CRFR1_HUMAN
ID CRFR1_HUMAN Reviewed; 444 AA.
AC P34998; B4DIE9; Q13008; Q4QRJ1; Q9UK64;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Corticotropin-releasing factor receptor 1;
DE Short=CRF-R-1;
DE Short=CRF-R1;
DE Short=CRFR-1;
DE AltName: Full=Corticotropin-releasing hormone receptor 1;
DE Short=CRH-R-1;
DE Short=CRH-R1;
DE Flags: Precursor;
GN Name=CRHR1; Synonyms=CRFR, CRFR1, CRHR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS CRF-R1 AND CRF-R2).
RC TISSUE=Pituitary;
RX PubMed=7692441; DOI=10.1073/pnas.90.19.8967;
RA Chen R., Lewis K.A., Perrin M.H., Vale W.W.;
RT "Expression cloning of a human corticotropin-releasing-factor receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:8967-8971(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF-R2), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8243652; DOI=10.1016/0014-5793(93)80427-v;
RA Vita N., Laurent P., Lefort S., Chalon P., Lelias J.-M., Kaghad M.,
RA le Fur G., Caput D., Ferrara P.;
RT "Primary structure and functional expression of mouse pituitary and human
RT brain corticotrophin releasing factor receptors.";
RL FEBS Lett. 335:1-5(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9757017; DOI=10.1016/s0378-1119(98)00322-9;
RA Sakai K., Yamada M., Horiba N., Wakui M., Demura H., Suda T.;
RT "The genomic organization of the human corticotropin-releasing factor type-
RT 1 receptor.";
RL Gene 219:125-130(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF-R3).
RC TISSUE=Hippocampus;
RX PubMed=7811272; DOI=10.1006/bbrc.1994.2884;
RA Ross P.C., Kostas C.M., Ramabhadran T.V.;
RT "A variant of the human corticotropin-releasing factor (CRF) receptor:
RT cloning, expression and pharmacology.";
RL Biochem. Biophys. Res. Commun. 205:1836-1842(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF-R4).
RX PubMed=10598591; DOI=10.1210/mend.13.12.0391;
RA Grammatopoulos D.K., Dai Y., Randeva H.S., Levine M.A., Karteris E.,
RA Easton A.J., Hillhouse E.W.;
RT "A novel spliced variant of the type 1 corticotropin-releasing hormone
RT receptor with a deletion in the seventh transmembrane domain present in the
RT human pregnant term myometrium and fetal membranes.";
RL Mol. Endocrinol. 13:2189-2202(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RA Sherrin T., Murthy S.R., Spiess J.;
RT "A novel CRF1 splice isoform involved in neurodegenerative and stress
RT disorders.";
RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRF-R2).
RC TISSUE=Brain;
RA King M.M., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRF-R2).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRF-R2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [13]
RP PROTEIN SEQUENCE OF 24-31, AND DISULFIDE BONDS.
RX PubMed=11425856; DOI=10.1074/jbc.m101838200;
RA Perrin M.H., Fischer W.H., Kunitake K.S., Craig A.G., Koerber S.C.,
RA Cervini L.A., Rivier J.E., Groppe J.C., Greenwald J., Moller Nielsen S.,
RA Vale W.W.;
RT "Expression, purification, and characterization of a soluble form of the
RT first extracellular domain of the human type 1 corticotropin releasing
RT factor receptor.";
RL J. Biol. Chem. 276:31528-31534(2001).
RN [14]
RP PHOSPHORYLATION AT SER-330.
RX PubMed=14657255; DOI=10.1210/me.2003-0365;
RA Papadopoulou N., Chen J., Randeva H.S., Levine M.A., Hillhouse E.W.,
RA Grammatopoulos D.K.;
RT "Protein kinase A-induced negative regulation of the corticotropin-
RT releasing hormone R1alpha receptor-extracellularly regulated kinase signal
RT transduction pathway: the critical role of Ser301 for signaling switch and
RT selectivity.";
RL Mol. Endocrinol. 18:624-639(2004).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18292205; DOI=10.1124/mol.107.043612;
RA Tao J., Hildebrand M.E., Liao P., Liang M.C., Tan G., Li S., Snutch T.P.,
RA Soong T.W.;
RT "Activation of corticotropin-releasing factor receptor 1 selectively
RT inhibits CaV3.2 T-type calcium channels.";
RL Mol. Pharmacol. 73:1596-1609(2008).
RN [16]
RP INTERACTION WITH CRF AND UCN.
