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P04610 (TAT_HV1BR) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Protein Tat
Alternative name(s):
Transactivating regulatory protein
Gene names
Name:tat
OrganismHuman immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI) (HIV-1) [Complete proteome]
Taxonomic identifier11686 [NCBI]
Taxonomic lineageVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length86 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat protein exerts as well a positive feedback on the translation of its cognate mRNA. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs By similarity. Ref.6 Ref.8 Ref.11 Ref.15 Ref.17 Ref.24 Ref.28 Ref.30 Ref.34 Ref.37 Ref.39 Ref.43

Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endosomal low pH allows Tat to cross the endosome membrane to enter the cytosol and eventually further translocate into the nucleus, thereby inducing severe cell dysfunctions ranging from cell activation to cell death. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of KAT5/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. May be involved in the derepression of host interleukin IL2 expression. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions By similarity. Ref.6 Ref.8 Ref.11 Ref.15 Ref.17 Ref.24 Ref.28 Ref.30 Ref.34 Ref.37 Ref.39 Ref.43

Subunit structure

Interacts with host CCNT1. Associates with the P-TEFb complex composed at least of Tat, P-TEFb (CDK9 and CCNT1), TAR RNA, RNA Pol II. Recruits the HATs CREBBP, TAF1/TFIID, EP300, PCAF and GCN5L2. Interacts with host KAT5/Tip60; this interaction targets the latter to degradation. Interacts with the host deacetylase SIRT1. Interacts with host capping enzyme RNGTT; this interaction stimulates RNGTT. Binds to host KDR, and to the host integrins ITGAV/ITGB3 and ITGA5/ITGB1. Interacts with host KPNB1/importin beta-1 without previous binding to KPNA1/importin alpha-1. Interacts with EIF2AK2. Interacts with host nucleosome assembly protein NAP1L1; this interaction may be required for the transport of Tat within the nucleus, since the two proteins interact at the nuclear rim. Interacts with host C1QBP/SF2P32; this interaction involves lysine-acetylated Tat. Interacts with the host chemokine receptors CCR2, CCR3 and CXCR4. Interacts with host DPP4/CD26; this interaction may trigger an anti-proliferative effect. Interacts with host LDLR. Interacts with the host extracellular matrix metalloproteinase MMP1. Interacts with host PRMT6; this interaction mediates Tat's methylation. Interacts with, and is ubiquitinated by MDM2/Hdm2. Interacts with host PSMC3 and HTATIP2. Interacts with STAB1; this interaction may overcome SATB1-mediated repression of IL2 and IL2RA (interleukin) in T cells by binding to the same domain than HDAC1. Interacts (when acetylated on Lys-50 and Lys-51) with human CDK13, thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef. Ref.3 Ref.4 Ref.5 Ref.7 Ref.9 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.21 Ref.22 Ref.25 Ref.26 Ref.27 Ref.29 Ref.31 Ref.32 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38

Subcellular location

Host nucleushost nucleolus. Host cytoplasm. Secreted. Note: Probably localizes to both nuclear and nucleolar compartments. Nuclear localization is mediated through the interaction of the nuclear localization signal with importin KPNB1. Secretion occurs through a Golgi-independent pathway. Tat is released from infected cells to the extracellular space where it remains associated to the cell membrane, or is secreted into the cerebrospinal fluid and sera. Extracellular Tat can be endocytosed by surrounding uninfected cells via binding to several receptors depending on the cell type.

