lmmol · Proteins

Corticotropin-releasing hormone receptor 1

UniProt P34998 Organism Homo sapiens Gene CRFR, CRFR1, CRHR, CRHR1

Also known as: CRFR, CRFR1, CRHR, CRHR1

Function

G protein-coupled receptor for CRH and UCN stress hormones, which plays a central role in whole body adaptation to stress. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and downstream effectors, such as adenylate cyclase. CRHR1 is mainly coupled to G(s) G protein (GNAS), mediating activation of adenylate cyclase activity and production of cAMP. In some conditions, can also couple to G(q) G protein (GNAQ) and mediate production of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers. CRHR1-dependent signaling is a primary mediator of the neuroendocrine, autonomic (fight-or-flight) and behavioral responses to stress, acting as a key regulator of adaptation by activating the hypothalamus-pituitary-adrenal axis, leading to corticotropin hormone (ACTH) production (By similarity). Mediates both anxiogenic and anxiolytic response to stress in glutamatergic and dopaminergic neurons, respectively (By similarity). CRHR1 also plays a critical role in addiction by mediating the brain's stress response, particularly during withdrawal and relapse: it drives the transition to compulsive drug seeking by increasing anxiety and negative emotional states (By similarity).

Classification

Family (Pfam)
PF00002 7tm_2, PF02793 HRM
InterPro
GPCR_2, GPCR_2-like_7TM, GPCR_2_CRF1_rcpt, GPCR_2_CRF_rcpt, GPCR_2_extracell_dom_sf, GPCR_2_extracellular_dom, GPCR_2_secretin-like, GPCR_2_secretin-like_CS
Functional cluster
Mixed Regulatory & Membrane Proteins

Experimental structures · PDB · 11

A predicted model is available from AlphaFold.

Gene Ontology · 23

Drugs targeting this protein · 5

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 20 cited papers

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