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Protein

Trypsin-1

Gene

PRSS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec. The single-chain form is more active than the two-chain form against all of these substrates.1 Publication

Caution

Tyr-154 was proposed to be phosphorylated (PubMed:8683601) but it has been shown (PubMed:17087724) to be sulfated instead. Phosphate and sulfate groups are similar in mass and size, and this can lead to erroneous interpretation of the results.2 Publications

Catalytic activityi

Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.

Cofactori

Ca2+Note: Binds 1 Ca2+ ion per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei63Charge relay system1
Metal bindingi75Calcium1
Metal bindingi77Calcium; via carbonyl oxygen1
Metal bindingi80Calcium; via carbonyl oxygen1
Metal bindingi85Calcium1
Active sitei107Charge relay system1
Sitei194Required for specificityBy similarity1
Active sitei200Charge relay system1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • serine-type endopeptidase activity Source: UniProtKB
  • serine-type peptidase activity Source: Reactome

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processDigestion
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-1592389 Activation of Matrix Metalloproteinases
R-HSA-196741 Cobalamin (Cbl, vitamin B12) transport and metabolism

Protein family/group databases

MEROPSiS01.127

Names & Taxonomyi

Protein namesi
Recommended name:
Trypsin-1 (EC:3.4.21.4)
Alternative name(s):
Beta-trypsin
Cationic trypsinogen
Serine protease 1
Trypsin I
Cleaved into the following 2 chains:
Gene namesi
Name:PRSS1
Synonyms:TRP1, TRY1, TRYP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000204983.12
HGNCiHGNC:9475 PRSS1
MIMi276000 gene
neXtProtiNX_P07477

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Pancreatitis, hereditary (PCTT)11 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA disease characterized by pancreas inflammation, permanent destruction of the pancreatic parenchyma, maldigestion, and severe abdominal pain attacks.
See also OMIM:167800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01169316A → V in PCTT; disrupts signal sequence cleavage site. 1 PublicationCorresponds to variant dbSNP:rs202003805EnsemblClinVar.1
Natural variantiVAR_01165222D → G in PCTT; increased rate of activation. 1 PublicationCorresponds to variant dbSNP:rs397507442EnsemblClinVar.1
Natural variantiVAR_01165323K → R in PCTT; increased rate of activation. 1 PublicationCorresponds to variant dbSNP:rs111033567EnsemblClinVar.1
Natural variantiVAR_00672029N → I in PCTT. 4 PublicationsCorresponds to variant dbSNP:rs111033566EnsemblClinVar.1
Natural variantiVAR_01271229N → T in PCTT. 1 PublicationCorresponds to variant dbSNP:rs111033566EnsemblClinVar.1
Natural variantiVAR_03790854N → S in PCTT; associated with Ile-29; the double mutant shows increased autocatalytic activation which is solely due to the Ile-29 mutation. 1 PublicationCorresponds to variant dbSNP:rs144422014EnsemblClinVar.1
Natural variantiVAR_03790979E → K in PCTT; Lys-79 trypsin activates anionic trypsinogen PRSS2 2-fold while the common pancreatitis-associated mutants His-122 or Ile-29 have no such effect. 1 PublicationCorresponds to variant dbSNP:rs111033564EnsemblClinVar.1
Natural variantiVAR_011654104L → P in PCTT. 1 Publication1
Natural variantiVAR_011655116R → C in PCTT. 1 PublicationCorresponds to variant dbSNP:rs387906698EnsemblClinVar.1
Natural variantiVAR_012713122R → C in PCTT; suppresses an autocleavage site. 1 PublicationCorresponds to variant dbSNP:rs111033568EnsemblClinVar.1
Natural variantiVAR_006721122R → H in PCTT; suppresses an autocleavage site which is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis. 5 PublicationsCorresponds to variant dbSNP:rs267606982EnsemblClinVar.1
Natural variantiVAR_011656139C → F in PCTT. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi154Y → F: Lack of sulfation. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5644
GeneReviewsiPRSS1
MalaCardsiPRSS1
MIMi167800 phenotype
OpenTargetsiENSG00000204983
Orphaneti676 Hereditary chronic pancreatitis
PharmGKBiPA33828

Chemistry databases

ChEMBLiCHEMBL209
DrugBankiDB06850 (S)-N-(4-carbamimidoylbenzyl)-1-(2-(cyclohexylamino)ethanoyl)pyrrolidine-2-carboxamide
DB07091 (S)-N-(4-carbamimidoylbenzyl)-1-(2-(cyclohexyloxy)ethanoyl)pyrrolidine-2-carboxamide
DB06845 (S)-N-(4-carbamimidoylbenzyl)-1-(2-(cyclopentylamino)ethanoyl)pyrrolidine-2-carboxamide
DB07088 (S)-N-(4-carbamimidoylbenzyl)-1-(2-(cyclopentyloxy)ethanoyl)pyrrolidine-2-carboxamide
DB07131 (S)-N-(4-carbamimidoylbenzyl)-1-(3-cyclohexylpropanoyl)pyrrolidine-2-carboxamide
DB07095 (S)-N-(4-carbamimidoylbenzyl)-1-(3-cyclopentylpropanoyl)pyrrolidine-2-carboxamide
DB07985 +/-METHYL 4-(AMINOIMINOMETHYL)-BETA-[3- INH (AMINOIMINO)PHENYL]BENZENE PENTANOATE
DB03337 1-(2-Amidinophenyl)-3-(Phenoxyphenyl)Urea
DB04336 1-(4-Amidinophenyl)-3-(4-Chlorophenyl)Urea
DB03417 1-(4-Tert-Butylcarbamoyl-Piperazine-1-Carbonyl)-3-(3-Guanidino-Propyl)-4-Oxo-Azetidine-2-Carboxylic Acid
DB08420 1-{[1-(2-AMINO-3-PHENYL-PROPIONYL)-PYRROLIDINE-2-CARBONYL]-AMINO}-2-(3-CYANO-PHENYL)-ETHANEBORONIC ACID
DB01905 2-(2-Hydroxy-5-Methoxy-Phenyl)-1h-Benzoimidazole-5-Carboxamidine
DB02193 2-(2-Hydroxy-Phenyl)-1h-Benzoimidazole-5-Carboxamidine
DB02463 2-(2-Hydroxy-Phenyl)-1h-Indole-5-Carboxamidine
DB02287 2-(2-Hydroxy-Phenyl)-3h-Benzoimidazole-5-Carboxamidine
DB08184 2-(2-METHYLPHENYL)-1H-INDOLE-5-CARBOXIMIDAMIDE
DB06918 2-(2-METHYLPHENYL)-1H-INDOLE-6-CARBOXIMIDAMIDE
DB06923 2-(3-METHYLPHENYL)-1H-INDOLE-5-CARBOXIMIDAMIDE
DB08254 2-NAPHTHALENESULFONIC ACID
DB04325 2-Phenylethylamine
DB04410 3-Phenylpropylamine
DB07368 4-(METHYLSULFONYL)BENZENECARBOXIMIDAMIDE
DB03243 4-Fluorobenzylamine
DB03136 4-Iodobenzo[B]Thiophene-2-Carboxamidine
DB04311 4-Phenylbutylamine
DB04654 4-PIPERIDIN-4-YLBUTANAL
DB02354 4-{[1-Methyl-5-(2-Methyl-Benzoimidazol-1-Ylmethyl)-1h-Benzoimidazol-2-Ylmethyl]-Amino}-Benzamidine
DB01939 5-Amidino-Benzimidazole
DB03865 6-Chloro-2-(2-Hydroxy-Biphenyl-3-Yl)-1h-Indole-5-Carboxamidine
DB04107 [(1-{2[(4-Carbamimidoyl-Phenylamino)-Methyl]-1-Methyl-1h-Benzoimidazol-5-Yl}-Cyclopropyl)-Pyridin-2-Yl-Methyleneaminooxy]-Acetic Acid Ethyl Ester
DB02269 [4-({[5-Benzyloxy-1-(3-Carbamimidoyl-Benzyl)-1h-Indole-2-Carbonyl]-Amino}-Methyl)-Phenyl]-Trimethyl-Ammonium
DB08763 [N-(BENZYLOXYCARBONYL)AMINO](4-AMIDINOPHENYL)METHANE-PHOSPHONATE
DB04391 Aeruginosin 98-B
DB02435 Aminomethylcyclohexane
DB02045 Amylamine
DB06692 Aprotinin
DB03127 Benzamidine
DB04446 Benzo[B]Thiophene-2-Carboxamidine
DB02464 Benzylamine
DB03213 Bis(5-Amidino-2-Benzimidazolyl)Methane Ketone
DB04301 Bis(5-Amidino-2-Benzimidazolyl)Methane Ketone Hydrate
DB01876 Bis(5-Amidino-2-Benzimidazolyl)Methanone
DB01705 Bis(5-Amidino-Benzimidazolyl)Methane
DB04008 Bis(5-Amidino-Benzimidazolyl)Methane Zinc
DB03443 Bis(5-Amidino-Benzimidazolyl)Methanone Zinc
DB02081 Bis-Benzamidine
DB03173 CRA_10433
DB02526 CRA_10655
DB04470 CRA_10656
DB02366 CRA_10762
DB03494 CRA_10950
DB02989 CRA_10972
DB01771 CRA_10991
DB03555 CRA_11092
DB03643 CRA_1144
DB02063 CRA_16847
DB02084 CRA_17312
DB01741 CRA_17693
DB03016 CRA_1801
DB02875 CRA_1802
DB04246 CRA_23653
DB01725 CRA_7806
DB03159 CRA_8696
DB04215 CRA_9076
DB02288 CRA_9334
DB04563 CRA_9678
DB03595 CRA_9785
DB03081 Crc200 (Chiron-Behring)
DB04269 Cyclotheonamide A
DB03608 Diminazene
DB01767 Hemi-Babim
DB01805 Monoisopropylphosphorylserine
DB04125 N-Alpha-(2-Naphthylsulfonyl)-N(3-Amidino-L-Phenylalaninyl)-4-Acetyl-Piperazine
DB01745 N-Alpha-(2-Naphthylsulfonyl)-N(3-Amidino-L-Phenylalaninyl)Isopipecolinic Acid Methyl Ester
DB04238 N-Alpha-(2-Naphthylsulfonyl)-N-(3-Amidino-L-Phenylalaninyl)-D-Pipecolinic Acid
DB06853 N-cycloheptylglycyl-N-(4-carbamimidoylbenzyl)-L-prolinamide
DB06858 N-cyclooctylglycyl-N-(4-carbamimidoylbenzyl)-L-prolinamide
DB03976 Phosphorylisopropane
DB04424 RPR128515
DB02744 RPR131247
DB03251 RWJ-51084
DB02665 Trans-2-Phenylcyclopropylamine
DB01665 ZK-800270
DB04432 ZK-805623
DB02112 Zk-806450
DB03373 ZK-806711
GuidetoPHARMACOLOGYi2397

Polymorphism and mutation databases

BioMutaiPRSS1
DMDMi136408

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 152 PublicationsAdd BLAST15
PropeptideiPRO_000002819716 – 23Activation peptide8
ChainiPRO_000002819824 – 247Trypsin-1Add BLAST224
ChainiPRO_000031357024 – 122Alpha-trypsin chain 1Add BLAST99
ChainiPRO_0000313571123 – 247Alpha-trypsin chain 2Add BLAST125

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi30 ↔ 160
Disulfide bondi48 ↔ 64
Disulfide bondi139 ↔ 206
Modified residuei154Sulfotyrosine2 Publications1
Disulfide bondi171 ↔ 185
Disulfide bondi196 ↔ 220

Post-translational modificationi

Occurs in a single-chain form and a two-chain form, produced by proteolytic cleavage after Arg-122.
Sulfation at Tyr-154 increases selectivity towards basic versus apolar residues at the P2' position of inhibitors that bind in a substrate-like fashion. Although the increase in selectivity is relatively small, it may facilitate digestion of a broader range of dietary proteins.1 Publication

Keywords - PTMi

Disulfide bond, Sulfation, Zymogen

Proteomic databases

EPDiP07477
PaxDbiP07477
PeptideAtlasiP07477
PRIDEiP07477
ProteomicsDBi52006

PTM databases

iPTMnetiP07477
PhosphoSitePlusiP07477

Miscellaneous databases

PMAP-CutDBiP07477

Expressioni

Gene expression databases

BgeeiENSG00000204983
ExpressionAtlasiP07477 baseline and differential
GenevisibleiP07477 HS

Organism-specific databases

HPAiCAB025487
CAB025538
HPA062452
HPA063471

Interactioni

Protein-protein interaction databases

BioGridi111626, 24 interactors
IntActiP07477, 5 interactors
MINTiP07477
STRINGi9606.ENSP00000308720

Chemistry databases

BindingDBiP07477

Structurei

Secondary structure

1247
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi38 – 54Combined sources17
Beta strandi57 – 60Combined sources4
Helixi62 – 64Combined sources3
Beta strandi70 – 74Combined sources5
Turni78 – 80Combined sources3
Beta strandi86 – 95Combined sources10
Turni101 – 103Combined sources3
Beta strandi109 – 115Combined sources7
Beta strandi120 – 122Combined sources3
Beta strandi138 – 144Combined sources7
Beta strandi149 – 151Combined sources3
Beta strandi159 – 165Combined sources7
Helixi168 – 174Combined sources7
Turni176 – 178Combined sources3
Beta strandi183 – 187Combined sources5
Beta strandi192 – 194Combined sources3
Beta strandi203 – 206Combined sources4
Beta strandi209 – 216Combined sources8
Beta strandi218 – 222Combined sources5
Beta strandi227 – 231Combined sources5
Helixi232 – 235Combined sources4
Helixi236 – 245Combined sources10

3D structure databases

ProteinModelPortaliP07477
SMRiP07477
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07477

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 244Peptidase S1PROSITE-ProRule annotationAdd BLAST221

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118862
HOVERGENiHBG013304
InParanoidiP07477
KOiK01312
OrthoDBiEOG091G0DF7
PhylomeDBiP07477
TreeFamiTF331065

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
InterProiView protein in InterPro
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
PROSITEiView protein in PROSITE
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P07477-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPLLILTFV AAALAAPFDD DDKIVGGYNC EENSVPYQVS LNSGYHFCGG
60 70 80 90 100
SLINEQWVVS AGHCYKSRIQ VRLGEHNIEV LEGNEQFINA AKIIRHPQYD
110 120 130 140 150
RKTLNNDIML IKLSSRAVIN ARVSTISLPT APPATGTKCL ISGWGNTASS
160 170 180 190 200
GADYPDELQC LDAPVLSQAK CEASYPGKIT SNMFCVGFLE GGKDSCQGDS
210 220 230 240
GGPVVCNGQL QGVVSWGDGC AQKNKPGVYT KVYNYVKWIK NTIAANS
Length:247
Mass (Da):26,558
Last modified:April 1, 1988 - v1
Checksum:iDD49A487B8062813
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4L → F in AAI28227 (PubMed:15489334).Curated1

Mass spectrometryi

Molecular mass is 24348±2 Da from positions 24 - 247. Determined by ESI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01169316A → V in PCTT; disrupts signal sequence cleavage site. 1 PublicationCorresponds to variant dbSNP:rs202003805EnsemblClinVar.1
Natural variantiVAR_01165222D → G in PCTT; increased rate of activation. 1 PublicationCorresponds to variant dbSNP:rs397507442EnsemblClinVar.1
Natural variantiVAR_01165323K → R in PCTT; increased rate of activation. 1 PublicationCorresponds to variant dbSNP:rs111033567EnsemblClinVar.1
Natural variantiVAR_00672029N → I in PCTT. 4 PublicationsCorresponds to variant dbSNP:rs111033566EnsemblClinVar.1
Natural variantiVAR_01271229N → T in PCTT. 1 PublicationCorresponds to variant dbSNP:rs111033566EnsemblClinVar.1
Natural variantiVAR_03790854N → S in PCTT; associated with Ile-29; the double mutant shows increased autocatalytic activation which is solely due to the Ile-29 mutation. 1 PublicationCorresponds to variant dbSNP:rs144422014EnsemblClinVar.1
Natural variantiVAR_03790979E → K in PCTT; Lys-79 trypsin activates anionic trypsinogen PRSS2 2-fold while the common pancreatitis-associated mutants His-122 or Ile-29 have no such effect. 1 PublicationCorresponds to variant dbSNP:rs111033564EnsemblClinVar.1
Natural variantiVAR_011654104L → P in PCTT. 1 Publication1
Natural variantiVAR_011655116R → C in PCTT. 1 PublicationCorresponds to variant dbSNP:rs387906698EnsemblClinVar.1
Natural variantiVAR_012713122R → C in PCTT; suppresses an autocleavage site. 1 PublicationCorresponds to variant dbSNP:rs111033568EnsemblClinVar.1
Natural variantiVAR_006721122R → H in PCTT; suppresses an autocleavage site which is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis. 5 PublicationsCorresponds to variant dbSNP:rs267606982EnsemblClinVar.1
Natural variantiVAR_036299137T → M in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs117497341EnsemblClinVar.1
Natural variantiVAR_011656139C → F in PCTT. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22612 mRNA Translation: AAA61231.1
L36092 Genomic DNA Translation: AAC80207.1
AK312199 mRNA Translation: BAG35132.1
AC231380 Genomic DNA No translation available.
CH236959 Genomic DNA Translation: EAL23773.1
CH471198 Genomic DNA Translation: EAW51925.1
BC128226 mRNA Translation: AAI28227.1
AF314534 Genomic DNA Translation: AAG30943.1
U70137 Genomic DNA Translation: AAC50728.1
AF315309 Genomic DNA Translation: AAG30947.1
AF315310 Genomic DNA Translation: AAG30948.1
AF315311 Genomic DNA Translation: AAG30949.1
CCDSiCCDS5872.1
PIRiA25852
S50020
S50021
RefSeqiNP_002760.1, NM_002769.4
UniGeneiHs.382212
Hs.449276
Hs.449281

Genome annotation databases

EnsembliENST00000311737; ENSP00000308720; ENSG00000204983
ENST00000616256; ENSP00000479217; ENSG00000274247
GeneIDi5644
KEGGihsa:5644
UCSCiuc003wak.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTRY1_HUMAN
AccessioniPrimary (citable) accession number: P07477
Secondary accession number(s): A1A509
, A6NJ71, B2R5I5, Q5NV57, Q7M4N3, Q7M4N4, Q92955, Q9HAN4, Q9HAN5, Q9HAN6, Q9HAN7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: June 20, 2018
This is version 198 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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