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Q7Z628

- ARHG8_HUMAN

UniProt

Q7Z628 - ARHG8_HUMAN

Protein

Neuroepithelial cell-transforming gene 1 protein

Gene

NET1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 103 (01 Oct 2014)
      Sequence version 1 (01 Oct 2003)
      Previous versions | rss
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    Functioni

    Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase. May be involved in activation of the SAPK/JNK pathway Stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death.1 Publication

    GO - Molecular functioni

    1. guanyl-nucleotide exchange factor activity Source: ProtInc
    2. Rho guanyl-nucleotide exchange factor activity Source: InterPro

    GO - Biological processi

    1. apoptotic signaling pathway Source: Reactome
    2. cellular response to hydrogen peroxide Source: UniProtKB
    3. cellular response to ionizing radiation Source: UniProtKB
    4. neurotrophin TRK receptor signaling pathway Source: Reactome
    5. positive regulation of apoptotic process Source: UniProtKB
    6. positive regulation of Rho GTPase activity Source: UniProtKB
    7. regulation of cell growth Source: UniProtKB
    8. regulation of small GTPase mediated signal transduction Source: Reactome
    9. signal transduction Source: ProtInc
    10. small GTPase mediated signal transduction Source: Reactome

    Keywords - Molecular functioni

    Guanine-nucleotide releasing factor

    Enzyme and pathway databases

    ReactomeiREACT_11051. Rho GTPase cycle.
    REACT_13638. NRAGE signals death through JNK.
    REACT_18407. G alpha (12/13) signalling events.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Neuroepithelial cell-transforming gene 1 protein
    Alternative name(s):
    Proto-oncogene p65 Net1
    Rho guanine nucleotide exchange factor 8
    Gene namesi
    Name:NET1
    Synonyms:ARHGEF8
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:14592. NET1.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Keywords - Diseasei

    Proto-oncogene

    Organism-specific databases

    PharmGKBiPA164742175.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 596596Neuroepithelial cell-transforming gene 1 proteinPRO_0000080924Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication
    Modified residuei21 – 211Phosphoserine1 Publication
    Modified residuei32 – 321Phosphoserine1 Publication
    Modified residuei106 – 1061Phosphoserine2 Publications
    Modified residuei508 – 5081PhosphoserineBy similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ7Z628.
    PaxDbiQ7Z628.
    PRIDEiQ7Z628.

    PTM databases

    PhosphoSiteiQ7Z628.

    Expressioni

    Tissue specificityi

    Widely expressed.1 Publication

    Inductioni

    By TGFB1. Up-regulated by DNA damaging agents like H2O2 or ionizing radiation (IR).2 Publications

    Gene expression databases

    ArrayExpressiQ7Z628.
    BgeeiQ7Z628.
    CleanExiHS_NET1.
    GenevestigatoriQ7Z628.

    Organism-specific databases

    HPAiHPA020068.

    Interactioni

    Subunit structurei

    Interacts with RHOA in its GTP- and GDP-bound states, and with CDC42 in its GTP-bound state. Interacts with the PDZ 1 domain of BAIAP1 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi115565. 7 interactions.
    IntActiQ7Z628. 2 interactions.
    STRINGi9606.ENSP00000347134.

    Structurei

    Secondary structure

    1
    596
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi170 – 19930
    Helixi201 – 2066
    Helixi212 – 2198
    Helixi222 – 23918
    Helixi250 – 2567
    Helixi257 – 2637
    Helixi264 – 2674
    Helixi270 – 28011
    Helixi284 – 29512
    Helixi304 – 3085
    Helixi309 – 32719
    Helixi335 – 35117

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3EO2X-ray2.60A161-373[»]
    ProteinModelPortaliQ7Z628.
    SMRiQ7Z628. Positions 166-499.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ7Z628.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini174 – 356183DHPROSITE-ProRule annotationAdd
    BLAST
    Domaini386 – 501116PHPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 7474Necessary for nuclear localizationBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi12 – 198Nuclear localization signalBy similarity
    Motifi66 – 727Nuclear localization signalBy similarity

    Sequence similaritiesi

    Contains 1 DH (DBL-homology) domain.PROSITE-ProRule annotation
    Contains 1 PH domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG5422.
    HOVERGENiHBG050567.
    InParanoidiQ7Z628.
    OMAiTTREIKR.
    OrthoDBiEOG7J446D.
    PhylomeDBiQ7Z628.
    TreeFamiTF328974.

    Family and domain databases

    Gene3Di1.20.900.10. 1 hit.
    2.30.29.30. 1 hit.
    InterProiIPR000219. DH-domain.
    IPR001331. GDS_CDC24_CS.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR015721. RhoGEF-like.
    [Graphical view]
    PANTHERiPTHR22825. PTHR22825. 1 hit.
    PfamiPF00169. PH. 1 hit.
    PF00621. RhoGEF. 1 hit.
    [Graphical view]
    SMARTiSM00233. PH. 1 hit.
    SM00325. RhoGEF. 1 hit.
    [Graphical view]
    SUPFAMiSSF48065. SSF48065. 1 hit.
    PROSITEiPS00741. DH_1. 1 hit.
    PS50010. DH_2. 1 hit.
    PS50003. PH_DOMAIN. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q7Z628-1) [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

    MEPELAAQKQ PRPRRRSRRA SGLSTEGATG PSADTSGSEL DGRCSLRRGS    50
    SFTFLTPGPN WDFTLKRKRR EKDDDVVSLS SLDLKEPSNK RVRPLARVTS 100
    LANLISPVRN GAVRRFGQTI QSFTLRGDHR SPASAQKFSS RSTVPTPAKR 150
    RSSALWSEML DITMKESLTT REIRRQEAIY EMSRGEQDLI EDLKLARKAY 200
    HDPMLKLSIM SEEELTHIFG DLDSYIPLHE DLLTRIGEAT KPDGTVEQIG 250
    HILVSWLPRL NAYRGYCSNQ LAAKALLDQK KQDPRVQDFL QRCLESPFSR 300
    KLDLWSFLDI PRSRLVKYPL LLKEILKHTP KEHPDVQLLE DAILIIQGVL 350
    SDINLKKGES ECQYYIDKLE YLDEKQRDPR IEASKVLLCH GELRSKSGHK 400
    LYIFLFQDIL VLTRPVTRNE RHSYQVYRQP IPVQELVLED LQDGDVRMGG 450
    SFRGAFSNSE KAKNIFRIRF HDPSPAQSHT LQANDVFHKQ QWFNCIRAAI 500
    APFQSAGSPP ELQGLPELHE ECEGNHPSAR KLTAQRRAST VSSVTQVEVD 550
    ENAYRCGSGM QMAEDSKSLK THQTQPGIRR ARDKALSGGK RKETLV 596
    Length:596
    Mass (Da):67,740
    Last modified:October 1, 2003 - v1
    Checksum:iE1AD964F14650D2C
    GO
    Isoform 2 (identifier: Q7Z628-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-54: Missing.
         55-85: LTPGPNWDFTLKRKRREKDDDVVSLSSLDLK → MVAHDETGGLLPIKRTIRVLDVNNQSFREQE

    Show »
    Length:542
    Mass (Da):61,885
    Checksum:i770F252F0FCA7E92
    GO

    Sequence cautioni

    The sequence AAB08847.1 differs from that shown. Reason: Frameshift at position 586.
    The sequence AAB37683.1 differs from that shown. Reason: Frameshift at positions 15 and 33.
    The sequence CAA08974.1 differs from that shown. Reason: Frameshift at positions 8, 55, 59, 70 and 586.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti39 – 391E → R in AAB37683. (PubMed:8649828)Curated
    Sequence conflicti61 – 611W → C in AAB37683. (PubMed:8649828)Curated
    Sequence conflicti143 – 1464TVPT → MDGW in AAB08847. (PubMed:8649828)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti202 – 2021D → N in a breast cancer sample; somatic mutation. 1 Publication
    VAR_035972
    Natural varianti417 – 4171T → I.
    Corresponds to variant rs34658946 [ dbSNP | Ensembl ].
    VAR_051982

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 5454Missing in isoform 2. 2 PublicationsVSP_011619Add
    BLAST
    Alternative sequencei55 – 8531LTPGP…SLDLK → MVAHDETGGLLPIKRTIRVL DVNNQSFREQE in isoform 2. 2 PublicationsVSP_011620Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    S82401 mRNA. Translation: AAB37683.1. Frameshift.
    U02081 mRNA. Translation: AAB08847.1. Frameshift.
    AJ010046 mRNA. Translation: CAA08974.1. Frameshift.
    BC010285 mRNA. Translation: AAH10285.1.
    BC053553 mRNA. Translation: AAH53553.1.
    CCDSiCCDS41483.1. [Q7Z628-1]
    CCDS7067.1. [Q7Z628-2]
    PIRiG01210.
    RefSeqiNP_001040625.1. NM_001047160.2. [Q7Z628-1]
    NP_005854.2. NM_005863.4. [Q7Z628-2]
    UniGeneiHs.25155.

    Genome annotation databases

    EnsembliENST00000355029; ENSP00000347134; ENSG00000173848. [Q7Z628-1]
    ENST00000380359; ENSP00000369717; ENSG00000173848. [Q7Z628-2]
    GeneIDi10276.
    KEGGihsa:10276.
    UCSCiuc001iia.4. human. [Q7Z628-1]

    Polymorphism databases

    DMDMi52782735.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    S82401 mRNA. Translation: AAB37683.1 . Frameshift.
    U02081 mRNA. Translation: AAB08847.1 . Frameshift.
    AJ010046 mRNA. Translation: CAA08974.1 . Frameshift.
    BC010285 mRNA. Translation: AAH10285.1 .
    BC053553 mRNA. Translation: AAH53553.1 .
    CCDSi CCDS41483.1. [Q7Z628-1 ]
    CCDS7067.1. [Q7Z628-2 ]
    PIRi G01210.
    RefSeqi NP_001040625.1. NM_001047160.2. [Q7Z628-1 ]
    NP_005854.2. NM_005863.4. [Q7Z628-2 ]
    UniGenei Hs.25155.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3EO2 X-ray 2.60 A 161-373 [» ]
    ProteinModelPortali Q7Z628.
    SMRi Q7Z628. Positions 166-499.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115565. 7 interactions.
    IntActi Q7Z628. 2 interactions.
    STRINGi 9606.ENSP00000347134.

    PTM databases

    PhosphoSitei Q7Z628.

    Polymorphism databases

    DMDMi 52782735.

    Proteomic databases

    MaxQBi Q7Z628.
    PaxDbi Q7Z628.
    PRIDEi Q7Z628.

    Protocols and materials databases

    DNASUi 10276.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000355029 ; ENSP00000347134 ; ENSG00000173848 . [Q7Z628-1 ]
    ENST00000380359 ; ENSP00000369717 ; ENSG00000173848 . [Q7Z628-2 ]
    GeneIDi 10276.
    KEGGi hsa:10276.
    UCSCi uc001iia.4. human. [Q7Z628-1 ]

    Organism-specific databases

    CTDi 10276.
    GeneCardsi GC10P005444.
    HGNCi HGNC:14592. NET1.
    HPAi HPA020068.
    MIMi 606450. gene.
    neXtProti NX_Q7Z628.
    PharmGKBi PA164742175.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5422.
    HOVERGENi HBG050567.
    InParanoidi Q7Z628.
    OMAi TTREIKR.
    OrthoDBi EOG7J446D.
    PhylomeDBi Q7Z628.
    TreeFami TF328974.

    Enzyme and pathway databases

    Reactomei REACT_11051. Rho GTPase cycle.
    REACT_13638. NRAGE signals death through JNK.
    REACT_18407. G alpha (12/13) signalling events.

    Miscellaneous databases

    ChiTaRSi NET1. human.
    EvolutionaryTracei Q7Z628.
    GeneWikii NET1.
    GenomeRNAii 10276.
    NextBioi 38926.
    PROi Q7Z628.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q7Z628.
    Bgeei Q7Z628.
    CleanExi HS_NET1.
    Genevestigatori Q7Z628.

    Family and domain databases

    Gene3Di 1.20.900.10. 1 hit.
    2.30.29.30. 1 hit.
    InterProi IPR000219. DH-domain.
    IPR001331. GDS_CDC24_CS.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR015721. RhoGEF-like.
    [Graphical view ]
    PANTHERi PTHR22825. PTHR22825. 1 hit.
    Pfami PF00169. PH. 1 hit.
    PF00621. RhoGEF. 1 hit.
    [Graphical view ]
    SMARTi SM00233. PH. 1 hit.
    SM00325. RhoGEF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48065. SSF48065. 1 hit.
    PROSITEi PS00741. DH_1. 1 hit.
    PS50010. DH_2. 1 hit.
    PS50003. PH_DOMAIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Isolation of a novel oncogene, NET1, from neuroepithelioma cells by expression cDNA cloning."
      Chan A.M.-L., Takai S., Yamada K., Miki T.
      Oncogene 12:1259-1266(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
      Tissue: Neuroepithelium.
    2. "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] (ISOFORMS 1 AND 2).
      Tissue: Eye and Placenta.
    3. "The activity of guanine exchange factor NET1 is essential for transforming growth factor-beta-mediated stress fiber formation."
      Shen X., Li J., Hu P.P.-C., Waddell D., Zhang J., Wang X.-F.
      J. Biol. Chem. 276:15362-15368(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION BY TGFB1.
    4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    5. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21; SER-32 AND SER-106, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    6. "The nuclear guanine nucleotide exchange factors Ect2 and Net1 regulate RhoB-mediated cell death after DNA damage."
      Srougi M.C., Burridge K.
      PLoS ONE 6:E17108-E17108(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION.
    7. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    8. "Crystal structure of the RhoGEF domain of human neuroepithelial cell-transforming gene 1 protein."
      Structural genomics consortium (SGC)
      Submitted (FEB-2009) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 161-373.
    9. Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-202.

    Entry informationi

    Entry nameiARHG8_HUMAN
    AccessioniPrimary (citable) accession number: Q7Z628
    Secondary accession number(s): Q12773
    , Q96D82, Q99903, Q9UEN6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 27, 2004
    Last sequence update: October 1, 2003
    Last modified: October 1, 2014
    This is version 103 of the entry and version 1 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 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3