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Protein

Corticotropin-releasing factor receptor 1

Gene

Crhr1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

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: RGD
  • behavioral response to cocaine Source: RGD
  • behavioral response to ethanol Source: RGD
  • behavioral response to pain Source: RGD
  • cell surface receptor signaling pathway Source: InterPro
  • cellular response to corticotropin-releasing hormone stimulus Source: UniProtKB
  • corticotropin secretion Source: UniProtKB
  • epithelial cell differentiation Source: RGD
  • fear response Source: RGD
  • feeding behavior Source: RGD
  • general adaptation syndrome, behavioral process Source: RGD
  • 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: RGD
  • neuropeptide signaling pathway Source: RGD
  • phospholipase C-activating G-protein coupled receptor signaling pathway Source: RGD
  • positive regulation of cAMP-mediated signaling Source: RGD
  • positive regulation of cytosolic calcium ion concentration Source: RGD
  • positive regulation of mast cell degranulation Source: RGD
  • regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway 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

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-RNO-373080 Class B/2 (Secretin family receptors)
R-RNO-418555 G alpha (s) signalling events

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi61276 Crhr1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 111ExtracellularBy similarityAdd BLAST88
Transmembranei112 – 142Helical; Name=1By similarityAdd BLAST31
Topological domaini143 – 149CytoplasmicBy similarity7
Transmembranei150 – 174Helical; Name=2By similarityAdd BLAST25
Topological domaini175 – 189ExtracellularBy similarityAdd BLAST15
Transmembranei190 – 218Helical; Name=3By similarityAdd BLAST29
Topological domaini219 – 225CytoplasmicBy similarity7
Transmembranei226 – 253Helical; Name=4By similarityAdd BLAST28
Topological domaini254 – 269ExtracellularBy similarityAdd BLAST16
Transmembranei270 – 295Helical; Name=5By similarityAdd BLAST26
Topological domaini296 – 306CytoplasmicBy similarityAdd BLAST11
Transmembranei307 – 331Helical; Name=6By similarityAdd BLAST25
Topological domaini332 – 338ExtracellularBy similarity7
Transmembranei339 – 368Helical; Name=7By similarityAdd BLAST30
Topological domaini369 – 415CytoplasmicBy similarityAdd BLAST47

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL4649
GuidetoPHARMACOLOGYi212

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Add BLAST23
ChainiPRO_000001281624 – 415Corticotropin-releasing factor receptor 1Add BLAST392

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi30 ↔ 541 Publication
Glycosylationi38N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi44 ↔ 871 Publication
Glycosylationi45N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi68 ↔ 1021 Publication
Glycosylationi78N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi90N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi98N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi188 ↔ 258By similarity
Modified residuei301Phosphoserine; by PKABy similarity1

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

Proteomic databases

PaxDbiP35353

PTM databases

iPTMnetiP35353
PhosphoSitePlusiP35353

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

BgeeiENSRNOG00000004900
ExpressionAtlasiP35353 baseline and differential
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

GO - Molecular functioni

  • G-protein alpha-subunit binding Source: RGD

Protein-protein interaction databases

BioGridi2486924 interactors.
IntActiP35353 1 interactor.
STRINGi10116.ENSRNOP00000006764

Chemistry databases

BindingDBiP35353

Structurei

3D structure databases

ProteinModelPortaliP35353
SMRiP35353
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni99 – 108Important for peptide agonist bindingBy similarity10
Regioni280 – 290Important for antagonist bindingBy similarityAdd BLAST11

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

eggNOGiKOG4564 Eukaryota
ENOG410XRS2 LUCA
GeneTreeiENSGT00900000140884
HOGENOMiHOG000230719
HOVERGENiHBG106921
InParanoidiP35353
KOiK04578
OMAiFICIGWC
OrthoDBiEOG091G0BBY
PhylomeDBiP35353
TreeFamiTF315710

Family and domain databases

CDDicd15445 7tmB1_CRF-R1, 1 hit
Gene3Di4.10.1240.101 hit
InterProiView protein in InterPro
IPR017981 GPCR_2-like
IPR003052 GPCR_2_CRF1_rcpt
IPR003051 GPCR_2_CRF_rcpt
IPR036445 GPCR_2_extracell_dom_sf
IPR001879 GPCR_2_extracellular_dom
IPR000832 GPCR_2_secretin-like
IPR017983 GPCR_2_secretin-like_CS
PfamiView protein in Pfam
PF00002 7tm_2, 1 hit
PF02793 HRM, 1 hit
PRINTSiPR01279 CRFRECEPTOR
PR01280 CRFRECEPTOR1
PR00249 GPCRSECRETIN
SMARTiView protein in SMART
SM00008 HormR, 1 hit
SUPFAMiSSF111418 SSF111418, 1 hit
PROSITEiView protein in 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

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
KEGGirno:58959

Similar proteinsi

Entry informationi

Entry nameiCRFR1_RAT
AccessioniPrimary (citable) accession number: P35353
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: April 25, 2018
This is version 146 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome