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Protein

Corticotropin-releasing factor receptor 1

Gene

Crhr1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

  • corticotrophin-releasing factor receptor activity Source: UniProtKB
  • corticotropin-releasing hormone binding Source: RGD
  • corticotropin-releasing hormone receptor activity Source: RGD
  • G-protein alpha-subunit binding Source: RGD
  • G-protein coupled receptor activity Source: RGD
  • peptide binding Source: RGD
  • protein complex binding Source: RGD

GO - Biological processi

  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: RGD
  • adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: RGD
  • adrenal gland development Source: Ensembl
  • behavioral response to cocaine Source: RGD
  • behavioral response to ethanol Source: Ensembl
  • behavioral response to pain Source: RGD
  • cellular response to corticotropin-releasing hormone stimulus Source: UniProtKB
  • corticotropin secretion Source: UniProtKB
  • epithelial cell differentiation Source: RGD
  • fear response Source: Ensembl
  • feeding behavior Source: RGD
  • general adaptation syndrome, behavioral process Source: Ensembl
  • hormone-mediated signaling pathway Source: GOC
  • hypothalamus development Source: RGD
  • locomotory exploration behavior Source: RGD
  • long-term synaptic potentiation Source: RGD
  • memory Source: RGD
  • negative regulation of epinephrine secretion Source: RGD
  • negative regulation of feeding behavior Source: RGD
  • negative regulation of neuron death Source: RGD
  • negative regulation of voltage-gated calcium channel activity Source: Ensembl
  • neuropeptide signaling pathway Source: RGD
  • phospholipase C-activating G-protein coupled receptor signaling pathway Source: RGD
  • positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway Source: UniProtKB
  • positive regulation of cAMP biosynthetic process Source: RGD
  • positive regulation of cytosolic calcium ion concentration Source: RGD
  • positive regulation of mast cell degranulation Source: RGD
  • regulation of corticosterone secretion Source: UniProtKB
  • regulation of synaptic plasticity Source: RGD
  • response to electrical stimulus Source: RGD
  • response to hypoxia Source: RGD
  • response to immobilization stress Source: RGD
  • visual learning Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_287445. G alpha (s) signalling events.
REACT_323768. Class B/2 (Secretin family receptors).

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Crhr1
Synonyms:Crhr
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi61276. Crhr1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 11188ExtracellularBy similarityAdd
BLAST
Transmembranei112 – 14231Helical; Name=1By similarityAdd
BLAST
Topological domaini143 – 1497CytoplasmicBy similarity
Transmembranei150 – 17425Helical; Name=2By similarityAdd
BLAST
Topological domaini175 – 18915ExtracellularBy similarityAdd
BLAST
Transmembranei190 – 21829Helical; Name=3By similarityAdd
BLAST
Topological domaini219 – 2257CytoplasmicBy similarity
Transmembranei226 – 25328Helical; Name=4By similarityAdd
BLAST
Topological domaini254 – 26916ExtracellularBy similarityAdd
BLAST
Transmembranei270 – 29526Helical; Name=5By similarityAdd
BLAST
Topological domaini296 – 30611CytoplasmicBy similarityAdd
BLAST
Transmembranei307 – 33125Helical; Name=6By similarityAdd
BLAST
Topological domaini332 – 3387ExtracellularBy similarity
Transmembranei339 – 36830Helical; Name=7By similarityAdd
BLAST
Topological domaini369 – 41547CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  • apical part of cell Source: RGD
  • cytosol Source: GOC
  • dendrite Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • intrinsic component of plasma membrane Source: UniProtKB
  • membrane Source: RGD
  • multivesicular body Source: RGD
  • neuronal cell body Source: RGD
  • plasma membrane Source: RGD
  • trans-Golgi network Source: RGD
  • vesicle Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Add
BLAST
Chaini24 – 415392Corticotropin-releasing factor receptor 1PRO_0000012816Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi30 ↔ 541 Publication
Glycosylationi38 – 381N-linked (GlcNAc...)1 Publication
Disulfide bondi44 ↔ 871 Publication
Glycosylationi45 – 451N-linked (GlcNAc...)1 Publication
Disulfide bondi68 ↔ 1021 Publication
Glycosylationi78 – 781N-linked (GlcNAc...)1 Publication
Glycosylationi90 – 901N-linked (GlcNAc...)1 Publication
Glycosylationi98 – 981N-linked (GlcNAc...)1 Publication
Disulfide bondi188 ↔ 258By similarity
Modified residuei301 – 3011Phosphoserine; by PKABy similarity

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

PTM databases

PhosphoSiteiP35353.

Expressioni

Tissue specificityi

Detected in brain, especially in cerebellum. Detected in pituitary gland, and at lower levels in the olfactory bulb.1 Publication

Gene expression databases

ExpressionAtlasiP35353. baseline.
GenevisibleiP35353. RN.

Interactioni

Subunit structurei

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.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
UcnP550903EBI-9030306,EBI-9030248

Protein-protein interaction databases

BioGridi248692. 4 interactions.
IntActiP35353. 1 interaction.
STRINGi10116.ENSRNOP00000006764.

