Protein Tat
Also known as: tat
Function
Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR) and recruits the cyclin T1-CDK9 complex (P-TEFb complex) that will in turn hyperphosphorylate the RNA polymerase II to allow efficient elongation. 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 by interacting with host RELA. Through its interaction with host TBP, Tat may also modulate transcription initiation. 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.
Classification
- Family (Pfam)
- PF00539 Tat
- InterPro
- IV_Tat, Tat_dom_sf
- Functional cluster
- Photosystem Cytochrome b559 & Membrane Proteins
Experimental structures · PDB · 7
A predicted model is available from AlphaFold.
Gene Ontology · 27
- GO:0005576 extracellular region
- GO:0030430 host cell cytoplasm
- GO:0044196 host cell nucleolus
- GO:0042025 host cell nucleus
- GO:0042805 actinin binding
- GO:0030332 cyclin binding
- GO:0035035 histone acetyltransferase binding
- GO:0046872 metal ion binding
- GO:0140313 molecular sequestering activity
- GO:0031491 nucleosome binding
- GO:0019904 protein domain specific binding
- GO:0004865 protein serine/threonine phosphatase inhibitor activity
- GO:0043175 RNA polymerase core enzyme binding
- GO:0001070 RNA-binding transcription regulator activity
- GO:1990970 trans-activation response element binding
- GO:0001223 transcription coactivator binding
- GO:0140537 transcription regulator activator activity
- GO:0006351 DNA-templated transcription
- GO:0043923 host-mediated activation of viral transcription
- GO:0032968 positive regulation of transcription elongation by RNA polymerase II
- GO:0050434 positive regulation of viral transcription
- GO:0042783 symbiont-mediated evasion of host immune response
- GO:0039525 symbiont-mediated perturbation of host chromatin organization
- GO:0039588 symbiont-mediated suppression of host antigen processing and presentation
- GO:0052170 symbiont-mediated suppression of host innate immune response
- GO:0039606 symbiont-mediated suppression of host translation initiation
- GO:0039502 symbiont-mediated suppression of host type I interferon-mediated signaling pathway
Drugs targeting this protein · 1
- RO-24-7429 antagonist
Related proteins · sequence + function similarity
- Protein Tat 0.96
- Protein Tat 0.92
- Protein Tat 0.92
- Protein Tat 0.86
- Protein Tat 0.83
- Protein Tat 0.82
- Protein Tat 0.82
- Protein Tat 0.78
- Protein Tat 0.76
- Protein Tat 0.76
- Protein Tat 0.71
- Protein Tat 0.70
Co-cited proteins · studied together in the literature
- Nucleosome assembly protein 1-like 1 1 shared papers
- Cyclin-dependent kinase 13 1 shared papers
- Phospholipid scramblase 1 1 shared papers
- Low-density lipoprotein receptor 1 shared papers
- Protein Tat 1 shared papers
- Protein Tat 3 shared papers
- Cyclin-dependent kinase 9 2 shared papers
- Complement component 1 Q subcomponent-binding protein, mitochondrial 1 shared papers
- Interferon-induced, double-stranded RNA-activated protein kinase 1 shared papers
- CREB-binding protein 1 shared papers
- Protein arginine N-methyltransferase 6 1 shared papers
- Cyclin-T1 1 shared papers
Literature · 25 cited papers
- Crystal structure of HIV-1 Tat complexed with human P-TEFb and AFF4. Cell Cycle · 2014
- Interaction of the phospholipid scramblase 1 with HIV-1 Tat results in the repression of Tat-dependent transcription. Biochem. Biophys. Res. Commun. · 2013
- Human immunodeficiency virus-1 Tat activates NF-kappaB via physical interaction with IkappaB-alpha and p65. Nucleic Acids Res. · 2012
- Crystal structure of HIV-1 Tat complexed with human P-TEFb. Nature · 2010
- Subcellular localization of the interaction between the human immunodeficiency virus transactivator Tat and the nucleosome assembly protein 1. Amino Acids · 2010
- CDK13, a new potential human immunodeficiency virus type 1 inhibitory factor regulating viral mRNA splicing. J. Virol. · 2008
- The histone chaperone protein Nucleosome Assembly Protein-1 (hNAP-1) binds HIV-1 Tat and promotes viral transcription. Retrovirology · 2008
- HIV-tat induces formation of an LRP-PSD-95- NMDAR-nNOS complex that promotes apoptosis in neurons and astrocytes. Proc. Natl. Acad. Sci. U.S.A. · 2007
- Arginine methylation of the human immunodeficiency virus type 1 Tat protein by PRMT6 negatively affects Tat Interactions with both cyclin T1 and the Tat transactivation region. J. Virol. · 2007
- HIV tat and neurotoxicity. Microbes Infect. · 2006
- The SWI/SNF chromatin-remodeling complex is a cofactor for Tat transactivation of the HIV promoter. J. Biol. Chem. · 2006
- Acetylated Tat regulates human immunodeficiency virus type 1 splicing through its interaction with the splicing regulator p32. J. Virol. · 2006
- … and 13 more in the literature graph