CRFR2_MOUSE
ID CRFR2_MOUSE Reviewed; 411 AA.
AC Q60748; B9EHB5; Q5GL24; Q60783; Q60808;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 22-JAN-2014, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Corticotropin-releasing factor receptor 2;
DE Short=CRF-R-2;
DE Short=CRF-R2;
DE Short=CRFR-2;
DE AltName: Full=CRF-RB;
DE AltName: Full=Corticotropin-releasing hormone receptor 2;
DE Short=CRH-R-2;
DE Short=CRH-R2;
GN Name=Crhr2; Synonyms=Crf2r;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-BETA).
RC TISSUE=Heart;
RX PubMed=7708757; DOI=10.1073/pnas.92.7.2969;
RA Perrin M., Donaldson C., Chen R., Blount A., Berggren T., Bilezikjian L.,
RA Sawchenko P., Vale W.;
RT "Identification of a second corticotropin-releasing factor receptor gene
RT and characterization of a cDNA expressed in heart.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:2969-2973(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-BETA).
RC STRAIN=BALB/cJ; TISSUE=Heart;
RX PubMed=7755719; DOI=10.1073/pnas.92.4.1108;
RA Kishimoto T., Pearse R.V. II, Lin C.R., Rosenfeld M.G.;
RT "A sauvagine/corticotropin-releasing factor receptor expressed in heart and
RT skeletal muscle.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:1108-1112(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-BETA).
RC STRAIN=BALB/cJ; TISSUE=Heart;
RX PubMed=7565810; DOI=10.1210/mend.9.5.7565810;
RA Stenzel P., Kesterson R., Yeung W., Cone R.D., Rittenberg M.B.,
RA Stenzel-Poore M.P.;
RT "Identification of a novel murine receptor for corticotropin-releasing
RT hormone expressed in the heart.";
RL Mol. Endocrinol. 9:637-645(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-ALPHA).
RC STRAIN=C57BL/6 X 129;
RX PubMed=15514029; DOI=10.1210/me.2004-0300;
RA Chen A., Perrin M., Brar B., Li C., Jamieson P., DiGruccio M., Lewis K.,
RA Vale W.;
RT "Mouse corticotropin-releasing factor receptor type 2alpha gene: isolation,
RT distribution, pharmacological characterization and regulation by stress and
RT glucocorticoids.";
RL Mol. Endocrinol. 19:441-458(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRF2-BETA).
RC TISSUE=Brain;
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 [6]
RP STRUCTURE BY NMR OF 39-133 (ISOFORM CRF2-BETA), AND DISULFIDE BONDS.
RX PubMed=15326300; DOI=10.1073/pnas.0404702101;
RA Grace C.R., Perrin M.H., DiGruccio M.R., Miller C.L., Rivier J.E.,
RA Vale W.W., Riek R.;
RT "NMR structure and peptide hormone binding site of the first extracellular
RT domain of a type B1 G protein-coupled receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12836-12841(2004).
RN [7]
RP STRUCTURE BY NMR OF 39-133 (ISOFORM CRF2-BETA) IN COMPLEX WITH PEPTIDE
RP LIGAND, DISULFIDE BONDS, AND MUTAGENESIS OF ASP-45.
RX PubMed=16888152; DOI=10.1196/annals.1317.065;
RA Perrin M.H., Grace C.R., Riek R., Vale W.W.;
RT "The three-dimensional structure of the N-terminal domain of corticotropin-
RT releasing factor receptors: sushi domains and the B1 family of G protein-
RT coupled receptors.";
RL Ann. N. Y. Acad. Sci. 1070:105-119(2006).
RN [8]
RP STRUCTURE BY NMR OF 39-133 (ISOFORM CRF2-BETA) IN COMPLEX WITH PEPTIDE
RP LIGAND, AND DISULFIDE BONDS.
RX PubMed=17360332; DOI=10.1073/pnas.0700682104;
RA Grace C.R., Perrin M.H., Gulyas J., Digruccio M.R., Cantle J.P.,
RA Rivier J.E., Vale W.W., Riek R.;
RT "Structure of the N-terminal domain of a type B1 G protein-coupled receptor
RT in complex with a peptide ligand.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:4858-4863(2007).
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 -!- SUBUNIT: Monomer. Interacts with CRF, UCN, UCN2 and UCN3 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=CRF2-alpha;
CC IsoId=Q60748-1; Sequence=Displayed;
CC Name=CRF2-beta;
CC IsoId=Q60748-2; Sequence=VSP_053568;
CC -!- TISSUE SPECIFICITY: Highly expressed in the heart. Also expressed in
CC lungs, skeletal muscle, gastrointestinal tract, epididymis, and brain.
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:0000250}.
CC -!- MISCELLANEOUS: [Isoform CRF2-beta]: Contains a disulfide bond in
CC positions 45-70. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC {ECO:0000305}.
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DR EMBL; U17858; AAA68026.1; -; mRNA.
DR EMBL; U21729; AAC52174.1; -; mRNA.
DR EMBL; U19939; AAC52243.1; -; mRNA.
DR EMBL; AY445512; AAS07021.1; -; mRNA.
DR EMBL; BC137592; AAI37593.1; -; mRNA.
DR CCDS; CCDS85052.1; -. [Q60748-1]
DR CCDS; CCDS85053.1; -. [Q60748-2]
DR PIR; A56726; A56726.
DR PIR; I49149; I49149.
DR PIR; I49279; I49279.
DR RefSeq; NP_001275548.1; NM_001288619.1. [Q60748-1]
DR PDB; 1U34; NMR; -; A=35-113.
DR PDB; 2JNC; NMR; -; A=35-113.
DR PDB; 2JND; NMR; -; A=35-113.
DR PDBsum; 1U34; -.
DR PDBsum; 2JNC; -.
DR PDBsum; 2JND; -.
DR AlphaFoldDB; Q60748; -.
DR SMR; Q60748; -.
DR BioGRID; 198882; 5.
DR DIP; DIP-61295N; -.
DR IntAct; Q60748; 1.
DR STRING; 10090.ENSMUSP00000003568; -.
DR BindingDB; Q60748; -.
DR ChEMBL; CHEMBL2253; -.
DR DrugCentral; Q60748; -.
DR GuidetoPHARMACOLOGY; 213; -.
DR GlyGen; Q60748; 5 sites.
DR iPTMnet; Q60748; -.
DR PhosphoSitePlus; Q60748; -.
DR PaxDb; Q60748; -.
DR PRIDE; Q60748; -.
DR Antibodypedia; 12618; 657 antibodies from 36 providers.
DR DNASU; 12922; -.
DR Ensembl; ENSMUST00000213026; ENSMUSP00000148297; ENSMUSG00000003476. [Q60748-1]
DR GeneID; 12922; -.
DR KEGG; mmu:12922; -.
DR UCSC; uc009caj.3; mouse. [Q60748-1]
DR UCSC; uc009cal.3; mouse. [Q60748-2]
DR CTD; 1395; -.
DR MGI; MGI:894312; Crhr2.
DR VEuPathDB; HostDB:ENSMUSG00000003476; -.
DR eggNOG; KOG4564; Eukaryota.
DR GeneTree; ENSGT00940000156795; -.
DR InParanoid; Q60748; -.
DR OMA; RINYSHC; -.
DR Reactome; R-MMU-373080; Class B/2 (Secretin family receptors).
DR Reactome; R-MMU-418555; G alpha (s) signalling events.
DR BioGRID-ORCS; 12922; 1 hit in 57 CRISPR screens.
DR ChiTaRS; Crhr2; mouse.
DR EvolutionaryTrace; Q60748; -.
DR PRO; PR:Q60748; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q60748; protein.
DR Bgee; ENSMUSG00000003476; Expressed in hindlimb stylopod muscle and 93 other tissues.
DR ExpressionAtlas; Q60748; baseline and differential.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
DR GO; GO:0070852; C:cell body fiber; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISO:MGI.
DR GO; GO:0043196; C:varicosity; ISO:MGI.
DR GO; GO:0015056; F:corticotrophin-releasing factor receptor activity; IDA:MGI.
DR GO; GO:0043404; F:corticotropin-releasing hormone receptor activity; ISO:MGI.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
DR GO; GO:0005179; F:hormone activity; IDA:MGI.
DR GO; GO:0017046; F:peptide hormone binding; ISO:MGI.
DR GO; GO:0007015; P:actin filament organization; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0035482; P:gastric motility; ISO:MGI.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISO:MGI.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:MGI.
DR GO; GO:0090281; P:negative regulation of calcium ion import; ISO:MGI.
DR GO; GO:2000293; P:negative regulation of defecation; ISO:MGI.
DR GO; GO:0032811; P:negative regulation of epinephrine secretion; ISO:MGI.
DR GO; GO:2000252; P:negative regulation of feeding behavior; ISO:MGI.
DR GO; GO:0046882; P:negative regulation of follicle-stimulating hormone secretion; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0033685; P:negative regulation of luteinizing hormone secretion; ISO:MGI.
DR GO; GO:0010700; P:negative regulation of norepinephrine secretion; ISO:MGI.
DR GO; GO:0045777; P:positive regulation of blood pressure; ISO:MGI.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; ISO:MGI.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0010460; P:positive regulation of heart rate; ISO:MGI.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0014064; P:positive regulation of serotonin secretion; ISO:MGI.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; ISO:MGI.
DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0019233; P:sensory perception of pain; ISO:MGI.
DR GO; GO:0048630; P:skeletal muscle tissue growth; ISO:MGI.
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 3D-structure; 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_0000012821"
FT SIGNAL 1..19
FT /note="Not cleaved"
FT /evidence="ECO:0000250"
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:0000255"
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 DISULFID 64..98
FT DISULFID 184..254
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..34
FT /note="MDAALLLSLLEANCSLALAEELLLDGWGVPPDPE -> MGTPGSLPSAQLLL
FT CLFSLLPVLQVAQPGQAPQDQPLWTLLEQYCHRTTIGNFS (in isoform CRF2-
FT beta)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7565810, ECO:0000303|PubMed:7708757,
FT ECO:0000303|PubMed:7755719"
FT /id="VSP_053568"
FT MUTAGEN 45
FT /note="D->A: Disrupts internal salt bridge and abrogates
FT ligand recognition."
FT /evidence="ECO:0000269|PubMed:16888152"
FT CONFLICT 106
FT /note="Missing (in Ref. 3; AAC52243)"
FT /evidence="ECO:0000305"
FT CONFLICT 372..373
FT /note="KR -> NG (in Ref. 3; AAC52243)"
FT /evidence="ECO:0000305"
FT CONFLICT 376..377
FT /note="RW -> SG (in Ref. 2; AAC52174)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="A -> R (in Ref. 2; AAC52174)"
FT /evidence="ECO:0000305"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:1U34"
FT STRAND 58..63
FT /evidence="ECO:0007829|PDB:2JNC"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:1U34"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:2JNC"
FT TURN 85..87
FT /evidence="ECO:0007829|PDB:2JNC"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:1U34"
FT CONFLICT Q60748-2:3..5
FT /note="TPG -> QQI (in Ref. 2; AAC52174)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 411 AA; 47623 MW; C0EAD0BC6A064683 CRC64;
MDAALLLSLL EANCSLALAE ELLLDGWGVP PDPEGPYTYC NTTLDQIGTC WPQSAPGALV
ERPCPEYFNG IKYNTTRNAY RECLENGTWA SRVNYSHCEP ILDDKQRKYD LHYRIALIVN
YLGHCVSVVA LVAAFLLFLV LRSIRCLRNV IHWNLITTFI LRNIAWFLLQ LIDHEVHEGN
EVWCRCITTI FNYFVVTNFF WMFVEGCYLH TAIVMTYSTE HLRKWLFLFI GWCIPCPIII
AWAVGKLYYE NEQCWFGKEA GDLVDYIYQG PVMLVLLINF VFLFNIVRIL MTKLRASTTS
ETIQYRKAVK ATLVLLPLLG ITYMLFFVNP GEDDLSQIVF IYFNSFLQSF QGFFVSVFYC
FFNGEVRAAL RKRWHRWQDH HALRVPVARA MSIPTSPTRI SFHSIKQTAA V
