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P00995

- ISK1_HUMAN

UniProt

P00995 - ISK1_HUMAN

Protein

Pancreatic secretory trypsin inhibitor

Gene

SPINK1

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

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei41 – 422Reactive bond

    GO - Molecular functioni

    1. endopeptidase inhibitor activity Source: ProtInc
    2. protein binding Source: UniProtKB
    3. serine-type endopeptidase inhibitor activity Source: UniProtKB-KW

    GO - Biological processi

    1. negative regulation of calcium ion import Source: Ensembl
    2. negative regulation of nitric oxide mediated signal transduction Source: Ensembl
    3. negative regulation of peptidyl-tyrosine phosphorylation Source: Ensembl
    4. negative regulation of serine-type endopeptidase activity Source: Ensembl
    5. regulation of acrosome reaction Source: Ensembl
    6. regulation of store-operated calcium entry Source: Ensembl

    Keywords - Molecular functioni

    Protease inhibitor, Serine protease inhibitor

    Protein family/group databases

    MEROPSiI01.011.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pancreatic secretory trypsin inhibitor
    Alternative name(s):
    Serine protease inhibitor Kazal-type 1
    Tumor-associated trypsin inhibitor
    Short name:
    TATI
    Gene namesi
    Name:SPINK1
    Synonyms:PSTI
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:11244. SPINK1.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Pancreatitis, hereditary (PCTT) [MIM:167800]: A disease characterized by pancreas inflammation, permanent destruction of the pancreatic parenchyma, maldigestion, and severe abdominal pain attacks.3 Publications
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti12 – 121L → F in PCTT. 1 Publication
    Corresponds to variant rs35877720 [ dbSNP | Ensembl ].
    VAR_032011
    Natural varianti14 – 141L → P in PCTT. 1 Publication
    VAR_011688
    Natural varianti34 – 341N → S in PCTT and TCP; may confer susceptibility to fibrocalculous pancreatic diabetes. 4 Publications
    Corresponds to variant rs17107315 [ dbSNP | Ensembl ].
    VAR_011689
    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.2 Publications
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti34 – 341N → S in PCTT and TCP; may confer susceptibility to fibrocalculous pancreatic diabetes. 4 Publications
    Corresponds to variant rs17107315 [ dbSNP | Ensembl ].
    VAR_011689

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi167800. phenotype.
    608189. phenotype.
    Orphaneti676. Hereditary chronic pancreatitis.
    103918. Tropical pancreatitis.
    PharmGKBiPA36074.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 23232 PublicationsAdd
    BLAST
    Chaini24 – 7956Pancreatic secretory trypsin inhibitorPRO_0000016557Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi32 ↔ 61
    Disulfide bondi39 ↔ 58
    Disulfide bondi47 ↔ 79

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    MaxQBiP00995.
    PaxDbiP00995.
    PeptideAtlasiP00995.
    PRIDEiP00995.

    Miscellaneous databases

    PMAP-CutDBP00995.

    Expressioni

    Gene expression databases

    ArrayExpressiP00995.
    BgeeiP00995.
    CleanExiHS_SPINK1.
    GenevestigatoriP00995.

    Organism-specific databases

    HPAiCAB026366.
    HPA027498.

    Interactioni

    Protein-protein interaction databases

    MINTiMINT-1504272.
    STRINGi9606.ENSP00000296695.

    Structurei

    Secondary structure

    1
    79
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi26 – 283
    Beta strandi37 – 404
    Beta strandi46 – 483
    Beta strandi53 – 564
    Helixi57 – 6711
    Beta strandi73 – 775

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CGIX-ray2.30I24-79[»]
    1CGJX-ray2.30I24-79[»]
    1HPTX-ray2.30A24-79[»]
    ProteinModelPortaliP00995.
    SMRiP00995. Positions 24-79.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP00995.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini26 – 7954Kazal-likePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 Kazal-like domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG320895.
    HOGENOMiHOG000090244.
    HOVERGENiHBG006182.
    InParanoidiP00995.
    OMAiCTKIYNP.
    OrthoDBiEOG7BW0M2.
    PhylomeDBiP00995.

