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FLASH GENE
Symbol FSHR contributors: mct - updated : 08-06-2016
HGNC name follicle stimulating hormone receptor
HGNC id 3969
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a large N terminal extracytoplasmic ectodomain (ECD), a large hormone-specific extracellular domain (AA 1-366), with leucine-rich repeats (LRRs; AA 18-259) connected to TMD by a hinge region, and segment 296-331 AAs acts as a tethered inverse agonist of the TMD and plays a very critical role in the hormonal activation of FSHR
  • nine leucine-rich repeat motifs, with a ligand-binding site of LRR-containing proteins that generally utilize extensive interface area and a large number of charged residues to facilitate high-affinity protein-protein interactions
  • a characteristic seven transmembrane segments (TMD AA 367-695)
  • a region 285-300 crucial for both FSH binding and cAMP generation
  • a C terminal cytoplasmic tail, serpentine region, implicated in transduction of the activation signal
  • extracellular domains were observed in the crystal structure as a trimer, which enabled us to propose a novel model for the receptor activation mechanism
  • mono polymer trimer
    isoforms Precursor
    HOMOLOGY
    interspecies homolog to murine Fshr
    Homologene
    FAMILY
  • G-protein coupled receptor 1 family
  • FSH/LSH/TSH subfamily
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
    text in females, levels of FSHR rise until the middle of the oestrus and then fall precipitously as LH triggers ovulation
    basic FUNCTION
  • follicle stimulating hormone receptor activity
  • might play a role in genetic susceptibility to polycystic ovary syndrome
  • FSH binds to FSHR on target cells in the ovary and testis, to regulate oogenesis and spermatogenesis, respectively
  • species-specific regulation of FSHR splicing plays diverse roles in mammalian ovarian function
  • roles of extragonadal FSHR in female reproductive physiology
  • participates in regulation of mesenchymal stem cells (MSCs) precursor pools in response to either FSH or HCG, integrating the effects of these two glycoprotein hormones
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development , reproduction/sex
    text gonad development
    PATHWAY
    metabolism
    signaling hormonal , signal transduction
    a component
  • exists as a functional trimer
  • coexpression of the LHCGR and FSHR enables heterodimerizaton between the 2 gonadotropin receptors and results in an attenuation of signaling through each receptor
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with ARRB2
  • intimate association between AR expression in immature granulosa cells, and the expression of FSHR in normal small antral follicles and between the follicular fluid levels of androgen and FSHR expression
  • APPL1 is an interacting protein with FSHR
  • MTA2 is a potent corepressor of FSHR transcription, because it can recruit histone deacetylase-1 onto the FSHR promoter
  • cell & other
    REGULATION
    induced by BMP6, in granulosa cells
    Other its expression is regulated distinctly in the osteoclast, and differently from other cells, such as the ovarian follicular and Leydig cells
    ASSOCIATED DISORDERS
    corresponding disease(s) ODG1 , OHSS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in ovarian sex cord tumors
    constitutional germinal mutation      
    leading to increased sensitivity to HCG and to development of spontaneous ovarian hyperstimulation syndrome
    tumoral     --over  
    may play a role in ovarian epithelial tumors development
    Susceptibility
  • to severe OHSS (ovarian hyperstimulation syndrome)
  • to polycystic ovary syndrome
  • Variant & Polymorphism other genotype in position 680 of the FSHR could be a predictor of severity of symptoms among OHSS patients
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS