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Q60748 (CRFR2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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):
CRF-RB
Corticotropin-releasing hormone receptor 2
Short name=CRH-R-2
Short name=CRH-R2
Gene names
Name:Crhr2
Synonyms:Crf2r
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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.

Subunit structure

Monomer. Interacts with CRF, UCN, UCN2 and UCN3 By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Highly expressed in the heart. Also expressed in lungs, skeletal muscle, gastrointestinal tract, epididymis, and brain.

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 By similarity.

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 term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from direct assay Ref.4. Source: MGI

cellular response to corticotropin-releasing hormone stimulus

Inferred from direct assay PubMed 12032352Ref.4. Source: GOC

negative regulation of angiogenesis

Inferred from mutant phenotype PubMed 12032352. Source: MGI

negative regulation of cAMP-mediated signaling

Inferred from direct assay PubMed 19246489. Source: MGI

positive regulation of cAMP-mediated signaling

Inferred from direct assay PubMed 19246489. Source: MGI

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 19246489. Source: MGI

cell surface

Inferred from direct assay PubMed 19246489. Source: MGI

endoplasmic reticulum

Inferred from direct assay PubMed 19246489. Source: MGI

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionG-protein coupled receptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

corticotrophin-releasing factor receptor activity

Inferred from direct assay PubMed 12032352Ref.4. Source: MGI

hormone activity

Inferred from direct assay Ref.4. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform CRF2-alpha (identifier: Q60748-1)

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.
Isoform CRF2-beta (identifier: Q60748-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MDAALLLSLLEANCSLALAEELLLDGWGVPPDPE → MGTPGSLPSA...CHRTTIGNFS
Note: Contains a disulfide bond in positions 45-70.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 411411Corticotropin-releasing factor receptor 2
PRO_0000012821
Signal peptide1 – 1919Not cleaved By similarity

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...) Potential
Glycosylation411N-linked (GlcNAc...) Potential
Glycosylation741N-linked (GlcNAc...) Potential
Glycosylation861N-linked (GlcNAc...) Potential
Glycosylation941N-linked (GlcNAc...) Potential
Disulfide bond14 ↔ 50 By similarity
Disulfide bond40 ↔ 83 Ref.6 Ref.7 Ref.8
Disulfide bond64 ↔ 98 Ref.6 Ref.7 Ref.8
Disulfide bond184 ↔ 254 By similarity

Natural variations

Alternative sequence1 – 3434MDAAL…PPDPE → MGTPGSLPSAQLLLCLFSLL PVLQVAQPGQAPQDQPLWTL LEQYCHRTTIGNFS in isoform CRF2-beta.
VSP_053568

Experimental info

Mutagenesis451D → A: Disrupts internal salt bridge and abrogates ligand recognition. Ref.7
Sequence conflict1061Missing in AAC52243. Ref.3
Sequence conflict372 – 3732KR → NG in AAC52243. Ref.3
Sequence conflict376 – 3772RW → SG in AAC52174. Ref.2
Sequence conflict3881A → R in AAC52174. Ref.2
Isoform CRF2-beta:
Sequence conflict3 – 53TPG → QQI in AAC52174. Ref.2

Secondary structure

............. 411
Helix Strand Turn

Details...

Sequences

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

Last modified January 22, 2014. Version 2.
Checksum: C0EAD0BC6A064683

FASTA41147,623
        10         20         30         40         50         60 
MDAALLLSLL EANCSLALAE ELLLDGWGVP PDPEGPYTYC NTTLDQIGTC WPQSAPGALV 

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

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

       190        200        210        220        230        240 
EVWCRCITTI FNYFVVTNFF WMFVEGCYLH TAIVMTYSTE HLRKWLFLFI GWCIPCPIII 

       250        260        270        280        290        300 
AWAVGKLYYE NEQCWFGKEA GDLVDYIYQG PVMLVLLINF VFLFNIVRIL MTKLRASTTS 

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

       370        380        390        400        410 
FFNGEVRAAL RKRWHRWQDH HALRVPVARA MSIPTSPTRI SFHSIKQTAA V 

« Hide

Isoform CRF2-beta [UniParc].

