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O43739

- CYH3_HUMAN

UniProt

O43739 - CYH3_HUMAN

Protein

Cytohesin-3

Gene

CYTH3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 2 (21 Feb 2001)
      Previous versions | rss
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    Functioni

    Promotes guanine-nucleotide exchange on ARF1 and ARF6. Promotes the activation of ARF factors through replacement of GDP with GTP.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei285 – 2851Phosphatidylinositol 3,4,5-trisphosphate1 Publication
    Binding sitei296 – 2961Phosphatidylinositol 3,4,5-trisphosphate1 Publication
    Binding sitei306 – 3061Phosphatidylinositol 3,4,5-trisphosphate1 Publication
    Binding sitei355 – 3551Phosphatidylinositol 3,4,5-trisphosphate1 Publication

    GO - Molecular functioni

    1. ARF guanyl-nucleotide exchange factor activity Source: UniProtKB
    2. phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB

    GO - Biological processi

    1. establishment of epithelial cell polarity Source: Ensembl
    2. Golgi vesicle transport Source: UniProtKB
    3. positive regulation of cell adhesion Source: Ensembl
    4. positive regulation of GTPase activity Source: GOC
    5. regulation of ARF protein signal transduction Source: InterPro
    6. regulation of cell adhesion Source: RefGenome

    Keywords - Molecular functioni

    Guanine-nucleotide releasing factor

    Keywords - Ligandi

    Lipid-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytohesin-3
    Alternative name(s):
    ARF nucleotide-binding site opener 3
    Short name:
    Protein ARNO3
    General receptor of phosphoinositides 1
    Short name:
    Grp1
    PH, SEC7 and coiled-coil domain-containing protein 3
    Gene namesi
    Name:CYTH3
    Synonyms:ARNO3, GRP1, PSCD3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:9504. CYTH3.

    Subcellular locationi

    Cytoplasmcytosol. Cell membrane; Peripheral membrane protein
    Note: Translocates from the cytosol to membranes enriched in phosphatidylinositol 3,4,5-trisphosphate.

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
    3. plasma membrane Source: UniProtKB
    4. ruffle Source: Ensembl

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi398 – 4003NKK → AAA: Abolishes autoinhibition and increases guanine-nucleotide exchange activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA164718590.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 400400Cytohesin-3PRO_0000120200Add
    BLAST

    Proteomic databases

    MaxQBiO43739.
    PaxDbiO43739.
    PRIDEiO43739.

    PTM databases

    PhosphoSiteiO43739.

    Expressioni

    Tissue specificityi

    Almost absent from liver, thymus and peripheral blood lymphocytes.

    Gene expression databases

    ArrayExpressiO43739.
    BgeeiO43739.
    CleanExiHS_CYTH3.
    GenevestigatoriO43739.

    Organism-specific databases

    HPAiHPA013979.

    Interactioni

    Subunit structurei

    Interacts with GRASP By similarity. Interacts with ARF6.By similarity1 Publication

    Protein-protein interaction databases

    BioGridi114686. 5 interactions.
    DIPiDIP-60444N.
    IntActiO43739. 2 interactions.
    MINTiMINT-1466258.
    STRINGi9606.ENSP00000297044.

    Structurei

    Secondary structure

    1
    400
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi259 – 2624
    Beta strandi266 – 2749
    Beta strandi282 – 2909
    Beta strandi293 – 2997
    Beta strandi306 – 3105
    Beta strandi315 – 3195
    Beta strandi322 – 33110
    Beta strandi333 – 3353
    Beta strandi343 – 3453
    Beta strandi351 – 3533
    Beta strandi359 – 3624
    Helixi366 – 37914
    Helixi384 – 39613

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4KAXX-ray1.85B247-400[»]
    ProteinModelPortaliO43739.
    SMRiO43739. Positions 63-397.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini77 – 206130SEC7PROSITE-ProRule annotationAdd
    BLAST
    Domaini264 – 381118PHPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni273 – 2819Phosphatidylinositol 3,4,5-trisphosphate binding
    Regioni392 – 4009C-terminal autoinhibitory region

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili14 – 6148Sequence AnalysisAdd
    BLAST

    Domaini

    Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate.
    Autoinhibited by its C-terminal basic region.

