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FLASH GENE
Symbol CRHR1 contributors: mct/shn/pgu - updated : 16-09-2010
HGNC name corticotropin releasing hormone receptor 1
HGNC id 2357
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • seven transmembrane segments (7TM) receptor
    • HOMOLOGY
    interspecies ortholog to crhr1, Danio rerio
    ortholog to CRHR1, Pan troglodytes
    ortholog to Crhr1, Mus musculus
    ortholog to Crhr1, Rattus norvegicus
    Homologene
    FAMILY
  • G-protein coupled receptor 2 family
    • CATEGORY signaling hormone , receptor membrane G
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text integral membrane protein
    basic FUNCTION
  • role in mediating the stress response and anxiety-related behaviour
  • plays an important role in the development of a functional HPA axis and in mediating behavioral changes associated with anxiety
  • play a facilitatory role in the non-clathrin-, non-caveolae-mediated endocytosis and intracellular signal transduction of urocortin
  • enhanced 5-HT2R signaling in neurons by promoting the recruitment of constitutively internalized 5-HT2R to the cell surface
  • critically controls behavioral adaptation to stress and is causally linked to emotional disorders
  • an imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disorders
  • role for this endogenous stress hormone in the resulting structural modifications and cognitive dysfunction
  • modulates early-life stress-programmed cognitive deficits
  • CRHR1 and CRHR2 differentially modulate the dendritic growth of hippocampal neurons
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling hormonal
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with HPGD (mediate divergent effects on PGDH expression, and this may provide a precise regulation of PGs levels from chorion to myometrium during pregnancy)
  • interacts with synapse-associated protein 97 (DLG1) (interactions with CRHR1 attenuate CRHR1 endocytosis)
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL17Q21 , DUP17Q21
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    promotes insulin secretion, thus contributing to the restoration of normoglycemic equilibrium
    constitutional     --over  
    in ectopic rather than eutopic endometrium of women with endometriosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • the medulla and the adrenal gland of mice lacking Crhr1 is atrophied and stress-induced release of adrenocorticotropic hormone (ACTH) and corticosterone is reduced
  • mice null for the CRFR1 gene display markedly reduced anxiety and fail to exhibit the characteristic hormonal response to stress
  • CRFR1-null mice have lower totalpancreatic islet numbers, consistent with a role for Crhr1 in the regulation of beta cell mass (Huising 2010)
  • constitutive Crhr1 knockout (KO, Crhr1KO) mice show reduced anxiety-related behavior