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P35353 (CRFR1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 117. 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·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Corticotropin-releasing factor receptor 1

Short name=CRF-R-1
Short name=CRF-R1
Short name=CRFR-1
Alternative name(s):
Corticotropin-releasing hormone receptor 1
Short name=CRH-R-1
Short name=CRH-R1
Gene names
Name:Crhr1
Synonyms:Crhr
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length415 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

G-protein coupled receptor for CRH (corticotropin-releasing factor) and UCN (urocortin). Has high affinity for CRH and 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. Inhibits the activity of the calcium channel CACNA1H. Required for normal embryonic development of the adrenal gland and for normal hormonal responses to stress. Plays a role in the response to anxiogenic stimuli. Ref.1 Ref.2 Ref.4

Subunit structure

Interacts (via N-terminal extracellular domain) with CRH and UCN. Interacts with DLG1; this inhibits endocytosis of CRHR1 after agonist binding By similarity. Heterodimer; heterodimerizes with GPER1. Ref.5

Subcellular location

Cell membrane; Multi-pass membrane protein. Endosome By similarity. Note: Agonist-binding promotes endocytosis By similarity. Ref.1 Ref.2

Tissue specificity

Detected in brain, especially in cerebellum. Detected in pituitary gland, and at lower levels in the olfactory bulb. Ref.2

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.

Post-translational modification

C-terminal Ser or Thr residues may be phosphorylated.

Phosphorylation at Ser-301 by PKA prevents maximal coupling to Gq-protein, and thereby negatively regulates downstream signaling By similarity.

Sequence similarities

Belongs to the G-protein coupled receptor 2 family.

Ontologies

Keywords
   Cellular componentCell membrane
Endosome
Membrane
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-activating G-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 15932935. Source: RGD

adenylate cyclase-modulating G-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 11784785. Source: RGD

adrenal gland development

Inferred from electronic annotation. Source: Ensembl

behavioral response to cocaine

Inferred from mutant phenotype PubMed 21813699. Source: RGD

behavioral response to ethanol

Inferred from electronic annotation. Source: Ensembl

behavioral response to pain

Inferred from mutant phenotype PubMed 17550594. Source: RGD

cellular response to corticotropin-releasing hormone stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

corticotropin secretion

Inferred from sequence or structural similarity. Source: UniProtKB

epithelial cell differentiation

Inferred from mutant phenotype PubMed 20551459. Source: RGD

fear response

Inferred from electronic annotation. Source: Ensembl

general adaptation syndrome, behavioral process

Inferred from electronic annotation. Source: Ensembl

hormone-mediated signaling pathway

Inferred from direct assay PubMed 12942143. Source: GOC

hypothalamus development

Inferred from expression pattern PubMed 20002962. Source: RGD

locomotory exploration behavior

Inferred from mutant phenotype PubMed 9299637. Source: RGD

long-term synaptic potentiation

Inferred from mutant phenotype PubMed 19376201. Source: RGD

memory

Inferred from mutant phenotype PubMed 15932935. Source: RGD

negative regulation of epinephrine secretion

Inferred from mutant phenotype PubMed 12606499. Source: RGD

negative regulation of feeding behavior

Inferred from mutant phenotype PubMed 14512273. Source: RGD

negative regulation of neuron death

Inferred from mutant phenotype PubMed 11784785. Source: RGD

negative regulation of voltage-gated calcium channel activity

Inferred from electronic annotation. Source: Ensembl

neuropeptide signaling pathway

Inferred from direct assay PubMed 11784785. Source: RGD

phospholipase C-activating G-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 15932935. Source: RGD

positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cAMP biosynthetic process

Inferred from mutant phenotype PubMed 20682782. Source: RGD

positive regulation of cytosolic calcium ion concentration

Inferred from mutant phenotype PubMed 16513211PubMed 18209484. Source: RGD

positive regulation of mast cell degranulation

Inferred from mutant phenotype PubMed 18209484. Source: RGD

regulation of corticosterone secretion

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of synaptic plasticity

Inferred from mutant phenotype PubMed 17079348. Source: RGD

response to electrical stimulus

Inferred from mutant phenotype PubMed 17015825. Source: RGD

response to hypoxia

Inferred from mutant phenotype PubMed 16099461. Source: RGD

response to immobilization stress

Inferred from expression pattern PubMed 21664419. Source: RGD

visual learning

Inferred from mutant phenotype PubMed 15932935. Source: RGD

   Cellular_componentapical part of cell

Inferred from direct assay PubMed 12911751. Source: RGD

dendrite

Inferred from direct assay PubMed 12911751. Source: RGD

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intrinsic component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

membrane

Inferred from direct assay PubMed 15932935. Source: RGD

multivesicular body

Inferred from direct assay PubMed 12911751. Source: RGD

neuronal cell body

Inferred from direct assay PubMed 12911751. Source: RGD

plasma membrane

Inferred from direct assay PubMed 21277852. Source: RGD

trans-Golgi network

Inferred from direct assay PubMed 12911751. Source: RGD

vesicle

Inferred from direct assay PubMed 12911751. Source: RGD

   Molecular_functionG-protein alpha-subunit binding

Inferred from physical interaction PubMed 20548297. Source: RGD

G-protein coupled receptor activity

Inferred from direct assay PubMed 11902119. Source: RGD

corticotrophin-releasing factor receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

corticotropin-releasing hormone binding

Inferred from direct assay PubMed 12942143. Source: RGD

corticotropin-releasing hormone receptor activity

Inferred from direct assay PubMed 12942143. Source: RGD

peptide binding

Inferred from direct assay PubMed 15049707. Source: RGD

protein binding

Inferred from physical interaction PubMed 24290358. Source: IntAct

protein complex binding

Inferred from physical interaction PubMed 20548297. Source: RGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

UcnP550903EBI-9030306,EBI-9030248

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323
Chain24 – 415392Corticotropin-releasing factor receptor 1
PRO_0000012816

Regions

Topological domain24 – 11188Extracellular By similarity
Transmembrane112 – 14231Helical; Name=1; By similarity
Topological domain143 – 1497Cytoplasmic By similarity
Transmembrane150 – 17425Helical; Name=2; By similarity
Topological domain175 – 18915Extracellular By similarity
Transmembrane190 – 21829Helical; Name=3; By similarity
Topological domain219 – 2257Cytoplasmic By similarity
Transmembrane226 – 25328Helical; Name=4; By similarity
Topological domain254 – 26916Extracellular By similarity
Transmembrane270 – 29526Helical; Name=5; By similarity
Topological domain296 – 30611Cytoplasmic By similarity
Transmembrane307 – 33125Helical; Name=6; By similarity
Topological domain332 – 3387Extracellular By similarity
Transmembrane339 – 36830Helical; Name=7; By similarity
Topological domain369 – 41547Cytoplasmic By similarity
Region99 – 10810Important for peptide agonist binding By similarity
Region280 – 29011Important for antagonist binding By similarity

Amino acid modifications

Modified residue3011Phosphoserine; by PKA By similarity
Glycosylation381N-linked (GlcNAc...) Ref.4
Glycosylation451N-linked (GlcNAc...) Ref.4
Glycosylation781N-linked (GlcNAc...) Ref.4
Glycosylation901N-linked (GlcNAc...) Ref.4
Glycosylation981N-linked (GlcNAc...) Ref.4
Disulfide bond30 ↔ 54 Ref.4
Disulfide bond44 ↔ 87 Ref.4
Disulfide bond68 ↔ 102 Ref.4
Disulfide bond188 ↔ 258 By similarity

Sequences

Sequence LengthMass (Da)Tools
P35353 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: 48D6704B31D4C013

FASTA41547,842
        10         20         30         40         50         60 
MGRRPQLRLV KALLLLGLNP VSTSLQDQRC ENLSLTSNVS GLQCNASVDL IGTCWPRSPA 

        70         80         90        100        110        120 
GQLVVRPCPA FFYGVRYNTT NNGYRECLAN GSWAARVNYS ECQEILNEEK KSKVHYHVAV 

