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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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei63 – 631Charge relay system
Metal bindingi75 – 751Calcium
Metal bindingi77 – 771Calcium; via carbonyl oxygen
Metal bindingi80 – 801Calcium; via carbonyl oxygen
Metal bindingi85 – 851Calcium
Active sitei107 – 1071Charge relay system
Sitei194 – 1941Required for specificityBy similarity
Active sitei200 – 2001Charge relay system

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

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti16 – 161A → V in PCTT; disrupts signal sequence cleavage site. 1 Publication
Corresponds to variant rs202003805 [ dbSNP | Ensembl ].
VAR_011693
Natural varianti22 – 221D → G in PCTT; increased rate of activation. 1 Publication
Corresponds to variant rs397507442 [ dbSNP | Ensembl ].
VAR_011652
Natural varianti23 – 231K → R in PCTT; increased rate of activation. 1 Publication
Corresponds to variant rs111033567 [ dbSNP | Ensembl ].
VAR_011653
Natural varianti29 – 291N → I in PCTT. 4 Publications
Corresponds to variant rs111033566 [ dbSNP | Ensembl ].
VAR_006720
Natural varianti29 – 291N → T in PCTT. 1 Publication
Corresponds to variant rs111033566 [ dbSNP | Ensembl ].
VAR_012712
Natural varianti54 – 541N → S in PCTT; associated with Ile-29; the double mutant shows increased autocatalytic activation which is solely due to the Ile-29 mutation. 1 Publication
Corresponds to variant rs144422014 [ dbSNP | Ensembl ].
VAR_037908
Natural varianti79 – 791E → 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 Publication
Corresponds to variant rs111033564 [ dbSNP | Ensembl ].
VAR_037909
Natural varianti104 – 1041L → P in PCTT. 1 Publication
VAR_011654
Natural varianti116 – 1161R → C in PCTT. 1 Publication
Corresponds to variant rs387906698 [ dbSNP | Ensembl ].
VAR_011655
Natural varianti122 – 1221R → C in PCTT; suppresses an autocleavage site. 1 Publication
Corresponds to variant rs111033568 [ dbSNP | Ensembl ].
VAR_012713
Natural varianti122 – 1221R → 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 Publications
Corresponds to variant rs267606982 [ dbSNP | Ensembl ].
VAR_006721
Natural varianti139 – 1391C → F in PCTT. 1 Publication
VAR_011656

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi154 – 1541Y → F: Lack of sulfation. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiPRSS1.
MIMi167800. phenotype.
Orphaneti676. Hereditary chronic pancreatitis.
PharmGKBiPA33828.

Chemistry

ChEMBLiCHEMBL2096988.
DrugBankiDB06692. Aprotinin.
GuidetoPHARMACOLOGYi2397.

Polymorphism and mutation databases

BioMutaiPRSS1.
DMDMi136408.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 15152 PublicationsAdd
BLAST
Propeptidei16 – 238Activation peptidePRO_0000028197
Chaini24 – 247224Trypsin-1PRO_0000028198Add
BLAST
Chaini24 – 12299Alpha-trypsin chain 1PRO_0000313570Add
BLAST
Chaini123 – 247125Alpha-trypsin chain 2PRO_0000313571Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi30 ↔ 160
Disulfide bondi48 ↔ 64
Disulfide bondi139 ↔ 206
Modified residuei154 – 1541Sulfotyrosine2 Publications
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.
MaxQBiP07477.
PaxDbiP07477.
PeptideAtlasiP07477.
PRIDEiP07477.

PTM databases

iPTMnetiP07477.
PhosphoSiteiP07477.

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 interactions.
IntActiP07477. 5 interactions.
STRINGi9606.ENSP00000308720.

Chemistry

BindingDBiP07477.

Structurei

Secondary structure

1
247
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi38 – 5417Combined sources
Beta strandi57 – 604Combined sources
Helixi62 – 643Combined sources
Beta strandi70 – 745Combined sources
Beta strandi76 – 805Combined sources
Beta strandi86 – 9510Combined sources
Turni101 – 1033Combined sources
Beta strandi109 – 1157Combined sources
Beta strandi120 – 1223Combined sources
Beta strandi138 – 1447Combined sources
Beta strandi149 – 1513Combined sources
Beta strandi159 – 1657Combined sources
Helixi168 – 1747Combined sources
Turni176 – 1783Combined sources
Beta strandi183 – 1875Combined sources
Beta strandi192 – 1943Combined sources
Beta strandi203 – 2064Combined sources
Beta strandi209 – 2168Combined sources
Beta strandi218 – 2225Combined sources
Beta strandi227 – 2315Combined sources
Helixi232 – 2354Combined sources
Helixi236 – 24510Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 24-247.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07477.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 244221Peptidase S1PROSITE-ProRule annotationAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti4 – 41L → F in AAI28227 (PubMed:15489334).Curated

Mass spectrometryi

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti16 – 161A → V in PCTT; disrupts signal sequence cleavage site. 1 Publication
Corresponds to variant rs202003805 [ dbSNP | Ensembl ].
VAR_011693
Natural varianti22 – 221D → G in PCTT; increased rate of activation. 1 Publication
Corresponds to variant rs397507442 [ dbSNP | Ensembl ].
VAR_011652
Natural varianti23 – 231K → R in PCTT; increased rate of activation. 1 Publication
Corresponds to variant rs111033567 [ dbSNP | Ensembl ].
VAR_011653
Natural varianti29 – 291N → I in PCTT. 4 Publications
Corresponds to variant rs111033566 [ dbSNP | Ensembl ].
VAR_006720
Natural varianti29 – 291N → T in PCTT. 1 Publication
Corresponds to variant rs111033566 [ dbSNP | Ensembl ].
VAR_012712
Natural varianti54 – 541N → S in PCTT; associated with Ile-29; the double mutant shows increased autocatalytic activation which is solely due to the Ile-29 mutation. 1 Publication
Corresponds to variant rs144422014 [ dbSNP | Ensembl ].
VAR_037908
Natural varianti79 – 791E → 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 Publication
Corresponds to variant rs111033564 [ dbSNP | Ensembl ].
VAR_037909
Natural varianti104 – 1041L → P in PCTT. 1 Publication
VAR_011654
Natural varianti116 – 1161R → C in PCTT. 1 Publication
Corresponds to variant rs387906698 [ dbSNP | Ensembl ].
VAR_011655
Natural varianti122 – 1221R → C in PCTT; suppresses an autocleavage site. 1 Publication
Corresponds to variant rs111033568 [ dbSNP | Ensembl ].
VAR_012713
Natural varianti122 – 1221R → 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 Publications
Corresponds to variant rs267606982 [ dbSNP | Ensembl ].
VAR_006721
Natural varianti137 – 1371T → M in a colorectal cancer sample; somatic mutation. 1 Publication
Corresponds to variant rs117497341 [ dbSNP | Ensembl ].
VAR_036299
Natural varianti139 – 1391C → F in PCTT. 1 Publication
VAR_011656

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
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. Positions 24-247.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111626. 19 interactions.
IntActiP07477. 5 interactions.
STRINGi9606.ENSP00000308720.

Chemistry

BindingDBiP07477.
ChEMBLiCHEMBL2096988.
DrugBankiDB06692. Aprotinin.
GuidetoPHARMACOLOGYi2397.

Protein family/group databases

MEROPSiS01.127.

PTM databases

iPTMnetiP07477.
PhosphoSiteiP07477.

Polymorphism and mutation databases

BioMutaiPRSS1.
DMDMi136408.

Proteomic databases

EPDiP07477.
MaxQBiP07477.
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.
GeneCardsiPRSS1.
GeneReviewsiPRSS1.
HGNCiHGNC:9475. PRSS1.
HPAiCAB025487.
CAB025538.
HPA062452.
HPA063471.
MalaCardsiPRSS1.
MIMi167800. phenotype.
276000. gene.
neXtProtiNX_P07477.
Orphaneti676. Hereditary chronic pancreatitis.
PharmGKBiPA33828.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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: September 7, 2016
This is version 185 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.