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P00995 (ISK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pancreatic secretory trypsin inhibitor
Alternative name(s):
Serine protease inhibitor Kazal-type 1
Tumor-associated trypsin inhibitor
Short name=TATI
Gene names
Name:SPINK1
Synonyms:PSTI
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length79 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This is a trypsin inhibitor, its physiological function is to prevent the trypsin-catalyzed premature activation of zymogens within the pancreas.

Subcellular location

Secreted.

Involvement in disease

Pancreatitis, hereditary (PCTT) [MIM:167800]: A disease characterized by pancreas inflammation, permanent destruction of the pancreatic parenchyma, maldigestion, and severe abdominal pain attacks.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.4 Ref.10 Ref.13

Tropical calcific pancreatitis (TCP) [MIM:608189]: Idiopathic, juvenile, nonalcoholic form of chronic pancreatitis widely prevalent in several tropical countries. It can be associated with fibrocalculous pancreatic diabetes (FCPD) depending on both environmental and genetic factors. TCP differs from alcoholic pancreatitis by a much younger age of onset, pancreatic calcification, a high incidence of insulin dependent but ketosis resistant diabetes mellitus, and an exceptionally high incidence of pancreatic cancer.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.11 Ref.12

Sequence similarities

Contains 1 Kazal-like domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.6 Ref.7
Chain24 – 7956Pancreatic secretory trypsin inhibitor
PRO_0000016557

Regions

Domain26 – 7954Kazal-like

Sites

Site41 – 422Reactive bond

Amino acid modifications

Disulfide bond32 ↔ 61
Disulfide bond39 ↔ 58
Disulfide bond47 ↔ 79

Natural variations

Natural variant121L → F in PCTT. Ref.13
Corresponds to variant rs35877720 [ dbSNP | Ensembl ].
VAR_032011
Natural variant141L → P in PCTT. Ref.4
VAR_011688
Natural variant341N → S in PCTT and TCP; may confer susceptibility to fibrocalculous pancreatic diabetes. Ref.4 Ref.10 Ref.11 Ref.12
Corresponds to variant rs17107315 [ dbSNP | Ensembl ].
VAR_011689
Natural variant551P → S. Ref.4 Ref.10 Ref.12
VAR_011690
Natural variant671R → H.
Corresponds to variant rs35523678 [ dbSNP | Ensembl ].
VAR_032012

Experimental info

Sequence conflict441D → N AA sequence Ref.6
Sequence conflict441D → N AA sequence Ref.7
Sequence conflict521N → D AA sequence Ref.6
Sequence conflict641N → G in CAA68697. Ref.3

Secondary structure

............ 79
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00995 [UniParc].

Last modified July 1, 1989. Version 2.
Checksum: 3583C8196952EB3A

FASTA798,507
        10         20         30         40         50         60 
MKVTGIFLLS ALALLSLSGN TGADSLGREA KCYNELNGCT KIYDPVCGTD GNTYPNECVL 

