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Q99418

- CYH2_HUMAN

UniProt

Q99418 - CYH2_HUMAN

Protein

Cytohesin-2

Gene

CYTH2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 2 (21 Feb 2001)
      Previous versions | rss
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    Functioni

    Acts as a guanine-nucleotide exchange factor (GEF). Promotes guanine-nucleotide exchange on ARF1, ARF3 and ARF6. Promotes the activation of ARF factors through replacement of GDP with GTP. The cell membrane form, in association with ARL4 proteins, recruits ARF6 to the plasma membrane.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei280 – 2801Phosphatidylinositol 1,4,5-trisphosphateBy similarity
    Binding sitei291 – 2911Phosphatidylinositol 1,4,5-trisphosphateBy similarity
    Binding sitei301 – 3011Phosphatidylinositol 1,4,5-trisphosphateBy similarity
    Binding sitei339 – 3391Phosphatidylinositol 1,4,5-trisphosphateBy similarity
    Binding sitei350 – 3501Phosphatidylinositol 1,4,5-trisphosphateBy similarity
    Binding sitei351 – 3511Phosphatidylinositol 1,4,5-trisphosphateBy similarity

    GO - Molecular functioni

    1. ARF guanyl-nucleotide exchange factor activity Source: UniProtKB
    2. inositol 1,4,5 trisphosphate binding Source: UniProtKB
    3. lipid binding Source: UniProtKB-KW
    4. protein binding Source: UniProtKB

    GO - Biological processi

    1. actin cytoskeleton organization Source: ProtInc
    2. endocytosis Source: ProtInc
    3. positive regulation of GTPase activity Source: GOC
    4. regulation of ARF protein signal transduction Source: InterPro
    5. regulation of cell adhesion Source: RefGenome

    Keywords - Molecular functioni

    Guanine-nucleotide releasing factor

    Keywords - Ligandi

    Lipid-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytohesin-2
    Alternative name(s):
    ARF exchange factor
    ARF nucleotide-binding site opener
    Short name:
    Protein ARNO
    PH, SEC7 and coiled-coil domain-containing protein 2
    Gene namesi
    Name:CYTH2
    Synonyms:ARNO, PSCD2, PSCD2L
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:9502. CYTH2.

    Subcellular locationi

    Cell membrane 1 Publication; Peripheral membrane protein 1 Publication. Cytoplasm 1 Publication
    Note: Both isoform 1 and isoform 2 are recruited to the cell membrane through their association with ARL4A, ARL4C and ARL4D. They require also interaction with phosphoinositides for targeting to the plasma membrane.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. membrane Source: ProtInc
    3. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi156 – 1561E → D: Inhibits GTP GDP exchange activity. Abolishes recruitment of ARF6 to the plasma membrane. 1 Publication
    Mutagenesisi268 – 2681K → R: Does not reduces ARL4D GTP-dependent interaction but inhibits targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication
    Mutagenesisi280 – 2801R → D: Does not reduces ARL4D GTP-dependent interaction but inhibits targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication
    Mutagenesisi303 – 3031I → A: Reduces ARL4D GTP-dependent interaction and targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication
    Mutagenesisi336 – 3361K → A: Reduces ARL4D GTP-dependent interaction and targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication

    Organism-specific databases

    PharmGKBiPA33849.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 400400Cytohesin-2PRO_0000120197Add
    BLAST

    Proteomic databases

    MaxQBiQ99418.
    PaxDbiQ99418.
    PRIDEiQ99418.

    PTM databases

    PhosphoSiteiQ99418.

    Expressioni

    Tissue specificityi

    Ubiquitous.

    Gene expression databases

    ArrayExpressiQ99418.
    BgeeiQ99418.
    CleanExiHS_CYTH2.
    GenevestigatoriQ99418.

    Organism-specific databases

    HPAiCAB014872.

    Interactioni

    Subunit structurei

    Heteromer. Composed of GRASP, CYTH2 and at least one GRM1 By similarity. Interacts with ARRB1. Interacts with ARL4D; the interaction is direct.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ADORA2AP292746EBI-448974,EBI-2902702
    ARF1P840774EBI-448974,EBI-447171
    ATP6V0A2Q9Y4872EBI-448974,EBI-988630
    EGFRP005335EBI-448974,EBI-297353

    Protein-protein interaction databases

    BioGridi114687. 16 interactions.
    DIPiDIP-31598N.
    IntActiQ99418. 10 interactions.
    MINTiMINT-3058896.
    STRINGi9606.ENSP00000408236.

    Structurei

    Secondary structure

    1
    400
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi63 – 7412
    Helixi76 – 8510
    Helixi93 – 10210
    Helixi108 – 1158
    Helixi120 – 13112
    Helixi140 – 14910
    Helixi157 – 17418
    Beta strandi178 – 1803
    Helixi182 – 20019
    Helixi210 – 2167
    Turni217 – 2204
    Beta strandi221 – 2244
    Helixi228 – 24013

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1PBVX-ray2.00A52-246[»]
    1R8MX-ray1.70E50-252[»]
    1R8QX-ray1.86E/F50-252[»]
    1R8SX-ray1.46E50-252[»]
    1S9DX-ray1.80E50-252[»]
    4JMIX-ray1.50A56-251[»]
    4JMOX-ray1.80A56-251[»]
    4JWLX-ray1.95A56-251[»]
    4JXHX-ray1.47A56-251[»]
    4L5MX-ray1.80A56-251[»]
    ProteinModelPortaliQ99418.
    SMRiQ99418. Positions 56-392.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ99418.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini72 – 201130SEC7PROSITE-ProRule annotationAdd
    BLAST
    Domaini259 – 376118PHPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni268 – 2769Phosphatidylinositol 1,4,5-trisphosphate bindingBy similarity
    Regioni387 – 3959C-terminal autoinhibitory regionBy similarity

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili10 – 6354Sequence AnalysisAdd
    BLAST

    Domaini

    Binds via its PH domain to the inositol head group of phosphatidylinositol 1,4,5-trisphosphate. The PH domain is necessary and sufficient for plasma membrane relocalization.
    Autoinhibited by its C-terminal basic region.By similarity

    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.
    InParanoidiQ99418.
    OrthoDBiEOG7RBZ9C.
    PhylomeDBiQ99418.
    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: Q99418-1) [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

    MEDGVYEPPD LTPEERMELE NIRRRKQELL VEIQRLREEL SEAMSEVEGL    50
    EANEGSKTLQ RNRKMAMGRK KFNMDPKKGI QFLVENELLQ NTPEEIARFL 100
    YKGEGLNKTA IGDYLGEREE LNLAVLHAFV DLHEFTDLNL VQALRQFLWS 150
    FRLPGEAQKI DRMMEAFAQR YCLCNPGVFQ STDTCYVLSF AVIMLNTSLH 200
    NPNVRDKPGL ERFVAMNRGI NEGGDLPEEL LRNLYDSIRN EPFKIPEDDG 250
    NDLTHTFFNP DREGWLLKLG GGRVKTWKRR WFILTDNCLY YFEYTTDKEP 300
    RGIIPLENLS IREVDDPRKP NCFELYIPNN KGQLIKACKT EADGRVVEGN 350
    HMVYRISAPT QEEKDEWIKS IQAAVSVDPF YEMLAARKKR ISVKKKQEQP 400
    Length:400
    Mass (Da):46,546
    Last modified:February 21, 2001 - v2
    Checksum:i70441A58483BD0E1
    GO
    Isoform 2 (identifier: Q99418-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         272-272: Missing.

    Show »
    Length:399
    Mass (Da):46,489
    Checksum:i436A1C1651C8894C
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti306 – 3061L → Q in AAH38713. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei272 – 2721Missing in isoform 2. 1 PublicationVSP_006036

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X99753 mRNA. Translation: CAA68084.1.
    U70728 mRNA. Translation: AAB09591.1.
    AK292405 mRNA. Translation: BAF85094.1.
    BC004361 mRNA. Translation: AAH04361.1.
    BC038713 mRNA. Translation: AAH38713.1.
    CCDSiCCDS12722.1. [Q99418-2]
    RefSeqiNP_004219.3. NM_004228.6. [Q99418-2]
    NP_059431.1. NM_017457.5. [Q99418-1]
    UniGeneiHs.144011.

    Genome annotation databases

    EnsembliENST00000452733; ENSP00000408236; ENSG00000105443. [Q99418-2]
    GeneIDi9266.
    KEGGihsa:9266.
    UCSCiuc002pjj.4. human. [Q99418-1]

    Polymorphism databases

    DMDMi13124707.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X99753 mRNA. Translation: CAA68084.1 .
    U70728 mRNA. Translation: AAB09591.1 .
    AK292405 mRNA. Translation: BAF85094.1 .
    BC004361 mRNA. Translation: AAH04361.1 .
    BC038713 mRNA. Translation: AAH38713.1 .
    CCDSi CCDS12722.1. [Q99418-2 ]
    RefSeqi NP_004219.3. NM_004228.6. [Q99418-2 ]
    NP_059431.1. NM_017457.5. [Q99418-1 ]
    UniGenei Hs.144011.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1PBV X-ray 2.00 A 52-246 [» ]
    1R8M X-ray 1.70 E 50-252 [» ]
    1R8Q X-ray 1.86 E/F 50-252 [» ]
    1R8S X-ray 1.46 E 50-252 [» ]
    1S9D X-ray 1.80 E 50-252 [» ]
    4JMI X-ray 1.50 A 56-251 [» ]
    4JMO X-ray 1.80 A 56-251 [» ]
    4JWL X-ray 1.95 A 56-251 [» ]
    4JXH X-ray 1.47 A 56-251 [» ]
    4L5M X-ray 1.80 A 56-251 [» ]
    ProteinModelPortali Q99418.
    SMRi Q99418. Positions 56-392.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114687. 16 interactions.
    DIPi DIP-31598N.
    IntActi Q99418. 10 interactions.
    MINTi MINT-3058896.
    STRINGi 9606.ENSP00000408236.

    Chemistry

    ChEMBLi CHEMBL5995.

    PTM databases

    PhosphoSitei Q99418.

    Polymorphism databases

    DMDMi 13124707.

    Proteomic databases

    MaxQBi Q99418.
    PaxDbi Q99418.
    PRIDEi Q99418.

    Protocols and materials databases

    DNASUi 9266.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000452733 ; ENSP00000408236 ; ENSG00000105443 . [Q99418-2 ]
    GeneIDi 9266.
    KEGGi hsa:9266.
    UCSCi uc002pjj.4. human. [Q99418-1 ]

    Organism-specific databases

    CTDi 9266.
    GeneCardsi GC19P048972.
    HGNCi HGNC:9502. CYTH2.
    HPAi CAB014872.
    MIMi 602488. gene.
    neXtProti NX_Q99418.
    PharmGKBi PA33849.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5307.
    HOGENOMi HOG000253023.
    HOVERGENi HBG002647.
    InParanoidi Q99418.
    OrthoDBi EOG7RBZ9C.
    PhylomeDBi Q99418.
    TreeFami TF352091.

    Miscellaneous databases

    EvolutionaryTracei Q99418.
    GeneWikii CYTH2.
    GenomeRNAii 9266.
    NextBioi 34733.
    PROi Q99418.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q99418.
    Bgeei Q99418.
    CleanExi HS_CYTH2.
    Genevestigatori Q99418.

    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. "A human exchange factor for ARF contains Sec7- and pleckstrin-homology domains."
      Chardin P., Paris S., Antonny B., Robineau S., Bernaud-Dufour S., Jackson C.L., Chabre M.
      Nature 384:481-484(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Brain.
    2. "ARNO is a guanine nucleotide exchange factor for ADP-ribosylation factor 6."
      Frank S.F., Upender S.K., Hansen S.H., Casanova J.E.
      J. Biol. Chem. 273:23-27(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CHARACTERIZATION.
      Tissue: Brain.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Testis.
    4. "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 1).
      Tissue: Lung and Testis.
    5. "The calcium-sensing receptor changes cell shape via a beta-arrestin-1 ARNO ARF6 ELMO protein network."
      Bouschet T., Martin S., Kanamarlapudi V., Mundell S., Henley J.M.
      J. Cell Sci. 120:2489-2497(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARRB1.
    6. "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: FUNCTION, INTERACTION WITH ARL4D AND ARRB1, MUTAGENESIS OF GLU-156; LYS-268; ARG-280; ILE-303 AND LYS-336, SUBCELLULAR LOCATION.
    7. "Structure of the guanine nucleotide exchange factor Sec7 domain of human ARNO and analysis of the interaction with ARF GTPase."
      Mossessova E., Gulbis J.M., Goldberg J.
      Cell 92:415-423(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 51-252.
    8. Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 51-252.
    9. "Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor."
      Renault L., Guibert B., Cherfils J.
      Nature 426:525-530(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 50-252 IN COMPLEX WITH ARF1; GDP AND BREFELDIN A.

    Entry informationi

    Entry nameiCYH2_HUMAN
    AccessioniPrimary (citable) accession number: Q99418
    Secondary accession number(s): A8K8P0, Q8IXY9, Q92958
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: February 21, 2001
    Last modified: October 1, 2014
    This is version 143 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 19
      Human chromosome 19: 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