 1 (Rough deal homolog) (hRod) (HsROD) (Rod) 1P55145 ARMET protein precursor (Arginine-rich protein) 1P54762 Ephrin type-B receptor 1 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-2) (N 1P55011 Solute carrier family 12 member 2 (Bumetanide-sensitive sodium-(potassium)-chloride cotrans 1P55157 Microsomal triglyceride transfer protein large subunit precursor 1O15287 Fanconi anemia group G protein (FACG protein) (DNA-repair protein XRCC9) 1P55774 Small inducible cytokine A18 precursor (CCL18) (Macrophage inflammatory protein 4) (MIP-4) 1P78333 Glypican-5 precursor 1P57075 UBASH3A protein 1O60237 Protein phosphatase 1 regulatory subunit 12B (Myosin phosphatase targeting subunit 2) (Myosi 1Q13185 Chromobox protein homolog 3 (Heterochromatin protein 1 homolog gamma) (HP1 gamma) (Modif 1Q13255 Metabotropic glutamate receptor 1 precursor (mGluR1) 1Q13129 Zinc finger protein Rlf (Rearranged L-myc fusion gene protein) (Zn-15 related protein) 1O00463 TNF receptor associated factor 5 (RING finger protein 84) 1O14556 Glyceraldehyde-3-phosphate dehydrogenase, testis-specific (EC 1.2.1.12) (Spermatogenic cell- 1O00567 Nucleolar protein Nop56 (Nucleolar protein 5A) 1Q13017 Rho-GTPase-activating protein 5 (p190-B) 1Q13049 Tripartite motif protein 32 (EC 6.3.2.-) (Zinc-finger protein HT2A) (72 kDa Tat-interacting pr 1Q14241 Transcription elongation factor B polypeptide 3 (RNA polymerase II transcription factor SIII 1O00161 Synaptosomal-associated protein 23 (SNAP-23) (Vesicle-membrane fusion protein SNAP-23) 1Q14721 Potassium voltage-gated channel subfamily B member 1 (Voltage-gated potassium channel subu 1Q14766 Latent transforming growth factor beta binding protein, isoform 1L precursor (LTBP-1) (Trans 1Q13618 Cullin homolog 3 (CUL-3) 1P06454 Prothymosin alpha 1P08069 Insulin-like growth factor I receptor precursor (EC 2.7.1.112) (CD221 antigen) 1O15081 KIAA0376 protein (Fragment) 1O15037 KIAA0323 protein (Fragment) 1Q11206 CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase (EC 2.4.99.-) (Beta- 1P78562 Phosphate regulating neutral endopeptidase (EC 3.4.24.-) (Metalloendopeptidase homolog PEX) 1P08107 Heat shock 70 kDa protein 1 (HSP70.1) (HSP70-1/HSP70-2) 1Q00056 Homeobox protein Hox-A4 (Hox-1D) (Hox-1.4) 1O14791 Apolipoprotein L1 precursor (Apolipoprotein L-I) (Apolipoprotein L) (ApoL-I) (Apo-L) (ApoL) 1P05455 Lupus La protein (Sjogren syndrome type B antigen) (SS-B) (La ribonucleoprotein) (La autoanti 1O14879 Interferon-induced protein with tetratricopeptide repeats 3 (IFIT-3) (IFIT-4) (Interferon-i 1Q08170 Splicing factor, arginine/serine-rich 4 (Pre-mRNA splicing factor SRP75) (SRP001LB) 1Q08211 ATP-dependent RNA helicase A (Nuclear DNA helicase II) (NDH II) (DEAH-box protein 9) 1P78344 Eukaryotic translation initiation factor 4 gamma 2 (eIF-4-gamma 2) (eIF-4G 2) (eIF4G 2) (p97 1Q02252 Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial precursor (EC 1.2.1.27 1

Q06418 Tyrosine-protein kinase receptor TYRO3 precursor (EC 2.7.1.112) (Tyrosine-protein kinase RSE 1P23229 Integrin alpha-6 precursor (VLA-6) (CD49f) 1Q6MZR4 Hypothetical protein DKFZp779N1969 (Fragment) 1O95684 FGFR1 oncogene partner (FOP) (OTTHUMP00000017612) (Fragment) 1O95503 Chromobox protein homolog 6 1P20592 Interferon-regulated resistance GTP-binding protein MxB (p78-related protein) 1O95398 RAP guanine-nucleotide-exchange factor 3 (cAMP-regulated guanine nucleotide exchange facto 1P20849 Collagen alpha 1(IX) chain precursor 1O95764 Hypothetical protein WUGSC:H_DJ0901A04.1 (Fragment) 1P24539 ATP synthase B chain, mitochondrial precursor (EC 3.6.3.14) 1O95235 Kinesin family member 20A (Rabkinesin-6) (Rab6-interacting kinesin-like protein) (GG10_2) 1P04150 Glucocorticoid receptor (GR) 1P23468 Receptor-type tyrosine-protein phosphatase delta precursor (EC 3.1.3.48) (Protein-tyrosine ph 1P24046 Gamma-aminobutyric-acid receptor rho-1 subunit precursor (GABA(A) receptor) 1P11177 Pyruvate dehydrogenase E1 component beta subunit, mitochondrial precursor (EC 1.2.4.1) (PDH 1P01042 Kininogen precursor (Alpha-2-thiol proteinase inhibitor) [Contains: Bradykinin (Kallidin I); Lysy 1P02730 Band 3 anion transport protein (Anion exchange protein 1) (AE 1) (CD233 antigen) 1P11487 INT-2 proto-oncogene protein precursor (Fibroblast growth factor-3) (FGF-3) (HBGF-3) 1P15144 Aminopeptidase N (EC 3.4.11.2) (hAPN) (Alanyl aminopeptidase) (Microsomal aminopeptidase) (A 1P18859 ATP synthase coupling factor 6, mitochondrial precursor (EC 3.6.3.14) (F6) 1P16152 Carbonyl reductase [NADPH] 1 (EC 1.1.1.184) (NADPH-dependent carbonyl reductase 1) (Prosta 1P41212 Transcription factor ETV6 (ETS-related protein Tel1) (Tel) (ETS translocation variant 6) 1P09923 Alkaline phosphatase, intestinal precursor (EC 3.1.3.1) (IAP) 1P09914 Interferon-induced protein with tetratricopeptide repeats 1 (IFIT-1) (Interferon-induced 56 1P36405 ADP-ribosylation factor-like protein 3 1O75223 Protein C7orf24 1P42694 Potential helicase with zinc-finger domain 1P10619 Lysosomal protective protein precursor (EC 3.4.16.5) (Cathepsin A) (Carboxypeptidase C) (Prot 1O60884 DnaJ homolog subfamily A member 2 (HIRA interacting protein 4) (Cell cycle progression rest 1P48426 Phosphatidylinositol-4-phosphate 5-kinase type II alpha (EC 2.7.1.149) (PIP5KII-alpha) (1-phos 1P42695 Hypothetical protein KIAA0056 (Fragment) 1O75055 KIAA0467 protein (Fragment) 1P43307 Translocon-associated protein, alpha subunit precursor (TRAP-alpha) (Signal sequence recepto 1P30533 Alpha-2-macroglobulin receptor-associated protein precursor (Alpha-2-MRAP) (Low density lip 1O94822 Zinc finger protein 294 1P28340 DNA polymerase delta catalytic subunit (EC 2.7.7.7) (DNA polymerase delta subunit p125) 1P28907 ADP-ribosyl cyclase 1 (EC 3.2.2.5) (Cyclic ADP-ribose hydrolase 1) (cADPr hydrolase 1) (Lympho 1P34932 Heat shock 70 kDa protein 4 (Heat shock 70-related protein APG-2) (HSP70RY) 1P35275 Zinc finger protein 126 (HZF-2) (Fragment) 1P35609 Alpha-actinin 2 (Alpha actinin skeletal muscle isoform 2) (F-actin cross linking protein) 1O75762 Transient receptor potential cation channel subfamily A member 1 (Ankyrin-like with transmem 1O75665 Oral-facial-digital syndrome 1 protein (Protein 71-7A) 1Q9GZN6 Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 (Solute carrier f 1Q9GZU8 NEFA-interacting nuclear protein NIP30 (CDA10/CDA018) 1Q9GZZ9 Hypothetical protein DKFZp434C2415 (Ubiquitin-activating enzyme E1-domain containing 1, iso 1Q9H1I8 Activating signal cointegrator 1 complex subunit 2 (ASC-1 complex subunit p100) (Trip4 comple 1Q9C0E2 Exportin 4 (Exp4) 1Q9H251 Cadherin-23 precursor (Otocadherin) 1Q9H2T7 Ran-binding protein 17 1Q9BYT9 Transmembrane protein 16C 1Q9BYW2 Huntingtin interacting protein 1 1Q9BYZ6 Rho-related BTB domain-containing protein 2 (Deleted in breast cancer 2 gene protein) (p83) 1Q9C060 LYST-interacting protein LIP8 (Fragment) 1Q9H3P7 Golgi resident protein GCP60 (Acyl-Coenzyme A binding domain containing 3) (Golgi phosphopro 1Q9H974 Hypothetical protein FLJ12960 (QTRTD1 protein) (Queuine tRNA-ribosyltransferase domain c 1Q9H9U2 Hypothetical protein FLJ12548 1Q9HAA5 Hypothetical protein FLJ11889 1Q9NNW5 WD-repeat protein 6 1Q9NP55 Protein Plunc precursor (Palate lung and nasal epithelium clone protein) (Lung specific X protein 1Q96EY1 DnaJ homolog subfamily A member 3, mitochondrial precursor (Tumorous imaginal discs protei 1Q9H8U9 Hypothetical protein FLJ13213 1Q9H788 Hypothetical protein FLJ21146 1Q9H7Z3 Protein C14orf102 1

Q9H819 Hypothetical protein FLJ13992 (Hypothetical protein MGC29463) 1Q9H5W0 Hypothetical protein FLJ22961 1Q96NL8 Hypothetical protein FLJ30600 1Q9BUF5 Tubulin beta MGC4083 1Q96MT8 Centrosomal protein of 63 kDa (Cep63 protein) 1Q96QE3 ATP(GTP)-binding protein 1Q96QH7 DJ54B20.4 (Novel KRAB box containing C2H2 type zinc finger protein) 1Q96N64 Hypothetical protein FLJ31359 1Q6KC79 Nipped-B-like protein (Delangin) (SCC2 homolog) 1Q96G01 Cytoskeleton-like bicaudal D protein homolog 1 1Q96HE7 ERO1-like protein alpha precursor (EC 1.8.4.-) (ERO1-Lalpha) (Oxidoreductin 1-lalpha) (Endopla 1Q96HR9 Chromosome 19 open reading frame 32 1Q96K12 Hypothetical protein FLJ14850 (Male sterility domain containing 1) 1Q96KJ4 Similar to pre-pro-megakarycyte potentiating factor 1Q99856 AT-rich interactive domain-containing protein 3A (ARID domain-containing protein 3A) (B-cell 1Q96RY5 Hypothetical protein KIAA1426 1Q99457 Nucleosome assembly protein 1-like 3 1Q99467 CD180 antigen precursor (Lymphocyte antigen 64) (Radioprotective 105 kDa protein) 1Q99572 P2X purinoceptor 7 (ATP receptor) (P2X7) (Purinergic receptor) (P2Z receptor) 1Q9UP23 PhLP1 1Q9UPT8 KIAA1064 protein (Fragment) 1Q9UPU3 VPS10 domain-containing receptor SorCS3 precursor 1Q9UPX3 KIAA1027 protein (Fragment) 1Q9UQL6 Histone deacetylase 5 (HD5) (Antigen NY-CO-9) 1Q9UPV7 KIAA1045 protein (Fragment) 1Q9UKV3 Apoptotic chromatin condensation inducer in the nucleus (Acinus) 1Q9ULH6 BIG3 1Q9ULJ8 Neurabin-I (Neural tissue-specific F-actin binding protein I) (Protein phosphatase 1 regulatory 1Q9ULV8 Signal transduction protein CBL-C (SH3-binding protein CBL-C) (CBL-3) (RING finger protein 5 1Q9UKY1 Zinc fingers and homeoboxes protein 1 1Q9Y4L2 Zinc finger protein PLAG1 1Q9Y4Z2 Neurogenin 3 1Q9Y6B5 PAK2 1Q9Y5Q9 General transcription factor 3C polypeptide 3 (Transcription factor IIIC-gamma subunit) (TF3 1Q9Y2D9 KIAA0924 protein (Fragment) 1Q9Y2V6 Hypothetical protein (Cardiac ankyrin repeat kinase) (OTTHUMP00000058703) 1Q9Y4I0 Zinc-finger helicase 1Q9Y3E1 CGI-142 protein (Hepatoma-derived growth factor 2) (Hypothetical protein FLJ10418) (Hepat 1Q9Y4E5 Zinc finger protein 451 (Coactivator for steroid receptors) 1Q9UJV9 DEAD-box protein abstrakt homolog (DEAD-box protein 41) 1Q9NW14 Hypothetical protein FLJ10376 1Q9NW75 G patch domain containing protein 2 1Q9NWU1 Hypothetical protein FLJ20604 1Q9NVE7 Pantothenate kinase 4 (EC 2.7.1.33) (Pantothenic acid kinase 4) (hPanK4) 1Q9NY33 Dipeptidyl-peptidase III (EC 3.4.14.4) (DPP III) (Dipeptidyl aminopeptidase III) (Dipeptidyl a 1Q9NYU2 UDP-glucose:glycoprotein glucosyltransferase 1 precursor 1Q9NYY3 Serine/threonine-protein kinase PLK2 (EC 2.7.1.37) (Polo-like kinase 1) (PLK-2) (Serine/threon 1Q9NRY4 Glucocorticoid receptor DNA binding factor 1 (Glucocorticoid receptor repression factor 1) (G 1Q9NR96 Toll-like receptor 9 precursor 1Q9NR99 Adlican 1Q9NVN3 Hypothetical protein FLJ10620 1Q9NZ71 Regulator of telomere elongation helicase 1 (Helicase-like protein NHL) 1Q9NS28 Regulator of G-protein signaling 18 (RGS18) 1Q9NRC8 NAD-dependent deacetylase sirtuin 7 (EC 3.5.1.-) (SIR2-like protein 7) 1Q9UHG0 Doublecortin domain-containing protein 2 (RU2S protein) 1Q9NZ08 Adipocyte-derived leucine aminopeptidase precursor (EC 3.4.11.-) (A-LAP) (ARTS-1) (Aminopep 1Q9UBF2 Coatomer gamma-2 subunit (Gamma-2 coat protein) (Gamma-2 COP) 1Q9UHV7 Thyroid hormone receptor-associated protein complex 240 kDa component (Trap240) (Activat 1Q9UI12 Vacuolar ATP synthase subunit H (EC 3.6.3.14) (V-ATPase H subunit) (Vacuolar proton pump H 1Q9P246 Stromal interaction molecule 2 precursor 1Q9NZJ4 Sacsin 1Q9UBR4 LIM/homeobox protein Lhx3 1Q9P2N4 ADAMTS-9 precursor (EC 3.4.24.-) (A disintegrin and metalloproteinase with thrombospondin 1

Q9UBB4 Ataxin-10 (Spinocerebellar ataxia type 10 protein) (Brain protein E46 homolog) 1Q6ZVI2 Hypothetical protein FLJ42553 1Q71RB0 PP7302 1Q6ZU14 Hypothetical protein FLJ44063 1Q6ZNJ8 FLJ00321 protein (Fragment) 1Q6ZNZ8 Hypothetical protein FLJ26816 1Q6ZP70 Hypothetical protein FLJ26432 1Q6ZP82 Hypothetical protein FLJ26337 1Q6ZR15 Hypothetical protein FLJ46734 1Q6ZR28 Hypothetical protein FLJ46703 1Q6ZR96 Hypothetical protein FLJ46536 1Q71RB1 PP7080 1Q6ZRR7 Hypothetical protein FLJ46156 1Q6ZT48 Hypothetical protein FLJ44959 1Q86T31 Hypothetical protein DKFZp313K2238 1Q86TV4 Full-length cDNA clone CS0DI085YI08 of Placenta of Homo sapiens (human) (Fragment) 1Q86UE4 LYRIC protein (Lysine-rich CEACAM1 co-isolated protein) (3D3/lyric) (Metastasis adhesion pr 1Q7RTR4 NOD16 1Q7RTU8 Harmonin isoform b3 1Q7Z2R7 MSTP131 1Q7Z524 HUMEEP 1Q7Z5L9 Interferon regulatory factor-2 binding protein 2A 1Q7Z6J8 C6orf157 protein (Fragment) 1Q7Z6L5 MYO1B protein 1Q16799 Reticulon 1 (Neuroendocrine-specific protein) 1Q16650 T-brain-1 protein (T-box brain protein 1) (TBR-1) (TES-56) 1Q5W064 Lipase-like, ab-hydrolase domain containing 1 1Q15006 Tetratricopeptide repeat protein KIAA0103 1Q15051 IQ calmodulin-binding motif containing protein 1 1Q15417 Calponin-3 (Calponin, acidic isoform) 1Q15751 P532 1Q15927 DNA-binding protein (Fragment) 1Q6PH81 Similar to RIKEN cDNA 4921524J17 1Q6UB98 Ankyrin repeat domain protein 12 (Ankyrin repeat-containing cofactor-2) (GAC-1 protein) 1Q6URC4 Diaphanous 1 1Q6UWF8 VSSW1971 1Q6UWT9 APRG372 1Q6NE83 Hypothetical protein DKFZp686O06111 1Q68D79 Hypothetical protein DKFZp686K16211 1Q8TEF8 FLJ00239 protein (Fragment) 1Q8TEW8 Amyotrophic lateral sclerosis 2 chromosome region candidate gene protein 19 (Partitioning-def 1Q8WTW4 Tumor suppressor candidate 4 (NPR2-like) (Gene 21 protein) (G21 protein) 1Q8WVS4 Hypothetical protein FLJ10300 1Q8WVU3 HT007 protein 1Q86XD5 KIAA0773 protein 1Q8NHS5 RNF151 protein (Fragment) 1Q8TAV4 Stomatin-like 3 1Q8TB36 Ganglioside-induced differentiation-associated protein 1 (GDAP1) 1Q8TBX8 Phosphatidylinositol-4-phosphate 5-kinase, type II, gamma 1Q8TCU5 Glutamate [NMDA] receptor subunit 3A precursor (N-methyl-D-aspartate receptor subtype N 1Q8TDX9 Polycystic kidney disease 1-like 1 protein (Polycystin 1L1) 1Q969J3 LOH12CR1 (Hypothetical protein FLJ90547) (LOH1CR12) 1Q96AJ9 Vesicle transport through interaction with t-SNAREs homolog 1A (Vesicle transport v-SNARE 1Q93038 Tumor necrosis factor receptor superfamily member 25 precursor (WSL-1 protein) (Apoptosis 1Q92993 Histone acetyltransferase HTATIP (EC 2.3.1.48) (60 kDa Tat interactive protein) (Tip60) (HIV 1Q96CX6 Hypothetical protein (Fragment) 1Q96BD8 Chromosome 18 open reading frame 24 1Q8WYS0 GL013 1Q8WYZ7 Hypothetical protein 1Q8WZA2 RAP guanine-nucleotide-exchange factor 4 (cAMP-regulated guanine nucleotide exchange facto 1Q92538 Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (BFA-resistant GEF 1Q92618 Zinc finger protein 516 1Q92625 Ankyrin repeat and SAM domain protein 1 1

Q92764 Keratin, type I cuticular HA5 (Hair keratin, type I HA5) 1Q92966 snRNA activating protein complex 50 kDa subunit (SNAPc 50 kDa subunit) (Proximal sequence 1Q8IZA3 Oocyte-specific histone H1 1Q8N2E9 Hypothetical protein PSEC0211 1Q8N4U5 Hypothetical protein MGC40368 1Q8N1Q8 Hypothetical protein FLJ37964 1Q8IVE6 KIAA2025 protein (Fragment) 1Q8IWN7 Retinitis pigmentosa 1-like 1 protein 1Q8IXT5 Similar to RIKEN cDNA 3000004N20 1Q8NDZ6 Hypothetical protein MGC33214 1Q8ND90 Paraneoplastic antigen Ma1 (Neuron- and testis-specific protein 1) (37 kDa neuronal protein) 1Q8NE67 NYD-SP12 protein 1Q8NF24 FLJ00378 protein (Fragment) 1Q8NF50 Dedicator of cytokinesis protein 8 (Fragment) 1Q8NF99 Zinc finger protein 397 (Zinc finger and SCAN domain containing protein 15) 1Q14827 MG21 protein (Fragment) 1Q8NDW3 Zinc finger protein 33b (Zinc finger protein 11b) (KOX 2) 1Q8N6F8 Williams-Beuren syndrome chromosome region 27 (WBSCR27) (Williams-Beuren syndrome crit 1Q8N8D6 Hypothetical protein FLJ39636 1Q8NBU9 Hypothetical protein FLJ90734 (PP10933) 1Q8N991 Hypothetical protein FLJ38192 1Q8N9V7 Hypothetical protein FLJ36157 1

Supplemental Table 3: Proteins identified only in mild differentiated HNSCC

PeptidesAccession Protein (number)

Q9Y3Z3 SAM domain and HD domain-containing protein 1 (Dendritic cell-derived IFNG-induced protein) 5P50914 60S ribosomal protein L14 (CAG-ISL 7) 3Q13057 Bifunctional coenzyme A synthase (CoA synthase) (NBP) (POV-2) [Includes: Phosphopantethein 3P45974 Ubiquitin carboxyl-terminal hydrolase 5 (EC 3.1.2.15) (Ubiquitin thiolesterase 5) (Ubiquitin-spec 3P49588 Alanyl-tRNA synthetase (EC 6.1.1.7) (Alanine--tRNA ligase) (AlaRS) 2Q12996 Cleavage stimulation factor 77kDa subunit 2Q14624 Inter-alpha-trypsin inhibitor heavy chain H4 precursor (ITI heavy chain H4) (Inter-alpha-inhib 2O15032 KIAA0316 protein (Fragment) 2Q01955 Collagen alpha 3(IV) chain precursor (Goodpasture antigen) 2O95661 Rho-related GTP-binding protein RhoI 2P23921 Ribonucleoside-diphosphate reductase large subunit (EC 1.17.4.1) (Ribonucleoside-diphosphate r 2P02656 Apolipoprotein C-III precursor (Apo-CIII) (ApoC-III) 2P12018 Immunoglobulin iota chain precursor (V(pre)B protein) (VpreB protein) (CD179a antigen) 2O75348 Vacuolar ATP synthase subunit G 1 (EC 3.6.3.14) (V-ATPase G subunit 1) (Vacuolar proton pump 2P38606 Vacuolar ATP synthase catalytic subunit A, ubiquitous isoform (EC 3.6.3.14) (V-ATPase A subun 2Q9HBK9 Cyt19 2Q96KR5 Leishmanolysin-like peptidase, variant 2 (EC 3.4.24.36) 2Q9BU70 Chromosome 9 open reading frame 156 2Q9Y265 RuvB-like 1 (EC 3.6.1.-) (49-kDa TATA box-binding protein-interacting protein) (49 kDa TBP-int 2Q9ULV0 Myosin Vb (Myosin 5B) 2Q9NWL6 Hypothetical protein FLJ20752 (HCV NS3-transactivated protein 1) 2Q9UJ70 N-acetylglucosamine kinase (EC 2.7.1.59) (GlcNAc kinase) 2Q6ZRD7 Hypothetical protein FLJ46433 2Q7Z7A1 CENTRIOLIN 2Q8TE28 BA351K23.4 (Novel protein) (Hypothetical protein FLJ25831) 2Q8IYW2 Chromosome 10 open reading frame 92 2Q8N7E2 Hypothetical protein FLJ25735 2P59045 NACHT-, LRR- and PYD-containing protein 11 (PYRIN-containing APAF1-like protein 6) (Nucleot 1P62191 26S protease regulatory subunit 4 (P26s4) (Proteasome 26S subunit ATPase 1) 1O43432 Eukaryotic translation initiation factor 4 gamma 3 (eIF-4-gamma 3) (eIF-4G 3) (eIF4G 3) (eIF 1P58107 Epiplakin (450 kDa epidermal antigen) 1O43681 Arsenical pump-driving ATPase (EC 3.6.3.16) (Arsenite-translocating ATPase) (Arsenical resista 1O43583 Density-regulated protein (DRP) (DRP1 protein) (Smooth muscle cell associated protein-3) (SM 1O43156 Protein KIAA0406 1O15398 N-methyl-D-aspartate receptor 2C subunit precursor 1O15372 Eukaryotic translation initiation factor 3 subunit 3 (eIF-3 gamma) (eIF3 p40 subunit) (eIF3h) 1O43182 Rho-GTPase-activating protein 6 (Rho-type GTPase-activating protein RhoGAPX-1) 1O60275 KIAA0522 protein (Fragment) 1P51572 B-cell receptor-associated protein 31 (BCR-associated protein Bap31) (p28 Bap31) (CDM protei 1P49646 Very very hypothetical protein RMSA-1 1P48681 Nestin 1P49247 Ribose-5-phosphate isomerase (EC 5.3.1.6) (Phosphoriboisomerase) 1P09001 Mitochondrial 39S ribosomal protein L3 (L3mt) (MRP-L3) 1P50443 Sulfate transporter (Diastrophic dysplasia protein) 1O43836 NMDA receptor glutamate-binding chain (Fragment) 1P52701 DNA mismatch repair protein MSH6 (MutS-alpha 160 kDa subunit) (G/T mismatch binding prot 1P05161 Ubiquitin cross-reactive protein precursor (Interferon-induced 17 kDa protein) (Interferon-in 1O60229 Huntingtin-associated protein-interacting protein (Duo protein) 1P54132 Bloom's syndrome protein (EC 3.6.1.-) (RecQ protein-like 3) (DNA helicase, RecQ-like, type 2) 1P52789 Hexokinase, type II (EC 2.7.1.1) (HK II) (Muscle form hexokinase) 1P53675 Clathrin heavy chain 2 (CLH-22) 1P53992 Protein transport protein Sec24C (SEC24-related protein C) 1P51888 Prolargin precursor (Proline-arginine-rich end leucine-rich repeat protein) 1P52566 Rho GDP-dissociation inhibitor 2 (Rho GDI 2) (Rho-GDI beta) (Ly-GDI) 1O00571 DEAD-box protein 3 (Helicase-like protein 2) (HLP2) (DEAD-box, X isoform) 1O00515 Ladinin 1 (Lad-1) (120 kDa linear IgA bullous dermatosis antigen) (97 kDa linear IgA bullous der 1Q13427 Peptidyl-prolyl cis-trans isomerase G (EC 5.2.1.8) (Peptidyl-prolyl isomerase G) (PPIase G) (Rota 1Q13283 Ras-GTPase-activating protein binding protein 1 (GAP SH3-domain binding protein 1) (G3BP-1) ( 1Q12887 Protoheme IX farnesyltransferase, mitochondrial precursor (EC 2.5.1.-) (Heme O synthase) 1

Q13023 A-kinase anchor protein 6 (Protein kinase A anchoring protein 6) (PRKA6) (A-kinase anchor prot 1Q13459 Myosin IXb (Unconventional myosin-9b) 1P06744 Glucose-6-phosphate isomerase (EC 5.3.1.9) (GPI) (Phosphoglucose isomerase) (PGI) (Phosphohe 1Q13698 Voltage-dependent L-type calcium channel alpha-1S subunit (Voltage-gated calcium channel alph 1Q14088 Ras-related protein Rab-33A (Small GTP-binding protein S10) 1O00311 Cell division cycle 7-related protein kinase (EC 2.7.1.-) (CDC7-related kinase) (HsCdc7) (huCdc7 1Q14151 Scaffold attachment factor B2 1Q01130 Splicing factor, arginine/serine-rich 2 (Splicing factor SC35) (SC-35) (Splicing component, 35 1Q01970 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta 3 (EC 3.1.4.11) (Phosphoinositid 1O15263 Beta-defensin 2 precursor (BD-2) (hBD-2) (Defensin, beta 2) (Skin-antimicrobial peptide 1) (SA 1Q00013 55 kDa erythrocyte membrane protein (p55) (Membrane protein, palmitoylated 1) 1Q08257 Quinone oxidoreductase (EC 1.6.5.5) (NADPH:quinone reductase) (Zeta-crystallin) 1O14776 Transcription elongation regulator 1 (TATA box-binding protein-associated factor 2S) (Transc 1O14771 Zinc finger protein 213 (Putative transcription factor CR53) 1P07711 Cathepsin L precursor (EC 3.4.22.15) (Major excreted protein) (MEP) 1O14810 Complexin 1 (Synaphin 2) 1O15020 Spectrin beta chain, brain 2 (Spectrin, non-erythroid beta chain 2) (Beta-III spectrin) 1Q02818 Nucleobindin 1 precursor (CALNUC) 1O14907 Tax interaction protein 1 (Glutaminase-interacting protein 3) (Tax-interacting protein 1) (Tax1 1Q06250 Wilms' tumor associated protein (WIT-1) 1P21817 Ryanodine receptor 1 (Skeletal muscle-type ryanodine receptor) (RyR1) (RYR-1) (Skeletal muscl 1O95672 Endothelin-converting enzyme-like 1 (EC 3.4.24.-) (Xce protein) 1P22223 Cadherin-3 precursor (Placental-cadherin) (P-cadherin) 1P22234 Multifunctional protein ADE2 [Includes: Phosphoribosylaminoimidazole-succinocarboxamide syn 1O95453 Poly(A)-specific ribonuclease (PARN protein) 1O60566 Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (EC 2.7.1.37) (hBUBR1) (MAD3/ 1P20618 Proteasome subunit beta type 1 (EC 3.4.25.1) (Proteasome component C5) (Macropain subunit C5 1O95777 U6 snRNA-associated Sm-like protein LSm8 1O95714 HERC2 protein 1O94880 PHD finger protein 14 1P26367 Paired box protein Pax-6 (Oculorhombin) (Aniridia, type II protein) 1P26447 S100 calcium-binding protein A4 (Metastasin) (Mts1 protein) (Placental calcium-binding protein 1P26639 Threonyl-tRNA synthetase, cytoplasmic (EC 6.1.1.3) (Threonine--tRNA ligase) (ThrRS) 1O94872 KIAA0774 protein (Fragment) 1O95271 Tankyrase 1 (EC 2.4.2.30) (TANK1) (Tankyrase I) (TNKS-1) (TRF1-interacting ankyrin-related A 1P23434 Glycine cleavage system H protein, mitochondrial precursor 1O95243 Methyl-CpG binding protein 4 (EC 3.2.2.-) (Methyl-CpG binding domain protein 4) (Methyl-CpG b 1P01771 Ig heavy chain V-III region HIL 1P13667 Protein disulfide-isomerase A4 precursor (EC 5.3.4.1) (Protein ERp-72) (ERp72) 1P13637 Sodium/potassium-transporting ATPase alpha-3 chain (EC 3.6.3.9) (Sodium pump 3) (Na+/K+ AT 1P13942 Collagen alpha 2(XI) chain precursor 1P01137 Transforming growth factor beta 1 precursor (TGF-beta 1) 1P01767 Ig heavy chain V-III region BUT 1P13533 Myosin heavy chain, cardiac muscle alpha isoform (MyHC-alpha) 1P01009 Alpha-1-antitrypsin precursor (Alpha-1 protease inhibitor) (Alpha-1-antiproteinase) (PRO0684/ 1P40616 ADP-ribosylation factor-like protein 1 1P36952 Maspin precursor (Protease inhibitor 5) 1O75427 Leucine-rich repeats and calponin homology domain containing protein 4 (Leucine-rich neuronal 1P38935 DNA-binding protein SMUBP-2 (Immunoglobulin mu binding protein 2) (SMUBP-2) (Glial factor- 1O75051 KIAA0463 protein (Fragment) 1O75037 Kinesin family member 21B (Fragment) 1O60888 Divalent cation tolerant protein CUTA (DJ570F3.2) (LOC51596 (Divalent cation tolerant prote 1O75154 Eferin 1P43897 Elongation factor Ts, mitochondrial precursor (EF-Ts) (EF-TsMt) 1O75912 Diacylglycerol kinase, iota (EC 2.7.1.107) (Diglyceride kinase) (DGK-iota) (DAG kinase iota) 1P29966 Myristoylated alanine-rich C-kinase substrate (MARCKS) (Protein kinase C substrate, 80 kDa p 1P30622 Restin (Cytoplasmic linker protein-170 alpha-2) (CLIP-170) (Reed-Sternberg intermediate filam 1O75923 Dysferlin (Dystrophy associated fer-1-like protein) (Fer-1 like protein 1) 1P27694 Replication protein A 70 kDa DNA-binding subunit (RP-A) (RF-A) (Replication factor-A protein 1P27708 CAD protein [Includes: Glutamine-dependent carbamoyl-phosphate synthase (EC 6.3.5.5); Aspa 1P04275 Von Willebrand factor precursor (vWF) [Contains: Von Willebrand antigen II] 1P29218 Inositol-1(or 4)-monophosphatase (EC 3.1.3.25) (IMPase) (IMP) (Inositol monophosphatase) (Lit 1O75995 SH3 protein expressed in lymphocytes homolog 1

P10909 Clusterin precursor (Complement-associated protein SP-40,40) (Complement cytolysis inhibitor 1P35052 Glypican-1 precursor 1O75821 Eukaryotic translation initiation factor 3 subunit 4 (eIF-3 delta) (eIF3 p44) (eIF-3 RNA-bindin 1P35754 Glutaredoxin (Thioltransferase) (TTase) 1P32780 TFIIH basal transcription factor complex p62 subunit (Basic transcription factor 62 kDa subu 1P33241 Lymphocyte-specific protein 1 (Protein pp52) (52 kDa phosphoprotein) (Lymphocyte-specific an 1P10912 Growth hormone receptor precursor (GH receptor) (Somatotropin receptor) [Contains: Growth 1P31645 Sodium-dependent serotonin transporter (5HT transporter) (5HTT) 1Q9GZU1 Mucolipin 1 (Mucolipidin) (MG-2) (MSTP080) 1Q9C0K0 B-cell lymphoma/leukemia 11B (B-cell CLL/lymphoma 11B) (Radiation-induced tumor suppressor g 1Q9H2E6 Semaphorin 6A precursor (Semaphorin VIA) (Sema VIA) (Semaphorin 6A-1) (SEMA6A-1) 1Q9H2J1 AD038 1Q9H2K0 DC38 (Mitochondrial translational initiation factor 3) 1Q9H372 PRO1433 1Q9H3C7 C3HC4-type zinc finger protein 1Q9NP95 Fibroblast growth factor-20 (FGF-20) 1Q9BVG3 Hypothetical protein FLJ10759 (Novel protein) 1Q9BXT8 RING finger protein 17 1Q9GZM6 Olfactory receptor 8D2 (Olfactory receptor-like protein JCG2) 1Q9C0C8 KIAA1735 protein (Fragment) 1Q9C0D7 KIAA1726 protein (Fragment) 1Q9H9P2 Chondrolectin precursor (Transmembrane protein MT75) (Protein PRED12) (UNQ872/PRO1890 1Q9HBH1 Peptide deformylase, mitochondrial precursor (EC 3.5.1.88) (PDF) (Polypeptide deformylase) 1Q9HCU4 Cadherin EGF LAG seven-pass G-type receptor 2 precursor (Epidermal growth factor-like 2) (M 1Q9NP31 SH2 domain protein 2A (T cell-specific adapter protein) (TSAd) (VEGF receptor-associated pr 1Q9H4M9 EH-domain containing protein 1 (Testilin) (hPAST1) 1Q9H559 BA526D8.4 (Novel KRAB box containing C2H2 type zinc finger protein) (Fragment) 1Q9H598 Vesicular inhibitory amino acid transporter (GABA and glycine transporter) (Vesicular GABA tr 1Q9H5I1 Histone-lysine N-methyltransferase, H3 lysine-9 specific 2 (EC 2.1.1.43) (Histone H3-K9 methy 1Q9H5L4 Hypothetical protein FLJ23323 1Q9H6B0 Hypothetical protein FLJ22422 1Q9H7L9 FLJ00052 protein (Fragment) 1Q9H7T0 Hypothetical protein FLJ14298 1Q96LZ7 Hypothetical protein FLJ32954 1Q96MH4 Hypothetical protein FLJ32377 1Q96MM0 Hypothetical protein FLJ32172 1Q96MN5 Hypothetical protein FLJ32112 (Novel protein) 1Q96NW3 FLJ00054 protein (Fragment) 1Q96Q34 ALS2CR13 protein (Fragment) 1Q96QE2 Proton myo-inositol cotransporter (H(+)-myo-inositol cotransporter) (Hmit) 1Q96FQ6 S100 calcium-binding protein A16 (S100F) 1Q96G46 Hypothetical protein LOC56931 1Q96HP4 Hypothetical protein MGC15763 1Q96LZ2 Hypothetical protein FLJ32965 1Q96I99 Succinyl-CoA ligase [GDP-forming] beta-chain, mitochondrial precursor (EC 6.2.1.4) (Succinyl-C 1Q96QX3 BA54H7.1 (KIAA0865 protein) (Fragment) 1Q96IF6 FBF1 protein (Fragment) 1Q96JH7 Deubiquitinating protein VCIP135 (EC 3.4.22.-) (Valosin-containing protein p97/p47 complex-int 1Q96K72 Hypothetical protein FLJ14464 1Q9BQA8 G patch domain and KOW motifs 1Q99733 Nucleosome assembly protein 1-like 4 (Nucleosome assembly protein 2) (NAP2) 1Q9BPU6 Dihydropyrimidinase related protein-5 (DRP-5) (ULIP6 protein) (Collapsin response mediator pr 1Q9BQ15 Hypothetical protein MGC2731 1Q96QK1 Vacuolar protein sorting 35 (Vesicle protein sorting 35) (hVPS35) (Maternal-embryonic 3) 1Q9BRJ2 39S ribosomal protein L45, mitochondrial precursor (L45mt) (MRP-L45) 1Q9BSE5 Agmatinase, mitochondrial precursor (EC 3.5.3.11) (Agmatine ureohydrolase) (AUH) 1Q9BSL1 Ubiquitin associated domain containing 1 (OTTHUMP00000022563) 1Q96RZ0 Hypothetical protein gs103 1Q99496 DinG protein (Ring finger protein BAP-1) (Ring finger protein 2) (OTTHUMP00000060668) 1Q99575 Ribonucleases P/MRP protein subunit POP1 (EC 3.1.26.5) (hPOP1) 1Q99650 Oncostatin-M specific receptor beta subunit 1Q9UNL2 Translocon-associated protein, gamma subunit (TRAP-gamma) (Signal sequence receptor gamma 1Q9UQ80 Proliferation-associated protein 2G4 (Cell cycle protein p38-2G4 homolog) (hG4-1) 1

Q9UQB3 Catenin delta-2 (Delta-catenin) (Neural plakophilin-related ARM-repeat protein) (NPRAP) (Neu 1Q9Y228 TRAF3-interacting JNK-activating modulator 1Q9Y250 Leucine zipper putative tumor suppressor 1 (F37/esophageal cancer-related gene-coding leucin 1Q9UJW8 Zinc finger protein 180 (HHZ168) 1Q9UKE5 TRAF2 and NCK interacting kinase (EC 2.7.1.37) 1Q9UL04 Membrane protein CH1 1Q9UL62 Short transient receptor potential channel 5 (TrpC5) (Htrp-5) (Htrp5) 1Q9ULZ3 Apoptosis-associated speck-like protein containing a CARD (hASC) (PYD and CARD domain cont 1Q9Y4I1 Myosin Va (Myosin 5A) (Dilute myosin heavy chain, non-muscle) (Myosin heavy chain 12) (Myoxin 1Q9Y5G7 Protocadherin gamma A6 precursor (PCDH-gamma-A6) 1Q9Y6C2 EMILIN 1 precursor (Elastin microfibril interface-located protein 1) (Elastin microfibril interf 1Q9Y3B1 Protein C20orf45 (CGI-107) 1Q9Y285 Phenylalanyl-tRNA synthetase alpha chain (EC 6.1.1.20) (Phenylalanine--tRNA ligase alpha chain 1Q9Y2E3 KIAA0931 protein (Fragment) 1Q9Y305 Putative acyl-CoA thioester hydrolase CGI-16 (EC 3.1.2.-) 1Q9Y3P9 Rab6 GTPase activating protein, GAPCenA (RABGAP1 protein) (OTTHUMP00000022081) 1Q9Y3R0 Glutamate receptor-interacting protein 1 (GRIP1 protein) 1Q9Y3R5 Protein C21orf5 1Q9Y4D7 Plexin D1 precursor 1Q9NVS3 Hypothetical protein FLJ10547 1Q9NY59 Neutral sphingomyelinase II (EC 3.1.4.12) 1Q9NY74 ETAA16 protein 1Q9NYI0 Pleckstrin and Sec7 domain containing protein 3 (Exchange factor for ADP-ribosylation factor 1Q9NYV9 Taste receptor type 2 member 13 (T2R13) (Taste receptor family B member 3) (TRB3) 1Q9NQ87 HEYL protein (Hairy/enhancer-of-split related with YRPW motif-like) (Hairy-related transcrip 1Q9NQW6 Actin binding protein anillin 1Q9NU39 Forkhead box protein D4-like 1 1Q9NV16 Hypothetical protein FLJ10993 1Q9NV64 Hypothetical protein FLJ10902 1Q9UBV7 Beta-1,4-galactosyltransferase 7 (EC 2.4.1.-) (Beta-1,4-GalTase 7) (Beta4Gal-T7) (b4Gal-T7) (U 1Q9UHP6 Rhabdoid tumor deletion region protein 1 1Q9UI33 Sodium channel protein type XI alpha subunit (Voltage-gated sodium channel alpha subunit Nav 1Q96EP1 Ubiquitin ligase protein CHFR (EC 6.3.2.-) (Checkpoint with forkhead and RING finger domains 1Q9NZM3 Intersectin 2 (SH3 domain-containing protein 1B) (SH3P18) (SH3P18-like WASP associated pro 1Q9NZT2 Opioid growth factor receptor (OGFr) (Zeta-type opioid receptor) (7-60 protein) 1Q9NZV1 Cysteine-rich repeat-containing protein S52 precursor (CRIM1) 1Q9P0K8 Forkhead box protein J2 (Fork head homologous X) 1Q9P0M7 HSPC252 1Q9P2I6 KIAA1361 protein (Fragment) 1Q9P2Y5 UV radiation resistance-associated gene protein (p63) 1Q9UBC3 DNA (cytosine-5)-methyltransferase 3B (EC 2.1.1.37) (Dnmt3b) (DNA methyltransferase HsaI 1Q9NZ56 Formin 2 (Fragments) 1Q6ZTV6 Hypothetical protein FLJ44186 1Q6ZU73 Hypothetical protein FLJ43954 1Q6ZUZ4 Hypothetical protein FLJ43187 1Q6ZVC0 Hypothetical protein FLJ42783 1Q6ZVY7 Hypothetical protein FLJ41907 1Q86XJ2 PLCL4 protein (Fragment) 1Q6ZRL9 Hypothetical protein FLJ46257 1Q6ZSR9 Hypothetical protein FLJ45252 1Q86SJ2 Amphoterin induced gene 2 (DEGA/AMIGO-2 precursor) (Alivin 1) (Transmembrane protein AM 1Q86U33 Full-length cDNA clone CS0DA005YA22 of Neuroblastoma of Homo sapiens (human) (Fragment 1Q86VH3 Hypothetical protein 1Q86U54 CD151 antigen (CD151 protein) 1Q76E58 Epiplakin 1Q7Z2W7 Transient receptor potential cation channel subfamily M member 8 (Transient receptor potent 1Q7Z7L7 Chromosome 9 open reading frame 60 (OTTHUMP00000022294) 1Q7Z6K5 Similar to mouse 2610034B18Rik protein 1Q7Z707 DJ1042K10.5 (Novel protein) (Fragment) 1Q7Z727 Hypothetical protein (Fragment) 1Q5VX49 OTTHUMP00000030575 1Q5VZR4 Hippocampus abundant gene transcript-like 2 1Q68CR0 Hypothetical protein DKFZp781K12107 (Fragment) 1

Q15057 Centaurin beta 2 (Cnt-b2) 1Q15058 Kinesin-like protein KIF14 1Q15361 Transcription factor 1Q15662 Transformation-related protein (Fragment) 1Q15782 Chitinase 3-like protein 2 precursor (YKL-39) (Chondrocyte protein 39) 1Q15884 Protein C9orf61 (Protein X123) (Fragment) 1Q6P9G8 Chromosome 6 open reading frame 60 1Q6PJI4 CBF1 interacting corepressor, isoform 2 1Q6XYD6 LP2477 1Q6ZNC2 Hypothetical protein FLJ16223 1Q6IS24 Putative polypeptide N-acetylgalactosaminyltransferase-like protein 3 (EC 2.4.1.41) (Protein-UD 1Q6ZNE3 Hypothetical protein FLJ16182 1Q68DN1 Hypothetical protein DKFZp781D2023 1Q69YQ3 Hypothetical protein DKFZp762I052 (OTTHUMP00000064740) 1Q6AI58 Hypothetical protein DKFZp781A0295 (Fragment) 1Q6IQ22 Hypothetical protein (Fragment) 1Q6P3W7 Similar to mouse D10Ertd802e protein 1Q6MZZ7 Hypothetical protein DKFZp686L13193 1Q6NZI2 Polymerase I and transcript release factor (PTRF protein) (FKSG13 protein) 1Q8TB37 Protein C14orf127 1Q8TB91 Prospero-related homeobox 1 1Q96BJ8 Engulfment and cell motility protein 3 1Q969X1 RECS1 protein homolog (PP1201) 1Q96A40 Hypothetical protein FLJ30760 (Paraneoplastic antigen like 6A) 1Q96AA8 Hypothetical protein KIAA0555 1Q96CT7 Hypothetical protein LOC115098 1Q96DY7 Mdm2, transformed 3T3 cell double minute 2, p53 binding protein binding protein 1Q92598 Heat-shock protein 105 kDa (Heat shock 110 kDa protein) (Antigen NY-CO-25) 1Q8WYX4 Hypothetical protein pp11662 1Q92484 Acid sphingomyelinase-like phosphodiesterase 3a precursor (EC 3.1.4.-) (ASM-like phosphodiest 1Q92542 Nicastrin precursor (UNQ1874/PRO4317) 1Q93097 Wnt-2b protein precursor (Wnt-13) 1Q92772 P56 KKIAMRE protein kinase 1Q92890 Ubiquitin fusion degradation protein 1 homolog (UB fusion protein 1) 1Q92562 Protein KIAA0274 1Q8N158 Glypican 2 (Hypothetical protein FLJ38962) (Hypothetical protein DKFZp547M109) 1Q8N3F8 Molecule interacting with Rab13 (MIRab13) (MICAL-like protein 1) 1Q8N3R9 MAGUK p55 subfamily member 5 1Q8N3T1 Polypeptide N-acetylgalactosaminyltransferase-like protein 2 (EC 2.4.1.41) (Protein-UDP acetyl 1Q8N4B6 Chromosome 6 open reading frame 10 1Q8IW25 Hypothetical protein KIAA1586 (OTTHUMP00000040022) 1Q8IVU3 HERC6 protein (Fragment) 1Q8N655 Chromosome 10 open reading frame 12 1Q8IW72 LOC374654 protein (Fragment) 1Q8IXL7 LOC253827 protein 1Q8IY92 BTB/POZ domain containing protein 12 1Q8NC44 Hypothetical protein FLJ90502 1Q8NC75 Hypothetical protein FLJ90437 1Q8NCA5 Hypothetical protein FLJ90386 1Q8NCN4 KIAA1991 protein (Fragment) 1Q8NBN0 Hypothetical protein PSEC0101 1Q8NFJ9 Bardet-Biedl syndrome 1 protein (BBS2-like protein 2) 1Q8NFN8 GABAB-related G-protein coupled receptor 1Q8NG48 WINS1 protein with Drosophila Lines (Lin) homologous domain 1Q8NA27 Hypothetical protein FLJ35908 1

Supplemental Table 4: Proteins identified only in poorly differentiated HNSCC

PeptidesAccession Protein (number)

Q6ZVY6 Hypothetical protein FLJ41910 8Q13015 Protein AF1q 6P23526 Adenosylhomocysteinase (EC 3.3.1.1) (S-adenosyl-L-homocysteine hydrolase) (AdoHcyase) 4P31040 Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial precursor (EC 1.3.5.1) (Fp) (Fl 4Q96FV1 KRT19 protein (Fragment) 4Q9UJS0 Calcium-binding mitochondrial carrier protein Aralar2 (Mitochondrial aspartate glutamate carrier 2) (So 4P36542 ATP synthase gamma chain, mitochondrial precursor (EC 3.6.3.14) 3O43143 Putative pre-mRNA splicing factor RNA helicase (DEAH box protein 15) (ATP-dependent RNA helicase # 2P51648 Fatty aldehyde dehydrogenase (EC 1.2.1.3) (Aldehyde dehydrogenase, microsomal) (ALDH class 3) 2P49736 DNA replication licensing factor MCM2 (Minichromosome maintenance protein 2 homolog) (Nuclear prot 2Q13263 Transcription intermediary factor 1-beta (TIF1-beta) (Tripartite motif protein 28) (Nuclear corepresso 2Q13423 NAD(P) transhydrogenase, mitochondrial precursor (EC 1.6.1.2) (Pyridine nucleotide transhydrogenase) ( 2Q08397 Lysyl oxidase homolog 1 precursor (EC 1.4.3.-) (Lysyl oxidase-like protein 1) (LOL) 2P00352 Aldehyde dehydrogenase 1A1 (EC 1.2.1.3) (Aldehyde dehydrogenase, cytosolic) (ALDH class 1) (Retinal d 2P09936 Ubiquitin carboxyl-terminal hydrolase isozyme L1 (EC 3.4.19.12) (UCH-L1) (Ubiquitin thiolesterase L1) (N 2O94826 Mitochondrial precursor proteins import receptor (Translocase of outer membrane TOM70) 2P43652 Afamin precursor (Alpha-albumin) (Alpha-Alb) 2P33992 DNA replication licensing factor MCM5 (CDC46 homolog) (P1-CDC46) 2Q9BZD6 Transmembrane gamma-carboxyglutamic acid protein 4 precursor (Proline-rich Gla protein 4) (Proline-ri 2Q9BZE4 Nucleolar GTP-binding protein 1 (Chronic renal failure gene protein) (GTP-binding protein NGB) 2Q9H977 Hypothetical protein FLJ12953 2Q9HB21 Pleckstrin homology domain-containing protein family A member 1 (Tandem PH domain containing protein 2Q96R06 Sperm associated antigen 5 (Astrin) (Mitotic spindle associated protein p126) (MAP126) (Deepest) 2Q9NU22 Midasin (MIDAS-containing protein) 2Q9UGU0 Transcription factor 20 (Stromelysin 1 PDGF-responsive element-binding protein) (SPRE-binding protein 2Q9UHB6 Epithelial protein lost in neoplasm 2Q6P4U5 Fatty acid synthase 2Q8IWU9 Tryptophan 5-hydroxylase 2 (EC 1.14.16.4) (Tryptophan 5-monooxygenase 2) (Neuronal tryptophan hydr 2Q8NB12 SET and MYND domain containing protein 1 2P08648 Integrin alpha-5 precursor (Fibronectin receptor alpha subunit) (Integrin alpha-F) (VLA-5) (CD49e) 1O43402 Neighbor of COX4 1O43396 Thioredoxin-like protein 1 (32 kDa thioredoxin-related protein) 1P60900 Proteasome subunit alpha type 6 (EC 3.4.25.1) (Proteasome iota chain) (Macropain iota chain) (Multicata 1O43324 Multisynthetase complex auxiliary component p18 1O43464 Serine protease HTRA2, mitochondrial precursor (EC 3.4.21.-) (High temperature requirement protein A 1P61106 Ras-related protein Rab-14 1O43490 Prominin 1 precursor (Prominin-like protein 1) (Antigen AC133) (CD133 antigen) 1P63208 S-phase kinase-associated protein 1A (Cyclin A/CDK2-associated protein p19) (p19A) (p19skp1) (RNA po 1P62888 60S ribosomal protein L30 1P08397 Porphobilinogen deaminase (EC 2.5.1.61) (Hydroxymethylbilane synthase) (HMBS) (Pre-uroporphyrinogen 1P62879 Guanine nucleotide-binding protein G(I)/G(S)/G(T) beta subunit 2 (Transducin beta chain 2) (G protein b 1O60296 Amyotrophic lateral sclerosis 2 chromosomal region candidate gene protein 3 1P51610 Host cell factor C1 (HCF) (VP16 accessory protein) (HFC1) (VCAF) (CFF) 1P51649 Succinate semialdehyde dehydrogenase, mitochondrial precursor (EC 1.2.1.24) (NAD(+)-dependent succi 1P49720 Proteasome subunit beta type 3 (EC 3.4.25.1) (Proteasome theta chain) (Proteasome chain 13) (Proteaso 1P49748 Acyl-CoA dehydrogenase, very-long-chain specific, mitochondrial precursor (EC 1.3.99.-) (VLCAD) 1P55084 Trifunctional enzyme beta subunit, mitochondrial precursor (TP-beta) (MSTP029) [Includes: 3-ketoacyl 1P53999 Activated RNA polymerase II transcriptional coactivator p15 (Positive cofactor 4) (PC4) (p14) 1P55769 NHP2-like protein 1 (High mobility group-like nuclear protein 2 homolog 1) ([U4/U6.U5] tri-snRNP 15.5 k 1P56192 Methionyl-tRNA synthetase (EC 6.1.1.10) (Methionine--tRNA ligase) (MetRS) 1P80404 4-aminobutyrate aminotransferase, mitochondrial precursor (EC 2.6.1.19) ((S)-3-amino-2-methylpropion 1O00560 Syntenin 1 (Syndecan binding protein 1) (Melanoma differentiation associated protein-9) (Mda-9) (Scaff 1Q13424 Alpha-1-syntrophin (59 kDa dystrophin-associated protein A1, acidic component 1) (Pro-TGF-alpha cytop 1Q12959 Presynaptic protein SAP97 (Synapse-associated protein 97) (Discs, large homolog 1) (hDlg) 1O00461 130 kD Golgi-localized phosphoprotein 1O00625 Pirin 1P07099 Epoxide hydrolase 1 (EC 3.3.2.3) (Microsomal epoxide hydrolase) (Epoxide hydratase) 1O00217 NADH-ubiquinone oxidoreductase 23 kDa subunit, mitochondrial precursor (EC 1.6.5.3) (EC 1.6.99.3) (Co 1O00308 Nedd-4-like E3 ubiquitin-protein ligase WWP2 (EC 6.3.2.-) (WW domain-containing protein 2) (Atropin- 1

O00154 Cytosolic acyl coenzyme A thioester hydrolase (EC 3.1.2.2) (Long chain acyl-CoA thioester hydrolase) (C 1O00366 Putative p150 1Q14139 Ubiquitin conjugation factor E4 A 1Q14166 Hypothetical protein KIAA0153 1Q01484 Ankyrin 2 (Brain ankyrin) (Ankyrin B) (Ankyrin, nonerythroid) 1Q00577 Transcriptional activator protein PUR-alpha (Purine-rich single-stranded DNA-binding protein alpha) 1Q01668 Voltage-dependent L-type calcium channel alpha-1D subunit (Voltage-gated calcium channel alpha subuni 1O15305 Phosphomannomutase 2 (EC 5.4.2.8) (PMM 2) 1P48047 ATP synthase oligomycin sensitivity conferral protein, mitochondrial precursor (EC 3.6.3.14) (OSCP) 1P08243 Asparagine synthetase [glutamine-hydrolyzing] (EC 6.3.5.4) (Glutamine-dependent asparagine synthetas 1O15127 Secretory carrier-associated membrane protein 2 (Secretory carrier membrane protein 2) 1P84157 Transmembrane anchor protein 1 1Q08378 Golgi autoantigen, golgin subfamily A member 3 (Golgin-160) (Golgi complex-associated protein of 170 k 1Q02880 DNA topoisomerase II, beta isozyme (EC 5.99.1.3) 1Q02338 D-beta-hydroxybutyrate dehydrogenase, mitochondrial precursor (EC 1.1.1.30) (BDH) (3-hydroxybutyra 1O14979 JKTBP2 (Heterogeneous nuclear ribonucleoprotein D-like) (HNRPDL protein) 1O14896 Interferon regulatory factor 6 (IRF-6) 1Q04637 Eukaryotic translation initiation factor 4 gamma 1 (eIF-4-gamma 1) (eIF-4G1) (eIF-4G) (p220) 1Q02790 FK506-binding protein 4 (EC 5.2.1.8) (Peptidyl-prolyl cis-trans isomerase) (PPIase) (Rotamase) (p59 prot 1P20396 Thyroliberin precursor (Thyrotropin releasing hormone) (TRH) (Thyrotropin releasing factor) (TSH-rele 1P21796 Voltage-dependent anion-selective channel protein 1 (VDAC-1) (hVDAC1) (Outer mitochondrial membran 1O95861 3'(2'),5'-bisphosphate nucleotidase 1 (EC 3.1.3.7) (Bisphosphate 3'-nucleotidase 1) (PAP-inositol-1,4-pho 1P11117 Lysosomal acid phosphatase precursor (EC 3.1.3.2) (LAP) 1P25092 Heat-stable enterotoxin receptor precursor (GC-C) (Intestinal guanylate cyclase) (EC 4.6.1.2) (STA rec 1P25205 DNA replication licensing factor MCM3 (DNA polymerase alpha holoenzyme-associated protein P1) (RLF 1P26196 Probable ATP-dependent RNA helicase p54 (Oncogene RCK) (DEAD-box protein 6) 1O95295 SNARE-associated protein Snapin (Synaptosomal-associated protein 25 binding protein) (SNAP-associa 1O94947 KIAA0870 protein (Fragment) 1P13674 Prolyl 4-hydroxylase alpha-1 subunit precursor (EC 1.14.11.2) (4-PH alpha-1) (Procollagen-proline,2-oxogl 1P11586 C-1-tetrahydrofolate synthase, cytoplasmic (C1-THF synthase) [Includes: Methylenetetrahydrofolate d 1P12277 Creatine kinase, B chain (EC 2.7.3.2) (B-CK) 1P13521 Secretogranin II precursor (SgII) (Chromogranin C) [Contains: Secretoneurin (SN)] 1P00797 Renin precursor (EC 3.4.23.15) (Angiotensinogenase) 1P17844 Probable RNA-dependent helicase p68 (DEAD-box protein p68) (DEAD-box protein 5) 1P11226 Mannose-binding protein C precursor (MBP-C) (MBP1) (Mannan-binding protein) (Mannose-binding lectin) 1P19404 NADH-ubiquinone oxidoreductase 24 kDa subunit, mitochondrial precursor (EC 1.6.5.3) (EC 1.6.99.3) 1P16415 Zinc finger protein ZFP-36 (Fragment) 1P11388 DNA topoisomerase II, alpha isozyme (EC 5.99.1.3) 1P17050 Alpha-N-acetylgalactosaminidase precursor (EC 3.2.1.49) (Alpha-galactosidase B) 1P11277 Spectrin beta chain, erythrocyte (Beta-I spectrin) 1P17538 Chymotrypsinogen B precursor (EC 3.4.21.1) 1P10253 Lysosomal alpha-glucosidase precursor (EC 3.2.1.20) (Acid maltase) 1P40227 T-complex protein 1, zeta subunit (TCP-1-zeta) (CCT-zeta) (CCT-zeta-1) (Tcp20) (HTR3) (Acute morphin 1P40617 ADP-ribosylation factor-like protein 4A 1O75396 Vesicle trafficking protein SEC22b (SEC22 vesicle trafficking protein-like 1) 1O75340 Programmed cell death protein 6 (Probable calcium-binding protein ALG-2) 1O75351 SKD1 protein (Vacuolar sorting protein 4b) 1P09874 Poly [ADP-ribose] polymerase-1 (EC 2.4.2.30) (PARP-1) (ADPRT) (NAD(+) ADP-ribosyltransferase-1) (Pol 1P42768 Wiskott-Aldrich syndrome protein (WASp) 1P30040 Endoplasmic reticulum protein ERp29 precursor (ERp31) (ERp28) 1P30050 60S ribosomal protein L12 1P30084 Enoyl-CoA hydratase, mitochondrial precursor (EC 4.2.1.17) (Short chain enoyl-CoA hydratase) (SCEH) ( 1O76095 JTB protein precursor (Jumping translocation breakpoint protein) (Prostate androgen regulated protein 1O75932 SYT interacting protein SIP (RBM14 protein) 1P33993 DNA replication licensing factor MCM7 (CDC47 homolog) (P1.1-MCM3) 1P35348 Alpha-1A adrenergic receptor (Alpha 1A-adrenoceptor) (Alpha 1A-adrenoreceptor) (Alpha-1C adrenergi 1P04632 Calpain small subunit 1 (CSS1) (Calcium-dependent protease small subunit 1) (Calcium-dependent proteas 1O75489 NADH-ubiquinone oxidoreductase 30 kDa subunit, mitochondrial precursor (EC 1.6.5.3) (EC 1.6.99.3) (Co 1O75592 Protein associated with Myc 1P31939 Bifunctional purine biosynthesis protein PURH (OK/SW-cl.86) [Includes: Phosphoribosylaminoimidazolec 1P32969 60S ribosomal protein L9 1O75667 N-acetylglucosamine-6-O-sulfotransferase (Carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 1Q9H492 Microtubule-associated proteins 1A/1B light chain 3A (MAP1A/MAP1B LC3 A) (MAP1A/1B light chain 3 A 1

Q9H053 Hypothetical protein DKFZp547K202 (Fragment) 1Q9H0I3 Hypothetical protein DKFZp434N1418 (HSPC065 protein) 1Q9H2A2 Aldehyde dehydrogenase 12 (OTTHUMP00000040210) 1Q9BUN8 Derlin-1 (Degradation in endoplasmic reticulum protein 1) (Der1-like protein 1) (DERtrin 1) (UNQ243/PR 1Q9BVA7 DKFZP586B1621 protein 1Q9BY66 Jumonji/ARID domain-containing protein 1D (SmcY protein) (Histocompatibility Y antigen) (H-Y) 1Q9BYN7 Zinc finger protein 341 1Q9BZ74 FKSG42 1Q9C0C2 182 kDa tankyrase 1-binding protein 1Q9H9B4 Sideroflexin 1 1Q9H9L9 Hypothetical protein FLJ12664 1Q9HAU0 Pleckstrin homology domain-containing protein family A member 5 (Phosphoinositol 3-phosphate-binding 1Q9HCL7 KIAA1555 protein (Fragment) 1Q9H4E7 Def-6 protein (OTTHUMP00000039602) 1Q9BU59 Smu-1 suppressor of mec-8 and unc-52 homolog (OTTHUMP00000045234) 1Q9H721 Hypothetical protein FLJ21497 1Q9H7Z0 Hypothetical protein FLJ14058 1Q96MM6 Heat shock 70 kDa protein 12B 1Q96L91 E1A binding protein p400 (EC 3.6.1.-) (p400 kDa SWI2/SNF2-related protein) (Domino homolog) (hDom 1Q96P70 Importin 9 (Imp9) (Ran-binding protein 9) (RanbP9) (HSPC273) 1Q96PY5 KIAA1902 protein (Fragment) 1Q96IF1 JUB protein (Ajuba) (Jub, ajuba homolog, isoform 1) 1Q96K26 Hypothetical protein FLJ14834 1Q9BPX5 Actin related protein 2/3 complex, subunit 5-like 1Q9BQA2 T1 protein 1Q99684 Zinc finger protein Gfi-1 (Growth factor independence-1) 1Q9BQE5 Apolipoprotein L2 (Apolipoprotein L-II) (ApoL-II) 1Q9BQJ1 Hypothetical protein DKFZp761G0712 1Q9BS43 Chromosome 14 open reading frame 168 1Q9BT43 Hypothetical protein MGC3200 (Hypothetical protein FLJ32422) 1Q9BTV7 Cdk5 and abl enzyme substrate 2 (Interactor with cdk3 2) (Ik3-2) 1Q9NQ11 Probable cation-transporting ATPase 1 (EC 3.6.3.-) 1Q99415 AAD14 protein (Fragment) 1Q96S08 Some homology with holliday junction DNA helicase RUVB like 1Q96S23 Hypothetical protein RJD1 1Q96ST8 Hypothetical protein FLJ14640 1Q99460 26S proteasome non-ATPase regulatory subunit 1 (26S proteasome regulatory subunit RPN2) (26S prot 1Q99627 COP9 signalosome complex subunit 8 (Signalosome subunit 8) (SGN8) (JAB1-containing signalosome subu 1Q96SA0 Hypothetical protein 1Q9UQ49 Sialidase 3 (EC 3.2.1.18) (Membrane sialidase) (Ganglioside sialidase) (N-acetyl-alpha-neuraminidase 3) 1Q9UMS4 PRP19/PSO4 homolog (Nuclear matrix protein 200) (hPso4) 1Q9Y230 RuvB-like 2 (EC 3.6.1.-) (48-kDa TATA box-binding protein-interacting protein) (48-kDa TBP-interacting 1Q9NP90 Ras-related protein Rab-9B (Rab-9L) (RAB9-like protein) 1Q9UL25 Ras-related protein Rab-21 1Q9ULK4 Cofactor required for Sp1 transcriptional activation subunit 3 (Transcriptional coactivator CRSP130) (V 1Q9Y5U9 HSPC039 protein (Hypothetical transmembrane protein) (Immediate early response 3 interacting prote 1Q9Y259 Choline/ethanolamine kinase [Includes: Choline kinase beta (EC 2.7.1.32) (CK); Ethanolamine kinase (EC 2 1Q9Y4K4 Mitogen-activated protein kinase kinase kinase kinase 5 (EC 2.7.1.37) (MAPK/ERK kinase kinase kinase 5 1Q9Y5S8 NADPH oxidase homolog 1 (NOX-1) (NOH-1) (NADH/NADPH mitogenic oxidase subunit P65-MOX) (Mit 1Q9Y4F1 CDEP (FERM, RhoGEF, and pleckstrin domain protein 1, isoform 1) (FERM, RhoGEF (ARHGEF) and plecks 1Q9Y694 Liver-specific transporter (Solute carrier family 22 member 7, isoform a) (OTTHUMP00000016429) (O 1Q9Y6E7 NAD-dependent deacetylase sirtuin 4 (EC 3.5.1.-) (SIR2-like protein 4) 1Q9Y2P0 BC37295_3 1Q9Y2U8 Inner nuclear membrane protein Man1 (LEM domain containing protein 3) 1Q9Y333 U6 snRNA-associated Sm-like protein LSm2 (SnRNP core Sm-like protein Sm-x5) (G7b protein) (Small n 1Q9Y3D9 Mitochondrial ribosomal protein S23 (S23mt) (MRP-S23) (CGI-138) (HSPC329) 1Q9Y485 X-like 1 protein 1Q9Y314 CGI-25 protein (ENOS interacting protein) 1Q9NVX0 Centrosomal protein of 27 kDa (Cep27 protein) 1Q9NVK9 Hypothetical protein FLJ10665 1Q9NY15 Stabilin 1 precursor (FEEL-1 protein) (MS-1 antigen) 1Q9NQ38 Serine protease inhibitor Kazal-type 5 precursor (Lympho-epithelial Kazal-type related inhibitor) (LEKT 1Q9NQT8 Kinesin-like protein KIF13B (Kinesin-like protein GAKIN) 1

Q9NRW7 Vacuolar protein sorting-associated protein 45 (h-VPS45) (hlVps45) 1Q9NS69 Mitochondrial import receptor subunit TOM22 homolog (Translocase of outer membrane 22 kDa subunit 1Q9NTG1 Polycystic kidney disease and receptor for egg jelly related protein precursor (PKD and REJ homolog) 1Q9UBU7 Activator of S phase Kinase (Dbf4 protein) 1Q9UII5 Zinc finger protein ZFD25 1Q9NZD2 Glycolipid transfer protein (GLTP) 1Q9P202 Whirlin (Autosomal recessive deafness type 31 protein) 1Q9P253 Vacuolar protein sorting 18 (hVPS18) 1Q9P2D0 KIAA1417 protein (Fragment) 1Q9UBB5 Methyl-CpG binding protein 2 (Methyl-CpG binding domain protein 2) (Demethylase) (DMTase) 1Q6ZU28 Hypothetical protein FLJ44037 1Q6ZTF8 Hypothetical protein FLJ44700 1Q70EK9 Ubiquitin carboxyl-terminal hydrolase 51 (EC 3.1.2.15) (Ubiquitin thiolesterase 51) (Ubiquitin-specific pr 1Q6ZVA7 Hypothetical protein FLJ42816 1Q6ZQP9 Hypothetical protein FLJ46332 1Q6ZS40 Hypothetical protein FLJ45856 1Q6ZSC0 Hypothetical protein FLJ45651 1Q712M9 Serotonin receptor 5-HT4 1Q86TI6 Hypothetical protein 1Q7Z7C1 E3 ubiquitin ligase 1Q86UP2 Kinectin (Kinesin receptor) (CG-1 antigen) 1Q86UX7 Unc-112 related protein 2 (Kindlin-3) (MIG2-like) 1Q86VG6 Hypothetical protein 1Q71S18 Titin (Fragment) 1Q5VWB1 OTTHUMP00000059958 (Sorting nexin family member 27) 1Q6ZNH7 Hypothetical protein FLJ16074 1Q16718 NADH-ubiquinone oxidoreductase 13 kDa-B subunit (EC 1.6.5.3) (EC 1.6.99.3) (Complex I-13Kd-B) (CI-13 1Q16719 Kynureninase (EC 3.7.1.3) (L-kynurenine hydrolase) 1Q16795 NADH-ubiquinone oxidoreductase 39 kDa subunit, mitochondrial precursor (EC 1.6.5.3) (EC 1.6.99.3) (Co 1Q16661 Uroguanylin precursor (UGN) (Guanylate cyclase activator 2B) (Guanylate cyclase C activating peptide I 1Q5VZV1 OTTHUMP00000018663 1Q659D6 Hypothetical protein DKFZp434O2321 (Fragment) 1Q66K66 Similar to RIKEN cDNA A230078I05 gene 1Q15185 Telomerase-binding protein p23 (Hsp90 co-chaperone) (Progesterone receptor complex p23) 1Q16558 Calcium-activated potassium channel beta subunit 1 (Calcium-activated potassium channel, subfamily M, 1Q6UWI4 Protein UNQ9166/PRO28631 precursor 1Q6PUV4 Complexin 2 (Synaphin 1) 1Q6XYB9 FP18315 1Q6DEN2 DPYSL3 protein 1Q6FHX4 MAP2K4 protein 1Q6GMX1 Hypothetical protein 1Q8TE87 Hypothetical protein FLJ23801 1Q8TF23 KIAA1979 protein (Fragment) 1Q8TE58 ADAMTS-15 precursor (EC 3.4.24.-) (A disintegrin and metalloproteinase with thrombospondin motifs 1 1Q8TF72 Shroom-related protein 1Q8NGV9 Seven transmembrane helix receptor 1Q8NHQ1 P10-binding protein 1Q8WYR1 FOAP-2 1Q969T9 WW domain binding protein 2 (WBP-2) 1Q969V1 Melanin-concentrating hormone receptor 2 (MCH receptor 2) (MCHR-2) (MCH-R2) (MCH2R) (MCH-2R) 1Q96BH1 RING finger protein 25 (EC 6.3.2.-) 1Q96CN9 GRIP and coiled-coil domain-containing protein 1 (Golgi coiled coil protein 1) 1Q92499 ATP-dependent helicase DDX1 (DEAD-box protein 1) (DEAD-box protein-retinoblastoma) (DBP-RB) 1Q92522 Histone H1x 1Q92572 Adapter-related protein complex 3 sigma 1 subunit (Sigma-adaptin 3a) (AP-3 complex sigma-3A subunit) 1Q92900 Regulator of nonsense transcripts 1 (Nonsense mRNA reducing factor 1) (NORF1) (Up-frameshift suppr 1Q8N262 Hypothetical protein FLJ33880 1Q8IZ83 Hypothetical protein MGC10204 1Q8IZQ1 ALFY 1Q8IZS5 MRDS1 protein (OTTHUMP00000039226) 1Q8N0U8 Vitamin K epoxide reductase complex, subunit 1-like 1 (VKORC1-like protein 1) 1Q8IYW6 Hypothetical protein FLJ35808 1Q8N1Z5 Hypothetical protein FLJ37183 1

Q8N3C2 Hypothetical protein DKFZp761P189 (Fragment) 1Q8N4H9 MGC39821 protein 1Q86XZ6 Hypothetical protein (Fragment) 1Q86YV5 FLJ00269 protein (Fragment) 1Q8IUD2 ERC protein 1 (ELKS protein) 1Q8IVL8 Zn-carboxypeptidase 1Q8IVW4 CDKL3 protein 1Q8IWA4 Transmembrane GTPase MFN1 (EC 3.6.5.-) (Mitofusin 1) (Fzo homolog) 1Q8IYA6 Hypothetical protein FLJ40629 1Q8IVV7 Hypothetical protein C17orf39 1Q8ND68 Hypothetical protein DKFZp667O074 (Fragment) 1Q8NDJ2 Hypothetical protein DKFZp547G125 (Fragment) 1Q8NEV8 Slp homolog lacking C2 domains-b (Exophilin 5) 1Q8N7Z8 Hypothetical protein FLJ40182 1Q8N8V2 Hypothetical protein FLJ38822 1Q8NBP7 Proprotein convertase subtilisin/kexin type 9 precursor (EC 3.4.21.-) (Proprotein convertase PC9) (Subt 1Q8NAU3 Hypothetical protein FLJ34780 1Q8N8L4 Hypothetical protein FLJ39262 1

Supplemental Table 5: Proteins identified only in normal and well differentiated HNSCC

PeptidesAccession Protein (number)

P12821 PIWIL3 protein 9Q9Y6X9 LOC132200 protein 4Q86US8 Leukocyte elastase inhibitor (LEI) (Monocyte/neutrophil elastase inhibitor) (M/NEI) (EI) 4Q8TE73 Glutamate receptor delta-1 subunit precursor (GluR delta-1) 4Q9HC35 Chromodomain-helicase-DNA-binding protein 6 (CHD-6) 3Q96RV3 Gamma-synergin 3Q9UM54 Zinc finger and BTB domain containing protein 4 (KAISO-like zinc finger protein 1) (KAISO- 3Q68CR2 Testis protein TEX15 2Q6EH31 Serine/threonine-protein kinase 3 (EC 2.7.1.37) (STE20-like kinase MST2) (MST-2) (Mamma 2Q8WXQ6 130 kDa leucine-rich protein (LRP 130) (GP130) (Leucine-rich PPR-motif containing protein) 2Q01546 ALMS1 protein 2O43175 Ubiquitin carboxyl-terminal hydrolase 25 (EC 3.1.2.15) (Ubiquitin thiolesterase 25) (Ubiquitin 2Q8TBI2 Apoptotic protease activating factor 1 (Apaf-1) 2P02768 Importin-alpha re-exporter (Chromosome segregation 1-like protein) (Cellular apoptosis susc 2O15553 Spermine synthase (EC 2.5.1.22) (Spermidine aminopropyltransferase) (SPMSY) 2P49792 Calpain 1, large [catalytic] subunit (EC 3.4.22.52) (Calcium-activated neutral proteinase) (CAN 2P08173 Laminin beta-1 chain precursor (Laminin B1 chain) 2P15374 Microtubule-associated protein 1B (MAP 1B) [Contains: MAP1 light chain LC1] 2Q9GZT9 Tyrosine-protein kinase SYK (EC 2.7.1.112) (Spleen tyrosine kinase) 2Q96EY4 U5 small nuclear ribonucleoprotein 200 kDa helicase (EC 3.6.1.-) (U5 snRNP-specific 200 kDa 2P28715 Kinesin heavy chain (Ubiquitous kinesin heavy chain) (UKHC) 2Q9NP61 Echinoderm microtubule-associated protein-like 4 (EMAP-4) (Restrictedly overexpressed pr 2Q15369 Pecanex-like protein 1 (Pecanex homolog) 2P07814 Myosin VI 2Q9H6N6 Zinc finger protein 64, isoforms 3 and 4 (Zinc finger protein 338) 2P30740 Hypothetical protein FLJ42406 2Q7Z2Y8 Ciliary dynein heavy chain 5 (Axonemal beta dynein heavy chain 5) (HL1) 2

Supplemental Table 6: Proteins identified only in well and mild differentiated HNSCC

PeptidesAccession Protein (number)

Q13753 Laminin gamma-2 chain precursor (Kalinin/nicein/epiligrin 100 kDa subunit) (Laminin B2t chai 13P08729 Keratin, type II cytoskeletal 7 (Cytokeratin 7) (K7) (CK 7) (Sarcolectin) 11P02675 Fibrinogen beta chain precursor [Contains: Fibrinopeptide B] 11P02647 Apolipoprotein A-I precursor (Apo-AI) (ApoA-I) 9Q13751 Laminin beta-3 chain precursor (Laminin 5 beta 3) (Laminin B1k chain) (Kalinin B1 chain) 9P01024 Complement C3 precursor [Contains: C3a anaphylatoxin] 8P02671 Fibrinogen alpha/alpha-E chain precursor [Contains: Fibrinopeptide A] 8Q8IVR4 COL23A1 protein 7Q6ZQN2 Hypothetical protein FLJ46846 7Q66K23 Hypothetical protein (Fragment) 7Q9UBI6 Guanine nucleotide-binding protein G(I)/G(S)/G(O) gamma-12 subunit 6P05198 Eukaryotic translation initiation factor 2 subunit 1 (Eukaryotic translation initiation factor 2 6Q9NQP4 Prefoldin subunit 4 (Protein C-1) 6P02787 Serotransferrin precursor (Transferrin) (Siderophilin) (Beta-1-metal binding globulin) (PRO1 5P61981 14-3-3 protein gamma (Protein kinase C inhibitor protein-1) (KCIP-1) 5P50991 T-complex protein 1, delta subunit (TCP-1-delta) (CCT-delta) (Stimulator of TAR RNA bindin 5P16615 Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (EC 3.6.3.8) (Calcium pump 2) (SERCA 5Q9NS15 Latent transforming growth factor beta binding protein 3 precursor (LTBP-3) 5P25815 S-100P protein 5Q6ZRU0 Hypothetical protein FLJ46111 5Q13409 Dynein intermediate chain 2, cytosolic (DH IC-2) (Cytoplasmic dynein intermediate chain 2) 5Q6P9F5 Tripartite motif 40 protein (RING finger protein 35) 5P20073 Annexin A7 (Annexin VII) (Synexin) (OK/SW-cl.95) 4P49590 Histidyl-tRNA synthetase homolog (EC 6.1.1.21) (Histidine--tRNA ligase homolog) (HisRS) 4P25103 Substance-P receptor (SPR) (NK-1 receptor) (NK-1R) (Tachykinin receptor 1) 4Q9Y5P3 Retinoic acid-induced protein 2 4Q8N9V6 Hypothetical protein FLJ36160 4O75533 Splicing factor 3B subunit 1 (Spliceosome associated protein 155) (SAP 155) (SF3b155) (Pre- 4Q9H7V7 Hypothetical protein FLJ14207 4Q86T83 Hypothetical protein DKFZp451J0218 4P38919 Probable ATP-dependent helicase DDX48 (DEAD-box protein 48) (Eukaryotic initiation facto 4P16144 Integrin beta-4 precursor (GP150) (CD104 antigen) 4Q8TD16 Cytoskeleton-like bicaudal D protein homolog 2 3P48200 Iron-responsive element binding protein 2 (IRE-BP 2) (Iron regulatory protein 2) (IRP2) 3P41218 Myeloid cell nuclear differentiation antigen 3Q6NXN2 Hypothetical protein 3Q86Z22 Hypothetical protein 3Q8IWJ2 GRIP and coiled-coil domain-containing protein 2 (Golgi coiled coil protein GCC185) (CTCL tum 3P40818 Ubiquitin carboxyl-terminal hydrolase 8 (EC 3.1.2.15) (Ubiquitin thiolesterase 8) (Ubiquitin-s 3P25786 Proteasome subunit alpha type 1 (EC 3.4.25.1) (Proteasome component C2) (Macropain subunit 3P29034 S100 calcium-binding protein A2 (S-100L protein) (CAN19) 3Q9BS26 Thioredoxin domain containing protein 4 precursor (Endoplasmic reticulum protein ERp44) 3P09622 Dihydrolipoyl dehydrogenase, mitochondrial precursor (EC 1.8.1.4) (Dihydrolipoamide dehydro 3P08708 40S ribosomal protein S17 3Q96KP4 Cytosolic nonspecific dipeptidase (Glutamate carboxypeptidase-like protein 1) (CNDP dipepti 3P14868 Aspartyl-tRNA synthetase (EC 6.1.1.12) (Aspartate--tRNA ligase) (AspRS) 3Q99497 DJ-1 protein (Oncogene DJ1) 3Q12840 Neuronal kinesin heavy chain (NKHC) (Kinesin heavy chain isoform 5A) (Kinesin heavy chain ne 3P00915 Carbonic anhydrase I (EC 4.2.1.1) (Carbonate dehydratase I) (CA-I) (Carbonic anhydrase B) 3P20962 Parathymosin 3Q99832 T-complex protein 1, eta subunit (TCP-1-eta) (CCT-eta) (HIV-1 Nef interacting protein) 3Q15175 Paraneoplastic antigen (Fragment) 3Q6UWP8 HLAR698 3P20930 Filaggrin precursor (Fragment) 2Q14789 Golgi autoantigen, golgin subfamily B member 1 (Giantin) (Macrogolgin) (Golgi complex-associa 2P21728 D(1A) dopamine receptor 2P17858 6-phosphofructokinase, liver type (EC 2.7.1.11) (Phosphofructokinase 1) (Phosphohexokinase) 2Q9H223 EH-domain containing protein 4 (FKSG7 protein) (Hepatocellular carcinoma-associated prote 2P43246 DNA mismatch repair protein Msh2 2

Q8N3H8 Hypothetical protein DKFZp761M1613 (Fragment) 2Q8IYX7 Chromosome 9 open reading frame 138 2Q8IV77 CNGA4 protein (Fragment) 2O94842 Epidermal Langerhans cell protein LCP1 2O75531 Barrier-to-autointegration factor (Breakpoint cluster region protein 1) 2Q9UKJ8 ADAM 21 precursor (EC 3.4.24.-) (A disintegrin and metalloproteinase domain 21) 2O15269 Serine palmitoyltransferase 1 (EC 2.3.1.50) (Long chain base biosynthesis protein 1) (LCB 1) ( 2P62195 26S protease regulatory subunit 8 (Proteasome subunit p45) (p45/SUG) (Proteasome 26S su 2P61221 ATP-binding cassette sub-family E member 1 (RNase L inhibitor) (Ribonuclease 4 inhibitor) (R 2P62269 40S ribosomal protein S18 (Ke-3) (Ke3) 2P07305 Histone H1.0 (H1(0)) (Histone H1') 2Q14697 Neutral alpha-glucosidase AB precursor (EC 3.2.1.84) (Glucosidase II alpha subunit) 2Q04837 Single-stranded DNA-binding protein, mitochondrial precursor (Mt-SSB) (MtSSB) (PWP1-int 2O95786 RNA helicase 2P18615 Negative elongation factor E (NELF-E) (RD protein) 2P18031 Tyrosine-protein phosphatase, non-receptor type 1 (EC 3.1.3.48) (Protein-tyrosine phosphata 2O75460 Serine/threonine protein kinase/endoribonuclease IRE1 precursor (Inositol-requiring 1) (hIR 2O60749 Sorting nexin 2 2P09455 Retinol-binding protein I, cellular (Cellular retinol-binding protein) (CRBP) 2O75074 Low-density lipoprotein receptor-related protein 3 precursor (hLRp105) 2P35580 Myosin heavy chain, nonmuscle type B (Cellular myosin heavy chain, type B) (Nonmuscle myosi 2P27105 Erythrocyte band 7 integral membrane protein (Stomatin) (Protein 7.2b) 2P33527 Multidrug resistance-associated protein 1 (ATP-binding cassette, sub-family C, member 1) 2Q96NL6 Hypothetical protein FLJ30655 2Q9BSV6 tRNA-splicing endonuclease subunit SEN34 (EC 3.1.27.9) (tRNA-intron endonuclease SEN34 2Q9Y4G6 Talin 2 2Q9Y6V0 Piccolo protein (Aczonin) 2Q9Y2B1 Transmembrane protein 5 2Q9NYF0 Dapper homolog 1 (hDPR1) (Heptacellular carcinoma novel gene-3 protein) 2Q6ZVZ3 Hypothetical protein FLJ41891 2Q6ZSR4 Hypothetical protein FLJ45273 2Q86TV6 Tetratricopeptide repeat protein 7B (Tetratricopeptide repeat protein 7 like-1) 2Q6UXR7 LTLL9335 2Q8TEG4 FLJ00233 protein (Fragment) 2Q8TDY2 Rb1-inducible coiled coil protein 2Q96BP3 KIAA0073 protein 2Q96DB5 CGI-90 protein 2Q8N531 F-box/LRR-repeat protein 6 (F-box and leucine-rich repeat protein 6) (F-box protein FBL6) 2

Supplemental Table 7: Proteins identified only in mid and poorly differentiated HNSCC

PeptidesAccession Protein (number)

P22695 Ubiquinol-cytochrome-c reductase complex core protein 2, mitochondrial precursor (EC 1.10.2.2) 6P11047 Laminin gamma-1 chain precursor (Laminin B2 chain) 5Q7Z5J4 Retinoic acid induced protein 1 4Q9UKJ0 Activating receptor PILRbeta (Hypothetical protein DKFZp434O079) 4Q9ULT2 KIAA1138 protein (Fragment) 4Q6ZSN1 Hypothetical protein FLJ45355 4O14686 Myeloid/lymphoid or mixed-lineage leukemia protein 2 (ALL1-related protein) 4P15088 Mast cell carboxypeptidase A precursor (EC 3.4.17.1) (MC-CPA) (Carboxypeptidase A3) 3O75694 Nuclear pore complex protein Nup155 (Nucleoporin Nup155) (155 kDa nucleoporin) 3Q96LJ8 UBX domain-containing protein 3 3P54577 Tyrosyl-tRNA synthetase, cytoplasmic (EC 6.1.1.1) (Tyrosyl--tRNA ligase) (TyrRS) 3O75915 JWA protein (DERP11) (Dermal papilla derived protein 11) (Putative MAPK activating protein) (JM5 protein) 3Q9H3N1 Thioredoxin domain containing protein 1 precursor (Transmembrane Trx-related protein) 3Q96MC2 Hypothetical protein FLJ32660 3Q6ZUF5 Hypothetical protein FLJ43756 3P62241 40S ribosomal protein S8 2P60228 Eukaryotic translation initiation factor 3 subunit 6 (eIF-3 p48) (eIF3e) (Viral integration site protein INT-6 ho 2P62701 40S ribosomal protein S4, X isoform (Single copy abundant mRNA protein) (SCR10) 2P50607 Tubby protein homolog 2P49419 Aldehyde dehydrogenase family 7 member A1 (EC 1.2.1.3) (Antiquitin 1) 2P14174 Macrophage migration inhibitory factor (MIF) (Phenylpyruvate tautomerase) (EC 5.3.2.1) 2P00367 Glutamate dehydrogenase 1, mitochondrial precursor (EC 1.4.1.3) (GDH) 2P40763 Signal transducer and activator of transcription 3 (Acute-phase response factor) 2O60674 Tyrosine-protein kinase JAK2 (EC 2.7.1.112) (Janus kinase 2) (JAK-2) 2P42345 FKBP12-rapamycin complex-associated protein (FK506-binding protein 12-rapamycin complex-associated protein 2P30520 Adenylosuccinate synthetase 2 (EC 6.3.4.4) (IMP--aspartate ligase 2) (AdSS 2) (AMPSase 2) 2P31948 Stress-induced-phosphoprotein 1 (STI1) (Hsc70/Hsp90-organizing protein) (Hop) 2Q9BW04 Specifically androgen-regulated protein (Hypothetical protein FLJ36507) 2Q9ULX9 Transcription factor MafF (V-maf musculoaponeurotic fibrosarcoma oncogene homolog F) (U-Maf) 2Q9UJ83 2-hydroxyphytanoyl-CoA lyase (EC 4.1.-.-) (2-HPCL) (HSPC279) 2Q16698 2,4-dienoyl-CoA reductase, mitochondrial precursor (EC 1.3.1.34) (2,4-dienoyl-CoA reductase [NADPH]) 2O00151 PDZ and LIM domain protein 1 (LIM domain protein CLP-36) (C-terminal LIM domain protein 1) (Elfin) 2Q8WTS1 CGI58 protein 2Q8TF30 KIAA1971 protein (Fragment) 2Q8WWL7 G2/mitotic-specific cyclin B3 2Q8NHS0 DnaJ homolog subfamily B member 8 2Q8TD84 Down syndrome cell adhesion molecule 2 2Q8TDM6 Discs, large homolog 5 (Placenta and prostate DLG) (Discs large protein P-dlg) 2Q96BQ1 Protein FAM3D precursor (UNQ567/PRO1130) 2Q92804 TATA-binding protein associated factor 2N (RNA-binding protein 56) (TAFII68) (TAF(II)68) 2

Supplemental Table 8: Gene Ontology Classification-Biological Process

Biological Process Proteins Normal Well D Mod D Poorly DCell Adhesion 134 25 42 39 28Cell Cycle 153 16 49 45 43Cell Differentiation 269 48 86 70 65Cellular Metabolic Process 1153 174 352 306 321Cell Motility 102 15 29 32 26Endopeptidase Activity 53 7 14 17 15Signal Transduction 371 53 125 101 92Transcription 246 38 80 62 66Translation 169 25 48 50 46

Supplemental Table 9: Proteins involved in signal transduction

Peptides Normal Well D Mod D Poorly DAccession Protein (number) (%) (%) (%) (%)

P04083 Annexin A1 (Annexin I) (Lipocortin I) (Calpactin II) (Chromobind 120 22 35 21 23Q13835 Plakophilin 1 (Band-6-protein) (B6P) 95 17 31 21 32P19971 Thymidine phosphorylase precursor (EC 2040204) (TdRPase) ( 58 2 50 34 14P61978 Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transfo 48 10 29 27 33P55072 Transitional endoplasmic reticulum ATPase (TER ATPase) (15S 37 3 51 32 14P11021 78 kDa glucose-regulated protein precursor (GRP 78) (Immuno 36 3 47 28 22P35579 Myosin heavy chain, nonmuscle type A (Cellular myosin heavy 36 3 42 31 25P30101 Protein disulfide-isomerase A3 precursor (EC 5030401) (Disulfid 36 3 36 39 22P06748 Nucleophosmin (NPM) (Nucleolar phosphoprotein B23) (Numat 21 14 29 14 43P10599 Thioredoxin (ATL-derived factor) (ADF) (Surface associated sul 21 14 29 38 19P22105 Tenascin X precursor (TN-X) (Hexabrachion-like) 17 0 41 29 29P61604 10 kDa heat shock protein, mitochondrial (Hsp10) (10 kDa chap 14 29 0 0 71P42224 Signal transducer and activator of transcription 1-alpha/beta (Tr 14 0 57 29 14Q9P2E9 Ribosome-binding protein 1 (Ribosome receptor protein) (180 k 14 0 43 36 21P46940 Ras GTPase-activating-like protein IQGAP1 (p195) 13 8 31 31 31P06703 Calcyclin (Prolactin receptor associated protein) (PRA) (Growth 12 0 67 25 8Q08881 Tyrosine-protein kinase ITK/TSK (EC 207010112) (T-cell-specif 11 18 36 27 18P02675 Fibrinogen beta chain precursor [Contains: Fibrinopeptide B] 11 0 64 36 0O75312 Zinc-finger protein ZPR1 (Zinc finger protein 259) 10 30 10 10 50Q01518 Adenylyl cyclase-associated protein 1 (CAP 1) 10 10 30 20 40P24821 Tenascin precursor (TN) (Hexabrachion) (Cytotactin) (Neuronec 10 0 60 40 0P52565 Rho GDP-dissociation inhibitor 1 (Rho GDI 1) (Rho-GDI alpha) 10 0 30 50 20O00299 Chloride intracellular channel protein 1 (Nuclear chloride ion cha 9 11 44 22 22P02671 Fibrinogen alpha/alpha-E chain precursor [Contains: Fibrinopep 8 0 63 38 0Q9NZT1 Calmodulin-like protein 5 (Calmodulin-like skin protein) 8 0 50 25 25P01024 Complement C3 precursor [Contains: C3a anaphylatoxin] 8 0 25 75 0Q9UJU6 Drebrin-like protein (SH3 domain-containing protein 7) (Drebrin 7 14 57 29 0P61088 Ubiquitin-conjugating enzyme E2 N (EC 60302019) (Ubiquitin-p 7 0 43 29 29P14314 Glucosidase II beta subunit precursor (Protein kinase C substra 7 0 29 57 14P27348 14-3-3 protein tau (14-3-3 protein theta) (14-3-3 protein T-cell) ( 7 0 29 43 29P63000 Ras-related C3 botulinum toxin substrate 1 (p21-Rac1) (Ras-like 6 67 0 0 33Q96RJ0 Trace amine receptor 1 (TaR-1) 6 0 67 17 17P61026 Ras-related protein Rab-10 6 0 50 17 33Q9UBI6 Guanine nucleotide-binding protein G(I)/G(S)/G(O) gamma-12 s 6 0 33 67 0P62258 14-3-3 protein epsilon (14-3-3E) 6 0 17 67 17P11233 Ras-related protein Ral-A 5 60 20 0 20Q9NS15 Latent transforming growth factor beta binding protein 3 precurs 5 0 60 40 0Q13442 28 kDa heat- and acid-stable phosphoprotein (PDGF-associated 5 0 40 40 20Q8N442 Hypothetical protein FLJ13220 5 0 40 40 20P35232 Prohibitin 5 0 20 20 60P61981 14-3-3 protein gamma (Protein kinase C inhibitor protein-1) (KC 5 0 20 80 0Q9Y3Z3 SAM domain and HD domain-containing protein 1 (Dendritic ce 5 0 0 100 0Q92918 Mitogen-activated protein kinase kinase kinase kinase 1 (EC 20 4 75 0 25 0Q99698 Lysosomal trafficking regulator (Beige homolog) 4 25 25 25 25P21333 Filamin A (Alpha-filamin) (Filamin 1) (Endothelial actin-binding p 4 25 0 25 50Q99665 Interleukin-12 receptor beta-2 chain precursor (IL-12 receptor b 4 25 0 50 25O14745 Ezrin-radixin-moesin binding phosphoprotein 50 (EBP50) (Na(+ 4 0 75 0 25P16144 Integrin beta-4 precursor (GP150) (CD104 antigen) 4 0 75 25 0

P00533 Epidermal growth factor receptor precursor (EC 207010112) (R 4 0 50 0 50P51149 Ras-related protein Rab-7 4 0 50 0 50P25103 Substance-P receptor (SPR) (NK-1 receptor) (NK-1R) (Tachykin 4 0 25 75 0Q9UKJ0 Activating receptor PILRbeta (Hypothetical protein DKFZp434O 4 0 0 50 50P35813 Protein phosphatase 2C alpha isoform (EC 30103016) (PP2C-a 3 100 0 0 0Q9Y561 Low-density lipoprotein receptor-related protein 12 precursor (S 3 100 0 0 0P29373 Retinoic acid-binding protein II, cellular (CRABP-II) 3 67 0 0 33P40145 Adenylate cyclase, type VIII (EC 4060101) (ATP pyrophosphate 3 33 0 0 67Q08380 Galectin-3 binding protein precursor (Lectin galactoside-binding 3 0 100 0 0P40818 Ubiquitin carboxyl-terminal hydrolase 8 (EC 30102015) (Ubiquit 3 0 67 33 0Q14573 Inositol 1,4,5-trisphosphate receptor type 3 (Type 3 inositol 1,4, 3 0 67 0 33

Q8WXD9 Cask-interacting protein 1 3 0 67 0 33Q99497 DJ-1 protein (Oncogene DJ1) 3 0 67 33 0Q9Y6E0 Serine/threonine-protein kinase 24 (EC 20701037) (STE20-like 3 0 67 0 33O14511 Pro-neuregulin-2 precursor (Pro-NRG2) [Contains: Neuregulin-2 3 0 33 33 33O43157 Plexin B1 precursor (Semaphorin receptor SEP) 3 0 33 33 33P51148 Ras-related protein Rab-5C (RAB5L) (L1880) 3 0 33 0 67Q7Z569 BRCA1-associated protein (EC 603020-) (BRAP2) (Impedes mi 3 0 33 0 67Q9H3N1 Thioredoxin domain containing protein 1 precursor (Transmemb 3 0 0 67 33O94916 Nuclear factor of activated T cells 5 (T cell transcription factor N 2 100 0 0 0P23458 Tyrosine-protein kinase JAK1 (EC 207010112) (Janus kinase 1 2 100 0 0 0Q6UXX9 QFRL9384 2 100 0 0 0O14727 Apoptotic protease activating factor 1 (Apaf-1) 2 50 50 0 0P43405 Tyrosine-protein kinase SYK (EC 207010112) (Spleen tyrosine 2 50 50 0 0Q13188 Serine/threonine-protein kinase 3 (EC 20701037) (STE20-like k 2 50 50 0 0P08173 Muscarinic acetylcholine receptor M4 2 50 0 50 0Q15303 Receptor tyrosine-protein kinase erbB-4 precursor (EC 2070101 2 50 0 0 50Q99996 A-kinase anchor protein 9 (Protein kinase A anchoring protein 9 2 50 0 0 50P12429 Annexin A3 (Annexin III) (Lipocortin III) (Placental anticoagulant 2 0 100 0 0P42261 Glutamate receptor 1 precursor (GluR-1) (GluR-A) (GluR-K1) (G 2 0 100 0 0P62805 Histone H4 2 0 100 0 0Q00587 CDC42 effector protein 1 (Serum protein MSE55) 2 0 100 0 0Q15485 Ficolin 2 precursor (Collagen/fibrinogen domain-containing prote 2 0 100 0 0Q8IW93 Rho guanine nucleotide exchange factor (GEF) 19 (Novel prote 2 0 100 0 0Q96PE1 Probable G protein-coupled receptor 124 precursor (Tumor end 2 0 100 0 0Q9NQS5 Inflammation-related G protein-coupled receptor EX33 (Putative 2 0 100 0 0O75116 Rho-associated protein kinase 2 (EC 20701037) (Rho-associate 2 0 50 0 50O75460 Serine/threonine protein kinase/endoribonuclease IRE1 precurs 2 0 50 50 0P18031 Tyrosine-protein phosphatase, non-receptor type 1 (EC 301030 2 0 50 50 0P21728 D(1A) dopamine receptor 2 0 50 50 0Q9NYF0 Dapper homolog 1 (hDPR1) (Heptacellular carcinoma novel gen 2 0 50 50 0O95661 Rho-related GTP-binding protein RhoI 2 0 0 100 0Q01955 Collagen alpha 3(IV) chain precursor (Goodpasture antigen) 2 0 0 100 0O60674 Tyrosine-protein kinase JAK2 (EC 207010112) (Janus kinase 2 2 0 0 50 50P00367 Glutamate dehydrogenase 1, mitochondrial precursor (EC 1040 2 0 0 50 50P14174 Macrophage migration inhibitory factor (MIF) (Phenylpyruvate ta 2 0 0 50 50P40763 Signal transducer and activator of transcription 3 (Acute-phase 2 0 0 50 50P42345 FKBP12-rapamycin complex-associated protein (FK506-binding 2 0 0 50 50

Q8TDM6 Discs, large homolog 5 (Placenta and prostate DLG) (Discs larg 2 0 0 50 50Q96R06 Sperm associated antigen 5 (Astrin) (Mitotic spindle associated 2 0 0 0 100Q9BZE4 Nucleolar GTP-binding protein 1 (Chronic renal failure gene pro 2 0 0 0 100O15013 Rho guanine nucleotide exchange factor 10 1 100 0 0 0

P22455 Fibroblast growth factor receptor 4 precursor (EC 207010112) ( 1 100 0 0 0P25054 Adenomatous polyposis coli protein (APC protein) 1 100 0 0 0P43403 Tyrosine-protein kinase ZAP-70 (EC 207010112) (70 kDa zeta- 1 100 0 0 0P48167 Glycine receptor beta chain precursor (Glycine receptor 58 kDa 1 100 0 0 0P51813 Cytoplasmic tyrosine-protein kinase BMX (EC 207010112) (Bon 1 100 0 0 0P78318 Immunoglobulin-binding protein 1 (CD79a-binding protein 1) (B 1 100 0 0 0Q07001 Acetylcholine receptor protein, delta chain precursor 1 100 0 0 0Q13445 Putative T1/ST2 receptor binding protein (Interleukin 1 receptor 1 100 0 0 0Q8NGS5 Olfactory receptor 13C4 1 100 0 0 0Q92914 Fibroblast growth factor-11 (FGF-11) (Fibroblast growth factor h 1 100 0 0 0Q96RB7 Olfactory receptor 5M11 1 100 0 0 0Q99704 Docking protein 1 (p62(dok)) (Downstream of tyrosine kinase 1) 1 100 0 0 0Q9H4A3 Serine/threonine-protein kinase WNK1 (EC 20701037) (Protein 1 100 0 0 0Q9UKU9 Angiopoietin-related protein 2 precursor (Angiopoietin-like 2) (U 1 100 0 0 0Q9UQE7 Structural maintenance of chromosome 3 (Chondroitin sulfate p 1 100 0 0 0Q9UQP3 Tenascin N precursor 1 100 0 0 0O00230 Cortistatin precursor [Contains: Cortistatin-29; Cortistatin-17] 1 0 100 0 0O00463 TNF receptor associated factor 5 (RING finger protein 84) 1 0 100 0 0O00548 Delta-like protein 1 precursor (Drosophila Delta homolog 1) (De 1 0 100 0 0O60237 Protein phosphatase 1 regulatory subunit 12B (Myosin phospha 1 0 100 0 0O60266 Adenylate cyclase type III (EC 4060101) (Adenylate cyclase, olf 1 0 100 0 0O95398 RAP guanine-nucleotide-exchange factor 3 (cAMP-regulated gu 1 0 100 0 0P04114 Apolipoprotein B-100 precursor (Apo B-100) [Contains: Apolipo 1 0 100 0 0P04150 Glucocorticoid receptor (GR) 1 0 100 0 0P08069 Insulin-like growth factor I receptor precursor (EC 207010112) ( 1 0 100 0 0P11487 INT-2 proto-oncogene protein precursor (Fibroblast growth facto 1 0 100 0 0P23229 Integrin alpha-6 precursor (VLA-6) (CD49f) 1 0 100 0 0P23468 Receptor-type tyrosine-protein phosphatase delta precursor (EC 1 0 100 0 0P24046 Gamma-aminobutyric-acid receptor rho-1 subunit precursor (GA 1 0 100 0 0P28907 ADP-ribosyl cyclase 1 (EC 3020205) (Cyclic ADP-ribose hydrola 1 0 100 0 0P36405 ADP-ribosylation factor-like protein 3 1 0 100 0 0P41236 Protein phosphatase inhibitor 2 (IPP-2) 1 0 100 0 0P54762 Ephrin type-B receptor 1 precursor (EC 207010112) (Tyrosine-p 1 0 100 0 0P55774 Small inducible cytokine A18 precursor (CCL18) (Macrophage i 1 0 100 0 0P57075 UBASH3A protein 1 0 100 0 0P59533 Taste receptor type 2 member 38 (T2R38) (T2R61) (PTC bitter 1 0 100 0 0P59768 Guanine nucleotide-binding protein G(I)/G(S)/G(O) gamma-2 su 1 0 100 0 0P84095 Rho-related GTP-binding protein RhoG 1 0 100 0 0Q06418 Tyrosine-protein kinase receptor TYRO3 precursor (EC 207010 1 0 100 0 0Q07325 Small inducible cytokine B9 precursor (CXCL9) (Gamma interfe 1 0 100 0 0Q13017 Rho-GTPase-activating protein 5 (p190-B) 1 0 100 0 0Q13255 Metabotropic glutamate receptor 1 precursor (mGluR1) 1 0 100 0 0Q16799 Reticulon 1 (Neuroendocrine-specific protein) 1 0 100 0 0Q5U651 Ras-interacting protein 1 1 0 100 0 0Q8IWN7 Retinitis pigmentosa 1-like 1 protein 1 0 100 0 0Q8TAV4 Stomatin-like 3 1 0 100 0 0Q8TDS5 G-protein coupled receptor TG1019 1 0 100 0 0Q8WZA2 RAP guanine-nucleotide-exchange factor 4 (cAMP-regulated gu 1 0 100 0 0Q92538 Golgi-specific brefeldin A-resistance guanine nucleotide exchan 1 0 100 0 0Q92993 Histone acetyltransferase HTATIP (EC 20301048) (60 kDa Tat 1 0 100 0 0Q93038 Tumor necrosis factor receptor superfamily member 25 precurs 1 0 100 0 0Q96EY1 DnaJ homolog subfamily A member 3, mitochondrial precursor 1 0 100 0 0

Q96HE7 ERO1-like protein alpha precursor (EC 108040-) (ERO1-Lalpha 1 0 100 0 0Q99572 P2X purinoceptor 7 (ATP receptor) (P2X7) (Purinergic receptor) 1 0 100 0 0Q9BYZ6 Rho-related BTB domain-containing protein 2 (Deleted in breas 1 0 100 0 0Q9H788 Hypothetical protein FLJ21146 1 0 100 0 0Q9H9U2 Hypothetical protein FLJ12548 1 0 100 0 0Q9NR61 Delta-like protein 4 precursor (Drosophila Delta homolog 4) (UN 1 0 100 0 0Q9NRA0 Sphingosine kinase 2 (EC 207010-) (SK 2) (SPK 2) 1 0 100 0 0Q9NRY4 Glucocorticoid receptor DNA binding factor 1 (Glucocorticoid rec 1 0 100 0 0Q9NS28 Regulator of G-protein signaling 18 (RGS18) 1 0 100 0 0Q9NVN3 Hypothetical protein FLJ10620 1 0 100 0 0Q9NYY3 Serine/threonine-protein kinase PLK2 (EC 20701037) (Polo-like 1 0 100 0 0Q9UHG0 Doublecortin domain-containing protein 2 (RU2S protein) 1 0 100 0 0Q9UHI8 ADAMTS-1 precursor (EC 3040240-) (A disintegrin and metallo 1 0 100 0 0Q9UHV7 Thyroid hormone receptor-associated protein complex 240 kDa 1 0 100 0 0Q9UKV3 Apoptotic chromatin condensation inducer in the nucleus (Acinu 1 0 100 0 0Q9ULV8 Signal transduction protein CBL-C (SH3-binding protein CBL-C) 1 0 100 0 0Q9UPU3 VPS10 domain-containing receptor SorCS3 precursor 1 0 100 0 0Q9Y4H2 Insulin receptor substrate-2 (IRS-2) 1 0 100 0 0O14907 Tax interaction protein 1 (Glutaminase-interacting protein 3) (Ta 1 0 0 100 0O15263 Beta-defensin 2 precursor (BD-2) (hBD-2) (Defensin, beta 2) (S 1 0 0 100 0O43182 Rho-GTPase-activating protein 6 (Rho-type GTPase-activating 1 0 0 100 0O60229 Huntingtin-associated protein-interacting protein (Duo protein) 1 0 0 100 0O60566 Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (E 1 0 0 100 0O75912 Diacylglycerol kinase, iota (EC 207010107) (Diglyceride kinase) 1 0 0 100 0O95672 Endothelin-converting enzyme-like 1 (EC 3040240-) (Xce protei 1 0 0 100 0P01137 Transforming growth factor beta 1 precursor (TGF-beta 1) 1 0 0 100 0P29218 Inositol-1(or 4)-monophosphatase (EC 30103025) (IMPase) (IM 1 0 0 100 0P33241 Lymphocyte-specific protein 1 (Protein pp52) (52 kDa phosphop 1 0 0 100 0P40616 ADP-ribosylation factor-like protein 1 1 0 0 100 0P52566 Rho GDP-dissociation inhibitor 2 (Rho GDI 2) (Rho-GDI beta) (L 1 0 0 100 0Q00013 55 kDa erythrocyte membrane protein (p55) (Membrane protein 1 0 0 100 0Q01970 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase bet 1 0 0 100 0Q13283 Ras-GTPase-activating protein binding protein 1 (GAP SH3-dom 1 0 0 100 0Q13459 Myosin IXb (Unconventional myosin-9b) 1 0 0 100 0Q14088 Ras-related protein Rab-33A (Small GTP-binding protein S10) 1 0 0 100 0Q7Z727 Hypothetical protein (Fragment) 1 0 0 100 0Q8NFN8 GABAB-related G-protein coupled receptor 1 0 0 100 0Q92542 Nicastrin precursor (UNQ1874/PRO4317) 1 0 0 100 0Q92772 P56 KKIAMRE protein kinase 1 0 0 100 0Q93097 Wnt-2b protein precursor (Wnt-13) 1 0 0 100 0Q99650 Oncostatin-M specific receptor beta subunit 1 0 0 100 0Q9BPU6 Dihydropyrimidinase related protein-5 (DRP-5) (ULIP6 protein) 1 0 0 100 0Q9C0C8 KIAA1735 protein (Fragment) 1 0 0 100 0Q9GZM6 Olfactory receptor 8D2 (Olfactory receptor-like protein JCG2) 1 0 0 100 0Q9H2E6 Semaphorin 6A precursor (Semaphorin VIA) (Sema VIA) (Sema 1 0 0 100 0Q9HCU4 Cadherin EGF LAG seven-pass G-type receptor 2 precursor (E 1 0 0 100 0Q9NP31 SH2 domain protein 2A (T cell-specific adapter protein) (TSAd) 1 0 0 100 0Q9NP95 Fibroblast growth factor-20 (FGF-20) 1 0 0 100 0Q9NYI0 Pleckstrin and Sec7 domain containing protein 3 (Exchange fac 1 0 0 100 0Q9NYV9 Taste receptor type 2 member 13 (T2R13) (Taste receptor fami 1 0 0 100 0Q9NZM3 Intersectin 2 (SH3 domain-containing protein 1B) (SH3P18) (SH 1 0 0 100 0Q9UKE5 TRAF2 and NCK interacting kinase (EC 20701037) 1 0 0 100 0

Q9ULZ3 Apoptosis-associated speck-like protein containing a CARD (hA 1 0 0 100 0Q9UQB3 Catenin delta-2 (Delta-catenin) (Neural plakophilin-related ARM 1 0 0 100 0Q9Y3R0 Glutamate receptor-interacting protein 1 (GRIP1 protein) 1 0 0 100 0O00366 Putative p150 1 0 0 0 100O00560 Syntenin 1 (Syndecan binding protein 1) (Melanoma differentiat 1 0 0 0 100O43396 Thioredoxin-like protein 1 (32 kDa thioredoxin-related protein) 1 0 0 0 100P00797 Renin precursor (EC 304023015) (Angiotensinogenase) 1 0 0 0 100P08648 Integrin alpha-5 precursor (Fibronectin receptor alpha subunit) ( 1 0 0 0 100P11388 DNA topoisomerase II, alpha isozyme (EC 50990103) 1 0 0 0 100P13521 Secretogranin II precursor (SgII) (Chromogranin C) [Contains: S 1 0 0 0 100P20396 Thyroliberin precursor (Thyrotropin releasing hormone) (TRH) (T 1 0 0 0 100P21796 Voltage-dependent anion-selective channel protein 1 (VDAC-1) 1 0 0 0 100P25092 Heat-stable enterotoxin receptor precursor (GC-C) (Intestinal gu 1 0 0 0 100P35348 Alpha-1A adrenergic receptor (Alpha 1A-adrenoceptor) (Alpha 1 1 0 0 0 100P40617 ADP-ribosylation factor-like protein 4A 1 0 0 0 100P61106 Ras-related protein Rab-14 1 0 0 0 100P62879 Guanine nucleotide-binding protein G(I)/G(S)/G(T) beta subunit 1 0 0 0 100Q01484 Ankyrin 2 (Brain ankyrin) (Ankyrin B) (Ankyrin, nonerythroid) 1 0 0 0 100Q15185 Telomerase-binding protein p23 (Hsp90 co-chaperone) (Proges 1 0 0 0 100

Q5VWB1 OTTHUMP00000059958 (Sorting nexin family member 27) 1 0 0 0 100Q712M9 Serotonin receptor 5-HT4 1 0 0 0 100Q8IUD2 ERC protein 1 (ELKS protein) 1 0 0 0 100Q8NGV9 Seven transmembrane helix receptor 1 0 0 0 100Q92572 Adapter-related protein complex 3 sigma 1 subunit (Sigma-adap 1 0 0 0 100Q969V1 Melanin-concentrating hormone receptor 2 (MCH receptor 2) (M 1 0 0 0 100Q9BUN8 Derlin-1 (Degradation in endoplasmic reticulum protein 1) (Der1 1 0 0 0 100Q9BZ74 FKSG42 1 0 0 0 100Q9H9L9 Hypothetical protein FLJ12664 1 0 0 0 100Q9NP90 Ras-related protein Rab-9B (Rab-9L) (RAB9-like protein) 1 0 0 0 100Q9NQT8 Kinesin-like protein KIF13B (Kinesin-like protein GAKIN) 1 0 0 0 100Q9NTG1 Polycystic kidney disease and receptor for egg jelly related prot 1 0 0 0 100Q9UL25 Ras-related protein Rab-21 1 0 0 0 100Q9Y4F1 CDEP (FERM, RhoGEF, and pleckstrin domain protein 1, isofor 1 0 0 0 100Q9Y4K4 Mitogen-activated protein kinase kinase kinase kinase 5 (EC 20 1 0 0 0 100