    Family and domain databases

    InterProiIPR002350. Kazal_dom.
    IPR001239. Prot_inh_Kazal-m.
    [Graphical view]
    PfamiPF00050. Kazal_1. 1 hit.
    [Graphical view]
    PRINTSiPR00290. KAZALINHBTR.
    SMARTiSM00280. KAZAL. 1 hit.
    [Graphical view]
    PROSITEiPS00282. KAZAL_1. 1 hit.
    PS51465. KAZAL_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P00995-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKVTGIFLLS ALALLSLSGN TGADSLGREA KCYNELNGCT KIYDPVCGTD   50
    GNTYPNECVL CFENRKRQTS ILIQKSGPC 79
    Length:79
    Mass (Da):8,507
    Last modified:July 1, 1989 - v2
    Checksum:i3583C8196952EB3A
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti44 – 441D → N AA sequence (PubMed:843082)Curated
    Sequence conflicti44 – 441D → N AA sequence (PubMed:7142173)Curated
    Sequence conflicti52 – 521N → D AA sequence (PubMed:843082)Curated
    Sequence conflicti64 – 641N → G in CAA68697. (PubMed:2961612)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti12 – 121L → F in PCTT. 1 Publication
    Corresponds to variant rs35877720 [ dbSNP | Ensembl ].
    VAR_032011
    Natural varianti14 – 141L → P in PCTT. 1 Publication
    VAR_011688
    Natural varianti34 – 341N → S in PCTT and TCP; may confer susceptibility to fibrocalculous pancreatic diabetes. 4 Publications
    Corresponds to variant rs17107315 [ dbSNP | Ensembl ].
    VAR_011689
    Natural varianti55 – 551P → S.3 Publications
    VAR_011690
    Natural varianti67 – 671R → H.
    Corresponds to variant rs35523678 [ dbSNP | Ensembl ].
    VAR_032012

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M20530
    , 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.
    CCDSiCCDS4286.1.
    PIRiA27484. TIHUA.
    RefSeqiNP_003113.2. NM_003122.3.
    XP_005268558.1. XM_005268501.1.
    UniGeneiHs.407856.

    Genome annotation databases

    EnsembliENST00000296695; ENSP00000296695; ENSG00000164266.
    GeneIDi6690.
    KEGGihsa:6690.
    UCSCiuc003los.2. human.

    Polymorphism databases

    DMDMi124856.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M20530
    , 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 .
    CCDSi CCDS4286.1.
    PIRi A27484. TIHUA.
    RefSeqi NP_003113.2. NM_003122.3.
    XP_005268558.1. XM_005268501.1.
    UniGenei Hs.407856.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1CGI X-ray 2.30 I 24-79 [» ]
    1CGJ X-ray 2.30 I 24-79 [» ]
    1HPT X-ray 2.30 A 24-79 [» ]
    ProteinModelPortali P00995.
    SMRi P00995. Positions 24-79.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-1504272.
    STRINGi 9606.ENSP00000296695.

    Protein family/group databases

    MEROPSi I01.011.

    Polymorphism databases

    DMDMi 124856.

    Proteomic databases

    MaxQBi P00995.
    PaxDbi P00995.
    PeptideAtlasi P00995.
    PRIDEi P00995.

    Protocols and materials databases

    DNASUi 6690.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000296695 ; ENSP00000296695 ; ENSG00000164266 .
    GeneIDi 6690.
    KEGGi hsa:6690.
    UCSCi uc003los.2. human.

    Organism-specific databases

    CTDi 6690.
    GeneCardsi GC05M147184.
    HGNCi HGNC:11244. SPINK1.
    HPAi CAB026366.
    HPA027498.
    MIMi 167790. gene.
    167800. phenotype.
    608189. phenotype.
    neXtProti NX_P00995.
    Orphaneti 676. Hereditary chronic pancreatitis.
    103918. Tropical pancreatitis.
    PharmGKBi PA36074.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG320895.
    HOGENOMi HOG000090244.
    HOVERGENi HBG006182.
    InParanoidi P00995.
    OMAi CTKIYNP.
    OrthoDBi EOG7BW0M2.
    PhylomeDBi P00995.

    Miscellaneous databases

    EvolutionaryTracei P00995.
    GeneWikii SPINK1.
    GenomeRNAii 6690.
    NextBioi 26073.
    PMAP-CutDB P00995.
    PROi P00995.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P00995.
    Bgeei P00995.
    CleanExi HS_SPINK1.
    Genevestigatori P00995.

    Family and domain databases

    InterProi IPR002350. Kazal_dom.
    IPR001239. Prot_inh_Kazal-m.
    [Graphical view ]
    Pfami PF00050. Kazal_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00290. KAZALINHBTR.
    SMARTi SM00280. KAZAL. 1 hit.
    [Graphical view ]
    PROSITEi PS00282. KAZAL_1. 1 hit.
    PS51465. KAZAL_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. 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. 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. Cited for: VARIANT PCTT PHE-12.

    Entry informationi

    Entry nameiISK1_HUMAN
    AccessioniPrimary (citable) accession number: P00995
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: July 1, 1989
    Last modified: October 1, 2014
    This is version 157 of the entry and version 2 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

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3