        70 
CFENRKRQTS ILIQKSGPC 

« Hide

References

« Hide 'large scale' references
[1]"Primary structure of human pancreatic secretory trypsin inhibitor (PSTI) gene."
Horii A., Kobayashi T., Tomita N., Yamamoto T., Fukushige S., Murotsu T., Ogawa M., Mori T., Matsubara K.
Biochem. Biophys. Res. Commun. 149:635-641(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Molecular cloning and nucleotide sequence of human pancreatic secretory trypsin inhibitor (PSTI) cDNA."
Yamamoto T., Nakamura Y., Nishide T., Emi M., Ogawa M., Mori T., Matsubara K.
Biochem. Biophys. Res. Commun. 132:605-612(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Expression of pancreatic secretory trypsin inhibitor gene in neoplastic tissues."
Tomita N., Horii A., Yamamoto T., Ogawa M., Mori T., Matsubara K.
FEBS Lett. 225:113-119(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis."
Witt H., Luck W., Hennies H.C., Classen M., Kage A., Lass U., Landt O., Becker M.
Nat. Genet. 25:213-216(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PCTT PRO-14 AND SER-34, VARIANT SER-55.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas and Spleen.
[6]"The primary structure of the human pancreatic secretory trypsin inhibitor. Amino acid sequence of the reduced S-aminoethylated protein."
Bartelt D.C., Shapanka R., Greene L.J.
Arch. Biochem. Biophys. 179:189-199(1977) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-79.
[7]"Purification and characterization of a tumor-associated trypsin inhibitor from the urine of a patient with ovarian cancer."
Huhtala M.-L., Pesonen K., Kalkkinen N., Stenman U.-H.
J. Biol. Chem. 257:13713-13716(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-46.
[8]"Three-dimensional structure of a recombinant variant of human pancreatic secretory trypsin inhibitor (Kazal type)."
Hecht H.-J., Szardenings M., Collins J., Schomburg D.
J. Mol. Biol. 225:1095-1103(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[9]"Solution structure of a variant of human pancreatic secretory trypsin inhibitor determined by nuclear magnetic resonance spectroscopy."
Klaus W., Schomburg D.
J. Mol. Biol. 229:695-706(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF MUTANT LEU-41/ARG-44.
[10]"Mutational analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene in hereditary and sporadic chronic pancreatitis."
Chen J.-M., Mercier B., Audrezet M.-P., Ferec C.
J. Med. Genet. 37:67-69(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PCTT SER-34, VARIANT SER-55.
[11]"SPINK1 is a susceptibility gene for fibrocalculous pancreatic diabetes in subjects from the Indian subcontinent."
Hassan Z., Mohan V., Ali L., Allotey R., Barakat K., Faruque M.O., Deepa R., McDermott M.F., Jackson A.E., Cassell P., Curtis D., Gelding S.V., Vijayaravaghan S., Gyr N., Whitcomb D.C., Azad Khan A.K., Hitman G.A.
Am. J. Hum. Genet. 71:964-968(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TCP SER-34, INVOLVEMENT IN FIBROCALCULOUS PANCREATIC DIABETES.
[12]"Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather than the cationic trypsinogen gene (PRSS1) are significantly associated with tropical calcific pancreatitis."
Chandak G.R., Idris M.M., Reddy D.N., Bhaskar S., Sriram P.V.J., Singh L.
J. Med. Genet. 39:347-351(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TCP SER-34, VARIANT SER-55.
[13]"Gene symbol: Spink1-Omim 167790. Disease: hereditary pancreatitis."
Deybach J.-C.D., Phung L., Lamoril J., Bouizegarene P., Levy P., Deybach J.-C., Ruszniewski P.
Hum. Genet. 113:369-369(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PCTT PHE-12.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M20530 expand/collapse EMBL AC list , M22971, M20528, M20529 Genomic DNA. Translation: AAA36522.1.
Y00705 mRNA. Translation: CAA68697.1.
M11949 mRNA. Translation: AAA36521.1.
AF286028 Genomic DNA. Translation: AAG00531.1.
BC025790 mRNA. Translation: AAH25790.1.
PIRTIHUA. A27484.
RefSeqNP_003113.2. NM_003122.3.
XP_005268558.1. XM_005268501.1.
UniGeneHs.407856.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CGIX-ray2.30I24-79[»]
1CGJX-ray2.30I24-79[»]
1HPTX-ray2.30A24-79[»]
ProteinModelPortalP00995.
SMRP00995. Positions 24-79.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-1504272.
STRING9606.ENSP00000296695.

Protein family/group databases

MEROPSI01.011.

Polymorphism databases

DMDM124856.

Proteomic databases

PaxDbP00995.
PeptideAtlasP00995.
PRIDEP00995.

Protocols and materials databases

DNASU6690.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296695; ENSP00000296695; ENSG00000164266.
GeneID6690.
KEGGhsa:6690.
UCSCuc003los.2. human.

Organism-specific databases

CTD6690.
GeneCardsGC05M147184.
HGNCHGNC:11244. SPINK1.
HPACAB026366.
HPA027498.
MIM167790. gene.
167800. phenotype.
608189. phenotype.
neXtProtNX_P00995.
Orphanet676. Hereditary chronic pancreatitis.
103918. Tropical pancreatitis.
PharmGKBPA36074.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG320895.
HOGENOMHOG000090244.
HOVERGENHBG006182.
InParanoidP00995.
OMACTKIYNP.
OrthoDBEOG7BW0M2.
PhylomeDBP00995.

Gene expression databases

ArrayExpressP00995.
BgeeP00995.
CleanExHS_SPINK1.
GenevestigatorP00995.

Family and domain databases

InterProIPR002350. Kazal_dom.
IPR001239. Prot_inh_Kazal-m.
[Graphical view]
PfamPF00050. Kazal_1. 1 hit.
[Graphical view]
PRINTSPR00290. KAZALINHBTR.
SMARTSM00280. KAZAL. 1 hit.
[Graphical view]
PROSITEPS00282. KAZAL_1. 1 hit.
PS51465. KAZAL_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00995.
GeneWikiSPINK1.
GenomeRNAi6690.
NextBio26073.
PMAP-CutDBP00995.
PROP00995.
SOURCESearch...

Entry information

Entry nameISK1_HUMAN
AccessionPrimary (citable) accession number: P00995
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 1, 1989
Last modified: April 16, 2014
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM