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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004382 (transcript variant 2) 13 - 2594 NP_004373 - 415 - 1999 10598591 also called CRHR1alpha or variant 2/isoform 2 NM_001145146 (transcript variant 1) 14 - 2681 NP_001138618 - 444 - 1999 10598591 also called CRH-R1beta or variant 1/isoform 1 NM_001145147 (transcript variant 3) 12 - 2474 NP_001138619 - 375 - 1999 10598591 also called CRH-R1c or variant 3/isoform 3 NM_001145148 (transcript variant 4) 12 - 2552 NP_001138620 - 401 pregnant term, myometrium 1999 10598591 also called CRH-R1d or variant 4/isoform 4 lacking tht seventh TM

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain forebrain cerebral cortex     Homo sapiens   brain midbrain       Homo sapiens   brain diencephalon hypothalamus       brain forebrain       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective         Muscular smooth

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Nervous adrenergic cell Homo sapiens Nervous dopaminergic neuron Homo sapiens nervous olfactory bulb Nervous optic nerve

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text

eye

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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