    Sequence similaritiesi

    Contains 1 PH domain.PROSITE-ProRule annotation
    Contains 1 SEC7 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Coiled coil

    Phylogenomic databases

    eggNOGiCOG5307.
    HOGENOMiHOG000253023.
    HOVERGENiHBG002647.
    InParanoidiO43739.
    OMAiNLTCVEE.
    OrthoDBiEOG7RBZ9C.
    PhylomeDBiO43739.
    TreeFamiTF352091.

    Family and domain databases

    Gene3Di1.10.1000.11. 1 hit.
    2.30.29.30. 1 hit.
    InterProiIPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR023394. Sec7_alpha_orthog.
    IPR000904. Sec7_dom.
    [Graphical view]
    PfamiPF00169. PH. 1 hit.
    PF01369. Sec7. 1 hit.
    [Graphical view]
    SMARTiSM00233. PH. 1 hit.
    SM00222. Sec7. 1 hit.
    [Graphical view]
    SUPFAMiSSF48425. SSF48425. 1 hit.
    PROSITEiPS50003. PH_DOMAIN. 1 hit.
    PS50190. SEC7. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O43739-1) [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

    MDEDGGGEGG GVPEDLSLEE REELLDIRRR KKELIDDIER LKYEIAEVMT    50
    EIDNLTSVEE SKTTQRNKQI AMGRKKFNMD PKKGIQFLIE NDLLQSSPED 100
    VAQFLYKGEG LNKTVIGDYL GERDEFNIKV LQAFVELHEF ADLNLVQALR 150
    QFLWSFRLPG EAQKIDRMME AFASRYCLCN PGVFQSTDTC YVLSFAIIML 200
    NTSLHNHNVR DKPTAERFIA MNRGINEGGD LPEELLRNLY ESIKNEPFKI 250
    PEDDGNDLTH TFFNPDREGW LLKLGGGRVK TWKRRWFILT DNCLYYFEYT 300
    TDKEPRGIIP LENLSIREVE DPRKPNCFEL YNPSHKGQVI KACKTEADGR 350
    VVEGNHVVYR ISAPSPEEKE EWMKSIKASI SRDPFYDMLA TRKRRIANKK 400
    Length:400
    Mass (Da):46,349
    Last modified:February 21, 2001 - v2
    Checksum:i87FB917899EE957D
    GO
    Isoform 2 (identifier: O43739-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         277-277: Missing.

    Show »
    Length:399
    Mass (Da):46,292
    Checksum:iDAFCAD4131A9C42D
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei277 – 2771Missing in isoform 2. 3 PublicationsVSP_006039

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ005197 mRNA. Translation: CAA06434.1.
    AJ223957 mRNA. Translation: CAA11686.1.
    CH236963 Genomic DNA. Translation: EAL23717.1.
    CH878731 Genomic DNA. Translation: EAW55046.1.
    BC028717 mRNA. Translation: AAH28717.1.
    CCDSiCCDS5346.1. [O43739-2]
    RefSeqiNP_004218.1. NM_004227.3. [O43739-2]
    UniGeneiHs.487479.

    Genome annotation databases

    EnsembliENST00000350796; ENSP00000297044; ENSG00000008256. [O43739-2]
    GeneIDi9265.
    KEGGihsa:9265.
    UCSCiuc003spt.3. human. [O43739-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ005197 mRNA. Translation: CAA06434.1 .
    AJ223957 mRNA. Translation: CAA11686.1 .
    CH236963 Genomic DNA. Translation: EAL23717.1 .
    CH878731 Genomic DNA. Translation: EAW55046.1 .
    BC028717 mRNA. Translation: AAH28717.1 .
    CCDSi CCDS5346.1. [O43739-2 ]
    RefSeqi NP_004218.1. NM_004227.3. [O43739-2 ]
    UniGenei Hs.487479.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4KAX X-ray 1.85 B 247-400 [» ]
    ProteinModelPortali O43739.
    SMRi O43739. Positions 63-397.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114686. 5 interactions.
    DIPi DIP-60444N.
    IntActi O43739. 2 interactions.
    MINTi MINT-1466258.
    STRINGi 9606.ENSP00000297044.

