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P0C213

- TAX_HTL1F

UniProt

P0C213 - TAX_HTL1F

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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

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.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri23 – 4927 Reviewed prediction
Add
BLAST

GO - Molecular functioni

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

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
Complete GO annotation...

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.

GO - Cellular componenti

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

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-1
PRO_0000260488Add
BLAST

Amino acid modifications

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

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.

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[»]

Miscellaneous databases

EvolutionaryTraceiP0C213.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 5857Interaction with CREB1 By similarity
Add
BLAST
Regioni81 – 9515Interaction with CREBBP/P300 By similarity
Add
BLAST
Regioni106 – 1116Interaction with IKBKG By similarity
Regioni116 – 14530Homodimerization By similarity
Add
BLAST
Regioni213 – 24836Homodimerization By similarity
Add
BLAST
Regioni289 – 32234Transactivation By similarity
Add
BLAST
Regioni312 – 3198Interaction with CREBBP C-terminus By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi73 – 808SH3-binding Reviewed prediction
Motifi188 – 20215Nuclear export signal By similarity
Add
BLAST
Motifi350 – 3534PDZ-binding By 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.

Sequence similaritiesi

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

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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...

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: February 19, 2014
This is version 38 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

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