TAX_HTL1C
ID TAX_HTL1C Reviewed; 353 AA.
AC P14079; O56231;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 2.
DT 23-FEB-2022, entry version 103.
DE RecName: Full=Protein Tax-1;
DE AltName: Full=Protein X-LOR;
DE Short=Protein PX;
DE AltName: Full=Trans-activating transcriptional regulatory protein of HTLV-1;
GN Name=tax;
OS Human T-cell leukemia virus 1 (isolate Caribbea HS-35 subtype A) (HTLV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Deltaretrovirus.
OX NCBI_TaxID=11927;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2899128; DOI=10.1099/0022-1317-69-7-1695;
RA Malik K.T.A., Even J., Karpas A.;
RT "Molecular cloning and complete nucleotide sequence of an adult T cell
RT leukaemia virus/human T cell leukaemia virus type I (ATLV/HTLV-I) isolate
RT of Caribbean origin: relationship to other members of the ATLV/HTLV-I
RT subgroup.";
RL J. Gen. Virol. 69:1695-1710(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Chappey C.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP REVIEW.
RX PubMed=16155604; DOI=10.1038/sj.onc.1208978;
RA Grassmann R., Aboud M., Jeang K.T.;
RT "Molecular mechanisms of cellular transformation by HTLV-1 Tax.";
RL Oncogene 24:5976-5985(2005).
RN [4]
RP INTERACTION WITH ZFP36, AND SUBCELLULAR LOCATION.
RX PubMed=14679154; DOI=10.1093/jnci/djg118;
RA Twizere J.-C., Kruys V., Lefebvre L., Vanderplasschen A., Collete D.,
RA Debacq C., Lai W.S., Jauniaux J.-C., Bernstein L.R., Semmes J.O., Burny A.,
RA Blackshear P.J., Kettmann R., Willems L.;
RT "Interaction of retroviral Tax oncoproteins with tristetraprolin and
RT regulation of tumor necrosis factor-alpha expression.";
RL J. Natl. Cancer Inst. 95:1846-1859(2003).
RN [5]
RP REVIEW.
RX PubMed=16155601; DOI=10.1038/sj.onc.1208973;
RA Kashanchi F., Brady J.N.;
RT "Transcriptional and post-transcriptional gene regulation of HTLV-1.";
RL Oncogene 24:5938-5951(2005).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 16-24.
RX PubMed=8955188;
RA Garboczi D.N., Utz U., Ghosh P., Seth A., Kim J., VanTienhoven E.A.,
RA Biddison W.E., Wiley D.C.;
RT "Assembly, specific binding, and crystallization of a human TCR-alphabeta
RT with an antigenic Tax peptide from human T lymphotropic virus type 1 and
RT the class I MHC molecule HLA-A2.";
RL J. Immunol. 157:5403-5410(1996).
CC -!- FUNCTION: Transcriptional activator that activates both the viral long
CC terminal repeat (LTR) and cellular promoters via activation of CREB,
CC NF-kappa-B, SRF and AP-1 pathways. Binds to three 21 bp repeat elements
CC located within the LTRs, referred to as Tax-responsive elements (TRE).
CC Binding to TRE requires the interaction with CREB1 and CREBBP. Also
CC induces chromatin remodeling of proviral LTR-mediated gene expression
CC by recruiting the histone acetyl transferases CREBBP and EP300 to the
CC chromatin, which results in histone acetylation. Via its interaction
CC with IKK regulatory subunit IKBKG, Tax-1 persistently stimulates I-
CC kappa-B kinase (IKK), resulting in constitutive activation of the
CC transcription factor NF-kappa-B. Induction of the nuclear expression of
CC members of the NFkB family of transcription factors, which leads to up-
CC regulated expression of many gene promoters containing NFkB motifs.
CC These genes include those encoding IL2, IL15, IL2RA and IL15RA, leading
CC to autocrine IL2/IL2RA and IL15/IL15RA loops. The resulting T-cell
CC proliferation leads to malignant transformation and to the development
CC of adult T-cell leukemia (ATL). IL13, known to be linked to
CC leukemogenesis, is also up-regulated by Tax-1. Interaction with PDZ
CC domain-containing proteins induce IL2-independent growth, which may be
CC a factor in multi-step leukemogenesis. Inhibits the action of at least
CC three cellular tumor suppressors p53/TP53, RB1 and DLG1, and suppresses
CC their abilities to dictate apoptosis in primary cells. Required for
CC viral replication (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with host CREB1, DLG1, IKBKG, KDM4A,
CC MAGI3 and TAX1BP1. recruits the coactivators CREBBP, EP300 and PCAF.
CC Interaction with human CARM1 enhances Tax transactivation and promotes
CC methylation of histone H3. Interacts with host SUV39H1 protein, leading
CC to abrogate Tax transactivation of HTLV-1 LTR (By similarity).
CC Interacts (via C-terminus) with host ZFP36 (via C-terminus); this
CC interaction inhibits TAX to transactivate viral long terminal repeat
CC (LTR) promoter (PubMed:14679154). {ECO:0000250,
CC ECO:0000269|PubMed:14679154}.
CC -!- INTERACTION:
CC P14079; Q53HC0: CCDC92; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-719994;
CC P14079; Q96MT8: CEP63; Xeno; NbExp=5; IntAct=EBI-9675698, EBI-741977;
CC P14079; P78560: CRADD; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-520375;
CC P14079; O14595: CTDSP2; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-2802973;
CC P14079; Q9BY27: DGCR6L; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-742953;
CC P14079; P43268: ETV4; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-6447147;
CC P14079; O15287: FANCG; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-81610;
CC P14079; Q969F0: FATE1; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-743099;
CC P14079; Q5T8I9: HENMT1; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-9675710;
CC P14079; O14964: HGS; Xeno; NbExp=4; IntAct=EBI-9675698, EBI-740220;
CC P14079; P19012: KRT15; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-739566;
CC P14079; P19013: KRT4; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-2371606;
CC P14079; P05787: KRT8; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-297852;
CC P14079; Q8N448: LNX2; Xeno; NbExp=4; IntAct=EBI-9675698, EBI-2340947;
CC P14079; P82932: MRPS6; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-716172;
CC P14079; P07196: NEFL; Xeno; NbExp=4; IntAct=EBI-9675698, EBI-475646;
CC P14079; Q9GZT8: NIF3L1; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-740897;
CC P14079; P29474: NOS3; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-1391623;
CC P14079; Q6ZVK8: NUDT18; Xeno; NbExp=5; IntAct=EBI-9675698, EBI-740486;
CC P14079; Q9NP87: POLM; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-9675790;
CC P14079; Q969H6: POP5; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-366525;
CC P14079; Q33E94: RFX4; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-9675925;
CC P14079; Q92546: RGP1; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-2823702;
CC P14079; Q9H4K1: RIBC2; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-740128;
CC P14079; Q6PF05: TTC23L; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-8656864;
CC P14079; Q8IZQ1: WDFY3; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-1569256;
CC P14079; Q8N883: ZNF614; Xeno; NbExp=3; IntAct=EBI-9675698, EBI-9675993;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:14679154}. Host
CC cytoplasm {ECO:0000269|PubMed:14679154}. Note=Shuttles from the nucleus
CC to the cytoplasm. Found predominantly in the nucleus, where it is
CC equally distributed between the nucleoplasm and the nuclear matrix (By
CC similarity). Colocalizes with host ZFP36 in the nucleus and the
CC cytoplasm in a region surrounding the nucleus (PubMed:14679154).
CC {ECO:0000250, ECO:0000269|PubMed:14679154}.
CC -!- INDUCTION: Down-regulated by P30II.
CC -!- DOMAIN: The 48 N-terminal residues contain a non-canonical functional
CC nuclear localization signal (NLS). {ECO:0000250}.
CC -!- DOMAIN: The PDZ-binding domain mediates binding to human DLG1 and
CC MAGI3. Interaction with other PDZ domain-containing protein induces
CC IL2-independent growth (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation at Thr-48 results in the loss of NF-kappa-B
CC activation function. Phosphorylation at Thr-215 results in loss of CREB
CC and NF-B responsive promoters activation. Phosphorylation at Thr-184
CC and Ser-336 have no effect on these Tax functions. Phosphorylation of
CC either Ser-300 or Ser-301 is necessary for localization to nuclear
CC bodies. Thr-48, Thr-184, Thr-215 and Ser-336 are highly phosphorylated,
CC whereas Ser-300 or Ser-301 are only rarely phosphorylated (By
CC similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: HTLV-1 lineages are divided in four clades, A
CC (Cosmopolitan), B (Central African group), C (Melanesian group) and D
CC (New Central African group).
CC -!- SIMILARITY: Belongs to the deltaretrovirus Tax protein family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D13784; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF033817; AAC82583.1; -; Genomic_DNA.
DR PIR; E28136; TNLJCN.
DR RefSeq; NP_057864.1; NC_001436.1.
DR PDB; 1AO7; X-ray; 2.60 A; C=11-19.
DR PDB; 1BD2; X-ray; 2.50 A; C=11-19.
DR PDB; 1HHK; X-ray; 2.50 A; C/F=11-19.
DR PDB; 1IM3; X-ray; 2.20 A; C/G/K/O=11-19.
DR PDB; 2AV1; X-ray; 1.95 A; C/F=11-19.
DR PDB; 2AV7; X-ray; 2.05 A; C/F=11-19.
DR PDB; 5IRO; X-ray; 2.64 A; B/F/J/N/R/V=11-19.
DR PDB; 6UZ1; X-ray; 3.14 A; C/H=11-19.
DR PDBsum; 1AO7; -.
DR PDBsum; 1BD2; -.
DR PDBsum; 1HHK; -.
DR PDBsum; 1IM3; -.
DR PDBsum; 2AV1; -.
DR PDBsum; 2AV7; -.
DR PDBsum; 5IRO; -.
DR PDBsum; 6UZ1; -.
DR SMR; P14079; -.
DR IntAct; P14079; 56.
DR MINT; P14079; -.
DR PRIDE; P14079; -.
DR GeneID; 1491938; -.
DR KEGG; vg:1491938; -.
DR EvolutionaryTrace; P14079; -.
DR Proteomes; UP000001061; Genome.
DR Proteomes; UP000110593; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:UniProtKB.
DR GO; GO:0039652; P:induction by virus of host NF-kappaB cascade; IEA:UniProtKB-KW.
DR GO; GO:0039646; P:modulation by virus of host G0/G1 transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0043488; P:regulation of mRNA stability; IMP:UniProtKB.
DR GO; GO:0039593; P:suppression by virus of host exit from mitosis; IEA:UniProtKB-KW.
DR InterPro; IPR004120; Tax.
DR Pfam; PF02959; Tax; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activation of host NF-kappa-B by virus; Activator;
KW DNA-binding; G0/G1 host cell cycle checkpoint dysregulation by virus;
KW G1/S host cell cycle checkpoint dysregulation by virus; Host cytoplasm;
KW Host nucleus; Host-virus interaction;
KW Inhibition of host mitotic exit by virus; Metal-binding;
KW Modulation of host cell cycle by virus; Oncogene; Phosphoprotein;
KW Reference proteome; SH3-binding; Transcription; Transcription regulation;
KW Zinc; Zinc-finger.
FT CHAIN 1..353
FT /note="Protein Tax-1"
FT /id="PRO_0000085495"
FT ZN_FING 23..49
FT /evidence="ECO:0000255"
FT REGION 2..58
FT /note="Interaction with CREB1"
FT /evidence="ECO:0000250"
FT REGION 81..95
FT /note="Interaction with CREBBP/P300"
FT /evidence="ECO:0000250"
FT REGION 106..111
FT /note="Interaction with IKBKG"
FT /evidence="ECO:0000250"
FT REGION 116..145
FT /note="Homodimerization"
FT /evidence="ECO:0000250"
FT REGION 213..248
FT /note="Homodimerization"
FT /evidence="ECO:0000250"
FT REGION 289..322
FT /note="Transactivation"
FT /evidence="ECO:0000250"
FT REGION 312..319
FT /note="Interaction with CREBBP C-terminus"
FT /evidence="ECO:0000250"
FT REGION 326..353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 73..80
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 188..202
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOTIF 350..353
FT /note="PDZ-binding"
FT /evidence="ECO:0000250"
FT MOD_RES 48
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 184
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 215
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 300
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 301
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 336
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
SQ SEQUENCE 353 AA; 39513 MW; 60DF69BFD58265F4 CRC64;
MAHFPGFGQS LLFGYPVYVF GDCVQGDWCP ISGGLCSARL HRHALLATCP EHQITWDPID
GRVIGSALQF LIPRLPSFPT QRTSKTLKVL TPPITHTTPN IPPSFLQAMR KYSPFRNGYM
EPTLGQHLPT LSFPDPGLRP QNLYTLWGGS VVCMYLYQLS PPITWPLLPH VIFCHPGQLG
AFLTNVPYKR IEKLLYKISL TTGALIILPE DCLPTTLFQP ARAPVTLTAW QNGLLPFHST
LTTPGLIWTF TDGTPMISGP CPKDGQPSLV LQSSSFIFHK FQTKAYHPSF LLSHGLIQYS
SFHNLHLLFE EYTNIPISLL FNEKEADDND HEPQISPGGL EPLSEKHFRE TEV
