ID CRFR2_RAT Reviewed; 411 AA. AC P47866; G3V948; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 22-JAN-2014, sequence version 2. DT 27-MAR-2024, entry version 167. DE RecName: Full=Corticotropin-releasing factor receptor 2; DE Short=CRF-R-2; DE Short=CRF-R2; DE Short=CRFR-2; DE AltName: Full=Corticotropin-releasing hormone receptor 2; DE Short=CRH-R-2; DE Short=CRH-R2; GN Name=Crhr2; Synonyms=Crf2r; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC STRAIN=Sprague-Dawley; TISSUE=Hypothalamus, and Lung; RX PubMed=7846062; DOI=10.1073/pnas.92.3.836; RA Lovenberg T.W., Liaw C.W., Grigoriadis D.E., Clevenger W., Chalmers D.T., RA de Souza E.B., Oltersdorf T.; RT "Cloning and characterization of a functionally distinct corticotropin- RT releasing factor receptor subtype from rat brain."; RL Proc. Natl. Acad. Sci. U.S.A. 92:836-840(1995). RN [2] RP ERRATUM OF PUBMED:7846062. RA Lovenberg T.W., Liaw C.W., Grigoriadis D.E., Clevenger W., Chalmers D.T., RA de Souza E.B., Oltersdorf T.; RL Proc. Natl. Acad. Sci. U.S.A. 92:5759-5759(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RA Mural R.J., Li P.W., Adams M.D., Amanatides P.G., Baden-Tillson H., RA Barnstead M., Chin S.H., Dew I., Evans C.A., Ferriera S., Flanigan M., RA Fosler C., Glodek A., Gu Z., Holt R.A., Jennings D., Kraft C.L., Lu F., RA Nguyen T., Nusskern D.R., Pfannkoch C.M., Sitter C., Sutton G.G., RA Venter J.C., Wang Z., Woodage T., Zheng X.H., Zhong F.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP GLYCOSYLATION AT ASN-13, MUTAGENESIS OF ASN-13, NON-CLEAVABLE SIGNAL RP SEQUENCE, AND SUBCELLULAR LOCATION. RX PubMed=16766521; DOI=10.1074/jbc.m601554200; RA Rutz C., Renner A., Alken M., Schulz K., Beyermann M., Wiesner B., RA Rosenthal W., Schulein R.; RT "The corticotropin-releasing factor receptor type 2a contains an N-terminal RT pseudo signal peptide."; RL J. Biol. Chem. 281:24910-24921(2006). CC -!- FUNCTION: G-protein coupled receptor for CRH (corticotropin-releasing CC factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. CC Ligand 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 {ECO:0000269|PubMed:7846062}. CC -!- SUBUNIT: Monomer. Interacts (via N-terminal extracellular domain) with CC CRF, UCN, UCN2 and UCN3 (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16766521, CC ECO:0000269|PubMed:7846062}; Multi-pass membrane protein CC {ECO:0000269|PubMed:16766521, ECO:0000269|PubMed:7846062}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=CRF2-alpha; CC IsoId=P47866-1; Sequence=Displayed; CC Name=CRF2-beta; CC IsoId=P47866-2; Sequence=VSP_002001; CC -!- TISSUE SPECIFICITY: Predominantly expressed in limbic regions of the CC brain such as the lateral septum, the entorhinal cortex, the CC hypothalamic ventromedial nucleus and several amygdaloid nuclei. Also CC detectable in lung, kidney and heart. {ECO:0000269|PubMed:7846062}. 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 (By similarity). {ECO:0000250}. CC -!- DOMAIN: The uncleaved pseudo signal peptide prevents receptor's CC oligomerization and coupling to G(i) subunits. It is also responsible CC for the rather low receptor localization at the plasma membrane (By CC similarity). {ECO:0000250}. CC -!- PTM: A N-glycosylation site within the signal peptide impedes its CC proper cleavage and function. {ECO:0000269|PubMed:16766521}. CC -!- MISCELLANEOUS: [Isoform CRF2-alpha]: Major isoform. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U16253; AAC52159.1; -; mRNA. DR EMBL; AABR06031050; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH474011; EDL88099.1; -; Genomic_DNA. DR PIR; A55610; A55610. DR RefSeq; NP_073205.1; NM_022714.1. [P47866-1] DR AlphaFoldDB; P47866; -. DR SMR; P47866; -. DR BioGRID; 249194; 7. DR IntAct; P47866; 1. DR MINT; P47866; -. DR STRING; 10116.ENSRNOP00000014925; -. DR BindingDB; P47866; -. DR ChEMBL; CHEMBL3581; -. DR DrugCentral; P47866; -. DR GuidetoPHARMACOLOGY; 213; -. DR GlyCosmos; P47866; 5 sites, No reported glycans. DR GlyGen; P47866; 5 sites. DR iPTMnet; P47866; -. DR PhosphoSitePlus; P47866; -. DR PaxDb; 10116-ENSRNOP00000014925; -. DR Ensembl; ENSRNOT00000033672.4; ENSRNOP00000035712.2; ENSRNOG00000011145.9. [P47866-1] DR Ensembl; ENSRNOT00055018256; ENSRNOP00055014665; ENSRNOG00055010798. [P47866-1] DR Ensembl; ENSRNOT00060038158; ENSRNOP00060031451; ENSRNOG00060021958. [P47866-1] DR GeneID; 64680; -. DR KEGG; rno:64680; -. DR UCSC; RGD:70547; rat. [P47866-1] DR AGR; RGD:70547; -. DR CTD; 1395; -. DR RGD; 70547; Crhr2. DR eggNOG; KOG4564; Eukaryota. DR GeneTree; ENSGT00940000156795; -. DR HOGENOM; CLU_002753_4_1_1; -. DR InParanoid; P47866; -. DR OrthoDB; 5345963at2759; -. DR Reactome; R-RNO-373080; Class B/2 (Secretin family receptors). DR PRO; PR:P47866; -. DR Proteomes; UP000002494; Chromosome 4. DR Proteomes; UP000234681; Chromosome 4. DR Bgee; ENSRNOG00000011145; Expressed in esophagus and 14 other cell types or tissues. DR ExpressionAtlas; P47866; baseline and differential. DR GO; GO:0030424; C:axon; IDA:RGD. DR GO; GO:0043679; C:axon terminus; IDA:RGD. DR GO; GO:0070852; C:cell body fiber; IDA:RGD. DR GO; GO:0030425; C:dendrite; IDA:RGD. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0043204; C:perikaryon; IDA:RGD. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0043196; C:varicosity; IDA:RGD. DR GO; GO:0015056; F:corticotrophin-releasing factor receptor activity; ISO:RGD. DR GO; GO:0043404; F:corticotropin-releasing hormone receptor activity; IDA:RGD. DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central. DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:RGD. DR GO; GO:0005179; F:hormone activity; ISO:RGD. DR GO; GO:0017046; F:peptide hormone binding; IPI:RGD. DR GO; GO:0007015; P:actin filament organization; IMP:RGD. DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0042423; P:catecholamine biosynthetic process; IMP:RGD. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro. DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEP:RGD. DR GO; GO:0021549; P:cerebellum development; IEP:RGD. DR GO; GO:0030855; P:epithelial cell differentiation; IMP:RGD. DR GO; GO:0007631; P:feeding behavior; NAS:RGD. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD. DR GO; GO:0035482; P:gastric motility; IMP:RGD. DR GO; GO:0021854; P:hypothalamus development; IEP:RGD. DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:RGD. DR GO; GO:0016525; P:negative regulation of angiogenesis; ISO:RGD. DR GO; GO:0090281; P:negative regulation of calcium ion import; IMP:RGD. DR GO; GO:2000293; P:negative regulation of defecation; IMP:RGD. DR GO; GO:0032811; P:negative regulation of epinephrine secretion; IMP:RGD. DR GO; GO:2000252; P:negative regulation of feeding behavior; IDA:RGD. DR GO; GO:0046882; P:negative regulation of follicle-stimulating hormone secretion; IMP:RGD. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:RGD. DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:RGD. DR GO; GO:0033685; P:negative regulation of luteinizing hormone secretion; IMP:RGD. DR GO; GO:0010700; P:negative regulation of norepinephrine secretion; IMP:RGD. DR GO; GO:0045777; P:positive regulation of blood pressure; IMP:RGD. DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IDA:RGD. DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IMP:RGD. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD. DR GO; GO:0010460; P:positive regulation of heart rate; IMP:RGD. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:RGD. DR GO; GO:0014064; P:positive regulation of serotonin secretion; IMP:RGD. DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IMP:RGD. DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; IMP:RGD. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:RGD. DR GO; GO:0007165; P:signal transduction; ISO:RGD. DR GO; GO:0048630; P:skeletal muscle tissue growth; IDA:RGD. DR Gene3D; 4.10.1240.10; GPCR, family 2, extracellular hormone receptor domain; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR017981; GPCR_2-like_7TM. DR InterPro; IPR003053; GPCR_2_CRF2_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 PANTHER; PTHR45620:SF19; CORTICOTROPIN-RELEASING FACTOR RECEPTOR 2; 1. DR PANTHER; PTHR45620; PDF RECEPTOR-LIKE PROTEIN-RELATED; 1. DR Pfam; PF00002; 7tm_2; 1. DR Pfam; PF02793; HRM; 1. DR PRINTS; PR01279; CRFRECEPTOR. DR PRINTS; PR01281; CRFRECEPTOR2. DR PRINTS; PR00249; GPCRSECRETIN. DR SMART; SM00008; HormR; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR SUPFAM; SSF111418; Hormone receptor domain; 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. DR Genevisible; P47866; RN. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Disulfide bond; KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor; KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix. FT CHAIN 1..411 FT /note="Corticotropin-releasing factor receptor 2" FT /id="PRO_0000012822" FT SIGNAL 1..19 FT /note="Not cleaved" FT TOPO_DOM 1..108 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 109..139 FT /note="Helical; Name=1" FT /evidence="ECO:0000250" FT TOPO_DOM 140..146 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 147..171 FT /note="Helical; Name=2" FT /evidence="ECO:0000250" FT TOPO_DOM 172..185 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 186..214 FT /note="Helical; Name=3" FT /evidence="ECO:0000250" FT TOPO_DOM 215..221 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 222..249 FT /note="Helical; Name=4" FT /evidence="ECO:0000250" FT TOPO_DOM 250..265 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 266..291 FT /note="Helical; Name=5" FT /evidence="ECO:0000250" FT TOPO_DOM 292..302 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 303..327 FT /note="Helical; Name=6" FT /evidence="ECO:0000250" FT TOPO_DOM 328..334 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 335..364 FT /note="Helical; Name=7" FT /evidence="ECO:0000250" FT TOPO_DOM 365..411 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT CARBOHYD 13 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16766521" FT CARBOHYD 41 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 74 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 86 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 94 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 14..50 FT /evidence="ECO:0000250" FT DISULFID 40..83 FT /evidence="ECO:0000250" FT DISULFID 64..98 FT /evidence="ECO:0000250" FT DISULFID 184..254 FT /evidence="ECO:0000250" FT VAR_SEQ 1..34 FT /note="MDAALLLSLLEANCSLALAEELLLDGWGEPPDPE -> MGHPGSLPSAQLLL FT CLYSLLPLLQVAQPGRPLQDQPLWTLLEQYCHRTTTRNFS (in isoform FT CRF2-beta)" FT /evidence="ECO:0000305" FT /id="VSP_002001" FT MUTAGEN 13 FT /note="N->A,F,I: Allows cleavage of signal peptide." FT /evidence="ECO:0000269|PubMed:16766521" FT CONFLICT 93 FT /note="V -> I (in Ref. 1; AAC52159)" FT /evidence="ECO:0000305" SQ SEQUENCE 411 AA; 47693 MW; F0BA7795F8C37AFE CRC64; MDAALLLSLL EANCSLALAE ELLLDGWGEP PDPEGPYSYC NTTLDQIGTC WPQSAPGALV ERPCPEYFNG IKYNTTRNAY RECLENGTWA SRVNYSHCEP ILDDKQRKYD LHYRIALIIN YLGHCVSVVA LVAAFLLFLV LRSIRCLRNV IHWNLITTFI LRNITWFLLQ LIDHEVHEGN EVWCRCVTTI FNYFVVTNFF WMFVEGCYLH TAIVMTYSTE HLRKWLFLFI GWCIPCPIIV AWAVGKLYYE NEQCWFGKEP GDLVDYIYQG PIILVLLINF VFLFNIVRIL MTKLRASTTS ETIQYRKAVK ATLVLLPLLG ITYMLFFVNP GEDDLSQIVF IYFNSFLQSF QGFFVSVFYC FFNGEVRSAL RKRWHRWQDH HALRVPVARA MSIPTSPTRI SFHSIKQTAA V //