TAX_HTL1F
ID TAX_HTL1F Reviewed; 353 AA.
AC P0C213;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 1.
DT 23-FEB-2022, entry version 54.
DE RecName: Full=Protein Tax-1;
DE AltName: Full=Protein X-LOR;
DE AltName: Full=Trans-activating transcriptional regulatory protein of HTLV-1;
GN Name=tax;
OS Human T-cell leukemia virus 1 (isolate Zaire EL subtype B) (HTLV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Deltaretrovirus.
OX NCBI_TaxID=39015;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2024459; DOI=10.1016/0042-6822(91)90654-t;
RA Paine E., Garcia J., Philpott T.C., Shaw G., Ratner L.;
RT "Limited sequence variation in human T-lymphotropic virus type 1 isolates
RT from North American and African patients.";
RL Virology 182:111-123(1991).
RN [2]
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 [3]
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).
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, SUV39H1, CARM1, DLG1,
CC IKBKG, KDM4A, MAGI3 and TAX1BP1. Recruits the coactivators CREBBP,
CC EP300 and PCAF (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P0C213; Q14160: SCRIB; Xeno; NbExp=2; IntAct=EBI-11793850, EBI-357345;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000250}. Host cytoplasm
CC {ECO:0000250}. Note=Shuttles from the nucleus to the cytoplasm. Found
CC predominantly in the nucleus, where it is equally distributed between
CC the nucleoplasm and the nuclear matrix (By similarity). {ECO:0000250}.
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}.
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DR EMBL; M67514; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR PDB; 1BD2; X-ray; 2.50 A; C=11-19.
DR PDB; 4E5X; X-ray; 1.95 A; C/F=11-19.
DR PDB; 4FTV; X-ray; 2.74 A; C=11-19.
DR PDBsum; 1BD2; -.
DR PDBsum; 4E5X; -.
DR PDBsum; 4FTV; -.
DR SMR; P0C213; -.
DR IntAct; P0C213; 3.
DR MINT; P0C213; -.
DR EvolutionaryTrace; P0C213; -.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
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: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:0045893; P:positive regulation of transcription, DNA-templated; IEA:InterPro.
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 SH3-binding; Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..353
FT /note="Protein Tax-1"
FT /id="PRO_0000260488"
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; 39517 MW; 1A475682702FD68F CRC64;
MAHFPGFGQS LLFGYPVYVF GDCVQGDWCP ISGGLCSARL HRHALLATCP EHQITWDPID
GRVIGSALQF LIPRLPSFPT QRTSKTLKVL TPPTTHTTPN IPPSFLQAMR KYSPFRNGYM
EPTLGQHLPT LSFPDPGLRP QNLYTLWGGS VVCMYLYQLS PPITWPLLPH VIFDHPDQLG
AFLTNVPYKR MEELLYKISL TTGALIILPE DCLPTTLFQP ARAPVTLTAW QSGLLPFHST
LTTPGLIWAF TDGTPMISGP CPKDGRPSLV LQSSSFIFHK FQTKAYHPSF LLSHGLIQYS
SFHNLHLLFE EYTNIPISLL FNEKEADDTD HEPQVSPGGL EPPSEKHFRE TEV
