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Q60748

- CRFR2_MOUSE

UniProt

Q60748 - CRFR2_MOUSE

Protein

Corticotropin-releasing factor receptor 2

Gene

Crhr2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 2 (22 Jan 2014)
      Previous versions | rss
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    Functioni

    G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for 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.

    GO - Molecular functioni

    1. corticotrophin-releasing factor receptor activity Source: MGI
    2. hormone activity Source: MGI
    3. protein binding Source: MGI

    GO - Biological processi

    1. cellular response to corticotropin-releasing hormone stimulus Source: GOC
    2. G-protein coupled receptor signaling pathway Source: MGI
    3. negative regulation of angiogenesis Source: MGI
    4. negative regulation of cAMP-mediated signaling Source: MGI
    5. positive regulation of cAMP-mediated signaling Source: MGI

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Corticotropin-releasing factor receptor 2
    Short name:
    CRF-R-2
    Short name:
    CRF-R2
    Short name:
    CRFR-2
    Alternative name(s):
    CRF-RB
    Corticotropin-releasing hormone receptor 2
    Short name:
    CRH-R-2
    Short name:
    CRH-R2
    Gene namesi
    Name:Crhr2
    Synonyms:Crf2r
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:894312. Crhr2.

    Subcellular locationi

    GO - Cellular componenti

    1. cell surface Source: MGI
    2. endoplasmic reticulum Source: MGI
    3. Golgi apparatus Source: MGI
    4. integral component of membrane Source: UniProtKB-KW
    5. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi45 – 451D → A: Disrupts internal salt bridge and abrogates ligand recognition. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 411411Corticotropin-releasing factor receptor 2PRO_0000012821Add
    BLAST
    Signal peptidei1 – 1919Not cleavedBy similarityAdd
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi13 – 131N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi14 ↔ 50By similarity
    Disulfide bondi40 ↔ 83
    Glycosylationi41 – 411N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi64 ↔ 98
    Glycosylationi74 – 741N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi86 – 861N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi94 – 941N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi184 ↔ 254By similarity

    Post-translational modificationi

    A N-glycosylation site within the signal peptide impedes its proper cleavage and function.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PRIDEiQ60748.

    PTM databases

    PhosphoSiteiQ60748.

    Expressioni

    Tissue specificityi

    Highly expressed in the heart. Also expressed in lungs, skeletal muscle, gastrointestinal tract, epididymis, and brain.

    Gene expression databases

    CleanExiMM_CRHR2.
    GenevestigatoriQ60748.

    Interactioni

    Subunit structurei

    Monomer. Interacts with CRF, UCN, UCN2 and UCN3 By similarity.By similarity

    Structurei

    Secondary structure

    1
    411
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi46 – 483
    Beta strandi58 – 636
    Beta strandi69 – 713
    Beta strandi78 – 836
    Turni85 – 873
    Beta strandi97 – 993

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1U34NMR-A35-113[»]
    2JNCNMR-A35-113[»]
    2JNDNMR-A35-113[»]
    ProteinModelPortaliQ60748.
    SMRiQ60748. Positions 3-113, 115-363.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ60748.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 108108ExtracellularBy similarityAdd
    BLAST
    Topological domaini140 – 1467CytoplasmicBy similarity
    Topological domaini172 – 18514ExtracellularBy similarityAdd
    BLAST
    Topological domaini215 – 2217CytoplasmicBy similarity
    Topological domaini250 – 26516ExtracellularBy similarityAdd
    BLAST
    Topological domaini292 – 30211CytoplasmicBy similarityAdd
    BLAST
    Topological domaini328 – 3347ExtracellularBy similarity
    Topological domaini365 – 41147CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei109 – 13931Helical; Name=1By similarityAdd
    BLAST
    Transmembranei147 – 17125Helical; Name=2By similarityAdd
    BLAST
    Transmembranei186 – 21429Helical; Name=3By similarityAdd
    BLAST
    Transmembranei222 – 24928Helical; Name=4By similarityAdd
    BLAST
    Transmembranei266 – 29126Helical; Name=5By similarityAdd
    BLAST
    Transmembranei303 – 32725Helical; Name=6By similarityAdd
    BLAST
    Transmembranei335 – 36430Helical; Name=7By similarityAdd
    BLAST

    Family & Domainsi

    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
    The uncleaved pseudo signal peptide prevents receptor's oligomerization and coupling to G(i) subunits. It is also responsible for the rather low receptor localization at the plasma membrane By similarity.By similarity

    Sequence similaritiesi

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG295825.
    HOGENOMiHOG000230719.
    HOVERGENiHBG106921.
    InParanoidiQ60748.
    KOiK04579.

    Family and domain databases

    InterProiIPR017981. GPCR_2-like.
    IPR003053. GPCR_2_CRF2_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.
    PR01281. CRFRECEPTOR2.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform CRF2-alpha (identifier: Q60748-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MDAALLLSLL EANCSLALAE ELLLDGWGVP PDPEGPYTYC NTTLDQIGTC    50
    WPQSAPGALV ERPCPEYFNG IKYNTTRNAY RECLENGTWA SRVNYSHCEP 100
    ILDDKQRKYD LHYRIALIVN YLGHCVSVVA LVAAFLLFLV LRSIRCLRNV 150
    IHWNLITTFI LRNIAWFLLQ LIDHEVHEGN EVWCRCITTI FNYFVVTNFF 200
    WMFVEGCYLH TAIVMTYSTE HLRKWLFLFI GWCIPCPIII AWAVGKLYYE 250
    NEQCWFGKEA GDLVDYIYQG PVMLVLLINF VFLFNIVRIL MTKLRASTTS 300
    ETIQYRKAVK ATLVLLPLLG ITYMLFFVNP GEDDLSQIVF IYFNSFLQSF 350
    QGFFVSVFYC FFNGEVRAAL RKRWHRWQDH HALRVPVARA MSIPTSPTRI 400
    SFHSIKQTAA V 411
    Length:411
    Mass (Da):47,623
    Last modified:January 22, 2014 - v2
    Checksum:iC0EAD0BC6A064683
    GO
    Isoform CRF2-beta (identifier: Q60748-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-34: MDAALLLSLLEANCSLALAEELLLDGWGVPPDPE → MGTPGSLPSA...CHRTTIGNFS

    Note: Contains a disulfide bond in positions 45-70.Curated

    Show »
    Length:431
    Mass (Da):49,923
    Checksum:iA6D9EDE575DB8061
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti106 – 1061Missing in AAC52243. (PubMed:7565810)Curated
    Sequence conflicti372 – 3732KR → NG in AAC52243. (PubMed:7565810)Curated
    Sequence conflicti376 – 3772RW → SG in AAC52174. (PubMed:7755719)Curated
    Sequence conflicti388 – 3881A → R in AAC52174. (PubMed:7755719)Curated
    Isoform CRF2-beta (identifier: Q60748-2)
    Sequence conflicti3 – 53TPG → QQI in AAC52174. (PubMed:7755719)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 3434MDAAL…PPDPE → MGTPGSLPSAQLLLCLFSLL PVLQVAQPGQAPQDQPLWTL LEQYCHRTTIGNFS in isoform CRF2-beta. 4 PublicationsVSP_053568Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U17858 mRNA. Translation: AAA68026.1.
    U21729 mRNA. Translation: AAC52174.1.
    U19939 mRNA. Translation: AAC52243.1.
    AY445512 mRNA. Translation: AAS07021.1.
    BC137592 mRNA. Translation: AAI37593.1.
    PIRiA56726.
    I49149.
    I49279.
    RefSeqiNP_001275548.1. NM_001288619.1. [Q60748-1]
    UniGeneiMm.236081.

    Genome annotation databases

    GeneIDi12922.
    KEGGimmu:12922.
    UCSCiuc009cal.2. mouse. [Q60748-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U17858 mRNA. Translation: AAA68026.1 .
    U21729 mRNA. Translation: AAC52174.1 .
    U19939 mRNA. Translation: AAC52243.1 .
    AY445512 mRNA. Translation: AAS07021.1 .
    BC137592 mRNA. Translation: AAI37593.1 .
    PIRi A56726.
    I49149.
    I49279.
    RefSeqi NP_001275548.1. NM_001288619.1. [Q60748-1 ]
    UniGenei Mm.236081.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1U34 NMR - A 35-113 [» ]
    2JNC NMR - A 35-113 [» ]
    2JND NMR - A 35-113 [» ]
    ProteinModelPortali Q60748.
    SMRi Q60748. Positions 3-113, 115-363.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi Q60748.
    ChEMBLi CHEMBL2253.
    GuidetoPHARMACOLOGYi 213.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q60748.

