Corticotropin-releasing hormone receptor 1
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
- 2L27 NMR
- 3EHS X-ray 2.76A
- 3EHT X-ray 3.40A
- 3EHU X-ray 1.96A
- 4K5Y X-ray 2.98A
- 4Z9G X-ray 3.18A
- 6P9X EM 2.91A
- 6PB0 EM 3.00A
- 8GTG X-ray 2.75A
- 8GTI X-ray 2.20A
- 8GTM X-ray 2.60A
A predicted model is available from AlphaFold.
Gene Ontology · 23
- GO:0005768 endosome
- GO:0098978 glutamatergic synapse
- GO:0016020 membrane
- GO:0043005 neuron projection
- GO:0005886 plasma membrane
- GO:0098839 postsynaptic density membrane
- GO:0015056 corticotrophin-releasing factor receptor activity
- GO:0051424 corticotropin-releasing hormone binding
- GO:0043404 corticotropin-releasing hormone receptor activity
- GO:0008528 G protein-coupled peptide receptor activity
- GO:0004930 G protein-coupled receptor activity
- GO:0007190 activation of adenylate cyclase activity
- GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
- GO:0030325 adrenal gland development
- GO:0007166 cell surface receptor signaling pathway
- GO:0071376 cellular response to corticotropin-releasing hormone stimulus
- GO:0051458 corticotropin secretion
- GO:0042596 fear response
- GO:0007565 female pregnancy
- GO:0006955 immune response
- GO:1901386 negative regulation of voltage-gated calcium channel activity
- GO:0007567 parturition
- GO:2000852 regulation of corticosterone secretion
Drugs targeting this protein · 5
- VERUCERFONT antagonist
- ONO-2333MS antagonist
- CRINECERFONT antagonist
- PEXACERFONT antagonist
- EMICERFONT antagonist
Related proteins · sequence + function similarity
- Corticotropin-releasing hormone receptor 1 1.00
- Corticotropin-releasing hormone receptor 1 1.00
- Corticotropin-releasing hormone receptor 1 0.99
- Corticotropin-releasing hormone receptor 1 0.99
- Corticotropin-releasing hormone receptor 1 0.97
- Corticotropin-releasing hormone receptor 1 0.93
- Corticotropin-releasing hormone receptor 2 0.88
- Corticotropin-releasing hormone receptor 2 0.87
- Corticotropin-releasing hormone receptor 2 0.86
- Corticotropin-releasing hormone receptor 2 0.86
- Gamma-aminobutyric acid type B receptor subunit 1 0.79
- Gamma-aminobutyric acid type B receptor subunit 1 0.79
Co-cited proteins · studied together in the literature
- Corticotropin-releasing hormone receptor 1 2 shared papers
- Urocortin 3 shared papers
- Corticotropin-releasing hormone 2 shared papers
- Corticotropin-releasing hormone receptor 2 2 shared papers
- Pituitary adenylate cyclase-activating polypeptide type I receptor 1 shared papers
- Urocortin-2 1 shared papers
- Pituitary adenylate cyclase-activating polypeptide 1 shared papers
- Urocortin-3 1 shared papers
Literature · 20 cited papers
- Molecular basis for hormone recognition and activation of corticotropin-releasing factor receptors. Mol. Cell · 2020
- Toward a structural understanding of class B GPCR peptide binding and activation. Mol. Cell · 2020
- Genetically encoded chemical probes in cells reveal the binding path of urocortin-I to CRF class B GPCR. Cell · 2013
- Structure of class B GPCR corticotropin-releasing factor receptor 1. Nature · 2013
- Role of SAP97 protein in the regulation of corticotropin-releasing factor receptor 1 endocytosis and extracellular signal-regulated kinase 1/2 signaling. J. Biol. Chem. · 2013
- Structural basis for hormone recognition by the Human CRFR2{alpha} G protein-coupled receptor. J. Biol. Chem. · 2010
- NMR structure of the first extracellular domain of corticotropin-releasing factor receptor 1 (ECD1-CRF-R1) complexed with a high affinity agonist. J. Biol. Chem. · 2010
- Human protein factory for converting the transcriptome into an in vitro-expressed proteome. Nat. Methods · 2008
- Molecular recognition of corticotropin-releasing factor by its G-protein-coupled receptor CRFR1. J. Biol. Chem. · 2008
- Activation of corticotropin-releasing factor receptor 1 selectively inhibits CaV3.2 T-type calcium channels. Mol. Pharmacol. · 2008
- DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature · 2006
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- … and 8 more in the literature graph