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Protein

Corticotropin-releasing factor receptor 1

Gene

Crhr1

Organism
Mus musculus (Mouse)
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.2 Publications

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
Alternative name(s):
Corticotropin-releasing hormone receptor 1
Short name:
CRH-R-1
Short name:
CRH-R1
Gene namesi
Name:Crhr1
Synonyms:Crhr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:88498. 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

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Heterozygous mice are fertile and produce homozygous pups at the expected Mendelian rate, but about 15% of the homozygous males die between 3 and 12 weeks after birth. Mice are deficient in CRF-mediated secretion of ACTH and show no increase in intracellular cAMP levels in response to CRF. Mice display a marked decrease in the size of the zona fasciculata of the adrenal gland, where corticosterone is produced, and have very low plasma corticosterone levels. Mutant mice display reduced anxiety. They fail to produce increased levels of ACTH and corticosterone in response to stress, contrary to wild type mice. Homozygous mice are fertile, but almost all of the pups die within 48 hours after birth, due to defects in lung inflation and alveolar collapse. Treatment of pregnant females with corticosterone-containing drinking water results in normal lung maturation and normal survival of their progeny.1 Publication

Chemistry

ChEMBLiCHEMBL2446.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence analysisAdd
BLAST
Chaini24 – 415392Corticotropin-releasing factor receptor 1PRO_0000012815Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi30 ↔ 54By similarity
Glycosylationi38 – 381N-linked (GlcNAc...)Sequence analysis
Disulfide bondi44 ↔ 87By similarity
Glycosylationi45 – 451N-linked (GlcNAc...)Sequence analysis
Disulfide bondi68 ↔ 102By similarity
Glycosylationi78 – 781N-linked (GlcNAc...)Sequence analysis
Glycosylationi90 – 901N-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.
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

PaxDbiP35347.
PRIDEiP35347.

PTM databases

iPTMnetiP35347.
PhosphoSiteiP35347.

Expressioni

Tissue specificityi

Detected in brain cortex (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000018634.
CleanExiMM_CRHR1.
ExpressionAtlasiP35347. baseline and differential.
GenevisibleiP35347. MM.

Interactioni

Subunit structurei

Heterodimer; heterodimerizes with GPER1 (By similarity). Interacts (via N-terminal extracellular domain) with CRH and UCN. Interacts with DLG1; this inhibits endocytosis of CRHR1 after agonist binding.By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000091455.

Chemistry

BindingDBiP35347.

Structurei

3D structure databases

ProteinModelPortaliP35347.
SMRiP35347. Positions 24-108, 117-367.
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

eggNOGiKOG4564. Eukaryota.
ENOG410XRS2. LUCA.
HOGENOMiHOG000230719.
HOVERGENiHBG106921.
InParanoidiP35347.
KOiK04578.
OMAiMFVCIGW.
OrthoDBiEOG091G0BBY.
PhylomeDBiP35347.
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.

P35347-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGQRPQLRLV KALLLLGLNP VSTSLQDQQC ESLSLASNVS GLQCNASVDL
60 70 80 90 100
IGTCWPRSPA GQLVVRPCPA FFYGVRYNTT NNGYRECLAN GSWAARVNYS
110 120 130 140 150
ECQEILNEEK KSKVHYHIAV 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
LYYDNEKCWF 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):47,769
Last modified:June 1, 1994 - v1
Checksum:i81423BDA6D1CA070
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X72305 mRNA. Translation: CAA51053.1.
AF483484 mRNA. Translation: AAL90758.1.
AF483485 mRNA. Translation: AAL90759.1.
CCDSiCCDS25526.1.
PIRiS39535.
RefSeqiNP_031788.1. NM_007762.5.
UniGeneiMm.1892.

Genome annotation databases

EnsembliENSMUST00000093925; ENSMUSP00000091455; ENSMUSG00000018634.
GeneIDi12921.
KEGGimmu:12921.
UCSCiuc007lvz.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X72305 mRNA. Translation: CAA51053.1.
AF483484 mRNA. Translation: AAL90758.1.
AF483485 mRNA. Translation: AAL90759.1.
CCDSiCCDS25526.1.
PIRiS39535.
RefSeqiNP_031788.1. NM_007762.5.
UniGeneiMm.1892.

3D structure databases

ProteinModelPortaliP35347.
SMRiP35347. Positions 24-108, 117-367.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000091455.

Chemistry

BindingDBiP35347.
ChEMBLiCHEMBL2446.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP35347.
PhosphoSiteiP35347.

Proteomic databases

PaxDbiP35347.
PRIDEiP35347.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000093925; ENSMUSP00000091455; ENSMUSG00000018634.
GeneIDi12921.
KEGGimmu:12921.
UCSCiuc007lvz.1. mouse.

Organism-specific databases

CTDi1394.
MGIiMGI:88498. Crhr1.

Phylogenomic databases

eggNOGiKOG4564. Eukaryota.
ENOG410XRS2. LUCA.
HOGENOMiHOG000230719.
HOVERGENiHBG106921.
InParanoidiP35347.
KOiK04578.
OMAiMFVCIGW.
OrthoDBiEOG091G0BBY.
PhylomeDBiP35347.
TreeFamiTF315710.

Miscellaneous databases

PROiP35347.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000018634.
CleanExiMM_CRHR1.
ExpressionAtlasiP35347. baseline and differential.
GenevisibleiP35347. MM.

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...

Entry informationi

Entry nameiCRFR1_MOUSE
AccessioniPrimary (citable) accession number: P35347
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: September 7, 2016
This is version 140 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. 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.