RX PubMed=20966082; DOI=10.1074/jbc.m110.186072;
RA Pal K., Swaminathan K., Xu H.E., Pioszak A.A.;
RT "Structural basis for hormone recognition by the Human CRFR2{alpha} G
RT protein-coupled receptor.";
RL J. Biol. Chem. 285:40351-40361(2010).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH DLG1.
RX PubMed=23576434; DOI=10.1074/jbc.m113.473660;
RA Dunn H.A., Walther C., Godin C.M., Hall R.A., Ferguson S.S.;
RT "Role of SAP97 protein in the regulation of corticotropin-releasing factor
RT receptor 1 endocytosis and extracellular signal-regulated kinase 1/2
RT signaling.";
RL J. Biol. Chem. 288:15023-15034(2013).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 24-119 IN COMPLEX WITH CRH,
RP FUNCTION, AND DISULFIDE BONDS.
RX PubMed=18801728; DOI=10.1074/jbc.m805749200;
RA Pioszak A.A., Parker N.R., Suino-Powell K., Xu H.E.;
RT "Molecular recognition of corticotropin-releasing factor by its G-protein-
RT coupled receptor CRFR1.";
RL J. Biol. Chem. 283:32900-32912(2008).
RN [19]
RP STRUCTURE BY NMR OF 25-109 IN COMPLEX WITH SYNTHETIC CRH ANALOG.
RX PubMed=20843795; DOI=10.1074/jbc.m110.121897;
RA Grace C.R., Perrin M.H., Gulyas J., Rivier J.E., Vale W.W., Riek R.;
RT "NMR structure of the first extracellular domain of corticotropin-releasing
RT factor receptor 1 (ECD1-CRF-R1) complexed with a high affinity agonist.";
RL J. Biol. Chem. 285:38580-38589(2010).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.98 ANGSTROMS) OF 104-373 IN COMPLEX WITH THE
RP SYNTHETIC ANTAGONIST CP-376395, FUNCTION, SUBCELLULAR LOCATION, MEMBRANE
RP TOPOLOGY, DISULFIDE BOND, ANTAGONIST BINDING SITES, AND MUTAGENESIS OF
RP PHE-232; MET-235; LEU-309; ASN-312; PHE-313; LEU-316; ILE-319; TYR-356 AND
RP GLN-384.
RX PubMed=23863939; DOI=10.1038/nature12357;
RA Hollenstein K., Kean J., Bortolato A., Cheng R.K., Dore A.S., Jazayeri A.,
RA Cooke R.M., Weir M., Marshall F.H.;
RT "Structure of class B GPCR corticotropin-releasing factor receptor 1.";
RL Nature 499:438-443(2013).
CC -!- FUNCTION: G-protein coupled receptor for CRH (corticotropin-releasing
CC factor) and UCN (urocortin). Has high affinity for CRH and UCN. Ligand
CC binding causes a conformation change that triggers signaling via
CC guanine nucleotide-binding proteins (G proteins) and down-stream
CC effectors, such as adenylate cyclase. Promotes the activation of
CC adenylate cyclase, leading to increased intracellular cAMP levels.
CC Inhibits the activity of the calcium channel CACNA1H. Required for
CC normal embryonic development of the adrenal gland and for normal
CC hormonal responses to stress. Plays a role in the response to
CC anxiogenic stimuli. {ECO:0000269|PubMed:18292205,
CC ECO:0000269|PubMed:18801728, ECO:0000269|PubMed:23576434,
CC ECO:0000269|PubMed:23863939}.
CC -!- SUBUNIT: Heterodimer; heterodimerizes with GPER1 (By similarity).
CC Interacts (via N-terminal extracellular domain) with CRH and UCN.
CC Interacts with DLG1; this inhibits endocytosis of CRHR1 after agonist
CC binding. {ECO:0000250, ECO:0000269|PubMed:18801728,
CC ECO:0000269|PubMed:20843795, ECO:0000269|PubMed:20966082,
CC ECO:0000269|PubMed:23576434, ECO:0000269|PubMed:23863939}.
CC -!- INTERACTION:
CC P34998; P06850: CRH; NbExp=5; IntAct=EBI-3870393, EBI-3870390;
CC P34998; Q12959: DLG1; NbExp=2; IntAct=EBI-3870393, EBI-357481;
CC P34998; Q14160: SCRIB; NbExp=3; IntAct=EBI-3870393, EBI-357345;
CC P34998; Q63622: Dlg2; Xeno; NbExp=2; IntAct=EBI-3870393, EBI-396947;
CC P34998; O88382: Magi2; Xeno; NbExp=2; IntAct=EBI-3870393, EBI-696179;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC Endosome. Note=Agonist-binding promotes endocytosis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=CRF-R1;
CC IsoId=P34998-1; Sequence=Displayed;
CC Name=CRF-R2;
CC IsoId=P34998-2; Sequence=VSP_001997;
CC Name=CRF-R3;
CC IsoId=P34998-3; Sequence=VSP_001996, VSP_001997;
CC Name=CRF-R4; Synonyms=1D;
CC IsoId=P34998-4; Sequence=VSP_001997, VSP_001998;
CC Name=5;
CC IsoId=P34998-5; Sequence=VSP_045434;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the cerebellum,
CC pituitary, cerebral cortex and olfactory lobe.
CC {ECO:0000269|PubMed:8243652}.
CC -!- DOMAIN: The transmembrane domain is composed of seven transmembrane
CC helices that are arranged in V-shape. Transmembrane helix 7 assumes a
CC sharply kinked structure. The antagonist CP-376395 binds at an
CC allosteric site, far from the presumed binding site for the
CC physiological peptide ligand.
CC -!- PTM: C-terminal Ser or Thr residues may be phosphorylated.
CC {ECO:0000269|PubMed:14657255}.
CC -!- PTM: Phosphorylation at Ser-330 by PKA prevents maximal coupling to Gq-
CC protein, and thereby negatively regulates downstream signaling.
CC {ECO:0000269|PubMed:14657255}.
CC -!- MISCELLANEOUS: [Isoform CRF-R2]: Major isoform. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform CRF-R3]: Does not bind to CRF with high
CC affinity. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC {ECO:0000305}.
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DR EMBL; L23333; AAA35719.1; -; mRNA.
DR EMBL; L23332; AAA35718.1; -; mRNA.
DR EMBL; X72304; CAA51052.1; -; mRNA.
DR EMBL; AF039523; AAC69993.1; -; Genomic_DNA.
DR EMBL; AF039510; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; AF039511; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; AF039512; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; AF039513; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; AF039514; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; AF039515; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; AF039516; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; AF039517; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; AF039518; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; AF039519; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; AF039520; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; AF039521; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; AF039522; AAC69993.1; JOINED; Genomic_DNA.
DR EMBL; U16273; AAC50073.1; -; mRNA.
DR EMBL; AF180301; AAD52688.1; -; mRNA.
DR EMBL; FJ543100; ACU68591.1; -; mRNA.
DR EMBL; AY457172; AAR19768.1; -; mRNA.
DR EMBL; AB451466; BAG70280.1; -; mRNA.
DR EMBL; AK295559; BAG58461.1; -; mRNA.
DR EMBL; AC126544; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC217770; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC217771; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC217774; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC225613; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471233; EAW93557.1; -; Genomic_DNA.
DR EMBL; BC096836; AAH96836.1; -; mRNA.
DR CCDS; CCDS42350.1; -. [P34998-2]
DR CCDS; CCDS45712.1; -. [P34998-1]
DR CCDS; CCDS45713.1; -. [P34998-4]
DR CCDS; CCDS45714.1; -. [P34998-3]
DR CCDS; CCDS58556.1; -. [P34998-5]
DR PIR; I38879; I38879.
DR PIR; I60975; A48260.
DR RefSeq; NP_001138618.1; NM_001145146.1. [P34998-1]
DR RefSeq; NP_001138619.1; NM_001145147.1. [P34998-3]
DR RefSeq; NP_001138620.1; NM_001145148.1. [P34998-4]
DR RefSeq; NP_001243228.1; NM_001256299.2. [P34998-5]
DR RefSeq; NP_001289945.1; NM_001303016.1.
DR RefSeq; NP_001289947.1; NM_001303018.1. [P34998-5]
DR RefSeq; NP_004373.2; NM_004382.4. [P34998-2]
DR PDB; 2L27; NMR; -; A=25-108.
DR PDB; 3EHS; X-ray; 2.76 A; A=24-119.
DR PDB; 3EHT; X-ray; 3.40 A; A=24-119.
DR PDB; 3EHU; X-ray; 1.96 A; A/B=24-119.
DR PDB; 4K5Y; X-ray; 2.98 A; A/B/C=104-373.
DR PDB; 4Z9G; X-ray; 3.18 A; A/B/C=104-249, A/B/C=252-401.
DR PDB; 6P9X; EM; 2.91 A; R=23-444.
