P47866 (CRFR2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	411 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	This is a receptor for corticotropin releasing factor. Shows high-affinity CRF binding. Also binds to urocortin I, II and III. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Subunit structure	Interacts (via N-terminal extracellular domain) with CRF, UCN, UCN2 and UCN3 By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein.
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.
Sequence similarities	Belongs to the G-protein coupled receptor 2 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin 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 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 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_component	Golgi apparatus 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 to membrane Inferred from electronic annotation. Source: UniProtKB-KW 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_function	G-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Potential
	Chain	18 – 411	394	Corticotropin-releasing factor receptor 2		PRO_0000012822
Regions
	Topological domain	18 – 118	101	Extracellular Potential
	Transmembrane	119 – 139	21	Helical; Name=1; Potential
	Topological domain	140 – 148	9	Cytoplasmic Potential
	Transmembrane	149 – 168	20	Helical; Name=2; Potential
	Topological domain	169 – 185	17	Extracellular Potential
	Transmembrane	186 – 209	24	Helical; Name=3; Potential
	Topological domain	210 – 223	14	Cytoplasmic Potential
	Transmembrane	224 – 245	22	Helical; Name=4; Potential
	Topological domain	246 – 264	19	Extracellular Potential
	Transmembrane	265 – 287	23	Helical; Name=5; Potential
	Topological domain	288 – 310	23	Cytoplasmic Potential
	Transmembrane	311 – 330	20	Helical; Name=6; Potential
	Topological domain	331 – 345	15	Extracellular Potential
	Transmembrane	346 – 365	20	Helical; Name=7; Potential
	Topological domain	366 – 411	46	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	41	1	N-linked (GlcNAc...) Potential
	Glycosylation	74	1	N-linked (GlcNAc...) Potential
	Glycosylation	86	1	N-linked (GlcNAc...) Potential
	Glycosylation	94	1	N-linked (GlcNAc...) Potential
	Disulfide bond	14 ↔ 50		By similarity
	Disulfide bond	40 ↔ 83		By similarity
	Disulfide bond	64 ↔ 98		By similarity
Natural variations
	Alternative sequence	1 – 34	34	MDAAL…PPDPE → MGHPGSLPSAQLLLCLYSLL PLLQVAQPGRPLQDQPLWTL LEQYCHRTTTRNFS in isoform CRF2-beta.		VSP_002001

Sequences

	Sequence		Length	Mass (Da)
	Isoform CRF2-alpha [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 1C6E85801BC94469	FASTA	411	47,707
	10 20 30 40 50 60 MDAALLLSLL EANCSLALAE ELLLDGWGEP PDPEGPYSYC NTTLDQIGTC WPQSAPGALV 70 80 90 100 110 120 ERPCPEYFNG IKYNTTRNAY RECLENGTWA SRINYSHCEP 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
	Isoform CRF2-beta [UniParc]. Checksum: B5EF7FF006813BEA	FASTA	431	50,201
	10 20 30 40 50 60 MGHPGSLPSA QLLLCLYSLL PLLQVAQPGR PLQDQPLWTL LEQYCHRTTT RNFSGPYSYC 70 80 90 100 110 120 NTTLDQIGTC WPQSAPGALV ERPCPEYFNG IKYNTTRNAY RECLENGTWA SRINYSHCEP 130 140 150 160 170 180 ILDDKQRKYD LHYRIALIIN YLGHCVSVVA LVAAFLLFLV LRSIRCLRNV IHWNLITTFI 190 200 210 220 230 240 LRNITWFLLQ LIDHEVHEGN EVWCRCVTTI FNYFVVTNFF WMFVEGCYLH TAIVMTYSTE 250 260 270 280 290 300 HLRKWLFLFI GWCIPCPIIV AWAVGKLYYE NEQCWFGKEP GDLVDYIYQG PIILVLLINF 310 320 330 340 350 360 VFLFNIVRIL MTKLRASTTS ETIQYRKAVK ATLVLLPLLG ITYMLFFVNP GEDDLSQIVF 370 380 390 400 410 420 IYFNSFLQSF QGFFVSVFYC FFNGEVRSAL RKRWHRWQDH HALRVPVARA MSIPTSPTRI 430 SFHSIKQTAA V

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]. 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)
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U16253 mRNA. Translation: AAC52159.1.
IPI	IPI00191135. IPI00231210.
PIR	A55610.
RefSeq	NP_073205.1. NM_022714.1.
UniGene	Rn.10023.
3D structure databases
ProteinModelPortal	P47866.
SMR	P47866. Positions 35-113.
ModBase	Search...
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P47866.
Proteomic databases
PRIDE	P47866.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	64680.
KEGG	rno:64680.
UCSC	RGD:70547. rat.
Organism-specific databases
CTD	1395.
RGD	70547. Crhr2.
Phylogenomic databases
eggNOG	NOG295825.
HOGENOM	HOG000230719.
HOVERGEN	HBG106921.
KO	K04579.
Gene expression databases
ArrayExpress	P47866.
Genevestigator	P47866.
GermOnline	ENSRNOG00000011145. Rattus norvegicus.
Family and domain databases
InterPro	IPR017981. 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]
PANTHER	PTHR12011:SF73. PTHR12011:SF73. 1 hit.
Pfam	PF00002. 7tm_2. 1 hit. PF02793. HRM. 1 hit. [Graphical view]
PRINTS	PR01279. CRFRECEPTOR. PR01281. CRFRECEPTOR2. PR00249. GPCRSECRETIN.
SMART	SM00008. HormR. 1 hit. [Graphical view]
PROSITE	PS00649. 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]
ProtoNet	Search...
Other
BindingDB	P47866.
ChEMBL	CHEMBL3581.
NextBio	613694.

Entry information

Entry name

CRFR2_RAT

Accession

Primary (citable) accession number: P47866

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	April 3, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program