       130        140        150        160        170        180 
IINYLGHCIS LVALLVAFVL FLRLRSIRCL RNIIHWNLIS AFILRNATWF VVQLTVSPEV 

       190        200        210        220        230        240 
HQSNVAWCRL VTAAYNYFHV TNFFWMFGEG CYLHTAIVLT YSTDRLRKWM FVCIGWGVPF 

       250        260        270        280        290        300 
PIIVAWAIGK LHYDNEKCWF GKRPGVYTDY IYQGPMILVL LINFIFLFNI VRILMTKLRA 

       310        320        330        340        350        360 
STTSETIQYR KAVKATLVLL PLLGITYMLF FVNPGEDEVS RVVFIYFNSF LESFQGFFVS 

       370        380        390        400        410 
VFYCFLNSEV RSAIRKRWRR WQDKHSIRAR VARAMSIPTS PTRVSFHSIK QSTAV 

« Hide

References

[1]"Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor."
Perrin M.H., Donaldson C.J., Chen R., Lewis K.A., Vale W.W.
Endocrinology 133:3058-3061(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
Strain: Sprague-Dawley.
Tissue: Brain.
[2]"Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain."
Chang C.P., Pearse R.V. II, O'Connell S., Rosenfeld M.G.
Neuron 11:1187-1195(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Strain: Sprague-Dawley.
Tissue: Cerebellum.
[3]"The genomic structure of the rat corticotropin releasing factor receptor. A member of the class II G protein-coupled receptors."
Tsai-Morris C.-H., Buczko E., Geng Y., Gamboa-Pinto A., Dufau M.L.
J. Biol. Chem. 271:14519-14525(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Testis.
[4]"Functional and protein chemical characterization of the N-terminal domain of the rat corticotropin-releasing factor receptor 1."
Hofmann B.A., Sydow S., Jahn O., van Werven L., Liepold T., Eckart K., Spiess J.
Protein Sci. 10:2050-2062(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISULFIDE BONDS, GLYCOSYLATION AT ASN-38; ASN-45; ASN-78; ASN-90 AND ASN-98.
[5]"Post-synaptic density-95 (PSD-95) binding capacity of G-protein-coupled receptor 30 (GPR30), an estrogen receptor that can be identified in hippocampal dendritic spines."
Akama K.T., Thompson L.I., Milner T.A., McEwen B.S.
J. Biol. Chem. 288:6438-6450(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L24096 mRNA. No translation available.
L25438 mRNA. Translation: AAA16441.1.
U53498 expand/collapse EMBL AC list , U53486, U53487, U53488, U53489, U53490, U53491, U53492, U53493, U53494, U53495, U53496, U53497 Genomic DNA. Translation: AAC53519.1.
PIRI58144.
RefSeqNP_112261.1. NM_030999.3.
UniGeneRn.10499.

3D structure databases

ProteinModelPortalP35353.
SMRP35353. Positions 20-116.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248692. 4 interactions.
IntActP35353. 1 interaction.
STRING10116.ENSRNOP00000060025.

Chemistry

BindingDBP35353.
ChEMBLCHEMBL2111360.
GuidetoPHARMACOLOGY212.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP35353.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000006764; ENSRNOP00000006764; ENSRNOG00000004900.
GeneID58959.
KEGGrno:58959.

Organism-specific databases

CTD1394.
RGD61276. Crhr1.

Phylogenomic databases

eggNOGNOG295825.
GeneTreeENSGT00750000117453.
HOGENOMHOG000230719.
HOVERGENHBG106921.
InParanoidP35353.
KOK04578.
OMAVGWCRLV.
OrthoDBEOG7CRTPR.
PhylomeDBP35353.
TreeFamTF315710.

Gene expression databases

GenevestigatorP35353.

Family and domain databases

InterProIPR017981. GPCR_2-like.
IPR003052. GPCR_2_CRF1_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.
PR01280. CRFRECEPTOR1.
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

NextBio611592.
PROP35353.

Entry information

Entry nameCRFR1_RAT
AccessionPrimary (citable) accession number: P35353
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: June 11, 2014
This is version 117 of the entry and version 1 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