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FLASH GENE
Symbol SPINT1 contributors: mct - updated : 01-09-2014
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
    Physical map
    GPR 15q14 putative G protein coupled receptor LOC388113 15 hypothetical gene supported by BC035481 MGC10997 15q13-q14 pseudogene MGC10997 SRP14 15q15.1-q21.1 signal recognition particle 14kDa (homologous Alu RNA binding protein) BMF 15q14 Bcl2 modifying factor BUB1B 15q15 BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast) PAK6 15q14 p21(CDKN1A)-activated kinase 6 LOC390577 15 similar to KIAA1728 protein PLCB2 15q15 phospholipase C, beta 2 LOC390578 15 similar to BLOCK 23 LOC388114 15 LOC388114 LOC388115 15 similar to RIKEN cDNA 2600011L02 LOC146071 15q14 similar to RIKEN cDNA 1810007E14; EST AA238765 DISP2 15q14 dispatched homolog 2 (Drosophila) FLJ14502 15q14 TRAF4 associated factor 1 IVD 15q14-q15 isovaleryl Coenzyme A dehydrogenase KIAA0945 D4ST-1 15q14 isovaleryl Coenzyme A dehydrogenase MGC20481 15q14 hypothetical protein MGC20481 C18B11 15q13.3 C18B11 homolog (44.9kD) AF15Q14 15q14 AF15q14 protein RAD51 15q15.1 RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae) FLJ10579 15q14 hypothetical protein FLJ10579 GCHFR 15q15 GTP cyclohydrolase I feedback regulatory protein FLJ10634 15q14 hypothetical protein FLJ10634 ZFYVE19 15q14 zinc finger, FYVE domain containing 19 PPP1R14D 15q13.3 protein phosphatase 1, regulatory (inhibitor) subunit 14D SPINT1 15q15 serine protease inhibitor, Kunitz type 1 ARHV 15q13.3 ras homolog gene family, member V VPS18 15q14-q15 vacuolar protein sorting protein 18 DLL4 15q14 delta-like 4 (Drosophila) MGC4504 15q14 hypothetical protein MGC4504 KIAA1259 15q14 hypothetical protein MGC4504 HCP37 15q15.1 cytochrome c, somatic pseudogene LOC388116 15 similar to RIKEN cDNA 6720467C03 MGC33637 15q14 hypothetical protein MGC33637 CHP 15q13.3 hypothetical protein MGC33637 OIP5 15q14 Opa-interacting protein 5 NUSAP1 15q14 nucleolar and spindle associated protein 1 CIA30 KIAA0252 15q14 nucleolar and spindle associated protein 1 ITPKA 15q14-q21 inositol 1,4,5-trisphosphate 3-kinase A LTK 15q15.1-q15.2 leukocyte tyrosine kinase DKFZP727M111 15q14 DKFZP727M111 protein LOC283747 15q14 similar to elongation factor SIII p15 subunit TYRO3 15q15.1-q21.1 TYRO3 protein tyrosine kinase MGA 15q15 MAX gene associated MAPKBP1 15q14 likely ortholog of mouse mitogen activated protein kinase binding proten 1 PLA2G4B 15q11.2-q21.3 phospholipase A2, group IVB (cytosolic)
    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
  • 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
  • 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