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P0C213

- TAX_HTL1F

UniProt

P0C213 - TAX_HTL1F

Protein

Protein Tax-1

Gene

tax

Organism
Human T-cell leukemia virus 1 (isolate Zaire EL subtype B) (HTLV-1)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 39 (01 Oct 2014)
      Sequence version 1 (28 Nov 2006)
      Previous versions | rss
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    Functioni

    Transcriptional activator that activates both the viral long terminal repeat (LTR) and cellular promoters via activation of CREB, NF-kappa-B, SRF and AP-1 pathways. Binds to three 21 bp repeat elements located within the LTRs, referred to as Tax-responsive elements (TRE). Binding to TRE requires the interaction with CREB1 and CREBBP. Also induces chromatin remodeling of proviral LTR-mediated gene expression by recruiting the histone acetyl transferases CREBBP and EP300 to the chromatin, which results in histone acetylation. Via its interaction with IKK regulatory subunit IKBKG, Tax-1 persistently stimulates I-kappa-B kinase (IKK), resulting in constitutive activation of the transcription factor NF-kappa-B. Induction of the nuclear expression of members of the NFkB family of transcription factors, which leads to up-regulated expression of many gene promoters containing NFkB motifs. These genes include those encoding IL2, IL15, IL2RA and IL15RA, leading to autocrine IL2/IL2RA and IL15/IL15RA loops. The resulting T-cell proliferation leads to malignant transformation and to the development of adult T-cell leukemia (ATL). IL13, known to be linked to leukemogenesis, is also up-regulated by Tax-1. Interaction with PDZ domain-containing proteins induce IL2-independent growth, which may be a factor in multi-step leukemogenesis. Inhibits the action of at least three cellular tumor suppressors p53/TP53, RB1 and DLG1, and suppresses their abilities to dictate apoptosis in primary cells. Required for viral replication By similarity.By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri23 – 4927Sequence AnalysisAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB-KW
    2. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. activation by virus of host NF-kappaB transcription factor activity Source: UniProtKB-KW
    2. modulation by virus of host G0/G1 transition checkpoint Source: UniProtKB-KW
    3. modulation by virus of host G1/S transition checkpoint Source: UniProtKB-KW
    4. positive regulation of transcription, DNA-templated Source: InterPro
    5. suppression by virus of host exit from mitosis Source: UniProtKB-KW
    6. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Activation of host NF-kappa-B by virus, G0/G1 host cell cycle checkpoint dysregulation by virus, G1/S host cell cycle checkpoint dysregulation by virus, Host-virus interaction, Inhibition of host mitotic exit by virus, Modulation of host cell cycle by virus, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein Tax-1
    Alternative name(s):
    Protein X-LOR
    Trans-activating transcriptional regulatory protein of HTLV-1
    Gene namesi
    Name:tax
    OrganismiHuman T-cell leukemia virus 1 (isolate Zaire EL subtype B) (HTLV-1)
    Taxonomic identifieri39015 [NCBI]
    Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeDeltaretrovirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]

    Subcellular locationi

    Host nucleus By similarity. Host cytoplasm By similarity
    Note: Shuttles from the nucleus to the cytoplasm. Found predominantly in the nucleus, where it is equally distributed between the nucleoplasm and the nuclear matrix By similarity.By similarity

    GO - Cellular componenti

    1. host cell cytoplasm Source: UniProtKB-SubCell
    2. host cell nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Host cytoplasm, Host nucleus

    Pathology & Biotechi

    Keywords - Diseasei

    Oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 353353Protein Tax-1PRO_0000260488Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei48 – 481Phosphothreonine; by hostBy similarity
    Modified residuei184 – 1841Phosphothreonine; by hostBy similarity
    Modified residuei215 – 2151Phosphothreonine; by hostBy similarity
    Modified residuei300 – 3001Phosphoserine; by hostBy similarity
    Modified residuei301 – 3011Phosphoserine; by hostBy similarity
    Modified residuei336 – 3361Phosphoserine; by hostBy similarity

    Post-translational modificationi

    Phosphorylation at Thr-48 results in the loss of NF-kappa-B activation function. Phosphorylation at Thr-215 results in loss of CREB and NF-B responsive promoters activation. Phosphorylation at Thr-184 and Ser-336 have no effect on these Tax functions. Phosphorylation of either Ser-300 or Ser-301 is necessary for localization to nuclear bodies. Thr-48, Thr-184, Thr-215 and Ser-336 are highly phosphorylated, whereas Ser-300 or Ser-301 are only rarely phosphorylated By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Expressioni