DR PDB; 6PB0; EM; 3.00 A; R=24-427.
DR PDBsum; 2L27; -.
DR PDBsum; 3EHS; -.
DR PDBsum; 3EHT; -.
DR PDBsum; 3EHU; -.
DR PDBsum; 4K5Y; -.
DR PDBsum; 4Z9G; -.
DR PDBsum; 6P9X; -.
DR PDBsum; 6PB0; -.
DR AlphaFoldDB; P34998; -.
DR SMR; P34998; -.
DR BioGRID; 107784; 20.
DR IntAct; P34998; 7.
DR MINT; P34998; -.
DR STRING; 9606.ENSP00000381333; -.
DR BindingDB; P34998; -.
DR ChEMBL; CHEMBL1800; -.
DR DrugBank; DB09067; Corticorelin ovine triflutate.
DR DrugCentral; P34998; -.
DR GuidetoPHARMACOLOGY; 212; -.
DR TCDB; 9.A.14.4.3; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P34998; 5 sites.
DR iPTMnet; P34998; -.
DR PhosphoSitePlus; P34998; -.
DR BioMuta; CRHR1; -.
DR DMDM; 461836; -.
DR MassIVE; P34998; -.
DR PaxDb; P34998; -.
DR PeptideAtlas; P34998; -.
DR PRIDE; P34998; -.
DR ProteomicsDB; 4300; -.
DR ProteomicsDB; 54968; -. [P34998-1]
DR ProteomicsDB; 54969; -. [P34998-2]
DR ProteomicsDB; 54970; -. [P34998-3]
DR ProteomicsDB; 54971; -. [P34998-4]
DR Antibodypedia; 8417; 398 antibodies from 31 providers.
DR DNASU; 1394; -.
DR Ensembl; ENST00000314537.10; ENSP00000326060.6; ENSG00000120088.15. [P34998-2]
DR Ensembl; ENST00000352855.9; ENSP00000344068.5; ENSG00000120088.15. [P34998-3]
DR Ensembl; ENST00000398285.7; ENSP00000381333.3; ENSG00000120088.15. [P34998-1]
DR Ensembl; ENST00000577353.5; ENSP00000462016.1; ENSG00000120088.15. [P34998-4]
DR Ensembl; ENST00000616274.4; ENSP00000480396.1; ENSG00000276191.4. [P34998-1]
DR Ensembl; ENST00000616748.4; ENSP00000478177.1; ENSG00000276191.4. [P34998-3]
DR Ensembl; ENST00000617905.4; ENSP00000483802.1; ENSG00000276191.4. [P34998-2]
DR Ensembl; ENST00000633723.1; ENSP00000488342.1; ENSG00000276191.4. [P34998-4]
DR GeneID; 104909134; -.
DR GeneID; 1394; -.
DR KEGG; hsa:104909134; -.
DR KEGG; hsa:1394; -.
DR MANE-Select; ENST00000314537.10; ENSP00000326060.6; NM_004382.5; NP_004373.2. [P34998-2]
DR UCSC; uc002ijm.4; human. [P34998-1]
DR CTD; 104909134; -.
DR CTD; 1394; -.
DR DisGeNET; 104909134; -.
DR DisGeNET; 1394; -.
DR GeneCards; CRHR1; -.
DR HGNC; HGNC:2357; CRHR1.
DR HPA; ENSG00000120088; Group enriched (brain, pituitary gland).
DR MIM; 122561; gene.
DR neXtProt; NX_P34998; -.
DR OpenTargets; ENSG00000120088; -.
DR OpenTargets; ENSG00000263715; -.
DR PharmGKB; PA26874; -.
DR VEuPathDB; HostDB:ENSG00000120088; -.
DR eggNOG; KOG4564; Eukaryota.
DR GeneTree; ENSGT00940000158410; -.
DR InParanoid; P34998; -.
DR OMA; EWIRAMA; -.
DR OrthoDB; 1163977at2759; -.
DR PhylomeDB; P34998; -.
DR TreeFam; TF315710; -.
DR PathwayCommons; P34998; -.
DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P34998; -.
DR SIGNOR; P34998; -.
DR BioGRID-ORCS; 104909134; 4 hits in 83 CRISPR screens.
DR BioGRID-ORCS; 1394; 14 hits in 1063 CRISPR screens.
DR EvolutionaryTrace; P34998; -.
DR GeneWiki; Corticotropin_releasing_hormone_receptor_1; -.