Supplemental Table 10: Proteins involved in protein phosphorylation

Peptides Normal Well D Mod D Poorly DAccession Protein (number) (%) (%) (%) (%)Q08881 Tyrosine-protein kinase ITK/TSK (EC 2.7.1.112) (T-cell-specific 11 18 36 27 18P78527 DNA-dependent protein kinase catalytic subunit (EC 2.7.1.37) ( 9 11 0 22 67O14757 Serine/threonine-protein kinase Chk1 (EC 2.7.1.37) 7 57 14 0 29P20794 Serine/threonine-protein kinase MAK (EC 2.7.1.37) (Male germ 6 0 33 50 17P00533 Epidermal growth factor receptor precursor (EC 2.7.1.112) (Rec 4 0 50 0 50Q6P3R8 MGC75495 protein (OTTHUMP00000040896) 4 0 25 25 50Q92918 Mitogen-activated protein kinase kinase kinase kinase 1 (EC 2.7 4 75 0 25 0Q9Y6E0 Serine/threonine-protein kinase 24 (EC 2.7.1.37) (STE20-like ki 3 0 67 0 33Q96Q04 KIAA1883 protein (Fragment) 3 33 33 0 33O75116 Rho-associated protein kinase 2 (EC 2.7.1.37) (Rho-associated 2 0 50 0 50O75460 Serine/threonine protein kinase/endoribonuclease IRE1 precurs 2 0 50 50 0O60674 Tyrosine-protein kinase JAK2 (EC 2.7.1.112) (Janus kinase 2) ( 2 0 0 50 50P43405 Tyrosine-protein kinase SYK (EC 2.7.1.112) (Spleen tyrosine ki 2 50 50 0 0Q13188 Serine/threonine-protein kinase 3 (EC 2.7.1.37) (STE20-like kin 2 50 50 0 0Q15303 Receptor tyrosine-protein kinase erbB-4 precursor (EC 2.7.1.11 2 50 0 0 50Q96QT4 Transient receptor potential cation channel subfamily M membe 2 50 0 0 50P23458 Tyrosine-protein kinase JAK1 (EC 2.7.1.112) (Janus kinase 1) ( 2 100 0 0 0P22455 Fibroblast growth factor receptor 4 precursor (EC 2.7.1.112) (FG 1 100 0 0 0P43403 Tyrosine-protein kinase ZAP-70 (EC 2.7.1.112) (70 kDa zeta-as 1 100 0 0 0P51813 Cytoplasmic tyrosine-protein kinase BMX (EC 2.7.1.112) (Bone 1 100 0 0 0

Q96RW7 Hemicentin 1 100 0 0 0Q9H4A3 Serine/threonine-protein kinase WNK1 (EC 2.7.1.37) (Protein ki 1 100 0 0 0P08069 Insulin-like growth factor I receptor precursor (EC 2.7.1.112) (C 1 0 100 0 0P54762 Ephrin type-B receptor 1 precursor (EC 2.7.1.112) (Tyrosine-pro 1 0 100 0 0Q06418 Tyrosine-protein kinase receptor TYRO3 precursor (EC 2.7.1.11 1 0 100 0 0Q14766 Latent transforming growth factor beta binding protein, isoform 1 1 0 100 0 0Q9NYY3 Serine/threonine-protein kinase PLK2 (EC 2.7.1.37) (Polo-like k 1 0 100 0 0Q9Y6B5 PAK2 1 0 100 0 0O00311 Cell division cycle 7-related protein kinase (EC 2.7.1.-) (CDC7-r 1 0 0 100 0O60566 Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (E 1 0 0 100 0P32780 TFIIH basal transcription factor complex p62 subunit (Basic tran 1 0 0 100 0

Q6P3W7 Similar to mouse D10Ertd802e protein 1 0 0 100 0Q92772 P56 KKIAMRE protein kinase 1 0 0 100 0Q9NZV1 Cysteine-rich repeat-containing protein S52 precursor (CRIM1) 1 0 0 100 0Q9UKE5 TRAF2 and NCK interacting kinase (EC 2.7.1.37) 1 0 0 100 0P25092 Heat-stable enterotoxin receptor precursor (GC-C) (Intestinal gu 1 0 0 0 100Q86YV5 FLJ00269 protein (Fragment) 1 0 0 0 100Q8IVW4 CDKL3 protein 1 0 0 0 100Q9Y4K4 Mitogen-activated protein kinase kinase kinase kinase 5 (EC 2.7 1 0 0 0 100

Supplemental Table 11: Proteins involved in endopeptidase activity

Peptides Normal Well D Mod D Poorly DAccession Protein (number) (%) (%) (%) (%)

P30101 Protein disulfide-isomerase A3 precursor (EC 5.3.4.1) (Disulfide 36 3 36 39 22P28065 Proteasome subunit beta type 9 precursor (EC 3.4.25.1) (Protea 15 0 47 40 13P07339 Cathepsin D precursor (EC 3.4.23.5) 13 0 62 23 15P06733 Alpha enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyas 9 11 22 33 33Q99797 Mitochondrial intermediate peptidase, mitochondrial precursor ( 6 0 50 17 33P22695 Ubiquinol-cytochrome-c reductase complex core protein 2, mito 6 0 0 33 67P25786 Proteasome subunit alpha type 1 (EC 3.4.25.1) (Proteasome co 3 0 67 33 0P40818 Ubiquitin carboxyl-terminal hydrolase 8 (EC 3.1.2.15) (Ubiquitin 3 0 67 33 0P45974 Ubiquitin carboxyl-terminal hydrolase 5 (EC 3.1.2.15) (Ubiquitin 3 0 0 100 0P07384 Calpain 1, large [catalytic] subunit (EC 3.4.22.52) (Calcium-activ 2 50 50 0 0Q9UKJ8 ADAM 21 precursor (EC 3.4.24.-) (A disintegrin and metalloprot 2 0 50 50 0P09936 Ubiquitin carboxyl-terminal hydrolase isozyme L1 (EC 3.4.19.12 2 0 0 0 100Q96KR5 Leishmanolysin-like peptidase, variant 2 (EC 3.4.24.36) 2 0 0 100 0O60235 Airway trypsin-like protease precursor (EC 3.4.21.-) 1 100 0 0 0P13798 Acylamino-acid-releasing enzyme (EC 3.4.19.1) (AARE) (Acyl-p 1 100 0 0 0Q9UBX1 Cathepsin F precursor (EC 3.4.22.41) (CATSF) 1 100 0 0 0Q9UKR3 Kallikrein 13 precursor (EC 3.4.21.-) (Kallikrein-like protein 4) (K 1 100 0 0 0O75173 ADAMTS-4 precursor (EC 3.4.24.82) (A disintegrin and metallo 1 0 100 0 0P51784 Ubiquitin carboxyl-terminal hydrolase 11 (EC 3.1.2.15) (Ubiquiti 1 0 100 0 0P78562 Phosphate regulating neutral endopeptidase (EC 3.4.24.-) (Meta 1 0 100 0 0Q9P2N4 ADAMTS-9 precursor (EC 3.4.24.-) (A disintegrin and metallopr 1 0 100 0 0Q9UHI8 ADAMTS-1 precursor (EC 3.4.24.-) (A disintegrin and metallopr 1 0 100 0 0O95672 Endothelin-converting enzyme-like 1 (EC 3.4.24.-) (Xce protein) 1 0 0 100 0P07711 Cathepsin L precursor (EC 3.4.22.15) (Major excreted protein) ( 1 0 0 100 0P20618 Proteasome subunit beta type 1 (EC 3.4.25.1) (Proteasome com 1 0 0 100 0Q6MZZ7 Hypothetical protein DKFZp686L13193 1 0 0 100 0Q9NZV1 Cysteine-rich repeat-containing protein S52 precursor (CRIM1) 1 0 0 100 0Q9ULZ3 Apoptosis-associated speck-like protein containing a CARD (hA 1 0 0 100 0O43464 Serine protease HTRA2, mitochondrial precursor (EC 3.4.21.-) 1 0 0 0 100P00797 Renin precursor (EC 3.4.23.15) (Angiotensinogenase) 1 0 0 0 100P04632 Calpain small subunit 1 (CSS1) (Calcium-dependent protease s 1 0 0 0 100P17538 Chymotrypsinogen B precursor (EC 3.4.21.1) 1 0 0 0 100P49720 Proteasome subunit beta type 3 (EC 3.4.25.1) (Proteasome the 1 0 0 0 100P60900 Proteasome subunit alpha type 6 (EC 3.4.25.1) (Proteasome iot 1 0 0 0 100Q8NBP7 Proprotein convertase subtilisin/kexin type 9 precursor (EC 3.4. 1 0 0 0 100Q8TE58 ADAMTS-15 precursor (EC 3.4.24.-) (A disintegrin and metallop 1 0 0 0 100

Supplemental Table 12: Proteins involved in cell motility

Peptides Normal Well D Mod D Poorly DAccession Protein (number) (%) (%) (%) (%)

P04083 Annexin A1 (Annexin I) (Lipocortin I) (Calpactin II) (Chromobind 120 22 35 21 23P04792 Heat-shock protein beta-1 (HspB1) (Heat shock 27 kDa protein) 83 5 29 31 35P08670 Vimentin 79 0 37 44 19P35579 Myosin heavy chain, nonmuscle type A (Cellular myosin heavy 36 3 42 31 25P61160 Actin-like protein 2 (Actin-related protein 2) 26 8 38 31 23P67936 Tropomyosin alpha 4 chain (Tropomyosin 4) (TM30p1) 22 0 41 32 27P10599 Thioredoxin (ATL-derived factor) (ADF) (Surface associated sul 21 14 29 38 19P18206 Vinculin (Metavinculin) 18 11 50 28 11O43707 Alpha-actinin 4 (Non-muscle alpha-actinin 4) (F-actin cross linki 16 0 44 19 38P26038 Moesin (Membrane-organizing extension spike protein) 15 0 13 60 27P31146 Coronin-1A (Coronin-like protein p57) (Coronin-like protein A) (C 11 0 27 45 27Q01518 Adenylyl cyclase-associated protein 1 (CAP 1) 10 10 30 20 40P52565 Rho GDP-dissociation inhibitor 1 (Rho GDI 1) (Rho-GDI alpha) 10 0 30 50 20P05023 Sodium/potassium-transporting ATPase alpha-1 chain precurso 7 0 29 43 29P63000 Ras-related C3 botulinum toxin substrate 1 (p21-Rac1) (Ras-like 6 67 0 0 33P12814 Alpha-actinin 1 (Alpha-actinin cytoskeletal isoform) (Non-muscle 6 0 83 0 17P25815 S-100P protein 5 0 80 20 0P52907 F-actin capping protein alpha-1 subunit (CapZ alpha-1) 4 25 25 25 25P21333 Filamin A (Alpha-filamin) (Filamin 1) (Endothelial actin-binding p 4 25 0 25 50P00533 Epidermal growth factor receptor precursor (EC 2.7.1.112) (Rec 4 0 50 0 50P29034 S100 calcium-binding protein A2 (S-100L protein) (CAN19) 3 0 67 33 0O43157 Plexin B1 precursor (Semaphorin receptor SEP) 3 0 33 33 33P54577 Tyrosyl-tRNA synthetase, cytoplasmic (EC 6.1.1.1) (Tyrosyl--tR 3 0 0 33 67P07942 Laminin beta-1 chain precursor (Laminin B1 chain) 2 50 50 0 0P43405 Tyrosine-protein kinase SYK (EC 2.7.1.112) (Spleen tyrosine ki 2 50 50 0 0Q8TE73 Ciliary dynein heavy chain 5 (Axonemal beta dynein heavy chai 2 50 50 0 0P35580 Myosin heavy chain, nonmuscle type B (Cellular myosin heavy 2 0 50 50 0P43246 DNA mismatch repair protein Msh2 2 0 50 50 0O60674 Tyrosine-protein kinase JAK2 (EC 2.7.1.112) (Janus kinase 2) ( 2 0 0 50 50P40763 Signal transducer and activator of transcription 3 (Acute-phase 2 0 0 50 50Q13591 Semaphorin 5A precursor (Semaphorin F) (Sema F) 1 100 0 0 0Q9UQP3 Tenascin N precursor 1 100 0 0 0O14556 Glyceraldehyde-3-phosphate dehydrogenase, testis-specific (EC 1 0 100 0 0O15143 ARP2/3 complex 41 kDa subunit (P41-ARC) (Actin-related prote 1 0 100 0 0P23229 Integrin alpha-6 precursor (VLA-6) (CD49f) 1 0 100 0 0

Q9UHG0 Doublecortin domain-containing protein 2 (RU2S protein) 1 0 100 0 0P01137 Transforming growth factor beta 1 precursor (TGF-beta 1) 1 0 0 100 0P13637 Sodium/potassium-transporting ATPase alpha-3 chain (EC 3.6.3 1 0 0 100 0P29966 Myristoylated alanine-rich C-kinase substrate (MARCKS) (Prote 1 0 0 100 0P33241 Lymphocyte-specific protein 1 (Protein pp52) (52 kDa phosphop 1 0 0 100 0P36952 Maspin precursor (Protease inhibitor 5) 1 0 0 100 0P52566 Rho GDP-dissociation inhibitor 2 (Rho GDI 2) (Rho-GDI beta) (L 1 0 0 100 0Q9BPU6 Dihydropyrimidinase related protein-5 (DRP-5) (ULIP6 protein) 1 0 0 100 0Q9H2E6 Semaphorin 6A precursor (Semaphorin VIA) (Sema VIA) (Sema 1 0 0 100 0O00560 Syntenin 1 (Syndecan binding protein 1) (Melanoma differentiat 1 0 0 0 100P13521 Secretogranin II precursor (SgII) (Chromogranin C) [Contains: S 1 0 0 0 100Q02880 DNA topoisomerase II, beta isozyme (EC 5.99.1.3) 1 0 0 0 100

Supplemental Table 13: Proteins involved in cell cycle regulation

Peptides Normal Well D Mod D Poorly DAccession Protein (number) (%) (%) (%) (%)

P04083 Annexin A1 (Annexin I) (Lipocortin I) (Calpactin II) (Chromobind 120 22 35 21 23P06748 Nucleophosmin (NPM) (Nucleolar phosphoprotein B23) (Numat 21 14 29 14 43O43707 Alpha-actinin 4 (Non-muscle alpha-actinin 4) (F-actin cross linki 16 0 44 19 38P42224 Signal transducer and activator of transcription 1-alpha/beta (Tr 14 0 57 29 14P78371 T-complex protein 1, beta subunit (TCP-1-beta) (CCT-beta) 13 15 31 31 23P06703 Calcyclin (Prolactin receptor associated protein) (PRA) (Growth 12 0 67 25 8P31146 Coronin-1A (Coronin-like protein p57) (Coronin-like protein A) (C 11 0 27 45 27Q9BPX3 Condensin subunit 3 (Chromosome-associated protein G) (Con 10 0 50 20 30P27797 Calreticulin precursor (CRP55) (Calregulin) (HACBP) (ERp60) ( 8 0 50 13 38O14757 Serine/threonine-protein kinase Chk1 (EC 2.7.1.37) 7 57 14 0 29P27348 14-3-3 protein tau (14-3-3 protein theta) (14-3-3 protein T-cell) ( 7 0 29 43 29Q16543 Hsp90 co-chaperone Cdc37 (Hsp90 chaperone protein kinase-t 6 0 67 0 33Q13561 Dynactin complex 50 kDa subunit (50 kDa dynein-associated po 5 0 100 0 0P50991 T-complex protein 1, delta subunit (TCP-1-delta) (CCT-delta) (S 5 0 40 60 0P35232 Prohibitin 5 0 20 20 60O60231 Putative pre-mRNA splicing factor RNA helicase (ATP-depende 4 25 25 25 25P00533 Epidermal growth factor receptor precursor (EC 2.7.1.112) (Rec 4 0 50 0 50Q13148 TAR DNA-binding protein-43 (TDP-43) 4 0 50 25 25Q9UHD8 Septin 9 (MLL septin-like fusion protein) (MLL septin-like fusion 4 0 50 25 25P07954 Fumarate hydratase, mitochondrial precursor (EC 4.2.1.2) (Fum 3 33 0 0 67P20962 Parathymosin 3 0 67 33 0Q99832 T-complex protein 1, eta subunit (TCP-1-eta) (CCT-eta) (HIV-1 3 0 67 33 0Q02224 Centromeric protein E (CENP-E protein) 3 0 33 33 33Q9HC35 Echinoderm microtubule-associated protein-like 4 (EMAP-4) (Re 2 50 50 0 0P46087 Proliferating-cell nucleolar antigen p120 (Proliferation-associate 2 50 0 0 50Q14526 Hypermethylated in cancer 1 protein (Hic-1) (Zinc finger and BT 2 50 0 0 50O60447 EVI-5 homolog 2 0 100 0 0P52292 Importin alpha-2 subunit (Karyopherin alpha-2 subunit) (SRP1-a 2 0 100 0 0O75460 Serine/threonine protein kinase/endoribonuclease IRE1 precurs 2 0 50 50 0P43246 DNA mismatch repair protein Msh2 2 0 50 50 0Q14566 DNA replication licensing factor MCM6 (P105MCM) 2 0 50 0 50Q8TDY2 Rb1-inducible coiled coil protein 2 0 50 50 0O60674 Tyrosine-protein kinase JAK2 (EC 2.7.1.112) (Janus kinase 2) ( 2 0 0 50 50O95661 Rho-related GTP-binding protein RhoI 2 0 0 100 0P33992 DNA replication licensing factor MCM5 (CDC46 homolog) (P1-C 2 0 0 0 100P42345 FKBP12-rapamycin complex-associated protein (FK506-binding 2 0 0 50 50P49736 DNA replication licensing factor MCM2 (Minichromosome maint 2 0 0 0 100P62701 40S ribosomal protein S4, X isoform (Single copy abundant mR 2 0 0 50 50

Q8TDM6 Discs, large homolog 5 (Placenta and prostate DLG) (Discs larg 2 0 0 50 50Q8WWL7 G2/mitotic-specific cyclin B3 2 0 0 50 50Q96R06 Sperm associated antigen 5 (Astrin) (Mitotic spindle associated 2 0 0 0 100Q9Y265 RuvB-like 1 (EC 3.6.1.-) (49-kDa TATA box-binding protein-inte 2 0 0 100 0O75122 KIAA0627 protein (Fragment) 1 100 0 0 0O75909 Cyclin K 1 100 0 0 0P25054 Adenomatous polyposis coli protein (APC protein) 1 100 0 0 0Q14674 Separin (EC 3.4.22.49) (Separase) (Caspase-like protein ESPL 1 100 0 0 0Q16164 G1 phase-specific gene protein (Fragment) 1 100 0 0 0Q96HI0 Sentrin-specific protease 5 (EC 3.4.22.-) (Sentrin/SUMO-specifi 1 100 0 0 0

Q9UQE7 Structural maintenance of chromosome 3 (Chondroitin sulfate p 1 100 0 0 0O15287 Fanconi anemia group G protein (FACG protein) (DNA-repair pr 1 0 100 0 0O43303 Centrosomal protein of 110 kDa (CP110 protein) 1 0 100 0 0O43663 Protein regulating cytokinesis 1 (Protein regulator of cytokinesis 1 0 100 0 0O60884 DnaJ homolog subfamily A member 2 (HIRA interacting protein 1 0 100 0 0P06454 Prothymosin alpha 1 0 100 0 0P08069 Insulin-like growth factor I receptor precursor (EC 2.7.1.112) (C 1 0 100 0 0P11487 INT-2 proto-oncogene protein precursor (Fibroblast growth facto 1 0 100 0 0P28340 DNA polymerase delta catalytic subunit (EC 2.7.7.7) (DNA poly 1 0 100 0 0P42695 Hypothetical protein KIAA0056 (Fragment) 1 0 100 0 0P50748 Kinetochore-associated protein 1 (Rough deal homolog) (hRod) 1 0 100 0 0P78344 Eukaryotic translation initiation factor 4 gamma 2 (eIF-4-gamma 1 0 100 0 0P84095 Rho-related GTP-binding protein RhoG 1 0 100 0 0Q01831 DNA-repair protein complementing XP-C cells (Xeroderma pigm 1 0 100 0 0Q13618 Cullin homolog 3 (CUL-3) 1 0 100 0 0Q6KC79 Nipped-B-like protein (Delangin) (SCC2 homolog) 1 0 100 0 0Q8TEW8 Amyotrophic lateral sclerosis 2 chromosome region candidate g 1 0 100 0 0Q8WTW4 Tumor suppressor candidate 4 (NPR2-like) (Gene 21 protein) (G 1 0 100 0 0Q9NRY4 Glucocorticoid receptor DNA binding factor 1 (Glucocorticoid rec 1 0 100 0 0Q9NYY3 Serine/threonine-protein kinase PLK2 (EC 2.7.1.37) (Polo-like k 1 0 100 0 0Q9UQL6 Histone deacetylase 5 (HD5) (Antigen NY-CO-9) 1 0 100 0 0O00311 Cell division cycle 7-related protein kinase (EC 2.7.1.-) (CDC7-r 1 0 0 100 0O60566 Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (E 1 0 0 100 0P01137 Transforming growth factor beta 1 precursor (TGF-beta 1) 1 0 0 100 0P27694 Replication protein A 70 kDa DNA-binding subunit (RP-A) (RF-A 1 0 0 100 0P30622 Restin (Cytoplasmic linker protein-170 alpha-2) (CLIP-170) (Ree 1 0 0 100 0P32780 TFIIH basal transcription factor complex p62 subunit (Basic tran 1 0 0 100 0P49646 Very very hypothetical protein RMSA-1 1 0 0 100 0P52789 Hexokinase, type II (EC 2.7.1.1) (HK II) (Muscle form hexokinas 1 0 0 100 0Q96EP1 Ubiquitin ligase protein CHFR (EC 6.3.2.-) (Checkpoint with fork 1 0 0 100 0Q99496 DinG protein (Ring finger protein BAP-1) (Ring finger protein 2) 1 0 0 100 0Q9H5I1 Histone-lysine N-methyltransferase, H3 lysine-9 specific 2 (EC 2 1 0 0 100 0

Q9NQW6 Actin binding protein anillin 1 0 0 100 0Q9NY59 Neutral sphingomyelinase II (EC 3.1.4.12) 1 0 0 100 0Q9ULZ3 Apoptosis-associated speck-like protein containing a CARD (hA 1 0 0 100 0Q9UQ80 Proliferation-associated protein 2G4 (Cell cycle protein p38-2G4 1 0 0 100 0Q9Y250 Leucine zipper putative tumor suppressor 1 (F37/esophageal ca 1 0 0 100 0Q9Y3P9 Rab6 GTPase activating protein, GAPCenA (RABGAP1 protein 1 0 0 100 0O00366 Putative p150 1 0 0 0 100O43324 Multisynthetase complex auxiliary component p18 1 0 0 0 100P25205 DNA replication licensing factor MCM3 (DNA polymerase alpha 1 0 0 0 100P33993 DNA replication licensing factor MCM7 (CDC47 homolog) (P1.1 1 0 0 0 100P51610 Host cell factor C1 (HCF) (VP16 accessory protein) (HFC1) (VC 1 0 0 0 100P55769 NHP2-like protein 1 (High mobility group-like nuclear protein 2 h 1 0 0 0 100Q00577 Transcriptional activator protein PUR-alpha (Purine-rich single-s 1 0 0 0 100Q12959 Presynaptic protein SAP97 (Synapse-associated protein 97) (D 1 0 0 0 100Q92900 Regulator of nonsense transcripts 1 (Nonsense mRNA reducing 1 0 0 0 100Q99460 26S proteasome non-ATPase regulatory subunit 1 (26S proteas 1 0 0 0 100Q99684 Zinc finger protein Gfi-1 (Growth factor independence-1) 1 0 0 0 100Q9BTV7 Cdk5 and abl enzyme substrate 2 (Interactor with cdk3 2) (Ik3-2 1 0 0 0 100Q9UBU7 Activator of S phase Kinase (Dbf4 protein) 1 0 0 0 100

Supplemental Table 14: Proteins involved in cell adhesion

Peptides Normal Well D Mod D Poorly DAccession Protein (number) (%) (%) (%) (%)Q13835 Plakophilin 1 (Band-6-protein) (B6P) 95 17 31 21 32P12111 Collagen alpha 3(VI) chain precursor 69 3 32 46 19P32926 Desmoglein 3 precursor (130 kDa pemphigus vulgaris antigen) 65 15 29 31 25P35579 Myosin heavy chain, nonmuscle type A (Cellular myosin heavy 36 3 42 31 25Q9Y446 Plakophilin 3 35 29 29 31 11P07737 Profilin-1 (Profilin I) 24 17 21 29 33P47929 Galectin-7 (Gal-7) (HKL-14) (PI7) (p53-induced protein 1) 24 8 67 13 13

Q8NFW1 Alpha 1 type XXII collagen 22 0 32 41 27Q14574 Desmocollin 3 precursor (Desmocollin 4) (HT-CP) 18 17 22 22 39P18206 Vinculin (Metavinculin) 18 11 50 28 11P22105 Tenascin X precursor (TN-X) (Hexabrachion-like) 17 0 41 29 29Q02413 Desmoglein 1 precursor (Desmosomal glycoprotein 1) (DG1) (D 14 14 36 43 7Q13753 Laminin gamma-2 chain precursor (Kalinin/nicein/epiligrin 100 k 13 0 62 38 0P24821 Tenascin precursor (TN) (Hexabrachion) (Cytotactin) (Neuronec 10 0 60 40 0P20908 Collagen alpha 1(V) chain precursor 10 0 50 30 20P52565 Rho GDP-dissociation inhibitor 1 (Rho GDI 1) (Rho-GDI alpha) 10 0 30 50 20Q02388 Collagen alpha 1(VII) chain precursor (Long-chain collagen) (LC 9 22 11 11 56Q13751 Laminin beta-3 chain precursor (Laminin 5 beta 3) (Laminin B1k 9 0 44 56 0Q02487 Desmocollin 2A/2B precursor (Desmosomal glycoprotein II and 7 0 43 29 29P63000 Ras-related C3 botulinum toxin substrate 1 (p21-Rac1) (Ras-like 6 67 0 0 33Q8N8Z6 Discoidin, CUB and LCCL domain containing protein 1 precurso 6 17 33 50 0P12814 Alpha-actinin 1 (Alpha-actinin cytoskeletal isoform) (Non-muscle 6 0 83 0 17P16615 Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (EC 3.6 5 0 40 60 0P11047 Laminin gamma-1 chain precursor (Laminin B2 chain) 5 0 0 60 40P16144 Integrin beta-4 precursor (GP150) (CD104 antigen) 4 0 75 25 0P00533 Epidermal growth factor receptor precursor (EC 2.7.1.112) (Rec 4 0 50 0 50Q08380 Galectin-3 binding protein precursor (Lectin galactoside-binding 3 0 100 0 0P13611 Versican core protein precursor (Large fibroblast proteoglycan) 2 100 0 0 0O14727 Apoptotic protease activating factor 1 (Apaf-1) 2 50 50 0 0P07942 Laminin beta-1 chain precursor (Laminin B1 chain) 2 50 50 0 0P43405 Tyrosine-protein kinase SYK (EC 2.7.1.112) (Spleen tyrosine ki 2 50 50 0 0Q96QT4 Transient receptor potential cation channel subfamily M membe 2 50 0 0 50Q15582 Transforming growth factor-beta induced protein IG-H3 precurso 2 0 100 0 0Q8TEG4 FLJ00233 protein (Fragment) 2 0 50 50 0Q99715 Collagen alpha 1(XII) chain precursor 2 0 50 0 50Q9Y4G6 Talin 2 2 0 50 50 0Q01955 Collagen alpha 3(IV) chain precursor (Goodpasture antigen) 2 0 0 100 0Q8TD84 Down syndrome cell adhesion molecule 2 2 0 0 50 50Q8TDM6 Discs, large homolog 5 (Placenta and prostate DLG) (Discs larg 2 0 0 50 50Q96KR5 Leishmanolysin-like peptidase, variant 2 (EC 3.4.24.36) 2 0 0 100 0O15537 Retinoschisin precursor (X-linked juvenile retinoschisis protein) 1 100 0 0 0P25054 Adenomatous polyposis coli protein (APC protein) 1 100 0 0 0Q13591 Semaphorin 5A precursor (Semaphorin F) (Sema F) 1 100 0 0 0Q86XX4 Extracellular matrix protein FRAS1 precursor 1 100 0 0 0Q96RW7 Hemicentin 1 100 0 0 0Q9UN73 Protocadherin alpha 6 precursor (PCDH-alpha6) 1 100 0 0 0Q9UQP3 Tenascin N precursor 1 100 0 0 0O00548 Delta-like protein 1 precursor (Drosophila Delta homolog 1) (De 1 0 100 0 0

P01042 Kininogen precursor (Alpha-2-thiol proteinase inhibitor) [Contain 1 0 100 0 0P20849 Collagen alpha 1(IX) chain precursor 1 0 100 0 0P23229 Integrin alpha-6 precursor (VLA-6) (CD49f) 1 0 100 0 0P35609 Alpha-actinin 2 (Alpha actinin skeletal muscle isoform 2) (F-acti 1 0 100 0 0Q06418 Tyrosine-protein kinase receptor TYRO3 precursor (EC 2.7.1.11 1 0 100 0 0Q13017 Rho-GTPase-activating protein 5 (p190-B) 1 0 100 0 0Q8TDX9 Polycystic kidney disease 1-like 1 protein (Polycystin 1L1) 1 0 100 0 0Q9H251 Cadherin-23 precursor (Otocadherin) 1 0 100 0 0Q9NRY4 Glucocorticoid receptor DNA binding factor 1 (Glucocorticoid rec 1 0 100 0 0O43182 Rho-GTPase-activating protein 6 (Rho-type GTPase-activating 1 0 0 100 0P04275 Von Willebrand factor precursor (vWF) [Contains: Von Willebran 1 0 0 100 0P13942 Collagen alpha 2(XI) chain precursor 1 0 0 100 0P22223 Cadherin-3 precursor (Placental-cadherin) (P-cadherin) 1 0 0 100 0P52566 Rho GDP-dissociation inhibitor 2 (Rho GDI 2) (Rho-GDI beta) (L 1 0 0 100 0Q86SJ2 Amphoterin induced gene 2 (DEGA/AMIGO-2 precursor) (Alivin 1 0 0 100 0Q9HCU4 Cadherin EGF LAG seven-pass G-type receptor 2 precursor (E 1 0 0 100 0Q9UQB3 Catenin delta-2 (Delta-catenin) (Neural plakophilin-related ARM 1 0 0 100 0Q9Y5G7 Protocadherin gamma A6 precursor (PCDH-gamma-A6) 1 0 0 100 0Q9Y6C2 EMILIN 1 precursor (Elastin microfibril interface-located protein 1 0 0 100 0P08648 Integrin alpha-5 precursor (Fibronectin receptor alpha subunit) ( 1 0 0 0 100Q12959 Presynaptic protein SAP97 (Synapse-associated protein 97) (D 1 0 0 0 100Q86UX7 Unc-112 related protein 2 (Kindlin-3) (MIG2-like) 1 0 0 0 100Q9NY15 Stabilin 1 precursor (FEEL-1 protein) (MS-1 antigen) 1 0 0 0 100

Supplemental Table 15: Novel proteins identified in HNSCC

Peptides Normal Well D Mod D Poorly DAccession Protein (number) (%) (%) (%) (%)Q8N7Z2 Hypothetical protein FLJ40198 15 0.00 40.00 33.33 26.67Q9BVC6 Hypothetical protein MGC5508 13 0.00 23.08 30.77 46.15Q96MG1 Hypothetical protein FLJ32421 10 10.00 50.00 30.00 10.00Q96CN5 Hypothetical protein MGC20806 10 30.00 40.00 10.00 20.00Q6ZT17 Hypothetical protein FLJ45043 8 12.50 25.00 25.00 37.50Q6ZVY6 Hypothetical protein FLJ41910 8 0.00 0.00 0.00 100.00Q6ZRH9 Hypothetical protein FLJ46347 7 0.00 42.86 42.86 14.29Q96LT0 Hypothetical protein FLJ25091 7 0.00 57.14 14.29 28.57Q6ZQN2 Hypothetical protein FLJ46846 7 0.00 42.90 57.10 0.00Q66K23 Hypothetical protein (Fragment) 7 0.00 42.90 57.10 0.00Q8N7I6 Hypothetical protein FLJ25506 6 16.67 16.67 33.33 33.33Q6ZVR1 Hypothetical protein FLJ42200 6 0.00 16.67 66.67 16.67Q5VVY7 OTTHUMP00000040479 6 0.00 50.00 33.33 16.67Q13015 Protein AF1q 6 0.00 0.00 0.00 100.00Q6IQ21 Hypothetical protein FLJ20582 5 0.00 40.00 40.00 20.00Q8N442 Hypothetical protein FLJ13220 5 0.00 40.00 40.00 20.00Q6ZRU0 Hypothetical protein FLJ46111 5 0.00 42.90 57.10 0.00Q8TBU6 Hypothetical protein FLJ11848 4 25.00 25.00 25.00 25.00Q9H8N1 Hypothetical protein FLJ13385 4 0.00 25.00 25.00 50.00Q6P3R8 MGC75495 protein (OTTHUMP00000040896) 4 0.00 25.00 25.00 50.00Q96FV1 KRT19 protein (Fragment) 4 0.00 0.00 0.00 100.00Q9Y6X9 LOC132200 protein 4 0.00 0.00 0.00 100.00Q8N9V6 Hypothetical protein FLJ36160 4 0.00 60.00 40.00 0.00Q9H7V7 Hypothetical protein FLJ14207 4 0.00 50.00 50.00 0.00Q86T83 Hypothetical protein DKFZp451J0218 4 0.00 66.70 33.30 0.00Q9ULT2 KIAA1138 protein (Fragment) 4 0.00 0.00 50.00 50.00Q6ZSN1 Hypothetical protein FLJ45355 4 0.00 0.00 75.00 25.00Q9BZK3 FKSG17 3 0.00 33.33 33.33 33.33Q96NZ8 Putative multivalent protease inhibitor WFIKKN 3 0.00 33.33 33.33 33.33Q6ZN03 Hypothetical protein FLJ16545 3 100.00 0.00 0.00 0.00Q9HCF8 KIAA1614 protein (Fragment) 3 0.00 100.00 0.00 0.00Q6NXN2 Hypothetical protein 3 0.00 66.70 33.30 0.00Q86Z22 Hypothetical protein 3 0.00 33.30 66.70 0.00Q6UWP8 HLAR698 3 0.00 66.70 33.30 0.00Q96MC2 Hypothetical protein FLJ32660 3 0.00 0.00 75.00 25.00Q6ZUF5 Hypothetical protein FLJ43756 3 0.00 0.00 50.00 50.00Q9H0M3 Hypothetical protein DKFZp434O0710 (Hypothetical protein KIA 2 100.00 0.00 0.00 0.00Q9UGU5 High-mobility group protein 2-like 1 (HMGBCG protein) 2 100.00 0.00 0.00 0.00Q6ZWK7 Hypothetical protein FLJ16045 2 100.00 0.00 0.00 0.00Q7Z7J3 Hypothetical protein 2 100.00 0.00 0.00 0.00Q6UXX9 QFRL9384 2 100.00 0.00 0.00 0.00Q96PE1 Probable G protein-coupled receptor 124 precursor (Tumor end 2 0.00 100.00 0.00 0.00O15074 KIAA0368 protein (Fragment) 2 0.00 100.00 0.00 0.00Q9H7W7 Hypothetical protein FLJ14183 2 0.00 100.00 0.00 0.00Q6ZNX0 Hypothetical protein FLJ26965 2 0.00 100.00 0.00 0.00Q63HQ8 Hypothetical protein DKFZp686M21196 2 0.00 100.00 0.00 0.00Q8IYW7 Hypothetical protein (Fragment) 2 0.00 100.00 0.00 0.00Q8IW93 Rho guanine nucleotide exchange factor (GEF) 19 (Novel prote 2 0.00 100.00 0.00 0.00

Q8N9S5 Hypothetical protein FLJ36608 2 0.00 100.00 0.00 0.00O15032 KIAA0316 protein (Fragment) 2 0.00 0.00 100.00 0.00Q9BU70 Chromosome 9 open reading frame 156 2 0.00 0.00 100.00 0.00Q9NWL6 Hypothetical protein FLJ20752 (HCV NS3-transactivated protein 2 0.00 0.00 100.00 0.00Q6ZRD7 Hypothetical protein FLJ46433 2 0.00 0.00 100.00 0.00Q8TE28 BA351K23.4 (Novel protein) (Hypothetical protein FLJ25831) 2 0.00 0.00 100.00 0.00Q8IYW2 Chromosome 10 open reading frame 92 2 0.00 0.00 100.00 0.00Q8N7E2 Hypothetical protein FLJ25735 2 0.00 0.00 100.00 0.00Q9H977 Hypothetical protein FLJ12953 2 0.00 0.00 0.00 100.00P30740 Hypothetical protein FLJ42406 2 50.00 50.00 0.00 0.00Q8N3H8 Hypothetical protein DKFZp761M1613 (Fragment) 2 0.00 50.00 50.00 0.00Q8IYX7 Chromosome 9 open reading frame 138 2 0.00 50.00 50.00 0.00Q8IV77 CNGA4 protein (Fragment) 2 0.00 50.00 50.00 0.00Q96NL6 Hypothetical protein FLJ30655 2 0.00 50.00 50.00 0.00Q6ZVZ3 Hypothetical protein FLJ41891 2 0.00 50.00 50.00 0.00Q6ZSR4 Hypothetical protein FLJ45273 2 0.00 50.00 50.00 0.00Q6UXR7 LTLL9335 2 0.00 50.00 50.00 0.00Q8TEG4 FLJ00233 protein (Fragment) 2 0.00 50.00 50.00 0.00Q96BP3 KIAA0073 protein 2 0.00 50.00 50.00 0.00Q96DB5 CGI-90 protein 2 0.00 50.00 50.00 0.00Q8WTS1 CGI58 protein 2 0.00 0.00 50.00 50.00Q8TF30 KIAA1971 protein (Fragment) 2 0.00 0.00 50.00 50.00