P0C213 (TAX_HTL1F) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 38. History...
Names and origin
|Protein names||Recommended name:|
Trans-activating transcriptional regulatory protein of HTLV-1
|Organism||Human T-cell leukemia virus 1 (isolate Zaire EL subtype B) (HTLV-1)|
|Taxonomic identifier||39015 [NCBI]|
|Taxonomic lineage||Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Deltaretrovirus ›|
|Virus host||Homo sapiens (Human) [TaxID: 9606]|
|Sequence length||353 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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.
Homodimer. Interacts with host CREB1, SUV39H1, CARM1, DLG1, IKBKG, KDM4A, MAGI3 and TAX1BP1. Recruits the coactivators CREBBP, EP300 and PCAF By similarity.
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.
Down-regulated by P30II.
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.
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.
HTLV-1 lineages are divided in four clades, A (Cosmopolitan), B (Central African group), C (Melanesian group) and D (New Central African group).
Belongs to the deltaretrovirus Tax protein family.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 353||353||Protein Tax-1||PRO_0000260488|
|Zinc finger||23 – 49||27||Potential|
|Region||2 – 58||57||Interaction with CREB1 By similarity|
|Region||81 – 95||15||Interaction with CREBBP/P300 By similarity|
|Region||106 – 111||6||Interaction with IKBKG By similarity|
|Region||116 – 145||30||Homodimerization By similarity|
|Region||213 – 248||36||Homodimerization By similarity|
|Region||289 – 322||34||Transactivation By similarity|
|Region||312 – 319||8||Interaction with CREBBP C-terminus By similarity|
|Motif||73 – 80||8||SH3-binding Potential|
|Motif||188 – 202||15||Nuclear export signal By similarity|
|Motif||350 – 353||4||PDZ-binding By similarity|
Amino acid modifications
|Modified residue||48||1||Phosphothreonine; by host By similarity|
|Modified residue||184||1||Phosphothreonine; by host By similarity|
|Modified residue||215||1||Phosphothreonine; by host By similarity|
|Modified residue||300||1||Phosphoserine; by host By similarity|
|Modified residue||301||1||Phosphoserine; by host By similarity|
|Modified residue||336||1||Phosphoserine; by host By similarity|
|||"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].
|||"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.
|||"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.
|+||Additional computationally mapped references.|
|M67514 Genomic RNA. No translation available.|
3D structure databases
Protocols and materials databases
Family and domain databases
|InterPro||IPR004120. Tax. |
|Pfam||PF02959. Tax. 1 hit. |
|Accession||Primary (citable) accession number: P0C213|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|