DR Pharos; P34998; Tclin.
DR PRO; PR:P34998; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P34998; protein.
DR Bgee; ENSG00000120088; Expressed in right hemisphere of cerebellum and 85 other tissues.
DR ExpressionAtlas; P34998; baseline and differential.
DR Genevisible; P34998; HS.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0015056; F:corticotrophin-releasing factor receptor activity; IDA:UniProtKB.
DR GO; GO:0051424; F:corticotropin-releasing hormone binding; IBA:GO_Central.
DR GO; GO:0043404; F:corticotropin-releasing hormone receptor activity; IBA:GO_Central.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
DR GO; GO:0017046; F:peptide hormone binding; IBA:GO_Central.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; TAS:ProtInc.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0030325; P:adrenal gland development; IEA:Ensembl.
DR GO; GO:0048149; P:behavioral response to ethanol; IEA:Ensembl.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0071376; P:cellular response to corticotropin-releasing hormone stimulus; IDA:UniProtKB.
DR GO; GO:0051458; P:corticotropin secretion; ISS:UniProtKB.
DR GO; GO:0042596; P:fear response; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; NAS:ProtInc.
DR GO; GO:0051867; P:general adaptation syndrome, behavioral process; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; IDA:UniProtKB.
DR GO; GO:0007567; P:parturition; TAS:ProtInc.
DR GO; GO:0010578; P:regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:2000852; P:regulation of corticosterone secretion; ISS:UniProtKB.
DR Gene3D; 4.10.1240.10; -; 1.
DR InterPro; IPR017981; GPCR_2-like.
DR InterPro; IPR003052; GPCR_2_CRF1_rcpt.
DR InterPro; IPR003051; GPCR_2_CRF_rcpt.
DR InterPro; IPR036445; GPCR_2_extracell_dom_sf.
DR InterPro; IPR001879; GPCR_2_extracellular_dom.
DR InterPro; IPR000832; GPCR_2_secretin-like.
DR InterPro; IPR017983; GPCR_2_secretin-like_CS.
DR Pfam; PF00002; 7tm_2; 1.
DR Pfam; PF02793; HRM; 1.
DR PRINTS; PR01279; CRFRECEPTOR.
DR PRINTS; PR01280; CRFRECEPTOR1.
DR PRINTS; PR00249; GPCRSECRETIN.
DR SMART; SM00008; HormR; 1.
DR SUPFAM; SSF111418; SSF111418; 1.
DR PROSITE; PS00649; G_PROTEIN_RECEP_F2_1; 1.
DR PROSITE; PS00650; G_PROTEIN_RECEP_F2_2; 1.
DR PROSITE; PS50227; G_PROTEIN_RECEP_F2_3; 1.
DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane;
KW Direct protein sequencing; Disulfide bond; Endosome;
KW G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Signal; Transducer; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:11425856"
FT CHAIN 24..444
FT /note="Corticotropin-releasing factor receptor 1"
FT /id="PRO_0000012814"
FT TOPO_DOM 24..111
FT /note="Extracellular"
FT TRANSMEM 112..142
FT /note="Helical; Name=1"
FT TOPO_DOM 143..178
FT /note="Cytoplasmic"
FT TRANSMEM 179..203
FT /note="Helical; Name=2"
FT TOPO_DOM 204..218
FT /note="Extracellular"
FT TRANSMEM 219..247
FT /note="Helical; Name=3"
FT TOPO_DOM 248..254
FT /note="Cytoplasmic"
FT TRANSMEM 255..282
FT /note="Helical; Name=4"
FT TOPO_DOM 283..298
FT /note="Extracellular"
FT TRANSMEM 299..324
FT /note="Helical; Name=5"
FT TOPO_DOM 325..335
FT /note="Cytoplasmic"
FT TRANSMEM 336..360
FT /note="Helical; Name=6"
FT TOPO_DOM 361..367
FT /note="Extracellular"
FT TRANSMEM 368..397
FT /note="Helical; Name=7"
FT TOPO_DOM 398..444
FT /note="Cytoplasmic"
FT REGION 99..108
FT /note="Important for peptide agonist binding"
FT REGION 309..319
FT /note="Important for antagonist binding"
FT MOD_RES 330
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:14657255"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 30..54
FT DISULFID 44..87
FT DISULFID 68..102
FT DISULFID 217..287
FT VAR_SEQ 1..204
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.6"
FT /id="VSP_045434"
FT VAR_SEQ 41..81
FT /note="GLQCNASVDLIGTCWPRSPAGQLVVRPCPAFFYGVRYNTTN -> D (in
FT isoform CRF-R3)"
FT /evidence="ECO:0000303|PubMed:7811272"
FT /id="VSP_001996"
FT VAR_SEQ 146..174
FT /note="Missing (in isoform CRF-R2, isoform CRF-R3 and
FT isoform CRF-R4)"
FT /evidence="ECO:0000303|PubMed:10598591,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:19054851,
FT ECO:0000303|PubMed:7692441, ECO:0000303|PubMed:7811272,
FT ECO:0000303|PubMed:8243652, ECO:0000303|Ref.7"
FT /id="VSP_001997"
FT VAR_SEQ 385..398
FT /note="Missing (in isoform CRF-R4)"
FT /evidence="ECO:0000303|PubMed:10598591"
FT /id="VSP_001998"
FT MUTAGEN 232
FT /note="F->A: Nearly abolishes antagonist binding."