    PTM databases

    PhosphoSitei O43739.

    Proteomic databases

    MaxQBi O43739.
    PaxDbi O43739.
    PRIDEi O43739.

    Protocols and materials databases

    DNASUi 9265.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000350796 ; ENSP00000297044 ; ENSG00000008256 . [O43739-2 ]
    GeneIDi 9265.
    KEGGi hsa:9265.
    UCSCi uc003spt.3. human. [O43739-2 ]

    Organism-specific databases

    CTDi 9265.
    GeneCardsi GC07M006168.
    HGNCi HGNC:9504. CYTH3.
    HPAi HPA013979.
    MIMi 605081. gene.
    neXtProti NX_O43739.
    PharmGKBi PA164718590.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5307.
    HOGENOMi HOG000253023.
    HOVERGENi HBG002647.
    InParanoidi O43739.
    OMAi NLTCVEE.
    OrthoDBi EOG7RBZ9C.
    PhylomeDBi O43739.
    TreeFami TF352091.

    Miscellaneous databases

    GeneWikii CYTH3.
    GenomeRNAii 9265.
    NextBioi 34729.
    PROi O43739.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O43739.
    Bgeei O43739.
    CleanExi HS_CYTH3.
    Genevestigatori O43739.

    Family and domain databases

    Gene3Di 1.10.1000.11. 1 hit.
    2.30.29.30. 1 hit.
    InterProi IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR023394. Sec7_alpha_orthog.
    IPR000904. Sec7_dom.
    [Graphical view ]
    Pfami PF00169. PH. 1 hit.
    PF01369. Sec7. 1 hit.
    [Graphical view ]
    SMARTi SM00233. PH. 1 hit.
    SM00222. Sec7. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48425. SSF48425. 1 hit.
    PROSITEi PS50003. PH_DOMAIN. 1 hit.
    PS50190. SEC7. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Nerve growth factor- and epidermal growth factor-stimulated translocation of the ADP-ribosylation factor-exchange factor GRP1 to the plasma membrane of PC12 cells requires activation of phosphatidylinositol 3-kinase and the GRP1 pleckstrin homology domain."
      Venkateswarlu K., Gunn-Moore F., Oatey P.B., Tavare J.M., Cullen P.J.
      Biochem. J. 335:139-146(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), LIPID-BINDING, DOMAIN, SUBCELLULAR LOCATION.
    2. "ARNO3, a Sec7-domain guanine nucleotide exchange factor for ADP ribosylation factor 1, is involved in the control of Golgi structure and function."
      Franco M., Boretto J., Robineau S., Monier S., Goud B., Chardin P., Chavrier P.
      Proc. Natl. Acad. Sci. U.S.A. 95:9926-9931(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION.
      Tissue: Placenta.
    3. "Human chromosome 7: DNA sequence and biology."
      Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
      , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
      Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    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 2).
      Tissue: Brain.
    6. "Similarities in function and gene structure of cytohesin-4 and cytohesin-1, guanine nucleotide-exchange proteins for ADP-ribosylation factors."
      Ogasawara M., Kim S.C., Adamik R., Togawa A., Ferrans V.J., Takeda K., Kirby M., Moss J., Vaughan M.
      J. Biol. Chem. 275:3221-3230(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING.
    7. "The Arl4 family of small G proteins can recruit the cytohesin Arf6 exchange factors to the plasma membrane."
      Hofmann I., Thompson A., Sanderson C.M., Munro S.
      Curr. Biol. 17:711-716(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    8. "Structural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors."
      Malaby A.W., van den Berg B., Lambright D.G.
      Proc. Natl. Acad. Sci. U.S.A. 110:14213-14218(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 247-400 IN COMPLEX WITH PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE AND ARF6, FUNCTION, DOMAIN, LIPID-BINDING, MUTAGENESIS OF 398-ASN--LYS-400, AUTOINHIBITORY REGION, INTERACTION WITH ARF6.

    Entry informationi

    Entry nameiCYH3_HUMAN
    AccessioniPrimary (citable) accession number: O43739
    Secondary accession number(s): A4D2N8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 21, 2001
    Last sequence update: February 21, 2001
    Last modified: October 1, 2014
    This is version 132 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) 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