Article

Reference

PROSITE: a dictionary of sites and patterns in proteins

BAIROCH, Amos Marc

Abstract

PROSITE is a compilation of sites and patterns found in protein sequences. The use of

protein sequence patterns (or motifs) to determine the function of proteins is becoming very

rapidly one of the essential tools of sequence analysis. This reality has been recognized by

many authors. While there have been a number of recent reports that review published

patterns, no attempt had been made until very recently [5,6] to systematically collect

biologically significant patterns or to discover new ones. It is for these reasons that we have

developed, since 1988, a dictionary of sites and patterns which we call PROSITE. Some of

the patterns compiled in PROSITE have been published in the literature, but the majority have

been developed,in the last two years, by the author.

BAIROCH, Amos Marc. PROSITE: a dictionary of sites and patterns in proteins. Nucleic Acids

Research, 1992, vol. 20 Suppl, p. 2013-8

DOI : 10.1093/nar/20.suppl.2013

PMID : 1598232

Available at:

http://archive-ouverte.unige.ch/unige:36259

Disclaimer: layout of this document may differ from the published version.

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Nucleic Acids Research, Vol. 20, Supplement 2013-2018

PROSITE: a dictionary of sites and patterns in proteinsAmos BairochDepartment of Medical Biochemistry, University of Geneva, 1 rue Michel Servet, 1211 Geneva 4,Switzerland

INTRODUCTIONPROSITE is a compilation of sites and patterns found in proteinsequences. The use of protein sequence patterns (or motifs) todetermine the function of proteins is becoming very rapidly oneof the essential tools of sequence analysis. This reality has beenrecognized by many authors [1,2]. While there have been anumber of recent reports [3,4] that review published patterns,no attempt had been made until very recently [5,6] tosystematically collect biologically significant patterns or todiscover new ones. It is for these reasons that we have developed,since 1988, a dictionary of sites and patterns which we callPROSITE.Some of the patterns compiled in PROSITE have been

published in the literature, but the majority have been developed,in the last two years, by the author.

FORMATThe PROSITE database is composed of two ASCII (text) files.The first file (PROSITE.DAT) is a computer-readable file thatcontains all the information necessary to programs that make useof PROSITE to scan sequence(s) with pattern(s). This file alsoincludes, for each of the patterns described, statistics on thenumber of hits obtained while scanning for that pattern in theSWISS-PROT protein sequence data bank [7]. Cross-referencesto the corresponding SWISS-PROT entries are also present inthat file. The second file (PROSITE.DOC), which we call thetextbook, contains textual information that documents eachpattern. A user manual (PROSUSER.TXT) is distributed withthe database, it fully describes the format of both files. A sampletextbook entry is shown in Figure 1 with the corresponding datafrom the pattern file.

LEADING CONCEPTSThe design of PROSITE follows four leading concepts:

Completeness. For such a compilation to be helpful in thedetermination of protein function, it is important that it containsa significant number of biologically meaningful patterns.High specificity of the patterns. In the majority of cases we

have chosen patterns that are specific enough not to detect toomany unrelated sequences, yet that detect most if not all sequencesthat clearly belong to the set in consideration.

Documentation. Each of the patterns is fully documented; thedocumentation includes a concise description of the family ofprotein that it is supposed to detect as well as an explanation onthe reasons that led to the selection of the particular pattern.

Periodic reviewing. It is important that each pattern beperiodically reviewed, so as to insure that it is still relevant.

CONTENT OF THE CURRENT RELEASERelease 8.10 of PROSITE (March 1992) contains 530 documen-tation entries describing 605 different patterns. The list of theseentries is provided in Appendix 1.

DISTRIBUTION

PROSITE is distributed on magnetic tape and on CD-ROM bythe EMBL Data Library. For all enquiries regarding thesubscription and distribution of PROSITE one should contact:

EMBL Data LibraryEuropean Molecular Biology LaboratoryPostfach 10.2209, Meyerhofstrasse 16900 Heidelberg, GermanyTelephone: (+49 6221) 387 258Telefax : (+49 6221) 387 519 or 387 306Electronic network address: datalib@EMBL-heidelberg.de

PROSITE can be obtained from the EMBL File Server [8].Detailed instructions on how to make best use of this service,and in particular on how to obtain PROSITE, can be obtainedby sending to the network address netserv@EMBL-heidelberg.dethe following message:

HELPHELP PROSITE

If you have access to a computer system linked to the Internetyou can obtain PROSITE using FTP (File Transfer Protocol),from the following file servers:GenBank On-line Service [9]Internet address: genbank.bio.net (134.172.1.160)NCBI (National Library of Medecine, NIH, Washington D.C.,

U.S.A.)Internet address: ncbi.nlm.nih.gov (130.14.20.1)Swiss EMBnet FTP server (Biozentrum, Basel, Switzerland)Internet address: bioftp.unibas.ch (131.152.1.7)ExPASy (Expert Protein Analysis System server, University

of Geneva, Switzerland)Internet address: expasy.hcuge.ch (129.195.254.61)

The present distribution frequency is four releases per year. Norestrictions are placed on use or redistribution of the data.

REFERENCES1. Doolittle R.F. (In) Of URFs and ORFs: a primer on how to analyze derived

amino acid sequences., University Science Books, Mill Valley, California,(1986).

2. Lesk A.M. (In) Computational Molecular Biology, Lesk A.M., Ed.,ppl7-26, Oxford University Press, Oxford (1988).

3. Barker W.C., Hunt T.L., George D.G. Protein Seq. Data Anal.1:363-373(1988).

4. Hodgman T.C. CABIOS 5:1-13(1989).5. Bork P. FEBS Lett. 257:191-195(1989).6. Smith H.O., Annau T.M., Chandrasegaran S. Proc. Natl. Acad. Sci. USA

87:826-830(1990).7. Bairoch A., Boeckmann B. Nucleic Acids Res. 20:2019-2022(1992).8. Stoehr P.J., Omond R.A.Nucleic Acids Res. 17:6763-6764(1989).9. Benton D. Nucleic Acids Res. 18:1517-1520(1990).

.=) 1992 Oxford University Press

2014 Nucleic Acids Research, Vol. 20, Supplement

a(PDOC001 07)(PS00116; DNA POLYMERASE B)(BEGIN)* DNA polymerase family B signature *

Repticative DNA polymerases (EC 2.7.7.7) are the key enzymes catalyzing theaccurate replication of DNA. They require either a sma(l RNA molecule or aprotein as a primer for the de novo synthesis of a DNA chain. On the basis ofsequence similarities a number of DNA polymerases have been grouped together(1 to 6] under the designation of DNA polymerase family B. The polymerasesthat belong to this family are:

- Human polymerase alpha.- Yeast polymerase I/alpha (gene POL1), polymerase II/epsilon (gene POL2),polymerase III/delta (gene POL3), and polymerase REV3.

- Escherichia coli polymerase II (gene dinA or poMB).- Polymerases of viruses from the herpesviridae family (Herpes type I and

II Epstein-Barr, Cytomegalovirus, and Varicella-zoster).- Po(ymerases from Adenoviruses.- Polymerases from Baculoviruses.- Polymerases from Poxviruses (Vaccinia virus and FowLpox virus).- Bacteriophage T4 polymerase.- Podoviridae bacteriophages Phi-29, M2, and PZA polymerase.- Tectiviridae bacteriophage PRD1 polymerase.- Polymerases encoded on linear DNA plasmids: Kluyveromyces lactis pGKL1 and

uGKL2Z Ascobolus immersus pAI2, and Claviceps purpurea pCLK1.- Putative polymerase from the maize mitochondriat plasmid-like Si DNA.

Six regions of similarity (numbered from I to VI) are found in atL or asubset of the above polymerases. The most conserved region (I) includes aperfectly conserved tetrapeptide which contains two aspartate residues. Thefunction of this conserved region is not yet known, however it has beensuggested (3] that it may be involved in binding a magnesium ion. We use thisconserved region as a signature for this family of DNA polymerases.

- Consensus pattern: [YAJ-x-D-T-D-S-(LIVMTJ- Sequences known to belong to this class detected by the pattern: ALL, except

for yeast polymerase II/epsilon which has Glu instead of Tyr/Ala and has Glyinstead of Ser, and for Ascobolus immersus plasmid pA12 which also has Glyinstead of Ser

- Other sequence(s) detected in SWISS-PROT: chicken vitellogenin 2.- Note: the residue in position 1 is Tyr in every family B polymerases, except

in phage T4, where it is Ala.- Last update: December 1991 / Text revised.