Structurei

3D structure databases

ProteinModelPortaliP35353.
SMRiP35353. Positions 20-116.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni99 – 10810Important for peptide agonist bindingBy similarity
Regioni280 – 29011Important for antagonist bindingBy similarityAdd
BLAST

Domaini

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).By similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG295825.
GeneTreeiENSGT00760000118800.
HOGENOMiHOG000230719.
HOVERGENiHBG106921.
InParanoidiP35353.
OMAiNYSQCQE.
OrthoDBiEOG7CRTPR.
PhylomeDBiP35353.
TreeFamiTF315710.

Family and domain databases

InterProiIPR017981. 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]
PfamiPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSiPR01279. CRFRECEPTOR.
PR01280. CRFRECEPTOR1.
PR00249. GPCRSECRETIN.
SMARTiSM00008. HormR. 1 hit.
[Graphical view]
PROSITEiPS00649. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P35353-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRRPQLRLV KALLLLGLNP VSTSLQDQRC ENLSLTSNVS GLQCNASVDL
60 70 80 90 100
IGTCWPRSPA GQLVVRPCPA FFYGVRYNTT NNGYRECLAN GSWAARVNYS
110 120 130 140 150
ECQEILNEEK KSKVHYHVAV IINYLGHCIS LVALLVAFVL FLRLRSIRCL
160 170 180 190 200
RNIIHWNLIS AFILRNATWF VVQLTVSPEV HQSNVAWCRL VTAAYNYFHV
210 220 230 240 250
TNFFWMFGEG CYLHTAIVLT YSTDRLRKWM FVCIGWGVPF PIIVAWAIGK
260 270 280 290 300
LHYDNEKCWF GKRPGVYTDY IYQGPMILVL LINFIFLFNI VRILMTKLRA
310 320 330 340 350
STTSETIQYR KAVKATLVLL PLLGITYMLF FVNPGEDEVS RVVFIYFNSF
360 370 380 390 400
LESFQGFFVS VFYCFLNSEV RSAIRKRWRR WQDKHSIRAR VARAMSIPTS
410
PTRVSFHSIK QSTAV
Length:415
Mass (Da):47,842
Last modified:June 1, 1994 - v1
Checksum:i48D6704B31D4C013
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L24096 mRNA. No translation available.
L25438 mRNA. Translation: AAA16441.1.
U53498
, U53486, U53487, U53488, U53489, U53490, U53491, U53492, U53493, U53494, U53495, U53496, U53497 Genomic DNA. Translation: AAC53519.1.
PIRiI58144.
RefSeqiNP_112261.1. NM_030999.4.
UniGeneiRn.10499.

Genome annotation databases

EnsembliENSRNOT00000006764; ENSRNOP00000006764; ENSRNOG00000004900.
GeneIDi58959.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L24096 mRNA. No translation available.
L25438 mRNA. Translation: AAA16441.1.
U53498
, U53486, U53487, U53488, U53489, U53490, U53491, U53492, U53493, U53494, U53495, U53496, U53497 Genomic DNA. Translation: AAC53519.1.
PIRiI58144.
RefSeqiNP_112261.1. NM_030999.4.
UniGeneiRn.10499.

3D structure databases

ProteinModelPortaliP35353.
SMRiP35353. Positions 20-116.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248692. 4 interactions.
IntActiP35353. 1 interaction.
STRINGi10116.ENSRNOP00000006764.

Chemistry

BindingDBiP35353.
ChEMBLiCHEMBL2111360.
GuidetoPHARMACOLOGYi212.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP35353.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000006764; ENSRNOP00000006764; ENSRNOG00000004900.
GeneIDi58959.

Organism-specific databases

CTDi1394.
RGDi61276. Crhr1.

Phylogenomic databases

eggNOGiNOG295825.
GeneTreeiENSGT00760000118800.
HOGENOMiHOG000230719.
HOVERGENiHBG106921.
InParanoidiP35353.
OMAiNYSQCQE.
OrthoDBiEOG7CRTPR.
PhylomeDBiP35353.
TreeFamiTF315710.

Enzyme and pathway databases

ReactomeiREACT_287445. G alpha (s) signalling events.
REACT_323768. Class B/2 (Secretin family receptors).

Miscellaneous databases

NextBioi611592.
PROiP35353.

Gene expression databases

ExpressionAtlasiP35353. baseline.
GenevisibleiP35353. RN.

Family and domain databases

InterProiIPR017981. 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]
PfamiPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSiPR01279. CRFRECEPTOR.
PR01280. CRFRECEPTOR1.
PR00249. GPCRSECRETIN.
SMARTiSM00008. HormR. 1 hit.
[Graphical view]
PROSITEiPS00649. 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]
ProtoNetiSearch...

Publicationsi

  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.

Entry informationi

Entry nameiCRFR1_RAT
AccessioniPrimary (citable) accession number: P35353
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 22, 2015
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.