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FLASH GENE
Symbol SERPINF1 contributors: mct - updated : 21-04-2010
HGNC name serine (or cysteine) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1
HGNC id 8824
DNA
TYPE functioning gene
STRUCTURE 15.61 kb     8 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 1542 50 418 - 2010 19945427
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart     Homo sapiens
Digestiveliver     Homo sapiens
Nervousbrain   highly Homo sapiens
 spinal cord     Homo sapiens
Respiratorylung     Homo sapiens
Skeleton      Homo sapiens
Visualeyeretina  highly Homo sapiens
 eyeanterior segmentcornea   Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow    Homo sapiens
Connectivebone    Homo sapiens
Epithelialbarrier liningretinal pigment epithelium (RPE)   Homo sapiens
Nervouscentral    Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
 digestive Homo sapiens
not specificchondrocyte Homo sapiens
Skeletonosteoblast Homo sapiens
Skeletonosteoclast Homo sapiens
cell lineage
cell lines
fluid/secretion CNS, plasma
at STAGE
physiological period fetal, pregnancy
cell cycle     cell cycle
Text retina, widely expressed throughout fetal tissues
life cycle quiescence
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal region confers a neurite-promoting activity to the protein
  • a signal peptide
  • a serpin domain
  • C terminus of PEDF (AAs 384–415) represents one of the four highly conserved regions of the protein
  • secondary structure neurotrophic active site is separated from the serpin reactive-site loop, not only in the primary structure, but also in the folded protein structure
    conjugated GlycoP , RiboP
    isoforms Precursor
    HOMOLOGY
    Homologene
    FAMILY
  • serpin family
  • CATEGORY enzyme , regulatory , structural protein
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • effective inhibitor of angiogenesis especially in controlling the growth of blood vessels in the eye and in bone (matrix remodeling)
  • preventing against early diabetic retinopathy
  • estrogen sensitive and inhibiting the growth of ovarian tissue
  • neuroprotective and anti-angiogenic factor, may play an important role in the pathogenesis of diabetic retinopathy
  • important neuromodulatory factor that can provide effective neuroprotection and a primary endogenous angiogenic inhibitor in the eye
  • may play a role in the pathogenesis of neurodegenerative diseases and angiogenic disorders, such as Alzheimer's disease, Parkinson disease, neovascular age-related macular degeneration and tumors
  • suspected tumor suppressor gene that plays a key role in the inhibition of epithelial tissue growth
  • inducing apoptosis in endothelial cells by activating MAPK14 dependent cleavage of multiple caspases
  • may play an important role in the pathogenesis of diabetic retinopathy, in cooperation with the VEGF gene
  • possibly involved in bone homeostasis as an inhibitor of bone resorption
  • inhibits osteoclast function via regulating osteoprotegerin expression, and thereby contributes to the maintenance of bone homeostasis
  • neurotrophic factor at first, but it also possesses neuro-protective, pro-differentiation, anti-proliferative and anti-angiogenic functions (most potent endogenous inhibitor of angiogenesis)
  • inhibits osteoclast differentiation and hence bone resorption via osteoprotegerin (OPG) and TNFSF11 (receptor activator of NF-kB ligand) in a dose-dependent manner
  • multifunctional protein and one of the strongest inhibitors of angiogenesis
  • stimulates macrophage-mediated cytotoxicity in a TNFSF10-dependent manner
  • able to enhance the antitumor efficacy of macrophages by inducing a TNFSF10-mediated tumoricidal activity
  • CELLULAR PROCESS cell life, cell death/apoptosis
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    text
  • most potent inhjbitor of angiogenesis, inhibiting advanced glycation and product-induced retinal vascular hypermeability
  • acting as a neurotrophic factor
  • PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • regulated through phosphorylation by PRKACA and CSNK2A1
  • novel transcriptional target for NCOR1 repressive action
  • interaction with SERPINF1 (NCOR1 expression is required to maintain intestinal epithelial cell in a proliferative state and identify SERPINF1 as a novel transcriptional target for NCOR1 repressive action)
  • suppressed TNFSF11 activity directly and indirectly
  • TNFSF10-mediated tumoricidal activity of macrophages can be stimulated by SERPINF1
  • mediates the induction of TNFSF10 expression by PPARG
  • may regulate SOST expression by osteocytes leading to enhanced osteoblastic differentiation and increased matrix mineralization (
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) OIVI
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    expression reduced in non small cell lung cancer
    constitutional        
    contributing to diabetic retinopathy
    tumoral     --low  
    in breast cancer is associated with increased tumor progression
    tumoral     --low  
    during malignant progression of human glioma, hepatoma, breast cancer, ovarian cancer, lung cancer, and melanoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene for diabetic retinopathy
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    osteoarticularboneothers
    a promising candidate for the development of a drug for the treatment of OI patients with inborn loss of PEDF and possibly also for the treatment of other low bone-mass phenotypes
    cancer  
    potential therapeutic value against skeletal disorders and cancers
    ANIMAL & CELL MODELS