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FLASH GENE
Symbol SPINT1 contributors: mct - updated : 01-09-2016
HGNC name serine protease inhibitor, Kunitz type 1
HGNC id 11246
Location 15q15.1      Physical location : 41.136.245 - 41.149.852
Synonym name hepatocyte growth factor activator inhibitor type 1
Synonym symbol(s) HAI1, HAI, MANSC2
DNA
TYPE functioning gene
STRUCTURE 13.61 kb     11 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   transcription factor
text structure
  • overlapping binding site for Egr-1-3 and Sp1 near the transcription start site is the key domain for SPINT1 transcription, and this site was also critical in both hypoxic- and oxidative stress-induced SPINT1 upregulation
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 2484 - 529 - 2005 16273651
  • HAI1B or V1
  • 11 - 2436 - 513 - 2005 16273651
    10 - 2342 - 513 - 2005 16273651
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly Homo sapiens
     liver   lowly
     stomach   highly
    Endocrinepancreas    
    Reproductivefemale systemplacenta  highly
     male systemprostate  highly
    Respiratorylung    
    Urinarykidney    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text placenta, kidney, lung
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal putative signal peptide sequence
  • a hydrophobic region encoding the processed, cleaved two regions of homology with Kunitz domains
  • three potential N glycosylation sites
  • low-density lipoprotein receptor A module (LDLRA) domain
  • a second Kunitz domain (Kunitz domain II) in the extracellular region
  • a MANSC domain
  • two inhibitory domains
  • a membrane associated C terminal region
  • conjugated GlycoP
    HOMOLOGY
    intraspecies homolog to SPINT2
    Homologene
    FAMILY Kunitz family of serine protease inhibitor
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text
  • in addition to its protease inhibitory function, plays a role in transporting ST14 as a ST14/SPINT1 complex from the basolateral plama membrane to the apical plasma membrane, as ST14 is known to interact with PRSS8, located at the apical plasma membrane
  • basic FUNCTION
  • inhibitor of hepatocyte growth factor activator (HGFAC)
  • involved in regulation of proteolytic activation of HGF in injured tissues
  • important role in maintaining the integrity of basement membrane most likely by regulating extracellular proteolytic activities during placental development
  • has critical roles in the regulated keratinization of the epidermis and hair development
  • Kunitz-type serine protease inhibitor that has a broad inhibitory spectrum against serine proteases
  • plays an important role in maintaining colonic epithelium integrity
  • is critically required for the cell surface localization of ST14 in trophoblasts, and, in the absence of SPINT1, physiological activation of PRSS8 and other protease(s) initiated by cell surface matriptase may be impaired
  • essential for branching morphogenesis in the chorioallantoic placenta and lack of SPINT1 function may result in placental failure
  • membrane-bound serine protease inhibitor expressed on the surface of epithelial cells
  • has a crucial role in suppressing intestinal tumorigenesis, which implies a novel link between epithelial cell surface serine protease inhibitors and protection from carcinogenic stimuli
  • SPINT1, SPINT2 influence proliferation and cell fate of
  • neural progenitor cells (NPCs) and their expression levels are linked to BMP signaling
  • SPINT1 regulates the activity of activated ST14, whereas SPINT2 has an essential role in regulating PRSS8-dependent ST14 zymogen activation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • inhibitor of matriptase, a membrane-associated serine proteinase
  • role of the stem domain in the interaction between ST14 and its physiological inhibitor, SPINT1
  • TMPRSS13 functions as an HGF-converting protease, the activity of which may be regulated by SPINT1
  • ST14 activity can be rapidly inhibited by SPINT1 and other SPINT1-like protease inhibitors and "locked" in an inactive autoactivation intermediate, all of which places ST14 under very tight control
  • activation of ST14 through the cleavage of SPINT1 is one of the MMP14 multifunctions essential for invasive growth of squamous carcinoma cells
  • PRSS8 activity eliminates SPINT1 and SPINT2 deficiency-associated developmental defects by preventing matriptase activation
  • activation of ST14 through the cleavage of SPINT1 is one of the MMP14 multifunctions essential for invasive growth of squamous carcinoma cells
  • TMPRSS11B is a catalytically active serine protease that is inhibited by the two Kunitz type serine protease inhibitors, hepatocyte growth factor activator inhibitor SPINT1 and SPINT2, as well as by SERPINA1
  • TMPRSS13 exhibits impaired cell-surface expression in the absence of the cognate Kunitz-type serine protease inhibitors, hepatocyte growth factor activator inhibitor SPINT1 or SPINT2
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in patients with prostate cancer was significantly higher than in those with negative prostate biopsy
    constitutional     --over  
    of SPINT1 and SPINT2 in the liver in cholangiopathies with ductular reactions which are possibly involved in liver fibrosis and hepatic differentiation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveuterus
    could be considered as therapeutic targets and used as favorable prognosis markers for endometrial cancer
    ANIMAL & CELL MODELS
  • in Spint1-deficient mouse placenta, laminin immunoreactivity around trophoblasts was irregular and occasionally showed an intense punctate pattern, which differed significantly from the linear distribution along the basement membrane observed in wild-type placenta
  • St14-mediated developmental defects in Spint1-deficient mice are Prss8-dependent