    Proteomic databases

    PRIDEi Q60748.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 12922.
    KEGGi mmu:12922.
    UCSCi uc009cal.2. mouse. [Q60748-1 ]

    Organism-specific databases

    CTDi 1395.
    MGIi MGI:894312. Crhr2.

    Phylogenomic databases

    eggNOGi NOG295825.
    HOGENOMi HOG000230719.
    HOVERGENi HBG106921.
    InParanoidi Q60748.
    KOi K04579.

    Miscellaneous databases

    EvolutionaryTracei Q60748.
    PROi Q60748.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_CRHR2.
    Genevestigatori Q60748.

    Family and domain databases

    InterProi IPR017981. GPCR_2-like.
    IPR003053. GPCR_2_CRF2_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.
    PR01281. CRFRECEPTOR2.
    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. "Identification of a second corticotropin-releasing factor receptor gene and characterization of a cDNA expressed in heart."
      Perrin M., Donaldson C., Chen R., Blount A., Berggren T., Bilezikjian L., Sawchenko P., Vale W.
      Proc. Natl. Acad. Sci. U.S.A. 92:2969-2973(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-BETA).
      Tissue: Heart.
    2. "A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle."
      Kishimoto T., Pearse R.V. II, Lin C.R., Rosenfeld M.G.
      Proc. Natl. Acad. Sci. U.S.A. 92:1108-1112(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-BETA).
      Strain: BALB/c.
      Tissue: Heart.
    3. "Identification of a novel murine receptor for corticotropin-releasing hormone expressed in the heart."
      Stenzel P., Kesterson R., Yeung W., Cone R.D., Rittenberg M.B., Stenzel-Poore M.P.
      Mol. Endocrinol. 9:637-645(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-BETA).
      Strain: BALB/c.
      Tissue: Heart.
    4. "Mouse corticotropin-releasing factor receptor type 2alpha gene: isolation, distribution, pharmacological characterization and regulation by stress and glucocorticoids."
      Chen A., Perrin M., Brar B., Li C., Jamieson P., DiGruccio M., Lewis K., Vale W.
      Mol. Endocrinol. 19:441-458(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-ALPHA).
      Strain: C57BL/6 X 129.
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRF2-BETA).
      Tissue: Brain.
    6. "NMR structure and peptide hormone binding site of the first extracellular domain of a type B1 G protein-coupled receptor."
      Grace C.R., Perrin M.H., DiGruccio M.R., Miller C.L., Rivier J.E., Vale W.W., Riek R.
      Proc. Natl. Acad. Sci. U.S.A. 101:12836-12841(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 39-133 (ISOFORM CRF2-BETA), DISULFIDE BONDS.
    7. "The three-dimensional structure of the N-terminal domain of corticotropin-releasing factor receptors: sushi domains and the B1 family of G protein-coupled receptors."
      Perrin M.H., Grace C.R., Riek R., Vale W.W.
      Ann. N. Y. Acad. Sci. 1070:105-119(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 39-133 (ISOFORM CRF2-BETA) IN COMPLEX WITH PEPTIDE LIGAND, DISULFIDE BONDS, MUTAGENESIS OF ASP-45.
    8. "Structure of the N-terminal domain of a type B1 G protein-coupled receptor in complex with a peptide ligand."
      Grace C.R., Perrin M.H., Gulyas J., Digruccio M.R., Cantle J.P., Rivier J.E., Vale W.W., Riek R.
      Proc. Natl. Acad. Sci. U.S.A. 104:4858-4863(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 39-133 (ISOFORM CRF2-BETA) IN COMPLEX WITH PEPTIDE LIGAND, DISULFIDE BONDS.

    Entry informationi

    Entry nameiCRFR2_MOUSE
    AccessioniPrimary (citable) accession number: Q60748
    Secondary accession number(s): B9EHB5
    , Q5GL24, Q60783, Q60808
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: January 22, 2014
    Last modified: October 1, 2014
    This is version 121 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3