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Protein

Trypsin-2

Gene

PRSS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

In the ileum, may be involved in defensin processing, including DEFA5.1 Publication

Catalytic activityi

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

Cofactori

Ca2+By similarityNote: Binds 1 Ca2+ ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei63 – 631Charge relay systemBy similarity
Metal bindingi75 – 751CalciumBy similarity
Metal bindingi77 – 771Calcium; via carbonyl oxygenBy similarity
Metal bindingi80 – 801Calcium; via carbonyl oxygenBy similarity
Metal bindingi85 – 851CalciumBy similarity
Active sitei107 – 1071Charge relay systemBy similarity
Sitei194 – 1941Required for specificityBy similarity
Active sitei200 – 2001Charge relay systemBy similarity

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • serine-type endopeptidase activity Source: UniProtKB

GO - Biological processi

  • collagen catabolic process Source: UniProtKB
  • digestion Source: UniProtKB-KW
  • extracellular matrix disassembly Source: Reactome
  • extracellular matrix organization Source: Reactome
  • innate immune response Source: Reactome
  • positive regulation of cell adhesion Source: UniProtKB
  • positive regulation of cell growth Source: UniProtKB
  • proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Digestion

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_115574. Alpha-defensins.
REACT_118682. Activation of Matrix Metalloproteinases.
REACT_150401. Collagen degradation.

Protein family/group databases

MEROPSiS01.258.

Names & Taxonomyi

Protein namesi
Recommended name:
Trypsin-2 (EC:3.4.21.4)
Alternative name(s):
Anionic trypsinogen
Serine protease 2
Trypsin II
Gene namesi
Name:PRSS2
Synonyms:TRY2, TRYP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:9483. PRSS2.

Subcellular locationi

GO - Cellular componenti

  • extracellular matrix Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

Orphaneti676. Hereditary chronic pancreatitis.
PharmGKBiPA33833.

Polymorphism and mutation databases

DMDMi136413.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 15151 PublicationAdd
BLAST
Propeptidei16 – 238Activation peptidePRO_0000028199
Chaini24 – 247224Trypsin-2PRO_0000028200Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi30 ↔ 160PROSITE-ProRule annotation
Disulfide bondi48 ↔ 64PROSITE-ProRule annotation
Modified residuei154 – 1541Sulfotyrosine2 Publications
Disulfide bondi171 ↔ 185PROSITE-ProRule annotation
Disulfide bondi196 ↔ 220PROSITE-ProRule annotation

Post-translational modificationi

Sulfated on tyrosine.1 Publication
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

PRIDEiP07478.

PTM databases

PhosphoSiteiP07478.

Expressioni

Tissue specificityi

Expressed in Paneth cells, at the base of small intestinal crypts.1 Publication

Gene expression databases

BgeeiP07478.
CleanExiHS_PRSS2.
GenevisibleiP07478. HS.

Organism-specific databases

HPAiHPA062452.
HPA063471.

Interactioni

Protein-protein interaction databases

BioGridi111627. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliP07478.
SMRiP07478. Positions 24-247.
ModBaseiSearch...
MobiDBiSearch...

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

HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP07478.
KOiK01312.

Family and domain databases

InterProiIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[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.

P07478-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNLLLILTFV AAAVAAPFDD DDKIVGGYIC EENSVPYQVS LNSGYHFCGG
60 70 80 90 100
SLISEQWVVS AGHCYKSRIQ VRLGEHNIEV LEGNEQFINA AKIIRHPKYN
110 120 130 140 150
SRTLDNDILL IKLSSPAVIN SRVSAISLPT APPAAGTESL ISGWGNTLSS
160 170 180 190 200
GADYPDELQC LDAPVLSQAE CEASYPGKIT NNMFCVGFLE GGKDSCQGDS
210 220 230 240
GGPVVSNGEL QGIVSWGYGC AQKNRPGVYT KVYNYVDWIK DTIAANS
Length:247
Mass (Da):26,488
Last modified:April 1, 1988 - v1
Checksum:i82B0F41EB8E3D5DB
GO

Polymorphismi

His-153 variation is a common polymorphism in African populations with a minor allele frequency of 9.2%, it eliminates sulfation at Tyr-154, with no consequences on digestive physiology.1 Publication

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti117 – 1171A → V.
Corresponds to variant rs11547028 [ dbSNP | Ensembl ].
VAR_051858
Natural varianti153 – 1531D → H Abolishes tyrosine sulfation. 1 Publication
VAR_071761

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M27602 mRNA. Translation: AAA61232.1.
PIRiB25852.
RefSeqiNP_002761.1. NM_002770.3.
UniGeneiHs.449281.
Hs.726742.
Hs.728780.

Genome annotation databases

GeneIDi5645.
KEGGihsa:5645.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M27602 mRNA. Translation: AAA61232.1.
PIRiB25852.
RefSeqiNP_002761.1. NM_002770.3.
UniGeneiHs.449281.
Hs.726742.
Hs.728780.

3D structure databases

ProteinModelPortaliP07478.
SMRiP07478. Positions 24-247.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111627. 1 interaction.

Chemistry

BindingDBiP07478.
ChEMBLiCHEMBL2096988.

Protein family/group databases

MEROPSiS01.258.

PTM databases

PhosphoSiteiP07478.

Polymorphism and mutation databases

DMDMi136413.

Proteomic databases

PRIDEiP07478.

Protocols and materials databases

DNASUi5645.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi5645.
KEGGihsa:5645.

Organism-specific databases

CTDi5645.
GeneCardsiGC07P9T0097.
HGNCiHGNC:9483. PRSS2.
HPAiHPA062452.
HPA063471.
MIMi601564. gene.
neXtProtiNX_P07478.
Orphaneti676. Hereditary chronic pancreatitis.
PharmGKBiPA33833.
GenAtlasiSearch...

Phylogenomic databases

HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP07478.
KOiK01312.

Enzyme and pathway databases

ReactomeiREACT_115574. Alpha-defensins.
REACT_118682. Activation of Matrix Metalloproteinases.
REACT_150401. Collagen degradation.

Miscellaneous databases

GenomeRNAii5645.
NextBioi21930.
PROiP07478.
SOURCEiSearch...

Gene expression databases

BgeeiP07478.
CleanExiHS_PRSS2.
GenevisibleiP07478. HS.

Family and domain databases

InterProiIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[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...

Publicationsi

  1. "Cloning, characterization and nucleotide sequences of two cDNAs encoding human pancreatic trypsinogens."
    Emi M., Nakamura Y., Ogawa M., Yamamoto T., Nishide T., Mori T., Matsubara K.
    Gene 41:305-310(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Immunoreactive anionic and cationic trypsin in human serum."
    Kimland M., Russick C., Marks W.H., Borgstroem A.
    Clin. Chim. Acta 184:31-46(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 16-49.
  3. "Paneth cell trypsin is the processing enzyme for human defensin-5."
    Ghosh D., Porter E., Shen B., Lee S.K., Wilk D., Drazba J., Yadav S.P., Crabb J.W., Ganz T., Bevins C.L.
    Nat. Immunol. 3:583-590(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  4. "Human cationic trypsinogen is sulfated on Tyr154."
    Sahin-Toth M., Kukor Z., Nemoda Z.
    FEBS J. 273:5044-5050(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SULFATION.
  5. "Tyrosine sulfation of human trypsin steers S2' subsite selectivity towards basic amino acids."
    Szabo A., Salameh M.A., Ludwig M., Radisky E.S., Sahin-Toth M.
    PLoS ONE 9:E102063-E102063(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: SULFATION AT TYR-154.
  6. "A common African polymorphism abolishes tyrosine sulfation of human anionic trypsinogen (PRSS2)."
    Ronai Z., Witt H., Rickards O., Destro-Bisol G., Bradbury A.R., Sahin-Toth M.
    Biochem. J. 418:155-161(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT HIS-153, CHARACTERIZATION OF VARIANT HIS-153.

Entry informationi

Entry nameiTRY2_HUMAN
AccessioniPrimary (citable) accession number: P07478
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: July 22, 2015
This is version 155 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

Keywords - Technical termi

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. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.