UniProt Accession

 TAX_HTL1A; P03409 

Genbank Protein ID

 J02029 

Genbank Nucleotide ID

  

Protein Name

 Protein Tax-1 

Protein Synonyms/Alias

 Protein X-LOR; Protein PX; Trans-activating transcriptional regulatory protein of HTLV-1 

Gene Name

 tax 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Human T-cell leukemia virus 1 (strain Japan ATK-1 subtype A) (HTLV-1) 

NCBI Taxa ID

 11926 

Lysine Modification

Position	Peptide	Type	References
280	SSSFIFHKFQTKAYH	sumoylation	[1, 2, 3, 4]
284	IFHKFQTKAYHPSFL	sumoylation	[1, 2, 3, 4]
346	GLEPPSEKHFRETEV	acetylation	[5]

Reference

 [1] Stable ubiquitination of human T-cell leukemia virus type 1 tax is required for proteasome binding.
 Chiari E, Lamsoul I, Lodewick J, Chopin C, Bex F, Pique C.
 J Virol. 2004 Nov;78(21):11823-32. [PMID: 15479824]
 [2] Exclusive ubiquitination and sumoylation on overlapping lysine residues mediate NF-kappaB activation by the human T-cell leukemia virus tax oncoprotein.
 Lamsoul I, Lodewick J, Lebrun S, Brasseur R, Burny A, Gaynor RB, Bex F.
 Mol Cell Biol. 2005 Dec;25(23):10391-406. [PMID: 16287853]
 [3] Tax ubiquitylation and sumoylation control critical cytoplasmic and nuclear steps of NF-kappaB activation.
 Nasr R, Chiari E, El-Sabban M, Mahieux R, Kfoury Y, Abdulhay M, Yazbeck V, Hermine O, de Thé H, Pique C, Bazarbachi A.
 Blood. 2006 May 15;107(10):4021-9. [PMID: 16424386]
 [4] The Sumo-targeted ubiquitin ligase RNF4 regulates the localization and function of the HTLV-1 oncoprotein Tax.
 Fryrear KA, Guo X, Kerscher O, Semmes OJ.
 Blood. 2012 Feb 2;119(5):1173-81. [PMID: 22106342]
 [5] Acetylation of the human T-cell leukemia virus type 1 Tax oncoprotein by p300 promotes activation of the NF-kappaB pathway.
 Lodewick J, Lamsoul I, Polania A, Lebrun S, Burny A, Ratner L, Bex F.
 Virology. 2009 Mar 30;386(1):68-78. [PMID: 19200568] 

Functional Description

 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. 

Sequence Annotation

 ZN_FING 23 49 Potential.
 REGION 2 58 Interaction with CREB1.
 REGION 81 95 Interaction with CREBBP/P300.
 REGION 106 111 Interaction with IKBKG.
 REGION 116 145 Homodimerization.
 REGION 213 248 Homodimerization.
 REGION 289 322 Transactivation.
 REGION 312 319 Interaction with CREBBP C-terminus.
 MOTIF 73 80 SH3-binding (Potential).
 MOTIF 188 202 Nuclear export signal.
 MOTIF 350 353 PDZ-binding.
 MOD_RES 48 48 Phosphothreonine; by host.
 MOD_RES 184 184 Phosphothreonine; by host.
 MOD_RES 215 215 Phosphothreonine; by host.
 MOD_RES 300 300 Phosphoserine; by host.
 MOD_RES 301 301 Phosphoserine; by host.
 MOD_RES 336 336 Phosphoserine; by host.  

Keyword

 Activation of host NF-kappa-B by virus; Activator; Complete proteome; DNA-binding; G0/G1 host cell cycle checkpoint dysregulation by virus; G1/S host cell cycle checkpoint dysregulation by virus; Host cytoplasm; Host nucleus; Host-virus interaction; Inhibition of host mitotic exit by virus; Metal-binding; Modulation of host cell cycle by virus; Oncogene; Phosphoprotein; SH3-binding; Transcription; Transcription regulation; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 353 AA 

Protein Sequence

Gene Ontology

 GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
 GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
 GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0039652; P:activation by virus of host NF-kappaB transcription factor activity; IEA:UniProtKB-KW.
 GO:0039646; P:modulation by virus of host G0/G1 transition checkpoint; IEA:UniProtKB-KW.
 GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; IEA:InterPro.
 GO:0039593; P:suppression by virus of host exit from mitosis; IEA:UniProtKB-KW.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 

Interpro

 IPR004120; Tax. 

Pfam

 PF02959; Tax 

SMART

  

PROSITE

  

PRINTS