Domain

The transactivation domain mediates the interaction with CCNT1, GCN5L2, and MDM2. Ref.31 Ref.44

The Arg-rich RNA-binding region binds the TAR RNA. This region also mediates the nuclear localization through direct binding to KPNB1 and is involved in Tat's transfer across cell membranes (protein transduction). The same region is required for the interaction with EP300, PCAF, EIF2AK2 and KDR. Ref.31 Ref.44

The Cys-rich region may bind 2 zinc ions Potential. This region is involved in binding to KAT5. Ref.31 Ref.44

The cell attachment site mediates the interaction with ITGAV/ITGB3 and ITGA5/ITGB1 integrins, leading to vascular cell migration and invasion. This interaction also provides endothelial cells with the adhesion signal they require to grow in response to mitogens. Ref.31 Ref.44

Post-translational modification

Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the transactivation activity of Tat. EP300-mediated acetylation of Lys-50 promotes dissociation of Tat from the TAR RNA through the competitive binding to PCAF's bromodomain. In addition, the non-acetylated Tat's N-terminus can also interact with PCAF. PCAF-mediated acetylation of Lys-28 enhances Tat's binding to CCNT1. Lys-50 is deacetylated by SIRT1 By similarity. Ref.20 Ref.23 Ref.27 Ref.35

Phosphorylated by EIF2AK2 on serine and threonine residues adjacent to the basic region important for TAR RNA binding and function. Phosphorylation of Tat by EIF2AK2 is dependent on the prior activation of EIF2AK2 by dsRNA.

Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1 By similarity.

Polyubiquitination by MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA.

Miscellaneous

This truncated variant has a premature stop codon. It may have arose as a consequence of tissue culture passaging.

The infectious clone pNL4-3 is a chimeric provirus that consists of DNA from HIV isolates NY5 (5' half) and BRU (3' half).

HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).

Sequence similarities

Belongs to the lentiviruses Tat family.

Ontologies

Keywords
   Biological processApoptosis
Host-virus interaction
Inhibition of host innate immune response by virus
Inhibition of host interferon signaling pathway by virus
Modulation of host chromatin by virus
Modulation of host PP1 activity by virus
Transcription
Transcription regulation
Viral immunoevasion
   Cellular componentHost cytoplasm
Host nucleus
Secreted
   Coding sequence diversityAlternative splicing
   DiseaseAIDS
   LigandMetal-binding
RNA-binding
Zinc
   Molecular functionActivator
   PTMAcetylation
Isopeptide bond
Methylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

membrane hyperpolarization

Inferred from direct assay PubMed 17202348. Source: CACAO

modulation by virus of host PP1 activity

Inferred from electronic annotation. Source: UniProtKB-KW

modulation by virus of host chromatin organization

Inferred from electronic annotation. Source: UniProtKB-KW

modulation of transcription in other organism involved in symbiotic interaction

Inferred from direct assay PubMed 22593154. Source: CACAO

negative regulation of cellular respiration

Inferred from direct assay PubMed 17202348. Source: CACAO

positive regulation of NF-kappaB transcription factor activity

Inferred from direct assay Ref.17. Source: CACAO

positive regulation of protein localization to nucleus

Inferred from direct assay PubMed 22219277. Source: CACAO

suppression by virus of host type I interferon-mediated signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell nucleolus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionRNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P04610-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Short (identifier: P04610-2)

The sequence of this isoform differs from the canonical sequence as follows:
     73-86: Missing.
Note: No experimental confirmation available. Expressed in the late stage of the infection cycle, when unspliced viral RNAs are exported to the cytoplasm by the viral Rev protein.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 8686Protein Tat
PRO_0000085346

Regions

Region1 – 4848Transactivation
Region1 – 2424Interaction with human CREBBP By similarity
Region22 – 3716Cysteine-rich
Region38 – 4811Core
Region49 – 8638Interaction with the host capping enzyme RNGTT
Motif49 – 579Nuclear localization signal, RNA-binding (TAR), and protein transduction Ref.16
Motif78 – 803Cell attachment site Potential

Sites

Site111Essential for Tat's translocation through the endosomal membrane By similarity

Amino acid modifications

Modified residue281N6-acetyllysine; by host PCAF Ref.20
Modified residue501N6-acetyllysine; by host EP300 and GCN5L2 Ref.20 Ref.23 Ref.27 Ref.35
Modified residue511N6-acetyllysine; by host EP300 and GCN5L2 Ref.23 Ref.27
Modified residue521Asymmetric dimethylarginine; by host PRMT6 By similarity
Modified residue531Asymmetric dimethylarginine; by host PRMT6 By similarity
Cross-link71Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.32

Natural variations

Alternative sequence73 – 8614Missing in isoform Short.
VSP_022299
Natural variant241T → N in strain: Clone pNL4-3.
Natural variant391T → M in strain: Clone pNL4-3.
Natural variant58 – 614PPQG → AHQN in strain: Clone pNL4-3.
Natural variant671V → A in strain: Clone pNL4-3.
Natural variant771P → S in strain: Clone pNL4-3.

Experimental info

Mutagenesis281K → A: Strong decrease in Tat transactivation. Ref.20
Mutagenesis501K → A: Strong decrease in Tat transactivation. Ref.20 Ref.23
Mutagenesis511K → A: Strong decrease in Tat transactivation. Ref.23

Secondary structure

.................... 86
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified August 13, 1987. Version 1.
Checksum: 9B1B4A915FAF8A14

FASTA869,769
        10         20         30         40         50         60 
MEPVDPRLEP WKHPGSQPKT ACTTCYCKKC CFHCQVCFTT KALGISYGRK KRRQRRRPPQ 

        70         80 
GSQTHQVSLS KQPTSQPRGD PTGPKE 

« Hide

Isoform Short [UniParc].

Checksum: ABA3031FB5F5FC45
Show »

FASTA728,321

References

[1]"Nucleotide sequence of the AIDS virus, LAV."
Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M.
Cell 40:9-17(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]Buckler C.E., Buckler-White A.J., Willey R.L., McCoy J.
Submitted (JUN-1988) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: Clone pNL4-3.
[3]"A cDNA for a protein that interacts with the human immunodeficiency virus Tat transactivator."
Nelbock P., Dillion P.J., Perkins A., Rosen C.A.
Science 248:1650-1653(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN PSMC3.
[4]"Direct interaction of human TFIID with the HIV-1 transactivator tat."
Kashanchi F., Piras G., Radonovich M.F., Duvall J.F., Fattaey A., Chiang C.M., Roeder R.G., Brady J.N.
Nature 367:295-299(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN TBP.
[5]"Human immunodeficiency virus 1 Tat binds to dipeptidyl aminopeptidase IV (CD26): a possible mechanism for Tat's immunosuppressive activity."
Gutheil W.G., Subramanyam M., Flentke G.R., Sanford D.G., Munoz E., Huber B.T., Bachovchin W.W.
Proc. Natl. Acad. Sci. U.S.A. 91:6594-6598(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN DPP4.
[6]"Specific binding of RNA polymerase II to the human immunodeficiency virus trans-activating region RNA is regulated by cellular cofactors and Tat."
Wu-Baer F., Sigman D., Gaynor R.B.
Proc. Natl. Acad. Sci. U.S.A. 92:7153-7157(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Evidence for functional interaction between the HIV-1 Tat transactivator and the TATA box binding protein in vivo."
Veschambre P., Simard P., Jalinot P.
J. Mol. Biol. 250:169-180(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN TBP.
[8]"Enhanced processivity of RNA polymerase II triggered by Tat-induced phosphorylation of its carboxy-terminal domain."
Parada C.A., Roeder R.G.
Nature 384:375-378(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator."
Kamine J., Elangovan B., Subramanian T., Coleman D., Chinnadurai G.
Virology 216:357-366(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN KAT5.
[10]"Structural characterization of the metal binding site in the cysteine-rich region of HIV-1 Tat protein."
Huang H.-W., Wang K.-T.
Biochem. Biophys. Res. Commun. 227:615-621(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: CYS-RICH REGION, ZINC-BINDING, IDENTIFICATION BY MASS SPECTROMETRY.
[11]"Activation of transcription factor NF-kappaB by the Tat protein of human immunodeficiency virus type 1."
Demarchi F., d'Adda di Fagagna F., Falaschi A., Giacca M.
J. Virol. 70:4427-4437(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Transcription elongation factor P-TEFb mediates Tat activation of HIV-1 transcription at multiple stages."
Zhou Q., Chen D., Pierstorff E., Luo K.
EMBO J. 17:3681-3691(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH P-TEFB; TAR RNA AND RNA POL II.
[13]"HIV-1 Tat protein mimicry of chemokines."
Albini A., Ferrini S., Benelli R., Sforzini S., Giunciuglio D., Aluigi M.G., Proudfoot A.E.I., Alouani S., Wells T.N.C., Mariani G., Rabin R.L., Farber J.M., Noonan D.M.
Proc. Natl. Acad. Sci. U.S.A. 95:13153-13158(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN CCR2 AND CCR3.
[14]"A cofactor, TIP30, specifically enhances HIV-1 Tat-activated transcription."
Xiao H., Tao Y., Greenblatt J., Roeder R.G.
Proc. Natl. Acad. Sci. U.S.A. 95:2146-2151(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN HTATIP2.
[15]"Cyclin T1 domains involved in complex formation with Tat and TAR RNA are critical for tat-activation."
Ivanov D., Kwak Y.T., Nee E., Guo J., Garcia-Martinez L.F., Gaynor R.B.
J. Mol. Biol. 288:41-56(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HUMAN CCNT1, IDENTIFICATION IN A COMPLEX WITH CCNT1; CDK9 AND TAR RNA.
[16]"The arginine-rich domains present in human immunodeficiency virus type 1 Tat and Rev function as direct importin beta-dependent nuclear localization signals."
Truant R., Cullen B.R.
Mol. Cell. Biol. 19:1210-1217(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEAR LOCALIZATION SIGNAL, INTERACTION WITH KPNB1.
[17]"Human immunodeficiency virus type 1 tat protein activates transcription factor NF-kappaB through the cellular interferon-inducible, double-stranded RNA-dependent protein kinase, PKR."
Demarchi F., Gutierrez M.I., Giacca M.
J. Virol. 73:7080-7086(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[18]"The Tat protein of human immunodeficiency virus type-1 promotes vascular cell growth and locomotion by engaging the alpha5beta1 and alphavbeta3 integrins and by mobilizing sequestered basic fibroblast growth factor."
Barillari G., Sgadari C., Fiorelli V., Samaniego F., Colombini S., Manzari V., Modesti A., Nair B.C., Cafaro A., Stuerzl M., Ensoli B.
Blood 94:663-672(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN ITGAV/ITGB3 AND ITGA5/ITGB1 INTEGRINS.
[19]"Analysis of the effect of natural sequence variation in Tat and in cyclin T on the formation and RNA binding properties of Tat-cyclin T complexes."
Bieniasz P.D., Grdina T.A., Bogerd H.P., Cullen B.R.
J. Virol. 73:5777-5786(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN CCNT1.
[20]"HIV-1 tat transcriptional activity is regulated by acetylation."
Kiernan R.E., Vanhulle C., Schiltz L., Adam E., Xiao H., Maudoux F., Calomme C., Burny A., Nakatani Y., Jeang K.-T., Benkirane M., Van Lint C.
EMBO J. 18:6106-6118(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-50 BY EP300, ACETYLATION AT LYS-28 BY PCAF, MUTAGENESIS OF LYS-28 AND LYS-50.
[21]"Selective CXCR4 antagonism by Tat: implications for in vivo expansion of coreceptor use by HIV-1."
Xiao H., Neuveut C., Tiffany H.L., Benkirane M., Rich E.A., Murphy P.M., Jeang K.-T.
Proc. Natl. Acad. Sci. U.S.A. 97:11466-11471(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN CXCR4.
Strain: Clone pNL4-3.
[22]"Identification of specific molecular structures of human immunodeficiency virus type 1 Tat relevant for its biological effects on vascular endothelial cells."
Mitola S., Soldi R., Zanon I., Barra L., Gutierrez M.I., Berkhout B., Giacca M., Bussolino F.
J. Virol. 74:344-353(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN KDR; ITGAV AND ITGB1.
[23]"Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated HIV-1 genome and enhances binding to core histones."
Deng L., de la Fuente C., Fu P., Wang L., Donnelly R., Wade J.D., Lambert P., Li H., Lee C.-G., Kashanchi F.
Virology 277:278-295(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-50 AND LYS-51 BY EP300, MUTAGENESIS OF LYS-50 AND LYS-51.
[24]"CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA."
Garber M.E., Mayall T.P., Suess E.M., Meisenhelder J., Thompson N.E., Jones K.A.
Mol. Cell. Biol. 20:6958-6969(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[25]"HIV-1 Tat protein interacts with mammalian capping enzyme and stimulates capping of TAR RNA."
Chiu Y.-L., Coronel E., Ho C.K., Shuman S., Rana T.M.
J. Biol. Chem. 276:12959-12966(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HOST RNGTT.
[26]"Internalization of HIV-1 tat requires cell surface heparan sulfate proteoglycans."
Tyagi M., Rusnati M., Presta M., Giacca M.
J. Biol. Chem. 276:3254-3261(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HEPARAN SULFATE PROTEOGLYCANS.
[27]"The histone acetyltransferase, hGCN5, interacts with and acetylates the HIV transactivator, Tat."
Col E., Caron C., Seigneurin-Berny D., Gracia J., Favier A., Khochbin S.
J. Biol. Chem. 276:28179-28184(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN GCN5L2, ACETYLATION AT LYS-50 AND LYS-51 BY HUMAN GCN5L2.
[28]"Phosphorylation of the RNA polymerase II carboxyl-terminal domain by CDK9 is directly responsible for human immunodeficiency virus type 1 Tat-activated transcriptional elongation."
Kim Y.K., Bourgeois C.F., Isel C., Churcher M.J., Karn J.
Mol. Cell. Biol. 22:4622-4637(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[29]"Differential acetylation of Tat coordinates its interaction with the co-activators cyclin T1 and PCAF."
Bres V., Tagami H., Peloponese J.-M., Loret E., Jeang K.-T., Nakatani Y., Emiliani S., Benkirane M., Kiernan R.E.
EMBO J. 21:6811-6819(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN PCAF.
[30]"Tat-controlled protein acetylation."
Col E., Gilquin B., Caron C., Khochbin S.
J. Biol. Chem. 277:37955-37960(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[31]"Transcriptional synergy between Tat and PCAF is dependent on the binding of acetylated Tat to the PCAF bromodomain."
Dorr A., Kiermer V., Pedal A., Rackwitz H.R., Henklein P., Schubert U., Zhou M.-M., Verdin E., Ott M.
EMBO J. 21:2715-2723(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN PCAF BROMODOMAIN.
[32]"A non-proteolytic role for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter."
Bres V., Kiernan R.E., Linares L.K., Chable-Bessia C., Plechakova O., Treand C., Emiliani S., Peloponese J.-M., Jeang K.-T., Coux O., Scheffner M., Benkirane M.
Nat. Cell Biol. 5:754-761(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-71 BY HUMAN MDM2, INTERACTION WITH HUMAN MDM2.
Strain: Clone pNL4-3.
[33]"Zn2+ binding to cysteine-rich domain of extracellular human immunodeficiency virus type 1 Tat protein is associated with Tat protein-induced apoptosis."
Misumi S., Takamune N., Ohtsubo Y., Waniguchi K., Shoji S.
AIDS Res. Hum. Retroviruses 20:297-304(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CYS-RICH REGION, ZINC-BINDING.
[34]"Displacement of SATB1-bound histone deacetylase 1 corepressor by the human immunodeficiency virus type 1 transactivator induces expression of interleukin-2 and its receptor in T cells."
Kumar P.P., Purbey P.K., Ravi D.S., Mitra D., Galande S.
Mol. Cell. Biol. 25:1620-1633(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HUMAN SATB1.
[35]"SIRT1 regulates HIV transcription via Tat deacetylation."
Pagans S., Pedal A., North B.J., Kaehlcke K., Marshall B.L., Dorr A., Hetzer-Egger C., Henklein P., Frye R., McBurney M.W., Hruby H., Jung M., Verdin E., Ott M.
PLoS Biol. 3:210-220(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN SIRT1, DEACETYLATION AT LYS-50 BY SIRT1.
[36]"HIV-1 Tat targets Tip60 to impair the apoptotic cell response to genotoxic stresses."
Col E., Caron C., Chable-Bessia C., Legube G., Gazzeri S., Komatsu Y., Yoshida M., Benkirane M., Trouche D., Khochbin S.
EMBO J. 24:2634-2645(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN KAT5.
Strain: Clone pNL4-3.
[37]"HIV-1 Tat stimulates transcription complex assembly through recruitment of TBP in the absence of TAFs."
Raha T., Cheng S.W.G., Green M.R.
PLoS Biol. 3:221-230(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HUMAN TBP.
[38]"Interaction of HIV Tat and matrix metalloproteinase in HIV neuropathogenesis: a new host defense mechanism."
Rumbaugh J., Turchan-Cholewo J., Galey D., St Hillaire C., Anderson C., Conant K., Nath A.
FASEB J. 20:1736-1738(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN MMP1.
[39]"Intracellular HIV-Tat expression induces IL-10 synthesis by the CREB-1 transcription factor through Ser133 phosphorylation and its regulation by the ERK1/2 MAPK in human monocytic cells."
Gee K., Angel J.B., Ma W., Mishra S., Gajanayaka N., Parato K., Kumar A.
J. Biol. Chem. 281:31647-31658(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[40]"Decoding Tat: the biology of HIV Tat posttranslational modifications."
Hetzer C., Dormeyer W., Schnolzer M., Ott M.
Microbes Infect. 7:1364-1369(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW, ALTERNATIVE SPLICING.
[41]"The multiple functions of HIV-1 Tat: proliferation versus apoptosis."
Peruzzi F.
Front. Biosci. 11:708-717(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[42]"HIV tat and neurotoxicity."
King J.E., Eugenin E.A., Buckner C.M., Berman J.W.
Microbes Infect. 8:1347-1357(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[43]"Mechanism of HIV-1 Tat RNA translation and its activation by the Tat protein."
Charnay N., Ivanyi-Nagy R., Soto-Rifo R., Ohlmann T., Lopez-Lastra M., Darlix J.L.
Retrovirology 6:74-74(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[44]"Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain."
Mujtaba S., He Y., Zeng L., Farooq A., Carlson J.E., Ott M., Verdin E., Zhou M.-M.
Mol. Cell 9:575-586(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 46-55 IN COMPLEX WITH PCAF BROMODOMAIN.
[45]"1H-13C nuclear magnetic resonance assignment and structural characterization of HIV-1 Tat protein."
Peloponese J.M. Jr., Gregoire C., Opi S., Esquieu D., Sturgis J., Lebrun E., Meurs E., Collette Y., Olive D., Aubertin A.M., Witvrow M., Pannecouque C., De Clercq E., Bailly C., Lebreton J., Loret E.P.
C. R. Acad. Sci. III, Sci. Vie 323:883-894(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K02013 Genomic RNA. Translation: AAB59745.1.
M19921 Genomic RNA. Translation: AAA44985.1.
PIRA25700.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1JFWNMR-A1-86[»]
1JM4NMR-A46-55[»]
ProteinModelPortalP04610.
SMRP04610. Positions 1-86.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP04610. 3 interactions.
MINTMINT-7908963.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D4.10.20.10. 1 hit.
InterProIPR001831. IV_Tat.
[Graphical view]
PfamPF00539. Tat. 1 hit.
[Graphical view]
PRINTSPR00055. HIVTATDOMAIN.
ProtoNetSearch...

Other

EvolutionaryTraceP04610.

Entry information

Entry nameTAT_HV1BR
AccessionPrimary (citable) accession number: P04610
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: April 16, 2014
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references