TARGETID

T93783

FORMERID

TTDS00322

UNIPROID

TAT_HV1H2

TARGNAME

Human immunodeficiency virus Tat protein (HIV tat)

GENENAME

HIV tat

TARGTYPE

Successful target

SYNONYMS

Transactivating regulatory protein; TAT protein

FUNCTION

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 celldysfunctions 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 toinhibit 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.

PDBSTRUC

6MCF; 6MCE; 5V61; 4OR5; 3MIA

BIOCLASS

Lentiviruses Tat family

SEQUENCE

MEPVDPRLEPWKHPGSQPKTACTNCYCKKCCFHCQVCFITKALGISYGRKKRRQRRRAHQNSQTHQASLSKQPTSQPRGDPTGPKE

DRUGINFO

Penicillamine

DRUGINFO

ALX-40-4C

DRUGINFO

Ro-24-7429

DRUGINFO

Anti-HIV ribozyme therapy

DRUGINFO

EM-2487

DRUGINFO

CGP 40336A

DRUGINFO

Durhamycin A