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Protein

Protein Tax-1

Gene

tax

Organism
Human T-cell leukemia virus 1 (isolate Caribbea HS-35 subtype A) (HTLV-1)
Status
Reviewed-Annotation score: Annotation score: 5 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).By similarity

Regions

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

GO - Molecular functioni

GO - Biological processi

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
Short name:
Protein PX
Trans-activating transcriptional regulatory protein of HTLV-1
Gene namesi
Name:tax
OrganismiHuman T-cell leukemia virus 1 (isolate Caribbea HS-35 subtype A) (HTLV-1)
Taxonomic identifieri11927 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeDeltaretrovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000001061 Componenti: Genome

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

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-1PRO_0000085495Add
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, DLG1, IKBKG, KDM4A, MAGI3 and TAX1BP1. recruits the coactivators CREBBP, EP300 and PCAF. Interaction with human CARM1 enhances Tax transactivation and promotes methylation of histone H3. Interacts with host SUV39H1 protein, leading to abrogate Tax transactivation of HTLV-1 LTR (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CCDC92Q53HC03EBI-9675698,EBI-719994From a different organism.
CEP63Q96MT85EBI-9675698,EBI-741977From a different organism.
CRADDP785603EBI-9675698,EBI-520375From a different organism.
CTDSP2O145953EBI-9675698,EBI-2802973From a different organism.
DGCR6LQ9BY273EBI-9675698,EBI-742953From a different organism.
ETV4P432683EBI-9675698,EBI-6447147From a different organism.
FANCGO152873EBI-9675698,EBI-81610From a different organism.
FATE1Q969F03EBI-9675698,EBI-743099From a different organism.
HENMT1Q5T8I93EBI-9675698,EBI-9675710From a different organism.
HGSO149644EBI-9675698,EBI-740220From a different organism.
KRT15P190123EBI-9675698,EBI-739566From a different organism.
KRT4P190133EBI-9675698,EBI-2371606From a different organism.
KRT8P057873EBI-9675698,EBI-297852From a different organism.
LNX2Q8N4484EBI-9675698,EBI-2340947From a different organism.
MRPS6P829323EBI-9675698,EBI-716172From a different organism.
NEFLP071964EBI-9675698,EBI-475646From a different organism.
NIF3L1Q9GZT83EBI-9675698,EBI-740897From a different organism.
NOS3P294743EBI-9675698,EBI-1391623From a different organism.
NUDT18Q6ZVK85EBI-9675698,EBI-740486From a different organism.
POLMQ9NP873EBI-9675698,EBI-9675790From a different organism.
POP5Q969H63EBI-9675698,EBI-366525From a different organism.
RFX4Q33E943EBI-9675698,EBI-9675925From a different organism.
RGP1Q925463EBI-9675698,EBI-2823702From a different organism.
RIBC2Q9H4K13EBI-9675698,EBI-740128From a different organism.
TTC23LQ6PF053EBI-9675698,EBI-8656864From a different organism.
WDFY3Q8IZQ13EBI-9675698,EBI-1569256From a different organism.
ZNF614Q8N8833EBI-9675698,EBI-9675993From a different organism.

Protein-protein interaction databases

IntActiP14079. 56 interactions.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AO7X-ray2.60C11-19[»]
1HHKX-ray2.50C/F11-19[»]
1IM3X-ray2.20C/G/K/O11-19[»]
2AV1X-ray1.95C/F11-19[»]
2AV7X-ray2.05C/F11-19[»]
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP14079.

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.

P14079-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAHFPGFGQS LLFGYPVYVF GDCVQGDWCP ISGGLCSARL HRHALLATCP
60 70 80 90 100
EHQITWDPID GRVIGSALQF LIPRLPSFPT QRTSKTLKVL TPPITHTTPN
110 120 130 140 150
IPPSFLQAMR KYSPFRNGYM EPTLGQHLPT LSFPDPGLRP QNLYTLWGGS
160 170 180 190 200
VVCMYLYQLS PPITWPLLPH VIFCHPGQLG AFLTNVPYKR IEKLLYKISL
210 220 230 240 250
TTGALIILPE DCLPTTLFQP ARAPVTLTAW QNGLLPFHST LTTPGLIWTF
260 270 280 290 300
TDGTPMISGP CPKDGQPSLV LQSSSFIFHK FQTKAYHPSF LLSHGLIQYS
310 320 330 340 350
SFHNLHLLFE EYTNIPISLL FNEKEADDND HEPQISPGGL EPLSEKHFRE

TEV
Length:353
Mass (Da):39,513
Last modified:May 16, 2006 - v2
Checksum:i60DF69BFD58265F4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13784 Genomic DNA. No translation available.
AF033817 Genomic DNA. Translation: AAC82583.1.
PIRiE28136. TNLJCN.
RefSeqiNP_057864.1. NC_001436.1.

Genome annotation databases

GeneIDi1491938.
KEGGivg:1491938.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13784 Genomic DNA. No translation available.
AF033817 Genomic DNA. Translation: AAC82583.1.
PIRiE28136. TNLJCN.
RefSeqiNP_057864.1. NC_001436.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AO7X-ray2.60C11-19[»]
1HHKX-ray2.50C/F11-19[»]
1IM3X-ray2.20C/G/K/O11-19[»]
2AV1X-ray1.95C/F11-19[»]
2AV7X-ray2.05C/F11-19[»]
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP14079. 56 interactions.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1491938.
KEGGivg:1491938.

Miscellaneous databases

EvolutionaryTraceiP14079.

Family and domain databases

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

Publicationsi

  1. "Molecular cloning and complete nucleotide sequence of an adult T cell leukaemia virus/human T cell leukaemia virus type I (ATLV/HTLV-I) isolate of Caribbean origin: relationship to other members of the ATLV/HTLV-I subgroup."
    Malik K.T.A., Even J., Karpas A.
    J. Gen. Virol. 69:1695-1710(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. Chappey C.
    Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "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.
  4. "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.
  5. "Assembly, specific binding, and crystallization of a human TCR-alphabeta with an antigenic Tax peptide from human T lymphotropic virus type 1 and the class I MHC molecule HLA-A2."
    Garboczi D.N., Utz U., Ghosh P., Seth A., Kim J., VanTienhoven E.A., Biddison W.E., Wiley D.C.
    J. Immunol. 157:5403-5410(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 16-24.

Entry informationi

Entry nameiTAX_HTL1C
AccessioniPrimary (citable) accession number: P14079
Secondary accession number(s): O56231
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: May 16, 2006
Last modified: June 8, 2016
This is version 85 of the entry and version 2 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, Complete proteome, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.