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Protein

Serine protease inhibitor Kazal-type 1

Gene

SPINK1

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

Functioni

Serine protease inhibitor which exhibits anti-trypsin activity (PubMed:7142173). In the pancreas, protects against trypsin-catalyzed premature activation of zymogens (By similarity).By similarity1 Publication
In the male reproductive tract, binds to sperm heads where it modulates sperm capacitance by inhibiting calcium uptake and nitrogen oxide (NO) production.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei41 – 42Reactive bond for trypsinPROSITE-ProRule annotationBy similarity2
Sitei43 – 44Necessary for sperm bindingBy similarity2

GO - Molecular functioni

  • endopeptidase inhibitor activity Source: ProtInc
  • serine-type endopeptidase inhibitor activity Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Protein family/group databases

MEROPSiI01.011.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine protease inhibitor Kazal-type 1Imported
Alternative name(s):
Pancreatic secretory trypsin inhibitor1 Publication
Tumor-associated trypsin inhibitor
Short name:
TATI
Gene namesi
Name:SPINK1
Synonyms:PSTI
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:11244. SPINK1.

Subcellular locationi

  • Secreted 1 Publication

GO - Cellular componenti

  • acrosomal vesicle Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Pancreatitis, hereditary (PCTT)5 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_03201112L → F in PCTT. 1 PublicationCorresponds to variant rs35877720dbSNPEnsembl.1
Natural variantiVAR_01168814L → P in PCTT. 1 PublicationCorresponds to variant rs104893939dbSNPEnsembl.1
Natural variantiVAR_01168934N → S in PCTT and TCP; associated with disease susceptibility; risk factor also for acute pancreatitis; may confer susceptibility to fibrocalculous pancreatic diabetes. 4 PublicationsCorresponds to variant rs17107315dbSNPEnsembl.1
Tropical calcific pancreatitis (TCP)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionIdiopathic, 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.
See also OMIM:608189
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01168934N → S in PCTT and TCP; associated with disease susceptibility; risk factor also for acute pancreatitis; may confer susceptibility to fibrocalculous pancreatic diabetes. 4 PublicationsCorresponds to variant rs17107315dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6690.
MalaCardsiSPINK1.
MIMi167800. phenotype.
608189. phenotype.
OpenTargetsiENSG00000164266.
Orphaneti676. Hereditary chronic pancreatitis.
103918. Tropical pancreatitis.
PharmGKBiPA36074.

Polymorphism and mutation databases

BioMutaiSPINK1.
DMDMi124856.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 232 PublicationsAdd BLAST23
ChainiPRO_000001655724 – 79Serine protease inhibitor Kazal-type 1Add BLAST56

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi32 ↔ 61
Disulfide bondi39 ↔ 58
Disulfide bondi47 ↔ 79

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiP00995.
PaxDbiP00995.
PeptideAtlasiP00995.
PRIDEiP00995.

PTM databases

iPTMnetiP00995.
PhosphoSitePlusiP00995.

Miscellaneous databases

PMAP-CutDBP00995.

Expressioni

Gene expression databases

BgeeiENSG00000164266.
CleanExiHS_SPINK1.
ExpressionAtlasiP00995. baseline and differential.
GenevisibleiP00995. HS.

Organism-specific databases

HPAiCAB026366.
HPA027498.

Interactioni

Protein-protein interaction databases

BioGridi112568. 1 interactor.
MINTiMINT-1504272.
STRINGi9606.ENSP00000296695.

Structurei

Secondary structure

179
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 28Combined sources3
Beta strandi37 – 40Combined sources4
Beta strandi46 – 48Combined sources3
Beta strandi53 – 56Combined sources4
Helixi57 – 67Combined sources11
Beta strandi73 – 77Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CGIX-ray2.30I24-79[»]
1CGJX-ray2.30I24-79[»]
1HPTX-ray2.30A24-79[»]
ProteinModelPortaliP00995.
SMRiP00995.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00995.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 79Kazal-likePROSITE-ProRule annotationAdd BLAST54

