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P35353

- CRFR1_RAT

UniProt

P35353 - CRFR1_RAT

Protein

Corticotropin-releasing factor receptor 1

Gene

Crhr1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 1 (01 Jun 1994)
      Previous versions | rss
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    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. corticotrophin-releasing factor receptor activity Source: UniProtKB
    2. corticotropin-releasing hormone binding Source: RGD
    3. corticotropin-releasing hormone receptor activity Source: RGD
    4. G-protein alpha-subunit binding Source: RGD
    5. G-protein coupled 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

    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

    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

    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

    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.By similarity1 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini24 – 11188ExtracellularBy similarityAdd
    BLAST
    Topological domaini143 – 1497CytoplasmicBy similarity
    Topological domaini175 – 18915ExtracellularBy similarityAdd
    BLAST
    Topological domaini219 – 2257CytoplasmicBy similarity
    Topological domaini254 – 26916ExtracellularBy similarityAdd
    BLAST
    Topological domaini296 – 30611CytoplasmicBy similarityAdd
    BLAST
    Topological domaini332 – 3387ExtracellularBy similarity
    Topological domaini369 – 41547CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei112 – 14231Helical; Name=1By similarityAdd
    BLAST
    Transmembranei150 – 17425Helical; Name=2By similarityAdd
    BLAST
    Transmembranei190 – 21829Helical; Name=3By similarityAdd
    BLAST
    Transmembranei226 – 25328Helical; Name=4By similarityAdd
    BLAST
    Transmembranei270 – 29526Helical; Name=5By similarityAdd
    BLAST
    Transmembranei307 – 33125Helical; Name=6By similarityAdd
    BLAST
    Transmembranei339 – 36830Helical; Name=7By similarityAdd
    BLAST

    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.
    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

    « Hide

    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: October 1, 2014
    This is version 118 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