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Protein

Protein Tax-1

Gene

tax

Organism
Human T-cell leukemia virus 1 (strain Japan ATK-1 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.5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri23 – 49Sequence analysisAdd BLAST27

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 (strain Japan ATK-1 subtype A) (HTLV-1)
Taxonomic identifieri11926 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeDeltaretrovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000007683 Componenti: Genome

Subcellular locationi

  • Host nucleus 1 Publication
  • Host cytoplasm 1 Publication

  • 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.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi48T → A: 30% loss of CREB activation. 70% loss of NF-kappa-B activation. 1 Publication1
Mutagenesisi48T → D: 50% loss of CREB activation. Almost complete loss of NF-kappa-B activation. 1 Publication1
Mutagenesisi184T → A: Slightly reduced CREB and NF-kappa-B activation. 1 Publication1
Mutagenesisi184T → D: Slightly reduced CREB and NF-kappa-B activation. 1 Publication1
Mutagenesisi200L → A: Complete loss of Tax-1 nuclear export. 1 Publication1
Mutagenesisi215T → A: 30% loss of CREB activation. Slightly reduced NF-kappa-B activation. 1 Publication1
Mutagenesisi215T → D: Almost complete loss of CREB and NF-kappa-B activation. 1 Publication1
Mutagenesisi300 – 301SS → AA: Almost complete loss of CREB and NF-kappa-B activation. 1 Publication2
Mutagenesisi300 – 301SS → DD: 30% loss of CREB activation. 80% loss of NF-kappa-B activation. 1 Publication2
Mutagenesisi336S → A: Slightly reduced CREB and NF-kappa-B activation. 1 Publication1
Mutagenesisi336S → D: Slightly reduced CREB and NF-kappa-B activation. 1 Publication1

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000854941 – 353Protein Tax-1Add BLAST353

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei48Phosphothreonine; by host1 Publication1
Modified residuei184Phosphothreonine; by host1 Publication1
Modified residuei215Phosphothreonine; by host1 Publication1
Modified residuei300Phosphoserine; by host1 Publication1
Modified residuei301Phosphoserine; by host1 Publication1
Modified residuei336Phosphoserine; by host1 Publication1

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.2 Publications

Keywords - PTMi

Phosphoprotein

PTM databases

iPTMnetiP03409.

Expressioni

Inductioni

Down-regulated by P30II.

Interactioni

Subunit structurei

Homodimer. Interacts with host CREB1, DLG1, IKBKG, KDM4A, MAGII3 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. Interaction with human CREB coactivators, CRTC1/TORC1, CRTC2/TORC2 and CRTC3/TORC3 enhances TAX transactivation.14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HDAC6Q9UBN74EBI-5236464,EBI-301697From a different organism.
IKBKBO149203EBI-5236464,EBI-81266From a different organism.

Protein-protein interaction databases

IntActiP03409. 4 interactors.
MINTiMINT-8205333.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 58Interaction with CREB1Add BLAST57
Regioni81 – 95Interaction with CREBBP/P300Add BLAST15
Regioni106 – 111Interaction with IKBKG6
Regioni116 – 145HomodimerizationAdd BLAST30
Regioni213 – 248HomodimerizationAdd BLAST36
Regioni289 – 322TransactivationAdd BLAST34
Regioni312 – 319Interaction with CREBBP C-terminus8

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi73 – 80SH3-bindingSequence analysis8
Motifi188 – 202Nuclear export signalAdd BLAST15
Motifi350 – 353PDZ-binding4

Domaini

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

Sequence similaritiesi

Belongs to the deltaretrovirus Tax protein family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri23 – 49Sequence analysisAdd BLAST27

Keywords - Domaini

SH3-binding, Zinc-finger

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

P03409-1 [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 IEELLYKISL
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
SFHSLHLLFE EYTNIPISLL FNEKEADDND HEPQISPGGL EPPSEKHFRE

TEV
Length:353
Mass (Da):39,471
Last modified:May 16, 2006 - v2
Checksum:iB3D2C05C26926D56
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02029 Genomic DNA. No translation available.
PIRiA93954. TNLJH1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02029 Genomic DNA. No translation available.
PIRiA93954. TNLJH1.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP03409. 4 interactors.
MINTiMINT-8205333.

PTM databases

iPTMnetiP03409.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

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

Entry informationi

Entry nameiTAX_HTL1A
AccessioniPrimary (citable) accession number: P03409
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: May 16, 2006
Last modified: November 2, 2016
This is version 79 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

Complete proteome

Documents

  1. 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.