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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)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 (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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi48 – 481T → A: 30% loss of CREB activation. 70% loss of NF-kappa-B activation. 1 Publication
Mutagenesisi48 – 481T → D: 50% loss of CREB activation. Almost complete loss of NF-kappa-B activation. 1 Publication
Mutagenesisi184 – 1841T → A: Slightly reduced CREB and NF-kappa-B activation. 1 Publication
Mutagenesisi184 – 1841T → D: Slightly reduced CREB and NF-kappa-B activation. 1 Publication
Mutagenesisi200 – 2001L → A: Complete loss of Tax-1 nuclear export. 1 Publication
Mutagenesisi215 – 2151T → A: 30% loss of CREB activation. Slightly reduced NF-kappa-B activation. 1 Publication
Mutagenesisi215 – 2151T → D: Almost complete loss of CREB and NF-kappa-B activation. 1 Publication
Mutagenesisi300 – 3012SS → AA: Almost complete loss of CREB and NF-kappa-B activation. 1 Publication
Mutagenesisi300 – 3012SS → DD: 30% loss of CREB activation. 80% loss of NF-kappa-B activation. 1 Publication
Mutagenesisi336 – 3361S → A: Slightly reduced CREB and NF-kappa-B activation. 1 Publication
Mutagenesisi336 – 3361S → D: Slightly reduced CREB and NF-kappa-B activation. 1 Publication

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 353353Protein Tax-1PRO_0000085494Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei48 – 481Phosphothreonine; by host1 Publication
Modified residuei184 – 1841Phosphothreonine; by host1 Publication
Modified residuei215 – 2151Phosphothreonine; by host1 Publication
Modified residuei300 – 3001Phosphoserine; by host1 Publication
Modified residuei301 – 3011Phosphoserine; by host1 Publication
Modified residuei336 – 3361Phosphoserine; by host1 Publication

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 interactions.
MINTiMINT-8205333.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 5857Interaction with CREB1Add
BLAST
Regioni81 – 9515Interaction with CREBBP/P300Add
BLAST
Regioni106 – 1116Interaction with IKBKG
Regioni116 – 14530HomodimerizationAdd
BLAST
Regioni213 – 24836HomodimerizationAdd
BLAST
Regioni289 – 32234TransactivationAdd
BLAST
Regioni312 – 3198Interaction with CREBBP C-terminus

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi73 – 808SH3-bindingSequence analysis
Motifi188 – 20215Nuclear export signalAdd
BLAST
Motifi350 – 3534PDZ-binding

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)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.

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 interactions.
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...

Publicationsi

  1. "Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA."
    Seiki M., Hattori S., Hirayama Y., Yoshida M.C.
    Proc. Natl. Acad. Sci. U.S.A. 80:3618-3622(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. Cited for: FUNCTION.
  3. "HTLV-I tax gene product activates transcription via pre-existing cellular factors and cAMP responsive element."
    Giam C.-Z., Xu Y.L.
    J. Biol. Chem. 264:15236-15241(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  4. "HTLV-I Tax is a zinc-binding protein: role of zinc in Tax structure and function."
    Semmes O.J., Jeang K.T.
    Virology 188:754-764(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN ZINC-FINGER.
  5. "Human T-cell lymphotropic virus type I (HTLV-I) transcriptional activator, Tax, enhances CREB binding to HTLV-I 21-base-pair repeats by protein-protein interaction."
    Zhao L.J., Giam C.-Z.
    Proc. Natl. Acad. Sci. U.S.A. 89:7070-7074(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RAT CREB1.
  6. "HTLV-I Tax self-association in optimal trans-activation function."
    Jin D.Y., Jeang K.T.
    Nucleic Acids Res. 25:379-387(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  7. "The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins."
    Rousset R., Fabre S., Desbois C., Bantignies F., Jalinot P.
    Oncogene 16:643-654(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN PDZ-BINDING.
  8. "Differential transcriptional activation by human T-cell leukemia virus type 1 Tax mutants is mediated by distinct interactions with CREB binding protein and p300."
    Bex F., Yin M.-J., Burny A., Gaynor R.B.
    Mol. Cell. Biol. 18:2392-2405(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST CREBBP AND EP300.
  9. "Human T-cell leukemia virus type 1 Tax requires direct access to DNA for recruitment of CREB binding protein to the viral promoter."
    Lenzmeier B.A., Giebler H.A., Nyborg J.K.
    Mol. Cell. Biol. 18:721-731(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: DNA-BINDING.
  10. "Phosphorylation of the human T-cell leukemia virus type 1 transactivator tax on adjacent serine residues is critical for tax activation."
    Bex F., Murphy K., Wattiez R., Burny A., Gaynor R.B.
    J. Virol. 73:738-745(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-300 AND SER-301.
  11. "Tax oncoprotein of HTLV-1 binds to the human homologue of Drosophila discs large tumor suppressor protein, hDLG, and perturbs its function in cell growth control."
    Suzuki T., Ohsugi Y., Uchida-Toita M., Akiyama T., Yoshida M.
    Oncogene 18:5967-5972(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN DLG1.
  12. "p300 and p300/cAMP-responsive element-binding protein associated factor interact with human T-cell lymphotropic virus type-1 Tax in a multi-histone acetyltransferase/activator-enhancer complex."
    Harrod R., Kuo Y.-L., Tang Y., Yao Y., Vassilev A., Nakatani Y., Giam C.-Z.
    J. Biol. Chem. 275:11852-11857(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN PCAF.
  13. "Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein."
    Xiao G., Sun S.C.
    Oncogene 19:5198-5203(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN IKBKG.
  14. "The oncoprotein Tax binds the SRC-1-interacting domain of CBP/p300 to mediate transcriptional activation."
    Scoggin K.E.S., Ulloa A., Nyborg J.K.
    Mol. Cell. Biol. 21:5520-5530(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST CREBBP AND EP300.
  15. "Acetylation of nucleosomal histones by p300 facilitates transcription from tax-responsive human T-cell leukemia virus type 1 chromatin template."
    Lu H., Pise-Masison C.A., Fletcher T.M., Schiltz R.L., Nagaich A.K., Radonovich M., Hager G., Cole P.A., Brady J.N.
    Mol. Cell. Biol. 22:4450-4462(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  16. "Characterization of a nuclear export signal within the human T cell leukemia virus type I transactivator protein Tax."
    Alefantis T., Barmak K., Harhaj E.W., Grant C., Wigdahl B.
    J. Biol. Chem. 278:21814-21822(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEAR EXPORT SIGNAL, MUTAGENESIS OF LEU-200.
  17. Cited for: INTERACTION WITH HUMAN TAX1BP1.
  18. "A 10-amino acid domain within human T-cell leukemia virus type 1 and type 2 tax protein sequences is responsible for their divergent subcellular distribution."
    Meertens L., Chevalier S., Weil R., Gessain A., Mahieux R.
    J. Biol. Chem. 279:43307-43320(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  19. "Enhanced activation of tax-dependent transcription of human T-cell leukemia virus type I (HTLV-I) long terminal repeat by TORC3."
    Koga H., Ohshima T., Shimotohno K.
    J. Biol. Chem. 279:52978-52983(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN CRTC3, FUNCTION.
  20. "HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral replication."
    Nicot C., Dundr M., Johnson J.M., Fullen J.R., Alonzo N., Fukumoto R., Princler G.L., Derse D., Misteli T., Franchini G.
    Nat. Med. 10:197-201(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOWN-REGULATION BY P30II.
  21. "Human T-cell leukemia virus type 1 Tax oncoprotein induces and interacts with a multi-PDZ domain protein, MAGI-3."
    Ohashi M., Sakurai M., Higuchi M., Mori N., Fukushi M., Oie M., Coffey R.J., Yoshiura K., Tanaka Y., Uchiyama M., Hatanaka M., Fujii M.
    Virology 320:52-62(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN MAGI3.
  22. "Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein."
    Gray S.G., Iglesias A.H., Lizcano F., Villanueva R., Camelo S., Jingu H., Teh B.T., Koibuchi N., Chin W.W., Kokkotou E., Dangond F.
    J. Biol. Chem. 280:28507-28518(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN KDM4A.
  23. "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.
  24. "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.
  25. "PDZ domain-binding motif of human T-cell leukemia virus type 1 Tax oncoprotein is essential for the interleukin 2 independent growth induction of a T-cell line."
    Tsubata C., Higuchi M., Takahashi M., Oie M., Tanaka Y., Gejyo F., Fujii M.
    Retrovirology 2:46-46(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN PDZ-BINDING.
  26. "TORC1 and TORC2 coactivators are required for tax activation of the human T-cell leukemia virus type 1 long terminal repeats."
    Siu Y.-T., Chin K.-T., Siu K.-L., Yee Wai Choy E., Jeang K.-T., Jin D.-Y.
    J. Virol. 80:7052-7059(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN CRTC1; CRTC2 AND CRTC3, FUNCTION.
  27. "Coactivator-associated arginine methyltransferase 1 enhances transcriptional activity of the human T-cell lymphotropic virus type 1 long terminal repeat through direct interaction with Tax."
    Jeong S.J., Lu H., Cho W.K., Park H.U., Pise-Masison C., Brady J.N.
    J. Virol. 80:10036-10044(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN CARM1.
  28. "Site-specific phosphorylation differentiates active from inactive forms of the HTLV-1 tax oncoprotein."
    Durkin S.S., Ward M.D., Fryrear K.A., Semmes O.J.
    J. Biol. Chem. 281:31705-31712(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-48; THR-184; THR-215 AND SER-336, MUTAGENESIS OF THR-48; THR-184; THR-215; 300-SER-SER-301 AND SER-336.
  29. "SUV39H1 interacts with HTLV-1 Tax and abrogates Tax transactivation of HTLV-1 LTR."
    Kamoi K., Yamamoto K., Misawa A., Miyake A., Ishida T., Tanaka Y., Mochizuki M., Watanabe T.
    Retrovirology 3:5-5(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN SUV39H1.

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: January 20, 2016
This is version 78 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.