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FLASH GENE
Symbol SFRP1 contributors: mct/shn/pgu - updated : 12-12-2018
HGNC name secreted frizzled-related protein 1
HGNC id 10776
Location 8p11.21      Physical location : 41.119.475 - 41.166.990
Synonym name
  • secreted apoptosis-related protein 2
  • frizzled-related protein 1
  • Synonym symbol(s) SARP2, FZDS1, FRP, FRP-1,sFRP-1, FrzA
    DNA
    TYPE functioning gene
    STRUCTURE 47.50 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • SFRP1 promoter was hypermethylated in keloid tissues, compared with that in normal skin tissues
  • MAPPING cloned Y linked N status confirmed
    Map pter - D8S532 - D8S1118 - SFRP1 - D8S268 - D8S1115 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 4465 36 314 - 1997 9192640
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   predominantly Homo sapiens
    Digestiveintestinelarge intestinecolon highly
     intestinesmall intestine  highly
    Lymphoid/Immunespleen   moderately
    Reproductivefemale systemplacenta  moderately
     female systemovary  highly
     male systemtestis  highly
     male systemprostate  highly
    Urinarykidney   highly
    Visualeyelens    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow    Homo sapiensAdult
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    Visuallens fibers Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    Text Brain and kidney
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a frizzled-like cysteine-rich domain (CRD)
  • a region between AAs 73-86 within the second loop of the CRD necessary for the optimal Wnt inhibitory function
  • a conserved hydrophilic carboxy-terminal domain
  • HOMOLOGY
    interspecies homolog to Drosophila frizzled polarity
    homolog to Sfrp1, Mus musculus
    ortholog to Sfrp1, Rattus norvegicus
    ortholog to SFRP1, Pan troglodytes
    ortholog to sfrp1a, Danio rerio
    Homologene
    FAMILY
  • secreted frizzled-related protein (sFRP) family
  • CATEGORY tumor suppressor , signaling
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    basic FUNCTION
  • may be involved in retina cell differentiation
  • having ability to guide growth cone movement via the frizzled 2 receptor
  • suppressed hepatoma cells growth through WNT canonical signaling pathway
  • WNT signalling antagonist, playing a role in the development of multiple solid tumour types
  • regulating hematopoietic stem cells
  • transcriptional repression target of the t(8;21) fusion protein
  • SFRP1 functions as a secreted mediator of senescence through inhibition of Wnt signaling and activation of the retinoblastoma (RB1) pathway
  • is an extracellular component of stress-induced senescence signaling that responds to potentially carcinogenic stresses such as DNA damage and oxidative insult and induces cellular senescence in an autocrine and paracrine fashion, which may lead to non-cell-autonomous tumor suppression
  • putative tumor suppressor gene that is frequently down-regulated in multiple carcinomas, is a crucial regulatory protein for spermiation
  • SFRP1, SFRP2 can either promote or suppress Wnt/CTNNB1 signaling, depending on cellular context, concentration and most likely the expression pattern of Fzd receptors
  • SFRP1, SFRP2 play a role in lens development, at least in part, by regulating aspects of WNT/CTNNB1 signaling in lens epithelial cells
  • expression of SFRP1 is a critical factor required for maintaining appropriate cellular signaling in response to the onset of obesity
  • SFRP1 and FRZB act as WNT signaling pathway antagonists and play an important role in embryonic development and carcinogenesis
  • role of SFRP1 in age-related cardiac deterioration and fibrosis
  • loss of SFRP1 likely contributes to tumor progression by altering the expression of a critical transcription factor in both the epithelium and the immune system
  • WNT7A and SFRP1 play likely opposite roles to ensure proper neural progenitors (NP) progeny in the developing cortex
  • multifunctional regulator of BMP, WNT and NOTCH1 signaling strongly expressed during early telencephalic development
  • by controlling WNT and NOTCH1 signaling in opposite directions, SFRP1 promotes hippocampal patterning and balances medio-lateral and antero-posterior cortex expansion
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • wingless-type MMTV integration site family member 1,WNT1 and wingless-type MMTV integration site family member 2, WNT2
  • wingless-type MMTV integration site family member 4,WNT4
  • Frizzled-2, Fz2
  • SFRP1, SFRP2 inhibits the ADAM10 metalloprotease, which might have important implications in pathological events, including cancer and Alzheimer disease
  • HR repressed the expression of Wnt inhibitors, including SOSTDC1, DKKL1, SFRP1, and SFRP2
  • DNA damage enhances SFRP1 secretion by a TP53-dependent mechanism
  • regulates spermatid adhesion in the testis via dephosphorylation of focal adhesion kinase and the nectin-3 adhesion protein complex
  • downregulation of CBX5 can decrease H3K9me3 enrichment and DNA methylation rate of SFRP1 promoter, resulting in restoring the expression of SFRP1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in breast carcinoma (expression was inversely correlated with tumor stage but not with tumor grade or lymph node status
    tumoral       loss of function
    by hypermethylation in colorectal cancer and in ovarian cancers
    tumoral       loss of function
    by hypermethylation in non-small-cell lung cancer (NSCLC)
    tumoral       loss of function
    by promoter hypermethylation, predominant mechanism of SFRP1 gene silencing in breast cancer and is associated with unfavourable prognosis
    tumoral     --low  
    in transitional cell carcinomas of the bladder
    tumoral     --low  
    silencing leads to oncogenic activation of the Wnt pathway and contributes to cervical cancer progression through the epithelial mesenchymal transition program
    tumoral     --low  
    markedly reduced in both the breast cancer cell lines and primary tumour specimens relative to normal primary mammary epithelial cells even when SFRP1 is amplified
    tumoral     --low  
    by hypermethylation in primary hepatocellular carcinoma
    tumoral     --low  
    methylation-associated silencing of SFRP1 frequently occurs in renal cell carcinoma and plays a pivotal role in early carcinogenesis
    tumoral     --low  
    by promoter methylation frequently found in renal cell carcinoma
    constitutional       loss of function
    of SFRP1 and SFRP2, two postulated Wnt antagonists, perturbs retinal neurogenesis
    constitutional     --low  
    by hypermethylation in keloid tissues, compared with that in normal skin tissues
    tumoral     --low  
    decreased markedly in patients with acute myeloid leukemia (AML) compared to controls
    constitutional     --low  
    of SFRP1 may contribute to the pathogenesis of IUGR placental dysfunction, whereas the loss of the protein may be involved in the development of human trophoblastic tumors
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousdermatology 
    might be a therapeutic target for keloid treatment
    ANIMAL & CELL MODELS
  • in postnatal Sfrp1-/- animals the anterior hippocampus is reduced and the neocortex is shorter in the antero-posterior and medio-lateral axis but is thicker
  • loss of Sfrp1 exacerbates weight gain, glucose homeostasis and inflammation in mice in response to diet induced obesity