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Protein

Trypsin-1

Gene

PRSS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Digestion

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS10703-MONOMER.
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

HGNCiHGNC:9475. PRSS1.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
Complete GO annotation...

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 rs202003805dbSNPEnsembl.1
Natural variantiVAR_01165222D → G in PCTT; increased rate of activation. 1 PublicationCorresponds to variant rs397507442dbSNPEnsembl.1
Natural variantiVAR_01165323K → R in PCTT; increased rate of activation. 1 PublicationCorresponds to variant rs111033567dbSNPEnsembl.1
Natural variantiVAR_00672029N → I in PCTT. 4 PublicationsCorresponds to variant rs111033566dbSNPEnsembl.1
Natural variantiVAR_01271229N → T in PCTT. 1 PublicationCorresponds to variant rs111033566dbSNPEnsembl.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 rs144422014dbSNPEnsembl.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 rs111033564dbSNPEnsembl.1
Natural variantiVAR_011654104L → P in PCTT. 1 Publication1
Natural variantiVAR_011655116R → C in PCTT. 1 PublicationCorresponds to variant rs387906698dbSNPEnsembl.1
Natural variantiVAR_012713122R → C in PCTT; suppresses an autocleavage site. 1 PublicationCorresponds to variant rs111033568dbSNPEnsembl.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 rs267606982dbSNPEnsembl.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.
MalaCardsiPRSS1.
MIMi167800. phenotype.
OpenTargetsiENSG00000204983.
ENSG00000274247.
Orphaneti676. Hereditary chronic pancreatitis.
PharmGKBiPA33828.

Chemistry databases

ChEMBLiCHEMBL209.
DrugBankiDB06692. Aprotinin.
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.

PTM databases

iPTMnetiP07477.
PhosphoSitePlusiP07477.

Miscellaneous databases

PMAP-CutDBP07477.

Expressioni

Gene expression databases

BgeeiENSG00000204983.
ExpressionAtlasiP07477. baseline and differential.
GenevisibleiP07477. HS.

Organism-specific databases

HPAiCAB025487.
CAB025538.
HPA062452.
HPA063471.

Interactioni

Protein-protein interaction databases

BioGridi111626. 19 interactors.
IntActiP07477. 5 interactors.
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
Beta strandi76 – 80Combined sources5
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FXYX-ray2.15A127-247[»]
1TRNX-ray2.20A/B24-247[»]
2RA3X-ray1.46A/B24-247[»]
4WWYX-ray1.70A/B24-247[»]
4WXVX-ray2.10A/B24-247[»]
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
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118862.
HOVERGENiHBG013304.
InParanoidiP07477.
KOiK01312.
OMAiNACVSTI.
OrthoDBiEOG091G0DF7.
PhylomeDBiP07477.
TreeFamiTF331065.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

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 rs202003805dbSNPEnsembl.1
Natural variantiVAR_01165222D → G in PCTT; increased rate of activation. 1 PublicationCorresponds to variant rs397507442dbSNPEnsembl.1
Natural variantiVAR_01165323K → R in PCTT; increased rate of activation. 1 PublicationCorresponds to variant rs111033567dbSNPEnsembl.1
Natural variantiVAR_00672029N → I in PCTT. 4 PublicationsCorresponds to variant rs111033566dbSNPEnsembl.1
Natural variantiVAR_01271229N → T in PCTT. 1 PublicationCorresponds to variant rs111033566dbSNPEnsembl.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 rs144422014dbSNPEnsembl.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 rs111033564dbSNPEnsembl.1
Natural variantiVAR_011654104L → P in PCTT. 1 Publication1
Natural variantiVAR_011655116R → C in PCTT. 1 PublicationCorresponds to variant rs387906698dbSNPEnsembl.1
Natural variantiVAR_012713122R → C in PCTT; suppresses an autocleavage site. 1 PublicationCorresponds to variant rs111033568dbSNPEnsembl.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 rs267606982dbSNPEnsembl.1
Natural variantiVAR_036299137T → M in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs117497341dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FXYX-ray2.15A127-247[»]
1TRNX-ray2.20A/B24-247[»]
2RA3X-ray1.46A/B24-247[»]
4WWYX-ray1.70A/B24-247[»]
4WXVX-ray2.10A/B24-247[»]
ProteinModelPortaliP07477.
SMRiP07477.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111626. 19 interactors.
IntActiP07477. 5 interactors.
STRINGi9606.ENSP00000308720.

Chemistry databases

BindingDBiP07477.
ChEMBLiCHEMBL209.
DrugBankiDB06692. Aprotinin.
GuidetoPHARMACOLOGYi2397.

Protein family/group databases

MEROPSiS01.127.

PTM databases

iPTMnetiP07477.
PhosphoSitePlusiP07477.

Polymorphism and mutation databases

BioMutaiPRSS1.
DMDMi136408.

Proteomic databases

EPDiP07477.
PaxDbiP07477.
PeptideAtlasiP07477.
PRIDEiP07477.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5644.
DisGeNETi5644.
GeneCardsiPRSS1.
GeneReviewsiPRSS1.
HGNCiHGNC:9475. PRSS1.
HPAiCAB025487.
CAB025538.
HPA062452.
HPA063471.
MalaCardsiPRSS1.
MIMi167800. phenotype.
276000. gene.
neXtProtiNX_P07477.
OpenTargetsiENSG00000204983.
ENSG00000274247.
Orphaneti676. Hereditary chronic pancreatitis.
PharmGKBiPA33828.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118862.
HOVERGENiHBG013304.
InParanoidiP07477.
KOiK01312.
OMAiNACVSTI.
OrthoDBiEOG091G0DF7.
PhylomeDBiP07477.
TreeFamiTF331065.

Enzyme and pathway databases

BioCyciZFISH:HS10703-MONOMER.
ReactomeiR-HSA-1592389. Activation of Matrix Metalloproteinases.
R-HSA-196741. Cobalamin (Cbl, vitamin B12) transport and metabolism.

Miscellaneous databases

EvolutionaryTraceiP07477.
GeneWikiiTrypsin_1.
GenomeRNAii5644.
PMAP-CutDBP07477.
PROiP07477.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000204983.
ExpressionAtlasiP07477. baseline and differential.
GenevisibleiP07477. HS.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

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 historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: November 2, 2016
This is version 187 of the entry and version 1 of the sequence. [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

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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.