The following text describes a protein:
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; 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.
Miscellaneous:
MISCELLANEOUS: The OYI isolate was taken from the blood of a healthy Gabonese individual; MISCELLANEOUS: 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); MISCELLANEOUS: [Isoform Short]: Expressed in the late stage of the infection cycle, when unspliced viral RNAs are exported to the cytoplasm by the viral Rev protein.
Subcellular Localization:
Host nucleus, host 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 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; The Cys-rich region may bind 2 zinc ions. This region is involved in binding to KAT5; The transactivation domain mediates the interaction with CCNT1, GCN5L2, and MDM2; 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.
Sequence:
MEPVDPRLEPWKHPGSQPKTASNNCYCKRCCLHCQVCFTKKGLGISYGRKKRRQRRRAPQDSKTHQVSLSKQPASQPRGDPTGPKESKKKVERETETDPED