    Inductioni

    Down-regulated by P30II.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with host CREB1, SUV39H1, CARM1, DLG1, IKBKG, KDM4A, MAGI3 and TAX1BP1. Recruits the coactivators CREBBP, EP300 and PCAF By similarity.By similarity

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1BD2X-ray2.50C11-19[»]
    4E5XX-ray1.95C/F11-19[»]
    4FTVX-ray2.74C11-19[»]
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP0C213.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni2 – 5857Interaction with CREB1By similarityAdd
    BLAST
    Regioni81 – 9515Interaction with CREBBP/P300By similarityAdd
    BLAST
    Regioni106 – 1116Interaction with IKBKGBy similarity
    Regioni116 – 14530HomodimerizationBy similarityAdd
    BLAST
    Regioni213 – 24836HomodimerizationBy similarityAdd
    BLAST
    Regioni289 – 32234TransactivationBy similarityAdd
    BLAST
    Regioni312 – 3198Interaction with CREBBP C-terminusBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi73 – 808SH3-bindingSequence Analysis
    Motifi188 – 20215Nuclear export signalBy similarityAdd
    BLAST
    Motifi350 – 3534PDZ-bindingBy similarity

    Domaini

    The 48 N-terminal residues contain a non-canonical functional nuclear localization signal (NLS).By similarity
    The PDZ-binding domain mediates binding to human DLG1 and MAGI3. Interaction with other PDZ domain-containing protein induces IL2-independent growth By similarity.By similarity

    Sequence similaritiesi

    Belongs to the deltaretrovirus Tax protein family.Curated

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri23 – 4927Sequence AnalysisAdd
    BLAST

    Keywords - Domaini

    SH3-binding, Zinc-finger

    Family and domain databases

    InterProiIPR004120. Tax.
    [Graphical view]
    PfamiPF02959. Tax. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P0C213-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAHFPGFGQS LLFGYPVYVF GDCVQGDWCP ISGGLCSARL HRHALLATCP    50
    EHQITWDPID GRVIGSALQF LIPRLPSFPT QRTSKTLKVL TPPTTHTTPN 100
    IPPSFLQAMR KYSPFRNGYM EPTLGQHLPT LSFPDPGLRP QNLYTLWGGS 150
    VVCMYLYQLS PPITWPLLPH VIFDHPDQLG AFLTNVPYKR MEELLYKISL 200
    TTGALIILPE DCLPTTLFQP ARAPVTLTAW QSGLLPFHST LTTPGLIWAF 250
    TDGTPMISGP CPKDGRPSLV LQSSSFIFHK FQTKAYHPSF LLSHGLIQYS 300
    SFHNLHLLFE EYTNIPISLL FNEKEADDTD HEPQVSPGGL EPPSEKHFRE 350
    TEV 353
    Length:353
    Mass (Da):39,517
    Last modified:November 28, 2006 - v1
    Checksum:i1A475682702FD68F
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M67514 Genomic RNA. No translation available.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M67514 Genomic RNA. No translation available.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1BD2 X-ray 2.50 C 11-19 [» ]
    4E5X X-ray 1.95 C/F 11-19 [» ]
    4FTV X-ray 2.74 C 11-19 [» ]
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Miscellaneous databases

    EvolutionaryTracei P0C213.

    Family and domain databases

    InterProi IPR004120. Tax.
    [Graphical view ]
    Pfami PF02959. Tax. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Limited sequence variation in human T-lymphotropic virus type 1 isolates from North American and African patients."
      Paine E., Garcia J., Philpott T.C., Shaw G., Ratner L.
      Virology 182:111-123(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "Molecular mechanisms of cellular transformation by HTLV-1 Tax."
      Grassmann R., Aboud M., Jeang K.T.
      Oncogene 24:5976-5985(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    3. "Transcriptional and post-transcriptional gene regulation of HTLV-1."
      Kashanchi F., Brady J.N.
      Oncogene 24:5938-5951(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.

    Entry informationi

    Entry nameiTAX_HTL1F
    AccessioniPrimary (citable) accession number: P0C213
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 28, 2006
    Last sequence update: November 28, 2006
    Last modified: October 1, 2014
    This is version 39 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    HTLV-1 lineages are divided in four clades, A (Cosmopolitan), B (Central African group), C (Melanesian group) and D (New Central African group).

    Keywords - Technical termi

    3D-structure

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3