| UniProt ID | TAT_HV1H2 | |
|---|---|---|
| UniProt AC | P04608 | |
| Protein Name | Protein Tat {ECO:0000255|HAMAP-Rule:MF_04079} | |
| Gene Name | tat {ECO:0000255|HAMAP-Rule:MF_04079} | |
| Organism | Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1). | |
| Sequence Length | 86 | |
| Subcellular Localization | Host nucleus, host nucleolus . Host cytoplasm . Secreted . Probably localizes to both nuclear and nucleolar compartments. Nuclear localization is mediated through the interaction of the nuclear localization signal with importin KPNB1. Secretion occur | |
| Protein 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 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.; 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. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. 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.. | |
| Protein Sequence | MEPVDPRLEPWKHPGSQPKTACTNCYCKKCCFHCQVCFITKALGISYGRKKRRQRRRAHQNSQTHQASLSKQPTSQPRGDPTGPKE | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 28 | Acetylation | ACTNCYCKKCCFHCQ CCCCCCCCCHHHHCC | 23.52 | - | |
| 50 | Acetylation | LGISYGRKKRRQRRR HCCCCCHHHHHHHHH | 46.39 | 18480452 | |
| 51 | Acetylation | GISYGRKKRRQRRRA CCCCCHHHHHHHHHH | 51.99 | 18480452 | |
| 52 | Methylation | ISYGRKKRRQRRRAH CCCCHHHHHHHHHHH | 42.89 | 17267505 | |
| 53 | Methylation | SYGRKKRRQRRRAHQ CCCHHHHHHHHHHHH | 43.14 | 17267505 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
Oops, there are no upstream regulatory protein records of TAT_HV1H2 !! | ||||||
| Modified Location | Modified Residue | Modification | Function | Reference | ||
|---|---|---|---|---|---|---|
Oops, there are no descriptions of PTM sites of TAT_HV1H2 !! | ||||||
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of TAT_HV1H2 !! | ||||||
| Kegg Drug | ||||||
|---|---|---|---|---|---|---|
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| Acetylation | |
| Reference | PubMed |
| "CDK13, a new potential human immunodeficiency virus type 1 inhibitoryfactor regulating viral mRNA splicing."; Berro R., Pedati C., Kehn-Hall K., Wu W., Klase Z., Even Y.,Geneviere A.M., Ammosova T., Nekhai S., Kashanchi F.; J. Virol. 82:7155-7166(2008). Cited for: FUNCTION, INTERACTION WITH HUMAN CDK13, ACETYLATION AT LYS-50 ANDLYS-51, AND MUTAGENESIS OF 50-LYS-LYS-51. | |
