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Protein

Corticotropin-releasing factor receptor 1

Gene

CRHR1

Organism
Macaca mulatta (Rhesus macaque)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript 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.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Names & Taxonomyi

Protein namesi
Recommended name:
Corticotropin-releasing factor receptor 1
Short name:
CRF-R-1
Short name:
CRF-R1
Short name:
CRFR-1
Gene namesi
Name:CRHR1
Synonyms:CRF1
OrganismiMacaca mulatta (Rhesus macaque)
Taxonomic identifieri9544 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca
Proteomesi
  • UP000006718 Componenti: Unplaced

Subcellular locationi

  • Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
  • Endosome By similarity

  • Note: Agonist-binding promotes endocytosis.By similarity

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

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence analysisAdd
BLAST
Chaini24 – 415392Corticotropin-releasing factor receptor 1PRO_0000240656Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi30 ↔ 54By similarity
Glycosylationi38 – 381N-linked (GlcNAc...)Sequence analysis
Disulfide bondi44 ↔ 87By similarity
Disulfide bondi68 ↔ 102By similarity
Glycosylationi78 – 781N-linked (GlcNAc...)Sequence analysis
Glycosylationi98 – 981N-linked (GlcNAc...)Sequence analysis
Disulfide bondi188 ↔ 258By similarity
Modified residuei301 – 3011Phosphoserine; by PKABy similarity

Post-translational modificationi

C-terminal Ser or Thr residues may be phosphorylated.By similarity
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

Expressioni

Tissue specificityi

Expressed abundantly in the pituitary, cerebral cortex, hippocampus, amygdala and cerebellum.1 Publication

Interactioni

Subunit structurei

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

Structurei

3D structure databases

ProteinModelPortaliQ76LL8.
SMRiQ76LL8. Positions 44-106.
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

HOGENOMiHOG000230719.
HOVERGENiHBG106921.
InParanoidiQ76LL8.
KOiK04578.

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.

Q76LL8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARHPQLRLV KALLLLGLNP VSASLQDQHC ESLSLASNIS 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 VVQLTMSPEV HQSNVGWCRL VTAAYNYFHV
210 220 230 240 250
TNFFWMFGEG CYLHTAIVLT YSTDRLRKWM FICIGWGVPF PIIVAWAIGK
260 270 280 290 300
LYYDNEKCWF GKRPGVYTDY IYQGPMILVL LINFIFLFNI VRILMTKLRA
310 320 330 340 350
STTSETIQYR KAVKATLVLL PLLGITYMLF FVNPGEDEVS RVVFIYFNSF
360 370 380 390 400
LESFQGFFVS VFYCFLNSEV RSAIRKRWHR WQDKHSIRAR VARAMSIPTS
410
PTRVSFHSIK QSTAV
Length:415
Mass (Da):47,784
Last modified:July 5, 2004 - v1
Checksum:i84C530DEC6DA97AD
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB078141 mRNA. Translation: BAD02831.1.
RefSeqiNP_001027975.1. NM_001032803.1.
UniGeneiMmu.3745.

Genome annotation databases

GeneIDi574095.
KEGGimcc:574095.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB078141 mRNA. Translation: BAD02831.1.
RefSeqiNP_001027975.1. NM_001032803.1.
UniGeneiMmu.3745.

3D structure databases

ProteinModelPortaliQ76LL8.
SMRiQ76LL8. Positions 44-106.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

GPCRDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi574095.
KEGGimcc:574095.

Organism-specific databases

CTDi1394.

Phylogenomic databases

HOGENOMiHOG000230719.
HOVERGENiHBG106921.
InParanoidiQ76LL8.
KOiK04578.

Miscellaneous databases

NextBioi20015228.

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. "Monkey corticotropin-releasing factor1 receptor: complementary DNA cloning and pharmacological characterization."
    Oshida Y., Ikeda Y., Chaki S., Okuyama S.
    Life Sci. 74:1911-1924(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiCRFR1_MACMU
AccessioniPrimary (citable) accession number: Q76LL8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: July 5, 2004
Last modified: November 11, 2015
This is version 71 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

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 one 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.