P0C213 (TAX_HTL1F) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein Tax-1

Alternative name(s):
Protein X-LOR
Trans-activating transcriptional regulatory protein of HTLV-1

Gene names

Name:

tax

Organism

Human T-cell leukemia virus 1 (isolate Zaire EL subtype B) (HTLV-1)

Taxonomic identifier

39015 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Deltaretrovirus › Primate T-lymphotropic virus 1 › Human T-lymphotropic virus 1 › HTLV-1 subtype B

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	353 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity.
Subunit structure	Homodimer. Interacts with host CREB1, SUV39H1, CARM1, DLG1, IKBKG, KDM4A, MAGI3 and TAX1BP1. Recruits the coactivators CREBBP, EP300 and PCAF By similarity.
Subcellular location	Host nucleus By similarity. Host cytoplasm By similarity. 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 By similarity.
Induction	Down-regulated by P30II.
Domain	The 48 N-terminal residues contain a non-canonical functional nuclear localization signal (NLS) By similarity. The PDZ-binding domain mediates binding to human DLG1 and MAGI3. Interaction with other PDZ domain-containing protein induces IL2-independent growth By similarity.
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 By similarity.
Miscellaneous	HTLV-1 lineages are divided in four clades, A (Cosmopolitan), B (Central African group), C (Melanesian group) and D (New Central African group).
Sequence similarities	Belongs to the deltaretrovirus Tax protein family.

Ontologies

Keywords
Biological process	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
Cellular component	Host cytoplasm Host nucleus
Disease	Oncogene
Domain	SH3-binding Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological_process	activation by virus of host NF-kappaB transcription factor activity Inferred from electronic annotation. Source: UniProtKB-KW modulation by virus of host G0/G1 transition checkpoint Inferred from electronic annotation. Source: UniProtKB-KW modulation by virus of host G1/S transition checkpoint Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro suppression by virus of host exit from mitosis Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 353	353	Protein Tax-1		PRO_0000260488
Regions
	Zinc finger	23 – 49	27	Potential
	Region	2 – 58	57	Interaction with CREB1 By similarity
	Region	81 – 95	15	Interaction with CREBBP/P300 By similarity
	Region	106 – 111	6	Interaction with IKBKG By similarity
	Region	116 – 145	30	Homodimerization By similarity
	Region	213 – 248	36	Homodimerization By similarity
	Region	289 – 322	34	Transactivation By similarity
	Region	312 – 319	8	Interaction with CREBBP C-terminus By similarity
	Motif	73 – 80	8	SH3-binding Potential
	Motif	188 – 202	15	Nuclear export signal By similarity
	Motif	350 – 353	4	PDZ-binding By similarity
Amino acid modifications
	Modified residue	48	1	Phosphothreonine; by host By similarity
	Modified residue	184	1	Phosphothreonine; by host By similarity
	Modified residue	215	1	Phosphothreonine; by host By similarity
	Modified residue	300	1	Phosphoserine; by host By similarity
	Modified residue	301	1	Phosphoserine; by host By similarity
	Modified residue	336	1	Phosphoserine; by host By similarity

Sequences

	Sequence		Length	Mass (Da)
	P0C213 [UniParc]. Last modified November 28, 2006. Version 1. Checksum: 1A475682702FD68F	FASTA	353	39,517
	10 20 30 40 50 60 MAHFPGFGQS LLFGYPVYVF GDCVQGDWCP ISGGLCSARL HRHALLATCP EHQITWDPID 70 80 90 100 110 120 GRVIGSALQF LIPRLPSFPT QRTSKTLKVL TPPTTHTTPN IPPSFLQAMR KYSPFRNGYM 130 140 150 160 170 180 EPTLGQHLPT LSFPDPGLRP QNLYTLWGGS VVCMYLYQLS PPITWPLLPH VIFDHPDQLG 190 200 210 220 230 240 AFLTNVPYKR MEELLYKISL TTGALIILPE DCLPTTLFQP ARAPVTLTAW QSGLLPFHST 250 260 270 280 290 300 LTTPGLIWAF TDGTPMISGP CPKDGRPSLV LQSSSFIFHK FQTKAYHPSF LLSHGLIQYS 310 320 330 340 350 SFHNLHLLFE EYTNIPISLL FNEKEADDTD HEPQVSPGGL EPPSEKHFRE TEV

References

[1]	"Limited sequence variation in human T-lymphotropic virus type 1 isolates from North American and African patients." Paine E., Garcia J., Philpott T.C., Shaw G., Ratner L. Virology 182:111-123(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"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.
[3]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M67514 Genomic RNA. No translation available.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BD2	X-ray	2.50	C	11-19	[»]
4E5X	X-ray	1.95	C/F	11-19	[»]

ModBase

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Protocols and materials databases

StructuralBiologyKnowledgebase

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Family and domain databases

InterPro

IPR004120. Tax.
[Graphical view]

Pfam

PF02959. Tax. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P0C213.

Entry information

Entry name

TAX_HTL1F

Accession

Primary (citable) accession number: P0C213

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	November 28, 2006
Last modified:	April 3, 2013
This is version 36 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program