Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P47866 (CRFR2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Corticotropin-releasing factor receptor 2

Short name=CRF-R-2
Short name=CRF-R2
Short name=CRFR-2
Alternative name(s):
Corticotropin-releasing hormone receptor 2
Short name=CRH-R-2
Short name=CRH-R2
Gene names
Name:Crhr2
Synonyms:Crf2r
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length411 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels. Ref.1

Subunit structure

Monomer. Interacts (via N-terminal extracellular domain) with CRF, UCN, UCN2 and UCN3 By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.1 Ref.5.

Tissue specificity

Predominantly expressed in limbic regions of the brain such as the lateral septum, the entorhinal cortex, the hypothalamic ventromedial nucleus and several amygdaloid nuclei. Also detectable in lung, kidney and heart. Ref.1

Domain

The transmembrane domain is composed of seven transmembrane helices that are arranged in V-shape. Transmembrane helix 7 assumes a sharply kinked structure By similarity.

The uncleaved pseudo signal peptide prevents receptor's oligomerization and coupling to G(i) subunits. It is also responsible for the rather low receptor localization at the plasma membrane By similarity.

Post-translational modification

A N-glycosylation site within the signal peptide impedes its proper cleavage and function.

Sequence similarities

Belongs to the G-protein coupled receptor 2 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin filament organization

Inferred from mutant phenotype PubMed 17194738. Source: RGD

catecholamine biosynthetic process

Inferred from mutant phenotype PubMed 17194738. Source: RGD

cellular response to glucocorticoid stimulus

Inferred from expression pattern PubMed 21106875. Source: RGD

cerebellum development

Inferred from expression pattern PubMed 16820012. Source: RGD

epithelial cell differentiation

Inferred from mutant phenotype PubMed 20551459. Source: RGD

feeding behavior

Non-traceable author statement PubMed 12446596. Source: RGD

gastric motility

Inferred from mutant phenotype PubMed 16012930. Source: RGD

hormone-mediated signaling pathway

Inferred from direct assay PubMed 12942143PubMed 19334530. Source: GOC

hypothalamus development

Inferred from expression pattern PubMed 20002962. Source: RGD

long-term synaptic potentiation

Inferred from mutant phenotype PubMed 17004937PubMed 19376201. Source: RGD

negative regulation of cAMP biosynthetic process

Inferred from direct assay PubMed 21277852. Source: RGD

negative regulation of calcium ion import

Inferred from mutant phenotype PubMed 19439178. Source: RGD

negative regulation of defecation

Inferred from mutant phenotype PubMed 21277852. Source: RGD

negative regulation of epinephrine secretion

Inferred from mutant phenotype PubMed 17194738. Source: RGD

negative regulation of feeding behavior

Inferred from direct assay PubMed 17050037. Source: RGD

negative regulation of follicle-stimulating hormone secretion

Inferred from mutant phenotype PubMed 19193717. Source: RGD

negative regulation of gene expression

Inferred from mutant phenotype PubMed 19193717. Source: RGD

negative regulation of insulin secretion involved in cellular response to glucose stimulus

Inferred from mutant phenotype PubMed 17360501. Source: RGD

negative regulation of luteinizing hormone secretion

Inferred from mutant phenotype PubMed 19193717. Source: RGD

negative regulation of norepinephrine secretion

Inferred from mutant phenotype PubMed 17194738. Source: RGD

positive regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype PubMed 19211730. Source: RGD

positive regulation of blood pressure

Inferred from mutant phenotype PubMed 20060787. Source: RGD

positive regulation of cAMP biosynthetic process

Inferred from direct assay PubMed 20682782. Source: RGD

positive regulation of cAMP metabolic process

Inferred from mutant phenotype PubMed 16005543. Source: RGD

positive regulation of gene expression

Inferred from mutant phenotype PubMed 19193717. Source: RGD

positive regulation of heart rate

Inferred from mutant phenotype PubMed 20060787. Source: RGD

positive regulation of interleukin-6 production

Inferred from mutant phenotype PubMed 19211730. Source: RGD

positive regulation of serotonin secretion

Inferred from mutant phenotype PubMed 20655906. Source: RGD

positive regulation of stress-activated MAPK cascade

Inferred from mutant phenotype PubMed 19211730. Source: RGD

protein kinase C-activating G-protein coupled receptor signaling pathway

Inferred from mutant phenotype PubMed 19439178. Source: RGD

regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype PubMed 21277852. Source: RGD

