P03409 · TAX_HTL1A
- ProteinProtein Tax-1
- GeneTax
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids353 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Transcriptional activator that governs the viral transcription from the 5'LTR via the recruitment of dimers of host phosphorylated CREB1. Together they bind cAMP response elements within the viral promoter and mediate high-level viral transcription (PubMed:22789739, PubMed:8970957).
Increases host CREB1 O-GlcNAcylation to further increase 5'LTR transactivation (PubMed:28742148).
Modulates also the expression of cellular genes leading to the deregulation of T-cell proliferation, perturbing the integrity of cell cycle checkpoints, the DNA damage response and apopototic pathways. Acts as an ubiquitin E3 ligase and stimulates host IKK complex by catalyzing the assembly of free mixed-linkage polyubiquitin chains, resulting in constitutive activation of the transcription factor NF-kappa-B (PubMed:27082114, PubMed:28103322).
Inhibits the host nonsense-mediated mRNA decay (NMD), a cellular process that can actively degrade mRNAs by interacting with host UPF1 (PubMed:27082114).
Increases host CREB1 O-GlcNAcylation to further increase 5'LTR transactivation (PubMed:28742148).
Modulates also the expression of cellular genes leading to the deregulation of T-cell proliferation, perturbing the integrity of cell cycle checkpoints, the DNA damage response and apopototic pathways. Acts as an ubiquitin E3 ligase and stimulates host IKK complex by catalyzing the assembly of free mixed-linkage polyubiquitin chains, resulting in constitutive activation of the transcription factor NF-kappa-B (PubMed:27082114, PubMed:28103322).
Inhibits the host nonsense-mediated mRNA decay (NMD), a cellular process that can actively degrade mRNAs by interacting with host UPF1 (PubMed:27082114).
Miscellaneous
HTLV-1 lineages are divided in four clades, A (Cosmopolitan), B (Central African group), C (Melanesian group) and D (New Central African group).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | host cell cytoplasm | |
Cellular Component | host cell nucleus | |
Molecular Function | DNA binding | |
Molecular Function | metal ion binding | |
Molecular Function | SH3 domain binding | |
Biological Process | positive regulation of DNA-templated transcription | |
Biological Process | symbiont-mediated activation of host NF-kappaB cascade | |
Biological Process | symbiont-mediated perturbation of host cell cycle G0/G1 transition checkpoint | |
Biological Process | symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint | |
Biological Process | symbiont-mediated perturbation of host exit from mitosis |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameProtein Tax-1
- Alternative names
Gene names
Organism names
- Taxonomic lineageViruses > Riboviria > Pararnavirae > Artverviricota > Revtraviricetes > Ortervirales > Retroviridae > Orthoretrovirinae > Deltaretrovirus > Primate T-lymphotropic virus 1
- Virus hosts
Accessions
- Primary accessionP03409
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Note: Shuttles from the host nucleus to the cytoplasm. Found predominantly in the nucleus, where it is equally distributed between the nucleoplasm and the nuclear matrix.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 48 | 30% loss of CREB activation. 70% loss of NF-kappa-B activation. | ||||
Sequence: T → A | ||||||
Mutagenesis | 48 | 50% loss of CREB activation. Almost complete loss of NF-kappa-B activation. | ||||
Sequence: T → D | ||||||
Mutagenesis | 184 | Slightly reduced CREB and NF-kappa-B activation. | ||||
Sequence: T → A | ||||||
Mutagenesis | 184 | Slightly reduced CREB and NF-kappa-B activation. | ||||
Sequence: T → D | ||||||
Mutagenesis | 200 | Complete loss of Tax-1 nuclear export. | ||||
Sequence: L → A | ||||||
Mutagenesis | 215 | 30% loss of CREB activation. Slightly reduced NF-kappa-B activation. | ||||
Sequence: T → A | ||||||
Mutagenesis | 215 | Almost complete loss of CREB and NF-kappa-B activation. | ||||
Sequence: T → D | ||||||
Mutagenesis | 300-301 | Almost complete loss of CREB and NF-kappa-B activation. | ||||
Sequence: SS → AA | ||||||
Mutagenesis | 300-301 | 30% loss of CREB activation. 80% loss of NF-kappa-B activation. | ||||
Sequence: SS → DD | ||||||
Mutagenesis | 336 | Slightly reduced CREB and NF-kappa-B activation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 336 | Slightly reduced CREB and NF-kappa-B activation. | ||||
Sequence: S → D |
Keywords
- Disease
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000085494 | 1-353 | Protein Tax-1 | |||
Sequence: MAHFPGFGQSLLFGYPVYVFGDCVQGDWCPISGGLCSARLHRHALLATCPEHQITWDPIDGRVIGSALQFLIPRLPSFPTQRTSKTLKVLTPPITHTTPNIPPSFLQAMRKYSPFRNGYMEPTLGQHLPTLSFPDPGLRPQNLYTLWGGSVVCMYLYQLSPPITWPLLPHVIFCHPGQLGAFLTNVPYKRIEELLYKISLTTGALIILPEDCLPTTLFQPARAPVTLTAWQNGLLPFHSTLTTPGLIWTFTDGTPMISGPCPKDGQPSLVLQSSSFIFHKFQTKAYHPSFLLSHGLIQYSSFHSLHLLFEEYTNIPISLLFNEKEADDNDHEPQISPGGLEPPSEKHFRETEV | ||||||
Modified residue | 48 | Phosphothreonine; by host | ||||
Sequence: T | ||||||
Modified residue | 184 | Phosphothreonine; by host | ||||
Sequence: T | ||||||
Modified residue | 215 | Phosphothreonine; by host | ||||
Sequence: T | ||||||
Modified residue | 300 | Phosphoserine; by host | ||||
Sequence: S | ||||||
Modified residue | 301 | Phosphoserine; by host | ||||
Sequence: S | ||||||
Modified residue | 336 | Phosphoserine; by host | ||||
Sequence: S |
Post-translational modification
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.
Modified by host ubiquitin related modifier 1/URM1, resulting in a redistribution of Tax to the cytoplasm.
Keywords
- PTM
PTM databases
Expression
Induction
Down-regulated by P30II.
Interaction
Subunit
Homodimer. Interacts with host CREB1 (PubMed:8970957).
Interacts with host DLG1, IKBKG, KDM4A, MAGII3 and TAX1BP1. Recruits the coactivators CREBBP, EP300 and PCAF (PubMed:10766811).
Interaction with human CARM1 enhances Tax transactivation and promotes methylation of histone H3 (PubMed:17005681).
Interacts with host SUV39H1 protein, leading to abrogate Tax transactivation of HTLV-1 LTR (PubMed:16409643).
Interaction with human CREB coactivators, CRTC1/TORC1, CRTC2/TORC2 and CRTC3/TORC3 enhances Tax transactivation (PubMed:15466468, PubMed:16809310).
Interacts with host UPF1; this interaction inhibits the host nonsense-mediated mRNA decay (NMD). Interacts (via N-terminus) with host PLSCR1; this interaction negatively regulates Tax transactivation activity by altering its subcellular distribution and homodimerization (PubMed:22789739).
Interacts with host DLG1, IKBKG, KDM4A, MAGII3 and TAX1BP1. Recruits the coactivators CREBBP, EP300 and PCAF (PubMed:10766811).
Interaction with human CARM1 enhances Tax transactivation and promotes methylation of histone H3 (PubMed:17005681).
Interacts with host SUV39H1 protein, leading to abrogate Tax transactivation of HTLV-1 LTR (PubMed:16409643).
Interaction with human CREB coactivators, CRTC1/TORC1, CRTC2/TORC2 and CRTC3/TORC3 enhances Tax transactivation (PubMed:15466468, PubMed:16809310).
Interacts with host UPF1; this interaction inhibits the host nonsense-mediated mRNA decay (NMD). Interacts (via N-terminus) with host PLSCR1; this interaction negatively regulates Tax transactivation activity by altering its subcellular distribution and homodimerization (PubMed:22789739).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | P03409 | HDAC6 Q9UBN7 | 4 | EBI-5236464, EBI-301697 | |
XENO | P03409 | IKBKB O14920 | 3 | EBI-5236464, EBI-81266 |
Protein-protein interaction databases
Chemistry
Family & Domains
Features
Showing features for region, zinc finger, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 2-58 | Interaction with CREB1 | ||||
Sequence: AHFPGFGQSLLFGYPVYVFGDCVQGDWCPISGGLCSARLHRHALLATCPEHQITWDP | ||||||
Zinc finger | 23-49 | |||||
Sequence: CVQGDWCPISGGLCSARLHRHALLATC | ||||||
Motif | 73-80 | SH3-binding | ||||
Sequence: PRLPSFPT | ||||||
Region | 81-95 | Interaction with CREBBP/P300 | ||||
Sequence: QRTSKTLKVLTPPIT | ||||||
Region | 106-111 | Interaction with IKBKG | ||||
Sequence: LQAMRK | ||||||
Region | 116-145 | Homodimerization | ||||
Sequence: RNGYMEPTLGQHLPTLSFPDPGLRPQNLYT | ||||||
Motif | 188-202 | Nuclear export signal | ||||
Sequence: YKRIEELLYKISLTT | ||||||
Region | 213-248 | Homodimerization | ||||
Sequence: LPTTLFQPARAPVTLTAWQNGLLPFHSTLTTPGLIW | ||||||
Region | 289-322 | Transactivation | ||||
Sequence: SFLLSHGLIQYSSFHSLHLLFEEYTNIPISLLFN | ||||||
Region | 312-319 | Interaction with CREBBP C-terminus | ||||
Sequence: YTNIPISL | ||||||
Region | 326-353 | Disordered | ||||
Sequence: ADDNDHEPQISPGGLEPPSEKHFRETEV | ||||||
Motif | 350-353 | PDZ-binding | ||||
Sequence: ETEV |
Domain
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 similarities
Belongs to the deltaretrovirus Tax protein family.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length353
- Mass (Da)39,471
- Last updated2006-05-16 v2
- ChecksumB3D2C05C26926D56
Keywords
- Technical term