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P35353

- CRFR1_RAT

UniProt

P35353 - CRFR1_RAT

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Protein
Corticotropin-releasing factor receptor 1
Gene
Crhr1, Crhr
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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

  1. G-protein alpha-subunit binding Source: RGD
  2. G-protein coupled receptor activity Source: RGD
  3. corticotrophin-releasing factor receptor activity Source: UniProtKB
  4. corticotropin-releasing hormone binding Source: RGD
  5. corticotropin-releasing hormone receptor activity Source: RGD
  6. peptide binding Source: RGD
  7. protein binding Source: IntAct
  8. protein complex binding Source: RGD

GO - Biological processi

  1. adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: RGD
  2. adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: RGD
  3. adrenal gland development Source: Ensembl
  4. behavioral response to cocaine Source: RGD
  5. behavioral response to ethanol Source: Ensembl
  6. behavioral response to pain Source: RGD
  7. cellular response to corticotropin-releasing hormone stimulus Source: UniProtKB
  8. corticotropin secretion Source: UniProtKB
  9. epithelial cell differentiation Source: RGD
  10. fear response Source: Ensembl
  11. general adaptation syndrome, behavioral process Source: Ensembl
  12. hormone-mediated signaling pathway Source: GOC
  13. hypothalamus development Source: RGD
  14. locomotory exploration behavior Source: RGD
  15. long-term synaptic potentiation Source: RGD
  16. memory Source: RGD
  17. negative regulation of epinephrine secretion Source: RGD
  18. negative regulation of feeding behavior Source: RGD
  19. negative regulation of neuron death Source: RGD
  20. negative regulation of voltage-gated calcium channel activity Source: Ensembl
  21. neuropeptide signaling pathway Source: RGD
  22. phospholipase C-activating G-protein coupled receptor signaling pathway Source: RGD
  23. positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway Source: UniProtKB
  24. positive regulation of cAMP biosynthetic process Source: RGD
  25. positive regulation of cytosolic calcium ion concentration Source: RGD
  26. positive regulation of mast cell degranulation Source: RGD
  27. regulation of corticosterone secretion Source: UniProtKB
  28. regulation of synaptic plasticity Source: RGD
  29. response to electrical stimulus Source: RGD
  30. response to hypoxia Source: RGD
  31. response to immobilization stress Source: RGD
  32. visual learning Source: RGD
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 10

Organism-specific databases

RGDi61276. Crhr1.

Subcellular locationi

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

Topology

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

GO - Cellular componenti

  1. apical part of cell Source: RGD
  2. dendrite Source: RGD
  3. integral component of membrane Source: UniProtKB-KW
  4. intrinsic component of plasma membrane Source: UniProtKB
  5. membrane Source: RGD
  6. multivesicular body Source: RGD
  7. neuronal cell body Source: RGD
  8. plasma membrane Source: RGD
  9. trans-Golgi network Source: RGD
  10. 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 – 2323
Add
BLAST
Chaini24 – 415392Corticotropin-releasing factor receptor 1
PRO_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 ↔ 258 By similarity
Modified residuei301 – 3011Phosphoserine; by PKA By 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

GenevestigatoriP35353.

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 GPER1.1 Publication

Binary interactionsi

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

Protein-protein interaction databases

BioGridi248692. 4 interactions.
IntActiP35353. 1 interaction.
STRINGi10116.ENSRNOP00000060025.

Structurei

3D structure databases

ProteinModelPortaliP35353.
SMRiP35353. Positions 20-116.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni99 – 10810Important for peptide agonist binding By similarity
Regioni280 – 29011Important for antagonist binding By similarity
Add
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.

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG295825.
GeneTreeiENSGT00750000117453.
HOGENOMiHOG000230719.
HOVERGENiHBG106921.
InParanoidiP35353.
KOiK04578.
OMAiVGWCRLV.
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

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MGRRPQLRLV KALLLLGLNP VSTSLQDQRC ENLSLTSNVS GLQCNASVDL    50
IGTCWPRSPA GQLVVRPCPA FFYGVRYNTT NNGYRECLAN GSWAARVNYS 100
ECQEILNEEK KSKVHYHVAV IINYLGHCIS LVALLVAFVL FLRLRSIRCL 150
RNIIHWNLIS AFILRNATWF VVQLTVSPEV HQSNVAWCRL VTAAYNYFHV 200
TNFFWMFGEG CYLHTAIVLT YSTDRLRKWM FVCIGWGVPF PIIVAWAIGK 250
LHYDNEKCWF GKRPGVYTDY IYQGPMILVL LINFIFLFNI VRILMTKLRA 300
STTSETIQYR KAVKATLVLL PLLGITYMLF FVNPGEDEVS RVVFIYFNSF 350
LESFQGFFVS VFYCFLNSEV RSAIRKRWRR WQDKHSIRAR VARAMSIPTS 400
PTRVSFHSIK QSTAV 415
Length:415
Mass (Da):47,842
Last modified:June 1, 1994 - v1
Checksum:i48D6704B31D4C013
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_030999.3.
UniGeneiRn.10499.

Genome annotation databases

EnsembliENSRNOT00000006764; ENSRNOP00000006764; ENSRNOG00000004900.
GeneIDi58959.
KEGGirno:58959.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
PIRi I58144.
RefSeqi NP_112261.1. NM_030999.3.
UniGenei Rn.10499.

3D structure databases

ProteinModelPortali P35353.
SMRi P35353. Positions 20-116.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 248692. 4 interactions.
IntActi P35353. 1 interaction.
STRINGi 10116.ENSRNOP00000060025.

Chemistry

BindingDBi P35353.
ChEMBLi CHEMBL2111360.
GuidetoPHARMACOLOGYi 212.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei P35353.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000006764 ; ENSRNOP00000006764 ; ENSRNOG00000004900 .
GeneIDi 58959.
KEGGi rno:58959.

Organism-specific databases

CTDi 1394.
RGDi 61276. Crhr1.

Phylogenomic databases

eggNOGi NOG295825.
GeneTreei ENSGT00750000117453.
HOGENOMi HOG000230719.
HOVERGENi HBG106921.
InParanoidi P35353.
KOi K04578.
OMAi VGWCRLV.
OrthoDBi EOG7CRTPR.
PhylomeDBi P35353.
TreeFami TF315710.

Miscellaneous databases

NextBioi 611592.
PROi P35353.

Gene expression databases

Genevestigatori P35353.

Family and domain databases

InterProi IPR017981. 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 ]
Pfami PF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view ]
PRINTSi PR01279. CRFRECEPTOR.
PR01280. CRFRECEPTOR1.
PR00249. GPCRSECRETIN.
SMARTi SM00008. HormR. 1 hit.
[Graphical view ]
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

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: June 11, 2014
This is version 117 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