1] Jung G., Leavitt M.C., Hsieh J.-C. Ito J.Proc. Natt. Acad. Sci. U.S.A. 84:8i87-8291(1987).

t 2] Bernad A., Zabatlos A. Salas M., Blanco L.EMBO J. 6.4219-4225(19A7).

( 3] Argos P.Nucleic Acids Res. 16:9909-9916(1988).

t 4] Wang T.S.-F Wong S.W., Korn D.FASEB J. 3:i4-21(1989).

[ 5] Delarue M., Poch O., Todro N., Moras D., Argos P.Protein Engineering 3:461-467(1990).

t 6] Ito J., Braithwaite D.K.Nucleic Acids Res. 19:4045-4057(1991).

(END)

bID DNA POLYMERASE B- PATTERN.AC PSOU116-

I

DT APR-1996 (CREATED)- NOV-1990 (DATA UPDATE); DEC-1991 (INFO UPDATE).DE DNA poLymerase family B signature.PA (YA]-x-D-T-D-S- [LIVMT].NR /RELEASE=20 22654;NR /TOTAL=31(3i); /POSITIVE=30(30); /UNKNOWN=0(0); /FALSE_POS=1(1); /FALSE_NEG=2(2);CC /TAXO-RANGE=?BEPV; /MAX-REPEAT=l;DR P09884, DPOA HUMAN, T; P13382, DPOA YEAST, T; P15436, DPOD YEAST, T;DR P14284, DPOX YEAST, T; P21189, DPO2 ECOLI, T; P03261, DPOLVADE02, T;DR P04495, DPOL_ADE05, T; P05664, DPOL7ADE07, T, P06538, DPOL7ADE12, T;DR P08546, DPOL HCMVA, T; P03198, DPOL EBV , T; P04293, DPOL HSV11, T;DR P07917, DPOL HSV1A, T; P04292, DPOL7HSV1K, T, P09854, DPOL HSV1S, T;DR P07918, DPOL HSV21, T; P09252, DPOL VZVD , T; P09804, DPO1 KLULA, T;DR P05468, DPO2-KLULA, T; P22373, DPOL CLAPU, T; P10582, DPOL-MAIZE, T;DR P18131, DPOL NPVAC, T; P20509, DPOL VACCC, T; P06856, DPOL VACCV, T;DR P21402, DPOLFOWPV, T; P03680, DPOLVBPPH2, T; P06950, DPOL BPPZA, T;DR P19894, DPOLVBPM2 , T; P10479, DPOL7BPPRD, T; P04415, DPOL_BPT4, T;DR P22374, DPOL ASCIM, N; P21951, DPOE_YEAST, NDR P02845 VIT2 CHICK, F;DO PDOCOOiO7;//

Figure 1. Sample data from PROSITE. a. A documentation (textbook) entry. b. The corresponding entry in the pattern file.

Nucleic Acids Research, Vol. 20, Supplement 2015

Appendix 1. List of patterns documentation entries in release 8.10 of PROSITE

Post-translational modificationsN-glycosylation siteGlycosaminoglycan attachment siteTyrosine sulfatation sitecAMP- and cGMP-dependent protein kinase phosphorylation siteProtein kinase C phosphorylation siteCasein kinase H phosphorylation siteTyrosine kinase phosphorylation siteN-myristoylation siteAmidation siteAspartic acid and asparagine hydroxylation siteVitamin K-dependent carboxylation domainPhosphopantetheine attachment siteProkaryotic membrane lipoprotein lipid attachment siteFarnesyl group binding site (CAAX box)

DomainsEndoplasmic reticulum targeting sequencePeroxisomal targeting sequenceGram-positive cocci surface proteins 'anchoring' hexapeptideNuclear targeting sequenceCell attachment sequenceATP/GTP-binding site motif A (P-loop)EF-hand calcium-binding domainActinin-type actin-binding domain signaturesCofilin/tropomyosin-type actin-binding domainApple domainKringle domain signatureEGF-like domain cysteine pattern signatureFibrinogen beta and gamma chains C-terminal domain signatureType II fibronectin collagen-binding domainHemopexin domain signatureSomatomedin B domain signatureThyroglobulin type-I repeat signature'Trefoil' domain signatureCellulose-binding domain, bacterial typeCellulose-binding domain, fungal typeChitin recognition or binding domain signatureWAP-type 'four-disulfide core' domain signaturePhorbol esters / diacylglycerol binding domainC2 domain signature

DNA or RNA associated proteins'Homeobox' domain signature'Homeobox' antennapedia-type protein signature'Homeobox' engrailed-type protein signature'Paired box' domain signature'POU' domain signaturesZinc finger, C2H2 type, domainZinc finger, C3HC4 type, signatureNuclear hormones receptors DNA-binding region signatureGATA-type zinc finger domainPoly(ADP-ribose) polymerase zinc finger domainFungal Zn(2)-Cys(6) binuclear cluster domainLeucine zipper patternFos/jun DNA-binding basic domain signatureMyb DNA-binding domain repeat signaturesMyc-type, 'helix-loop-helix' putative DNA-binding domain signaturep53 tumor antigen signature'Cold-shock' DNA-binding domain signatureCTF/NF-I signatureEts-domain signaturesHSF-type DNA-binding domain signatureIRF family signatureLIM domain signatureSRF-type transcription factors DNA-binding and dimerization domainTEA domain signatureTranscription factor TFIID repeat signatureTFIIS cysteine-rich domain signatureDEAD-box family ATP-dependent helicases signatureEukaryotic putative RNA-binding region RNP-I signatureFibrillarin signature

Bacterial regulatory proteins, araC family signatureBacterial regulatory proteins, asnC family signatureBacterial regulatory proteins, crp family signatureBacterial regulatory proteins, gntR family signatureBacterial regulatory proteins, lacI family signatureBacterial regulatory proteins, lysR family signatureBacterial regulatory proteins, merR family signatureBacterial histone-like DNA-binding proteins signatureHistone H2A signatureHistone H2B signatureHistone H3 signatureHistone H4 signatureHMG1/2 signatureHMG-I and HMG-Y DNA-binding domain (A+T-hook)HMG14 and HMG17 signatureChromo domainProtamine P1 signatureNuclear transition protein 1 signatureRibosomal protein L2 signatureRibosomal protein L3 signatureRibosomal protein L5 signatureRibosomal protein L6 signatureRibosomal protein LII signatureRibosomal protein L14 signatureRibosomal protein L15 signatureRibosomal protein L16 signatureRibosomal protein L22 signatureRibosomal protein L23 signatureRibosomal protein L29 signatureRibosomal protein L33 signatureRibosomal protein L19e signatureRibosomal protein L32e signatureRibosomal protein L46e signatureRibosomal protein S3 signatureRibosomal protein S5 signatureRibosomal protein S7 signatureRibosomal protein S8 signatureRibosomal protein S9 signatureRibosomal protein SiO signatureRibosomal protein SI I signatureRibosomal protein S12 signatureRibosomal protein S14 signatureRibosomal protein S15 signatureRibosomal protein S17 signatureRibosomal protein S18 signatureRibosomal protein Si 9 signatureRibosomal protein S4e signatureRibosomal protein S6e signatureRibosomal protein S24e signatureDNA mismatch repair proteins mutL / hexB / PMSI signatureDNA mismatch repair proteins mutS / hexA / Ducl / Repl signature

EnzymesOxidoreductasesZinc-containing alcohol dehydrogenases signatureIron-containing alcohol dehydrogenases signatureShort-chain alcohol dehydrogenase family signatureAldo/keto reductase family signaturesL-lactate dehydrogenase active siteGlycerate-type 2-hydroxyacid dehydrogenases signatureHydroxymethylglutaryl-coenzyme A reductases signatures3-hydroxyacyl-CoA dehydrogenase signatureMalate dehydrogenase active site signatureMalic enzymes signatureIsocitrate and isopropylmalate dehydrogenases signature6-phosphogluconate dehydrogenase signatureGlucose-6-phosphate dehydrogenase active siteIMP dehydrogenase / GMP reductase signatureBacterial quinoprotein dehydrogenases signaturesFMN-dependent alpha-hydroxy acid dehydrogenases active siteEukaryotic molybdopterin oxidoreductases signatureProkaryotic molybdopterin oxidoreductases signatures

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Aldehyde dehydrogenases active siteGlyceraldehyde 3-phosphate dehydrogenase active siteFumarate reductase / succinate dehydrogenase FAD-binding siteAcyl-CoA dehydrogenases signaturesGlutamate / Leucine / Phenylalanine dehydrogenases active siteDelta 1-pyrroline-5-carboxylate reductase signatureDihydrofolate reductase signaturePyridine nucleotide-disulphide oxidoreductases class-I active sitePyridine nucleotide-disulphide oxidoreductases class-II active siteRespiratory chain NADH dehydrogenase 30 Kd subunit signatureRespiratory chain NADH dehydrogenase 49 Kd subunit signatureNitrite reductases and sulfite reductase putative siroheme-binding sitesUricase signatureCytochrome c oxidase subunit I, copper B binding region signatureCytochrome c oxidase subunit II, copper A binding region signatureMulticopper oxidases signaturesPeroxidases signaturesCatalase signaturesGlutathione peroxidase selenocysteine active siteLipoxygenases, putative iron-binding region signatureExtradiol ring-cleavage dioxygenases signatureIntradiol ring-cleavage dioxygenases signatureBacterial ring hydroxylating dioxygenases alpha-subunit signatureBacterial luciferase subunits signatureBiopterin-dependent aromatic amino acid hydroxylases signatureCopper type II, ascorbate-dependent monooxygenases signaturesTyrosinase signaturesFatty acid desaturases signaturesCytochrome P450 cysteine heme-iron ligand signatureHeme oxygenase signatureCopper/Zinc superoxide dismutase signaturesManganese and iron superoxide dismutases signatureRibonucleotide reductase large subunit signatureRibonucleotide reductase small subunit signatureNitrogenases component 1 alpha and beta subunits signatureNickel-dependent hydrogenases large subunit signatures

TransferasesThymidylate synthase active siteMethylated-DNA--protein-cysteine methyltransferase active siteN-6 Adenine-specific DNA methylases signatureN4 cytosine-specific DNA methylases signatureC-5 cytosine-specific DNA methylases signaturesSerine hydroxymethyltransferase pyridoxal-phosphate attachment sitePhosphoribosylglycinamide formyltransferase active siteAspartate and ornithine carbamoyltransferases signatureAcyltransferases ChoActase / COT / CPT-II family signaturesThiolases signaturesChloramphenicol acetyltransferase active sitecysE / lacA / nifP / nodL acetyltransferases signatureBeta-ketoacyl synthases active siteChalcone and resveratrol synthases active siteGamma-glutamyltranspeptidase signatureTransglutaminases active sitePhosphorylase pyridoxal-phosphate attachment siteUDP-glucoronosyl and UDP-glucosyl transferases signaturePurine/pyrimidine phosphoribosyl transferases signatureGlutamine amidotransferases class-I active siteGlutamine amidotransferases class-II active siteS-Adenosylmethionine synthetase signaturesPolyprenyl synthetases signatureEPSP synthase active siteAspartate aminotransferases pyridoxal-phosphate attachment siteAminotransferases class-Il pyridoxal-phosphate attachment siteAminotransferases class-IHI pyridoxal-phosphate attachment sitePhosphoserine aminotransferase signatureHexokinases signatureGalactokinase signaturePhosphofructokinase signaturepfkB family prokaryotic carbohydrate kinases signaturesPhosphoribulokinase signatureThymidine kinase cellular-type signatureProkaryotic carbohydrate kinases signatureProtein kinases signaturesPyruvate kinase active site signature

Phosphoglycerate kinase signatureAspartokinase signatureATP:guanido phosphotransferases active sitePTS Hpr component phosphorylation sites signaturesPTS permeases phosphorylation sites signaturesAdenylate kinase signatureNucleoside diphosphate kinases active sitePhosphoribosyl pyrophosphate synthetase signatureBacteriophage-type RNA polymerase family active site signatureEukaryotic RNA polymerase II heptapeptide repeatEukaryotic RNA polymerases 30 to 40 Kd subunits signatureDNA polymerase family A signatureDNA polymerase family B signatureDNA polymerase familyxsignatureGalactose-l-phosphate uridyl transferase active site signatureCDP-alcohol phosphatidyltransferases signaturePEP-utilizing enzymes phosphorylation site signatureRhodanese active siteHydrolases

Phospholipase A2 active sites signaturesLipases, serine active siteColipase signatureCarboxylesterases type-B active sitePectinesterase signatureAlkaline phosphatase active siteFructose-I - 6-bisphosphatase active siteSerine/threonine specific protein phosphatases signatureTyrosine specific protein phosphatases active siteProkaryotic zinc-dependent phospholipase C signature3'5'-cyclic nucleotide phosphodiesterases signaturecAMP phosphodiesterases class-II signatureSulfatases signaturesRibonuclease III family signatureRibonuclease T2 family histidine active sitesPancreatic ribonuclease family signatureBeta-amylase signaturePolygalacturonase signatureClostridium cellulases repeated domain signatureAlpha-lactalbumin / lysozyme C signatureLysosomal alpha-glucosidase / sucrase-isomaltase active siteAlpha-galactosidase signatureAlpha-L-fucosidase putative active siteGlycosyl hydrolases family 1 active siteGlycosyl hydrolases family 9 active siteGlycosyl hydrolases family 10 active siteGlycosyl hydrolases family 17 signatureAlkylbase DNA glycosidases alkA family signatureUracil-DNA glycosylase signatureAminopeptidase P and proline dipeptidase signatureSerine carboxypeptidases, active sitesZinc carboxypeptidases, zinc-binding regions signaturesSerine proteases, trypsin family, active sitesSerine proteases, subtilase family, active sitesClpP proteases active sitesEukaryotic thiol (cysteine) proteases active siteUbiquitin carboxyl-terminal hydrolase, putative active-site signatureEukaryotic aspartyl proteases active siteNeutral zinc metallopeptidases, zinc-binding region signatureMatrixins cysteine switchInsulinase family signaturerecA signatureProteasome subunits signatureSignal peptidase complex SPC21/SPC18 subunits signatureAmidases signatureAsparaginase / glutaminase active siteUrease active siteDihydroorotase signaturesBeta-lactamases classes -A, -C, and -D active siteArginase and agmatinase signaturesAdenosine and AMP deaminase signatureInorganic pyrophosphatase signatureAcylphosphatase signaturesATP synthase alpha and beta subunits signatureATP synthase gamma subunit signatureATP synthase delta (OSCP) subunit signatureATP synthase a subunit signature

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ATP synthase c subunit signatureEl-E2 ATPases phosphorylation siteSodium and potassium ATPases beta subunits signaturesCutinase, serine active site

LyasesDDC / GAD / HDC pyridoxal-phosphate attachment siteOrotidine 5'-phosphate decarboxylase signaturePhosphoenolpyruvate carboxylase active sitePhosphoenolpyruvate carboxykinase (GTP) signaturePhosphoenolpyruvate carboxykinase (ATP) signatureRibulose bisphosphate carboxylase large chain active siteFructose-bisphosphate aldolase class-I active siteFructose-bisphosphate aldolase class-Il signatureMalate synthase signatureCitrate synthase signatureKDPG and KHG aldolases active site signaturesIsocitrate lyase signatureDNA photolyases signatureCarbonic anhydrases signatureFumarate lyases signatureAconitase family signatureEnolase signatureSerine/threonine dehydratases pyridoxal-phosphate attachment siteEnoyl-CoA hydratase/isomerase signatureTryptophan synthase alpha chain signatureTryptophan synthase beta chain pyridoxal-phosphate attachment siteDelta-aminolevulinic acid dehydratase active sitePhenylalanine and histidine ammonia-lyases signaturePorphobilinogen deaminase cofactor-binding siteGuanylate cyclases signatureFerrochelatase signature