FT /evidence="ECO:0000269|PubMed:23863939"
FT MUTAGEN 235
FT /note="M->A: Strongly reduces antagonist binding."
FT /evidence="ECO:0000269|PubMed:23863939"
FT MUTAGEN 309
FT /note="L->A: Nearly abolishes antagonist binding."
FT /evidence="ECO:0000269|PubMed:23863939"
FT MUTAGEN 312
FT /note="N->A: Nearly abolishes antagonist binding."
FT /evidence="ECO:0000269|PubMed:23863939"
FT MUTAGEN 313
FT /note="F->A: Slightly reduces antagonist binding."
FT /evidence="ECO:0000269|PubMed:23863939"
FT MUTAGEN 316
FT /note="L->A: Strongly reduces antagonist binding."
FT /evidence="ECO:0000269|PubMed:23863939"
FT MUTAGEN 319
FT /note="I->A: Strongly reduces antagonist binding."
FT /evidence="ECO:0000269|PubMed:23863939"
FT MUTAGEN 356
FT /note="Y->A: Strongly reduces antagonist binding."
FT /evidence="ECO:0000269|PubMed:23863939"
FT MUTAGEN 384
FT /note="Q->A: Increases antagonist binding."
FT /evidence="ECO:0000269|PubMed:23863939"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:3EHT"
FT HELIX 28..32
FT /evidence="ECO:0007829|PDB:3EHU"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:2L27"
FT STRAND 62..67
FT /evidence="ECO:0007829|PDB:3EHU"
FT STRAND 70..74
FT /evidence="ECO:0007829|PDB:3EHU"
FT STRAND 81..87
FT /evidence="ECO:0007829|PDB:3EHU"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:2L27"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:3EHS"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:2L27"
FT HELIX 103..107
FT /evidence="ECO:0007829|PDB:3EHS"
FT HELIX 114..143
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:4K5Y"
FT HELIX 179..203
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 207..212
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 215..235
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 237..247
FT /evidence="ECO:0007829|PDB:6P9X"
FT STRAND 249..252
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 257..264
FT /evidence="ECO:0007829|PDB:6P9X"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 268..281
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 299..330
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 334..347
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 349..352
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 355..358
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 367..382
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 384..392
FT /evidence="ECO:0007829|PDB:6P9X"
FT HELIX 397..408
FT /evidence="ECO:0007829|PDB:6P9X"
SQ SEQUENCE 444 AA; 50719 MW; 7221AEFB0E7AA8ED CRC64;
MGGHPQLRLV KALLLLGLNP VSASLQDQHC ESLSLASNIS GLQCNASVDL IGTCWPRSPA
GQLVVRPCPA FFYGVRYNTT NNGYRECLAN GSWAARVNYS ECQEILNEEK KSKVHYHVAV
IINYLGHCIS LVALLVAFVL FLRLRPGCTH WGDQADGALE VGAPWSGAPF QVRRSIRCLR
NIIHWNLISA FILRNATWFV VQLTMSPEVH QSNVGWCRLV TAAYNYFHVT NFFWMFGEGC
YLHTAIVLTY STDRLRKWMF ICIGWGVPFP IIVAWAIGKL YYDNEKCWFG KRPGVYTDYI
YQGPMILVLL INFIFLFNIV RILMTKLRAS TTSETIQYRK AVKATLVLLP LLGITYMLFF
VNPGEDEVSR VVFIYFNSFL ESFQGFFVSV FYCFLNSEVR SAIRKRWHRW QDKHSIRARV
ARAMSIPTSP TRVSFHSIKQ STAV
