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FLASH GENE

Symbol

FSHR

contributors: mct - updated : 08-06-2016

HGNC name	follicle stimulating hormone receptor
HGNC id	3969

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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