Sequence similaritiesi

Contains 1 Kazal-like domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3649. Eukaryota.
ENOG410YC3T. LUCA.
GeneTreeiENSGT00530000064228.
HOGENOMiHOG000090244.
HOVERGENiHBG006182.
InParanoidiP00995.
OMAiCTKIYNP.
OrthoDBiEOG091G14HG.
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

        10         20         30         40         50
MKVTGIFLLS ALALLSLSGN TGADSLGREA KCYNELNGCT KIYDPVCGTD
60 70
GNTYPNECVL CFENRKRQTS ILIQKSGPC
Length:79
Mass (Da):8,507
Last modified:July 1, 1989 - v2
Checksum:i3583C8196952EB3A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti44D → N AA sequence (PubMed:843082).Curated1
Sequence conflicti44D → N AA sequence (PubMed:7142173).Curated1
Sequence conflicti52N → D AA sequence (PubMed:843082).Curated1
Sequence conflicti64N → G in CAA68697 (PubMed:2961612).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03201112L → F in PCTT. 1 PublicationCorresponds to variant rs35877720dbSNPEnsembl.1
Natural variantiVAR_01168814L → P in PCTT. 1 PublicationCorresponds to variant rs104893939dbSNPEnsembl.1
Natural variantiVAR_01168934N → S in PCTT and TCP; associated with disease susceptibility; risk factor also for acute pancreatitis; may confer susceptibility to fibrocalculous pancreatic diabetes. 4 PublicationsCorresponds to variant rs17107315dbSNPEnsembl.1
Natural variantiVAR_01169055P → S.4 PublicationsCorresponds to variant rs111966833dbSNPEnsembl.1
Natural variantiVAR_03201267R → H.Corresponds to variant rs35523678dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_003122.4.
UniGeneiHs.407856.

Genome annotation databases

EnsembliENST00000296695; ENSP00000296695; ENSG00000164266.
GeneIDi6690.
KEGGihsa:6690.
UCSCiuc003los.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_003122.4.
UniGeneiHs.407856.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CGIX-ray2.30I24-79[»]
1CGJX-ray2.30I24-79[»]
1HPTX-ray2.30A24-79[»]
ProteinModelPortaliP00995.
SMRiP00995.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112568. 1 interactor.
MINTiMINT-1504272.
STRINGi9606.ENSP00000296695.

Protein family/group databases

MEROPSiI01.011.

PTM databases

iPTMnetiP00995.
PhosphoSitePlusiP00995.

Polymorphism and mutation databases

BioMutaiSPINK1.
DMDMi124856.

Proteomic databases

MaxQBiP00995.
PaxDbiP00995.
PeptideAtlasiP00995.
PRIDEiP00995.

Protocols and materials databases

DNASUi6690.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296695; ENSP00000296695; ENSG00000164266.
GeneIDi6690.
KEGGihsa:6690.
UCSCiuc003los.3. human.

Organism-specific databases

CTDi6690.
DisGeNETi6690.
GeneCardsiSPINK1.
HGNCiHGNC:11244. SPINK1.
HPAiCAB026366.
HPA027498.
MalaCardsiSPINK1.
MIMi167790. gene.
167800. phenotype.
608189. phenotype.
neXtProtiNX_P00995.
OpenTargetsiENSG00000164266.
Orphaneti676. Hereditary chronic pancreatitis.
103918. Tropical pancreatitis.
PharmGKBiPA36074.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3649. Eukaryota.
ENOG410YC3T. LUCA.
GeneTreeiENSGT00530000064228.
HOGENOMiHOG000090244.
HOVERGENiHBG006182.
InParanoidiP00995.
OMAiCTKIYNP.
OrthoDBiEOG091G14HG.
PhylomeDBiP00995.

Miscellaneous databases

ChiTaRSiSPINK1. human.
EvolutionaryTraceiP00995.
GeneWikiiSPINK1.
GenomeRNAii6690.
PMAP-CutDBP00995.
PROiP00995.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164266.
CleanExiHS_SPINK1.
ExpressionAtlasiP00995. baseline and differential.
GenevisibleiP00995. HS.

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]
ProtoNetiSearch...

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: November 30, 2016
This is version 176 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

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.