Checksum: A6D9EDE575DB8061
Show »

FASTA43149,923

References

« Hide 'large scale' references
[1]"Identification of a second corticotropin-releasing factor receptor gene and characterization of a cDNA expressed in heart."
Perrin M., Donaldson C., Chen R., Blount A., Berggren T., Bilezikjian L., Sawchenko P., Vale W.
Proc. Natl. Acad. Sci. U.S.A. 92:2969-2973(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-BETA).
Tissue: Heart.
[2]"A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle."
Kishimoto T., Pearse R.V. II, Lin C.R., Rosenfeld M.G.
Proc. Natl. Acad. Sci. U.S.A. 92:1108-1112(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-BETA).
Strain: BALB/c.
Tissue: Heart.
[3]"Identification of a novel murine receptor for corticotropin-releasing hormone expressed in the heart."
Stenzel P., Kesterson R., Yeung W., Cone R.D., Rittenberg M.B., Stenzel-Poore M.P.
Mol. Endocrinol. 9:637-645(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-BETA).
Strain: BALB/c.
Tissue: Heart.
[4]"Mouse corticotropin-releasing factor receptor type 2alpha gene: isolation, distribution, pharmacological characterization and regulation by stress and glucocorticoids."
Chen A., Perrin M., Brar B., Li C., Jamieson P., DiGruccio M., Lewis K., Vale W.
Mol. Endocrinol. 19:441-458(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-ALPHA).
Strain: C57BL/6 X 129.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRF2-BETA).
Tissue: Brain.
[6]"NMR structure and peptide hormone binding site of the first extracellular domain of a type B1 G protein-coupled receptor."
Grace C.R., Perrin M.H., DiGruccio M.R., Miller C.L., Rivier J.E., Vale W.W., Riek R.
Proc. Natl. Acad. Sci. U.S.A. 101:12836-12841(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 39-133 (ISOFORM CRF2-BETA), DISULFIDE BONDS.
[7]"The three-dimensional structure of the N-terminal domain of corticotropin-releasing factor receptors: sushi domains and the B1 family of G protein-coupled receptors."
Perrin M.H., Grace C.R., Riek R., Vale W.W.
Ann. N. Y. Acad. Sci. 1070:105-119(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 39-133 (ISOFORM CRF2-BETA) IN COMPLEX WITH PEPTIDE LIGAND, DISULFIDE BONDS, MUTAGENESIS OF ASP-45.
[8]"Structure of the N-terminal domain of a type B1 G protein-coupled receptor in complex with a peptide ligand."
Grace C.R., Perrin M.H., Gulyas J., Digruccio M.R., Cantle J.P., Rivier J.E., Vale W.W., Riek R.
Proc. Natl. Acad. Sci. U.S.A. 104:4858-4863(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 39-133 (ISOFORM CRF2-BETA) IN COMPLEX WITH PEPTIDE LIGAND, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U17858 mRNA. Translation: AAA68026.1.
U21729 mRNA. Translation: AAC52174.1.
U19939 mRNA. Translation: AAC52243.1.
AY445512 mRNA. Translation: AAS07021.1.
BC137592 mRNA. Translation: AAI37593.1.
PIRA56726.
I49149.
I49279.
RefSeqNP_001275548.1. NM_001288619.1.
UniGeneMm.236081.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1U34NMR-A39-133[»]
2JNCNMR-A39-133[»]
2JNDNMR-A39-133[»]
ProteinModelPortalQ60748.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBQ60748.
ChEMBLCHEMBL2253.
GuidetoPHARMACOLOGY213.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ60748.

Proteomic databases

PRIDEQ60748.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID12922.
UCSCuc009cal.2. mouse. [Q60748-1]

Organism-specific databases

MGIMGI:894312. Crhr2.

Phylogenomic databases

eggNOGNOG295825.
HOGENOMHOG000230719.
HOVERGENHBG106921.
InParanoidQ60748.

Gene expression databases

CleanExMM_CRHR2.
GenevestigatorQ60748.

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

EvolutionaryTraceQ60748.
PROQ60748.
SOURCESearch...

Entry information

Entry nameCRFR2_MOUSE
AccessionPrimary (citable) accession number: Q60748
Secondary accession number(s): B9EHB5 expand/collapse secondary AC list , Q5GL24, Q60783, Q60808
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 22, 2014
Last modified: April 16, 2014
This is version 117 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries