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FLASH GENE
Symbol SPINT2 contributors: mct - updated : 15-12-2016
HGNC name serine peptidase inhibitor, Kunitz type, 2
HGNC id 11247
DNA
TYPE functioning gene
STRUCTURE 28.16 kb     7 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Map cen - D19S425 - D19S208 - D19S224 - SCN1B - D19S228 - SPINT2 - D19S421 - D19S223 - D19S217 - D19S219 - D19S412 - D19S606 - D19S907 - D19S927 - D19S418 - qter
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
7 - 1817 28.1 252 - 2002 12553733
  • isoform a
  • precursor
  • 6 - 1646 - 195 - 2002 12553733
  • isoform b
  • precursor
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas    
    Lymphoid/Immunethymus    
    Nervousbrain   lowly
    Reproductivefemale systemplacenta   
     male systemtestis  highly Homo sapiens
     male systemprostate   
    Respiratorylung    
     respiratory tracttrachea   
    Urinarykidney    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivespermatocyte Homo sapiens
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text highly and in kidney with an endogenous soluble form called placental bikunin
    PROTEIN
    PHYSICAL PROPERTIES Hydrophilic
    STRUCTURE
    motifs/domains
  • putative N terminal signal peptide
  • sequentially, two Kunitz domains each of 58 AA containing three intrachain disulfide bonds, and Kunitz domain 1 cause ST14 accumulation in a membrane-bound form on the basolateral plasma membrane
  • a putative transmembrane segment (TM1)
  • C terminal hydrophilic tail
  • conjugated GlycoP
    isoforms Precursor proteolytically cleaved and secreted (Kawaguchi 1997)
    HOMOLOGY
    intraspecies homolog to SPINT1
    Homologene
    FAMILY
  • Kunitz family of serine protease inhibitor
  • CATEGORY enzyme , tumor suppressor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm
    text either insertion of SPINT2 into the plasma membrane, with the Kunitz domains localizing extracellularly, or an intracellular role of the protein
    basic FUNCTION
  • Kunitz-type serine-protease inhibitor, potent inhibitor of a number of serine proteases involved in blood coagulation and fibrinolysis such as pancreatic trypsin, plasmin, kallikrein-11 and hepatocyte growth factor activator
  • playing an important regulatory role in pericellular activation of hepatocyte growth factor/scatter factor (HGF/SF), critically involved in the development and regeneration of various tissues
  • may play a role in the process of spermatogenesis
  • may regulate ST14 activity
  • SPINT1, SPINT2 influence proliferation and cell fate of
  • neural progenitor cells (NPCs) and their expression levels are linked to BMP signaling
  • imbalance between SPINT2 and ST14 expression led to ST14 activation, thereby increasing cell migration, invasion, tumorigenicity and metastasis
  • SPINT1 regulates the activity of activated ST14, whereas SPINT2 has an essential role in regulating PRSS8-dependent ST14 zymogen activation
  • is associated with tumor-suppressive functions in melanoma by inhibiting an extracellular signal regulator of HGF, which is typically activated by tumor-stromal interactions
  • involvement of SPINT2 in Prostate carcinoma tumorigenesis, probably in association with a post-translational regulation of SPINT2
  • is a tumor suppressor gene that inhibits proteases implicated in cancer progression, like HGFAC, hepsin and ST14
  • inhibits proteases involved in activation of both influenza viruses and metapneumoviruses
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PRSS8 activity eliminates SPINT1 and SPINT2 deficiency-associated developmental defects by preventing matriptase activation
  • SPINT2 is an inhibitor of PRSS6 that modulates the synthesis of HAMP and provides new insights into the regulatory mechanism of iron homoeostasis
  • is important for regulation of ST14
  • IER3IP1, PPIB, EMC7, SPINT2, C14orf1/PEBP28, TMEM147, YIPF6, and KRTCAP2 interacting with SLC41A1
  • 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) CSODS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in pancreatic cancer
    tumoral     --low  
    frequently hypermethylated and underexpressed in HCC
    tumoral     --low  
    in ovarian and cervical cancers
    tumoral        
    silenced by promoter hypermethylation in pediatric medulloblastoma
    tumoral     --low  
    hypermethylated in RCC
    tumoral     --low  
    in myelodysplastic syndromes and modulates cell-cell adhesion
    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
    cancerreproductiveovary
    could be considered a therapeutic target for treatment approches in ovarian and cervical cancers
    cancerreproductivebreast
    SPINT2 expression in breast cancer correlates with tumor aggressiveness
    cancerreproductivebreast
    low level of SPINT2 in the breast cancer tissues is associated with an overall poor outlook
    cancerreproductiveuterus
    could be considered as therapeutic targets and used as favorable prognosis markers for endometrial cancer
    ANIMAL & CELL MODELS
  • reduced Prss8 activity restores placental differentiation, embryonic survival, and neural tube closure in Spint2–deficient mice