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P07478

- TRY2_HUMAN

UniProt

P07478 - TRY2_HUMAN

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Protein

Trypsin-2

Gene

PRSS2

Organism
Homo sapiens (Human)
Status
Reviewed - 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

Binds 1 calcium 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

  1. calcium ion binding Source: UniProtKB
  2. serine-type endopeptidase activity Source: UniProtKB

GO - Biological processi

  1. collagen catabolic process Source: UniProtKB
  2. digestion Source: UniProtKB-KW
  3. extracellular matrix disassembly Source: Reactome
  4. extracellular matrix organization Source: Reactome
  5. innate immune response Source: Reactome
  6. positive regulation of cell adhesion Source: UniProtKB
  7. positive regulation of cell growth Source: UniProtKB
  8. 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: Unplaced

Organism-specific databases

HGNCiHGNC:9483. PRSS2.

Subcellular locationi

GO - Cellular componenti

  1. extracellular matrix Source: UniProtKB
  2. extracellular region Source: UniProtKB
  3. extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

Orphaneti676. Hereditary chronic pancreatitis.
PharmGKBiPA33833.

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

MaxQBiP07478.
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.
GenevestigatoriP07478.

Interactioni

Protein-protein interaction databases

BioGridi111627. 1 interaction.
STRINGi9606.ENSP00000308720.

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.
OMAiHPKYSSW.

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:
EMBL
GenBank
DDBJ
Links Updated
M27602 mRNA. Translation: AAA61232.1.
PIRiB25852.
RefSeqiNP_002761.1. NM_002770.2.
UniGeneiHs.449281.
Hs.726742.
Hs.728780.

Genome annotation databases

GeneIDi5645.
KEGGihsa:5645.

Polymorphism databases

DMDMi136413.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M27602 mRNA. Translation: AAA61232.1 .
PIRi B25852.
RefSeqi NP_002761.1. NM_002770.2.
UniGenei Hs.449281.
Hs.726742.
Hs.728780.

3D structure databases

ProteinModelPortali P07478.
SMRi P07478. Positions 24-247.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111627. 1 interaction.
STRINGi 9606.ENSP00000308720.

Chemistry

BindingDBi P07478.
ChEMBLi CHEMBL2096988.

Protein family/group databases

MEROPSi S01.258.

PTM databases

PhosphoSitei P07478.

Polymorphism databases

DMDMi 136413.

Proteomic databases

MaxQBi P07478.
PRIDEi P07478.

Protocols and materials databases

DNASUi 5645.
Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 5645.
KEGGi hsa:5645.

Organism-specific databases

CTDi 5645.
GeneCardsi GC07P9T0097.
HGNCi HGNC:9483. PRSS2.
MIMi 601564. gene.
neXtProti NX_P07478.
Orphaneti 676. Hereditary chronic pancreatitis.
PharmGKBi PA33833.
GenAtlasi Search...

Phylogenomic databases

HOGENOMi HOG000251820.
HOVERGENi HBG013304.
InParanoidi P07478.
KOi K01312.
OMAi HPKYSSW.

Enzyme and pathway databases

Reactomei REACT_115574. Alpha-defensins.
REACT_118682. Activation of Matrix Metalloproteinases.
REACT_150401. Collagen degradation.

Miscellaneous databases

GenomeRNAii 5645.
NextBioi 21930.
PROi P07478.
SOURCEi Search...

Gene expression databases

Bgeei P07478.
CleanExi HS_PRSS2.
Genevestigatori P07478.

Family and domain databases

InterProi IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view ]
Pfami PF00089. Trypsin. 1 hit.
[Graphical view ]
PRINTSi PR00722. CHYMOTRYPSIN.
SMARTi SM00020. Tryp_SPc. 1 hit.
[Graphical view ]
SUPFAMi SSF50494. SSF50494. 1 hit.
PROSITEi PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: October 29, 2014
This is version 147 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