CRFR2_RAT
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 03-AUG-2022, entry version 158.
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}.
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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 STRING; 10116.ENSRNOP00000014925; -.
DR BindingDB; P47866; -.
DR ChEMBL; CHEMBL3581; -.
DR DrugCentral; P47866; -.
DR GuidetoPHARMACOLOGY; 213; -.
DR GlyGen; P47866; 5 sites.
DR iPTMnet; P47866; -.
DR PhosphoSitePlus; P47866; -.
DR PaxDb; P47866; -.
DR Ensembl; ENSRNOT00000033672; ENSRNOP00000035712; ENSRNOG00000011145. [P47866-1]
DR GeneID; 64680; -.
DR KEGG; rno:64680; -.
DR UCSC; RGD:70547; rat. [P47866-1]
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 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 tissues.
DR ExpressionAtlas; P47866; baseline and differential.
DR Genevisible; P47866; RN.
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:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; IDA:RGD.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:RGD.
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:0051092; P:positive regulation of NF-kappaB transcription factor activity; 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:0019233; P:sensory perception of pain; IMP:RGD.
DR GO; GO:0048630; P:skeletal muscle tissue growth; IDA:RGD.
DR Gene3D; 4.10.1240.10; -; 1.
DR InterPro; IPR017981; GPCR_2-like.
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 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; 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 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 CRF2-
FT 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