Isomerases

Alanine racemase pyridoxal-phosphate attachment siteAldose 1-epimerase putative active siteCyclophilin-type peptidyl-prolyl cis-trans isomerase signatureFKBP-type peptidyl-prolyl cis-trans isomerase signaturesTriosephosphate isomerase active siteXylose isomerase signaturesPhosphoglucose isomerase signaturePhosphoglycerate mutase family phosphohistidine signatureMethylmalonyl-CoA mutase signatureEukaryotic DNA topoisomerase I active siteProkaryotic DNA topoisomerase I active siteDNA topoisomerase II signature

LigasesAminoacyl-transfer RNA synthetases class-I signatureAminoacyl-transfer RNA synthetases class-Il signaturesATP-citrate lyase and succinyl-CoA ligases active siteGlutamine synthetase signaturesUbiquitin-activating enzyme signatureUbiquitin-conjugating enzymes active siteAdenylosuccinate synthetase active siteArgininosuccinate synthase signaturesPhosphoribosylglycinamide synthetase signatureATP-dependent DNA ligase putative active site

Others

Isopenicillin N synthetase signaturesSite-specific recombinases signaturesThiamine pyrophosphate enzymes signatureBiotin-requiring enzymes attachment site2-oxo acid dehydrogenases acyltransferase component lipoyl binding sitePutative AMP-binding domain signature

Electron transport proteinsCytochrome c family heme-binding site signatureCytochrome b5 family, heme-binding domain signatureCytochrome b/b6 signaturesCytochrome b559 subunits heme-binding site signatureThioredoxin family active siteGlutaredoxin active site

Type-I copper (blue) proteins signature2Fe-2S ferredoxins, iron-sulfur binding region signature4Fe-4S ferredoxins, iron-sulfur binding region signatureHigh potential iron-sulfur proteins signatureRieske iron-sulfur protein signaturesFlavodoxin signatureRubredoxin signature

Other transport proteinsClass I metallothioneins signatureFerritin iron-binding regions signaturesBacterioferritin signatureTransferrins signaturesPlant hemoglobins signatureHemerythrins signatureArthropod hemocyanins / insect LSPs signaturesATP-binding proteins 'active transport' family signatureBinding-protein-dependent transport systems inner membrane component signatureSerum albumin family signatureAvidin / Streptavidin family signatureEukaryotic cobalamin-binding proteins signatureLipocalin signatureCytosolic fatty-acid binding proteins signatureLBP / BPI / CETP family signaturePlant lipid transfer proteins signatureUteroglobin family signaturesMitochondrial energy transfer proteins signatureSugar transport proteins signaturesSodium symporters signaturesProkaryotic sulfate-binding proteins signatureAmino acid permeases signatureAromatic amino acids permeases signatureAnion exchangers family signaturesMIP family signatureGeneral diffusion gram-negative porins signatureEukaryotic porin signatureInsulin-like growth factor binding proteins signature

Structural proteins43 Kd postsynaptic protein signatureActins signaturesAnnexins repeated domain signatureClathrin light chains signaturesClusterin signaturesConnexins signaturesCrystallins beta and gamma 'Greek key' motif signatureDynamin family signatureIntermediate filaments signatureKinesin motor domain signatureMyelin basic protein signatureMyelin P0 protein signatureMyelin proteolipid protein signatureNeuromodulin (GAP-43) signaturesProfilin signatureSurfactant associated polypeptide SP-C palmytoylation sitesSynapsins signaturesSynaptobrevin signatureSynaptophysin / synaptoporin signatureTropomyosins signatureTubulin subunits alpha, beta, and gamma signatureTubulin-beta mRNA autoregulation signalTau and MAP2 proteins repeated region signatureNeuraxin and MAPIB proteins repeated region signatureF-actin capping protein beta subunit signatureAmyloidogenic glycoprotein signaturesCadherins extracellular repeated domain signatureInsect flexible cuticle proteins signatureGas vesicles protein GVPa signatureGas vesicles protein GVPc repeated domain signatureFlagella basal body rod proteins signatureType4 pili methylation sitePlant viruses icosahedral capsid proteins 'S' region signaturePotexviruses and carlaviruses coat protein signature

2018 Nucleic Acids Research, Vol. 20, SupplementReceptorsNeurotransmitter-gated ion-channels signatureG-protein coupled receptors signatureVisual pigments (opsins) retinal binding siteBacterial rhodopsins retinal binding siteReceptor tyrosine kinase class II signatureReceptor tyrosine kinase class III signatureGrowth factor and cytokines receptors family signaturesIntegrins alpha chain signatureIntegrins beta chain cysteine-rich domain signatureNatriuretic peptides receptors signaturePhotosynthetic reaction center proteins signaturePhotosystem I psaA and psaB proteins signaturePhytochrome chromophore attachment siteSperact receptor repeated domain signatureTonB-dependent receptor proteins signatureType-II membrane antigens family signatureBacterial chemotaxis sensory transducers signature

Cytokines and growth factorsHBGF/FGF family signatureNerve growth factor family signaturePlatelet-derived growth factor (PDGF) family signatureSmall cytokines signaturesTGF-beta family signatureTNF family signatureWnt-l family signatureInterferon alpha and beta family signatureInterleukin- I signatureInterleukin-2 signatureInterleukin-6 / G-CSF / MGF family signatureInterleukin-7 signatureInterleukin-10 signatureLIF / OSM family signature

Hormones and active peptidesAdipokinetic hormone family signatureBombesin-like peptides family signatureCalcitonin / CGRP / LAPP family signatureCorticotropin-releasing factor family signatureGranins signaturesGastrin / cholecystokinin family signatureGlucagon / GIP / secretin / VIP family signatureGlycoprotein hormones beta chain signatureGonadotropin-releasing hormones signatureInsulin family signatureNatriuretic peptides signatureNeurohypophysial hormones signaturePancreatic hormone family signatureParathyroid hormone family signaturePyrokinins signatureSomatotropin, prolactin and related hormones signaturesTachykinin family signatureThymosin beta-4 family signatureCecropin family signatureMammalian defensins signatureInsect defensins signatureEndothelins / sarafotoxins signature

ToxinsPlant thionins signatureSnake toxins signatureMyotoxins signature

Heat-stable enterotoxins signatureAerolysin type toxins signatureShiga/ricin ribosomal inactivating toxins active site signatureChannel forming colicins signatureHok/gef family cell toxic proteins signatureStaphyloccocal enterotoxins / Streptococcal pyrogenic exotoxins signaturesThiol-activated cytolysins signatureMembrane attack complex components / perforin signature

InhibitorsPancreatic trypsin inhibitor (Kunitz) family signatureBowman-Birk serine protease inhibitors family signatureKazal sefine protease inhibitors family signatureSoybean trypsin inhibitor (Kunitz) protease inhibitors family signatureSerpins signaturePotato inhibitor I family signatureSquash family of serine protease inhibitors signatureCysteine proteases inhibitors signatureTissue inhibitors of metalloproteinases signatureCereal trypsin/alpha-amylase inhibitors family signatureAlpha-2-macroglobulin family thiolester region signatureDisintegrins signatureLambdoid phages regulatory protein CIII signature

OthersPentraxin family signatureImmunoglobulins and major histocompatibility complex proteins signaturePrion protein signatureCyclins signatureProliferating cell nuclear antigen signatureArrestins signatureChaperonins signatureHeat shock hsp70 proteins family signaturesHeat shock hsp90 proteins family signatureUbiquitin signatureGTPase-activating proteins signatureStathmin family signatureSRP54-type proteins GTP-binding domain signatureGTP-binding elongation factors signatureEukaryotic initiation factor 5A hypusine signatureS-100/ICaBP type calcium binding protein signatureHemolysin-type putative calcium-binding region signatureHIyD family secretion proteins signatureP-II protein urydylation siteSmall, acid-soluble spore proteins, alpha/beta type, signatureCaseins alpha/beta signatureLegume lectins signaturesVertebrate galactoside-binding lectin signatureLysosome-associated membrane glycoproteins signaturesGlycophorin A signatureSeminal vesicle protein I repeats signatureSeminal vesicle protein II repeats signatureHCP repeats signatureBacterial ice-nucleation proteins octamer repeatCell cycle proteins ftsW / rodA / spoVE signatureStaphylocoagulase repeat signatureI l-S plant seed storage proteins signatureDehydrins signatureSmall hydrophilic plant seed proteins signaturePathogenesis-related proteins Betvl family signatureThaumatin family signature