CPLM-002134

Genbank Nucleotide ID

Protein Synonyms/Alias

Transactivating regulatory protein

Human immunodeficiency virus type 1 group M subtype B (isolat

Position	Peptide	Type	References
28	ACTTCYCKKCCFHCQ	acetylation	[1, 2, 3]
50	LGISYGRKKRRQRRR	acetylation	[1, 2, 3, 4, 5, 6, 7, 8]
50	LGISYGRKKRRQRRR	methylation	[9]
51	GISYGRKKRRQRRRP	acetylation	[1, 4]
51	GISYGRKKRRQRRRP	methylation	[9]

[1] HIV-1 tat transcriptional activity is regulated by acetylation.
Kiernan RE, Vanhulle C, Schiltz L, Adam E, Xiao H, Maudoux F, Calomme C, Burny A, Nakatani Y, Jeang KT, Benkirane M, Van Lint C.
EMBO J. 1999 Nov 1;18(21):6106-18. [PMID: 10545121]
[2] Tat acetyl-acceptor lysines are important for human immunodeficiency virus type-1 replication.
Brès V, Kiernan R, Emiliani S, Benkirane M.
J Biol Chem. 2002 Jun 21;277(25):22215-21. [PMID: 11956210]
[3] Differential acetylation of Tat coordinates its interaction with the co-activators cyclin T1 and PCAF.
Brès V, Tagami H, Péloponèse JM, Loret E, Jeang KT, Nakatani Y, Emiliani S, Benkirane M, Kiernan RE.
EMBO J. 2002 Dec 16;21(24):6811-9. [PMID: 12486002]
[4] 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. 2001 Jul 27;276(30):28179-84. [PMID: 11384967]
[5] Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain.
Mujtaba S, He Y, Zeng L, Farooq A, Carlson JE, Ott M, Verdin E, Zhou MM.
Mol Cell. 2002 Mar;9(3):575-86. [PMID: 11931765]
[6] Acetylation of the HIV-1 Tat protein: an in vitro study.
Dormeyer W, Dorr A, Ott M, Schnölzer M.
Anal Bioanal Chem. 2003 Aug;376(7):994-1005. [PMID: 12904943]
[7] Probing lysine acetylation in proteins: strategies, limitations, and pitfalls of in vitro acetyltransferase assays.
Dormeyer W, Ott M, Schnölzer M.
Mol Cell Proteomics. 2005 Sep;4(9):1226-39. [PMID: 15933374]
[8] Analysis of p300 acetyltransferase substrate specificity by MALDI TOF mass spectrometry.
Dormeyer W, Ott M, Schnölzer M.
Methods. 2005 Aug;36(4):376-82. [PMID: 16085422]
[9] Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR.
Van Duyne R, Easley R, Wu W, Berro R, Pedati C, Klase Z, Kehn-Hall K, Flynn EK, Symer DE, Kashanchi F.
Retrovirology. 2008 May 22;5:40. [PMID: 18498648]

Functional Description

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).

REGION 1 48 Transactivation.
REGION 1 24 Interaction with human CREBBP (By
REGION 22 37 Cysteine-rich.
REGION 38 48 Core.
REGION 49 86 Interaction with the host capping enzyme
MOTIF 49 57 Nuclear localization signal, RNA-binding
MOTIF 78 80 Cell attachment site (Potential).
MOD_RES 28 28 N6-acetyllysine; by host PCAF.
MOD_RES 50 50 N6-acetyllysine; by host EP300 and
MOD_RES 51 51 N6-acetyllysine; by host EP300 and
MOD_RES 52 52 Asymmetric dimethylarginine; by host
MOD_RES 53 53 Asymmetric dimethylarginine; by host
CROSSLNK 71 71 Glycyl lysine isopeptide (Lys-Gly)

3D-structure; Acetylation; Activator; AIDS; Alternative splicing; Apoptosis; Complete proteome; Host cytoplasm; Host nucleus; Host-virus interaction; Inhibition of host innate immune response by virus; Inhibition of host interferon signaling pathway by virus; Isopeptide bond; Metal-binding; Methylation; Modulation of host chromatin by virus; Modulation of host PP1 activity by virus; Phosphoprotein; RNA-binding; Secreted; Transcription; Transcription regulation; Ubl conjugation; Viral immunoevasion; Zinc.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
GO:0044196; C:host cell nucleolus; IEA:UniProtKB-SubCell.
GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO:0039525; P:modulation by virus of host chromatin organization; IEA:UniProtKB-KW.
GO:0039586; P:modulation by virus of host PP1 activity; IEA:UniProtKB-KW.
GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.

PR00055; HIVTATDOMAIN.