sensory perception of pain

Inferred from mutant phenotype PubMed 19065825. Source: RGD

skeletal muscle tissue growth

Inferred from direct assay PubMed 21235761. Source: RGD

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 16820012. Source: RGD

axon

Inferred from direct assay PubMed 16820012. Source: RGD

axon terminus

Inferred from direct assay PubMed 21481539. Source: RGD

cell body fiber

Inferred from direct assay PubMed 21277852. Source: RGD

dendrite

Inferred from direct assay PubMed 16820012. Source: RGD

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

neuronal cell body

Inferred from direct assay PubMed 21277852PubMed 21481539. Source: RGD

perikaryon

Inferred from direct assay PubMed 21453754. Source: RGD

plasma membrane

Inferred from direct assay PubMed 20682782. Source: RGD

rough endoplasmic reticulum

Inferred from direct assay PubMed 16820012. Source: RGD

varicosity

Inferred from direct assay PubMed 21481539. Source: RGD

   Molecular_functionG-protein coupled receptor activity

Traceable author statement PubMed 11784785. Source: RGD

corticotropin-releasing hormone receptor activity

Inferred from direct assay PubMed 12942143PubMed 19334530. Source: RGD

peptide hormone binding

Inferred from physical interaction PubMed 19334530. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform CRF2-alpha (identifier: P47866-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Major isoform.
Isoform CRF2-beta (identifier: P47866-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MDAALLLSLLEANCSLALAEELLLDGWGEPPDPE → MGHPGSLPSA...CHRTTTRNFS

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 411411Corticotropin-releasing factor receptor 2
PRO_0000012822
Signal peptide1 – 1919Not cleaved

Regions

Topological domain1 – 108108Extracellular By similarity
Transmembrane109 – 13931Helical; Name=1; By similarity
Topological domain140 – 1467Cytoplasmic By similarity
Transmembrane147 – 17125Helical; Name=2; By similarity
Topological domain172 – 18514Extracellular By similarity
Transmembrane186 – 21429Helical; Name=3; By similarity
Topological domain215 – 2217Cytoplasmic By similarity
Transmembrane222 – 24928Helical; Name=4; By similarity
Topological domain250 – 26516Extracellular By similarity
Transmembrane266 – 29126Helical; Name=5; By similarity
Topological domain292 – 30211Cytoplasmic By similarity
Transmembrane303 – 32725Helical; Name=6; By similarity
Topological domain328 – 3347Extracellular By similarity
Transmembrane335 – 36430Helical; Name=7; By similarity
Topological domain365 – 41147Cytoplasmic By similarity

Amino acid modifications

Glycosylation131N-linked (GlcNAc...) Ref.5
Glycosylation411N-linked (GlcNAc...) Potential
Glycosylation741N-linked (GlcNAc...) Potential
Glycosylation861N-linked (GlcNAc...) Potential
Glycosylation941N-linked (GlcNAc...) Potential
Disulfide bond14 ↔ 50 By similarity
Disulfide bond40 ↔ 83 By similarity
Disulfide bond64 ↔ 98 By similarity
Disulfide bond184 ↔ 254 By similarity

Natural variations

Alternative sequence1 – 3434MDAAL…PPDPE → MGHPGSLPSAQLLLCLYSLL PLLQVAQPGRPLQDQPLWTL LEQYCHRTTTRNFS in isoform CRF2-beta.
VSP_002001

Experimental info

Mutagenesis131N → A, F or I: Allows cleavage of signal peptide. Ref.5
Sequence conflict931V → I in AAC52159. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform CRF2-alpha [UniParc].

Last modified January 22, 2014. Version 2.
Checksum: F0BA7795F8C37AFE

FASTA41147,693
        10         20         30         40         50         60 
MDAALLLSLL EANCSLALAE ELLLDGWGEP PDPEGPYSYC NTTLDQIGTC WPQSAPGALV 

        70         80         90        100        110        120 
ERPCPEYFNG IKYNTTRNAY RECLENGTWA SRVNYSHCEP ILDDKQRKYD LHYRIALIIN 

       130        140        150        160        170        180 
YLGHCVSVVA LVAAFLLFLV LRSIRCLRNV IHWNLITTFI LRNITWFLLQ LIDHEVHEGN 

       190        200        210        220        230        240 
EVWCRCVTTI FNYFVVTNFF WMFVEGCYLH TAIVMTYSTE HLRKWLFLFI GWCIPCPIIV 

       250        260        270        280        290        300 
AWAVGKLYYE NEQCWFGKEP GDLVDYIYQG PIILVLLINF VFLFNIVRIL MTKLRASTTS 

       310        320        330        340        350        360 
ETIQYRKAVK ATLVLLPLLG ITYMLFFVNP GEDDLSQIVF IYFNSFLQSF QGFFVSVFYC 

       370        380        390        400        410 
FFNGEVRSAL RKRWHRWQDH HALRVPVARA MSIPTSPTRI SFHSIKQTAA V 

« Hide

Isoform CRF2-beta [UniParc].

Checksum: 593B8DE5E58B057D
Show »

FASTA43150,187

References

« Hide 'large scale' references
[1]"Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain."
Lovenberg T.W., Liaw C.W., Grigoriadis D.E., Clevenger W., Chalmers D.T., de Souza E.B., Oltersdorf T.
Proc. Natl. Acad. Sci. U.S.A. 92:836-840(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Strain: Sprague-Dawley.
Tissue: Hypothalamus and Lung.
[2]Erratum
Lovenberg T.W., Liaw C.W., Grigoriadis D.E., Clevenger W., Chalmers D.T., de Souza E.B., Oltersdorf T.
Proc. Natl. Acad. Sci. U.S.A. 92:5759-5759(1995)
[3]"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. expand/collapse author list , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
[4]Mural R.J., Li P.W., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S.H., Dew I., Evans C.A., Ferriera S., Flanigan M., Fosler C., Glodek A., Gu Z., Holt R.A., Jennings D., Kraft C.L., Lu F. expand/collapse author list , Nguyen T., Nusskern D.R., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Wang Z., Woodage T., Zheng X.H., Zhong F.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
[5]"The corticotropin-releasing factor receptor type 2a contains an N-terminal pseudo signal peptide."
Rutz C., Renner A., Alken M., Schulz K., Beyermann M., Wiesner B., Rosenthal W., Schulein R.
J. Biol. Chem. 281:24910-24921(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-13, MUTAGENESIS OF ASN-13, NON-CLEAVABLE SIGNAL SEQUENCE, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U16253 mRNA. Translation: AAC52159.1.
AABR06031050 Genomic DNA. No translation available.
CH474011 Genomic DNA. Translation: EDL88099.1.
PIRA55610.
RefSeqNP_073205.1. NM_022714.1.
UniGeneRn.10023.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249194. 7 interactions.

Chemistry

BindingDBP47866.
ChEMBLCHEMBL2111360.
GuidetoPHARMACOLOGY213.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP47866.

Proteomic databases

PRIDEP47866.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000033672; ENSRNOP00000035712; ENSRNOG00000011145. [P47866-1]
GeneID64680.
KEGGrno:64680.
UCSCRGD:70547. rat. [P47866-1]

Organism-specific databases

CTD1395.
RGD70547. Crhr2.

Phylogenomic databases

eggNOGNOG295825.
GeneTreeENSGT00750000117453.
HOGENOMHOG000230719.
HOVERGENHBG106921.
KOK04579.

Gene expression databases

GenevestigatorP47866.

Family and domain databases

InterProIPR017981. GPCR_2-like.
IPR003053. GPCR_2_CRF2_rcpt.
IPR003051. GPCR_2_CRF_rcpt.
IPR001879. GPCR_2_extracellular_dom.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]
PfamPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSPR01279. CRFRECEPTOR.
PR01281. CRFRECEPTOR2.
PR00249. GPCRSECRETIN.
SMARTSM00008. HormR. 1 hit.
[Graphical view]
PROSITEPS00649. G_PROTEIN_RECEP_F2_1. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio35584281.
PROP47866.

Entry information

Entry nameCRFR2_RAT
AccessionPrimary (citable) accession number: P47866
Secondary accession number(s): G3V948
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 22, 2014
Last modified: July 9, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries