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Protein

Protein Tat

Gene

tat

Organism
Human immunodeficiency virus 1
Status
Unreviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

Functioni

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.UniRule annotation

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).UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei11Essential for Tat translocation through the endosomal membraneUniRule annotation1
Metal bindingi22Zinc 1UniRule annotation1
Metal bindingi25Zinc 2UniRule annotation1
Metal bindingi27Zinc 2UniRule annotation1
Metal bindingi30Zinc 2UniRule annotation1
Metal bindingi33Zinc 1; via pros nitrogenUniRule annotation1
Metal bindingi34Zinc 1UniRule annotation1
Metal bindingi37Zinc 1UniRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivatorUniRule annotationSAAS annotation, RNA-bindingUniRule annotationSAAS annotation
Biological processApoptosisUniRule annotation, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Modulation of host chromatin by virusUniRule annotation, Modulation of host PP1 activity by virusUniRule annotation, Transcription, Transcription regulationUniRule annotationSAAS annotation, Viral immunoevasion
LigandMetal-bindingUniRule annotation, ZincUniRule annotation

Names & Taxonomyi

Protein namesi
Recommended name:
Protein TatUniRule annotationSAAS annotation
Alternative name(s):
Transactivating regulatory proteinUniRule annotation
Gene namesi
Name:tatUniRule annotationImported
OrganismiHuman immunodeficiency virus 1Imported
Taxonomic identifieri11676 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000106034 Componenti: Genome

Subcellular locationi

  • host nucleolus UniRule annotation
  • Host cytoplasm UniRule annotation
  • Secreted UniRule annotation
  • 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.UniRule annotation

GO - Cellular componenti

Keywords - Cellular componenti

Host cytoplasmUniRule annotation, Host nucleusUniRule annotationSAAS annotation, SecretedUniRule annotation

PTM / Processingi

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei28N6-acetyllysine; by host PCAFUniRule annotation1
Modified residuei50N6-acetyllysine; by host EP300 and GCN5L2UniRule annotation1
Modified residuei51N6-acetyllysine; by host EP300 and GCN5L2UniRule annotation1
Modified residuei52Asymmetric dimethylarginine; by host PRMT6UniRule annotation1
Modified residuei53Asymmetric dimethylarginine; by host PRMT6UniRule annotation1
Cross-linki71Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)UniRule annotation

Post-translational modificationi

Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the transactivation activity of Tat. EP300-mediated acetylation of Lys-50 promotes dissociation of Tat from the TAR RNA through the competitive binding to PCAF's bromodomain. In addition, the non-acetylated Tat's N-terminus can also interact with PCAF. PCAF-mediated acetylation of Lys-28 enhances Tat's binding to CCNT1. Lys-50 is deacetylated by SIRT1.UniRule annotation
Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1.UniRule annotation
Phosphorylated by EIF2AK2 on serine and threonine residues adjacent to the basic region important for TAR RNA binding and function. Phosphorylation of Tat by EIF2AK2 is dependent on the prior activation of EIF2AK2 by dsRNA.UniRule annotation
Polyubiquitination by host MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA.UniRule annotation

Keywords - PTMi

AcetylationUniRule annotation, Isopeptide bondUniRule annotation, MethylationUniRule annotation, PhosphoproteinUniRule annotation, Ubl conjugationUniRule annotation

Interactioni

Subunit structurei

Interacts with host CCNT1. Associates with the P-TEFb complex composed at least of Tat, P-TEFb (CDK9 and CCNT1), TAR RNA, RNA Pol II. Recruits the HATs CREBBP, TAF1/TFIID, EP300, PCAF and GCN5L2. Interacts with host KAT5/Tip60; this interaction targets the latter to degradation. Interacts with the host deacetylase SIRT1. Interacts with host capping enzyme RNGTT; this interaction stimulates RNGTT. Binds to host KDR, and to the host integrins ITGAV/ITGB3 and ITGA5/ITGB1. Interacts with host KPNB1/importin beta-1 without previous binding to KPNA1/importin alpha-1. Interacts with EIF2AK2. Interacts with host nucleosome assembly protein NAP1L1; this interaction may be required for the transport of Tat within the nucleus, since the two proteins interact at the nuclear rim. Interacts with host C1QBP/SF2P32; this interaction involves lysine-acetylated Tat. Interacts with the host chemokine receptors CCR2, CCR3 and CXCR4. Interacts with host DPP4/CD26; this interaction may trigger an anti-proliferative effect. Interacts with host LDLR. Interacts with the host extracellular matrix metalloproteinase MMP1. Interacts with host PRMT6; this interaction mediates Tat's methylation. Interacts with, and is ubiquitinated by MDM2/Hdm2. Interacts with host PSMC3 and HTATIP2. Interacts with STAB1; this interaction may overcome SATB1-mediated repression of IL2 and IL2RA (interleukin) in T cells by binding to the same domain than HDAC1. Interacts (when acetylated) with human CDK13, thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef.Interacts with host TBP; this interaction modulates the activity of transcriptional pre-initiation complex. Interacts with host RELA.UniRule annotation

GO - Molecular functioni

Structurei

3D structure databases

ProteinModelPortaliO41786.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 48TransactivationUniRule annotationAdd BLAST48
Regioni1 – 24Interaction with human CREBBPUniRule annotationAdd BLAST24
Regioni22 – 37Cysteine-richUniRule annotationAdd BLAST16
Regioni38 – 48CoreUniRule annotationAdd BLAST11
Regioni49 – 86Interaction with the host capping enzyme RNGTTUniRule annotationAdd BLAST38

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi49 – 57Nuclear localization signal, RNA-binding (TAR), and protein transductionUniRule annotation9

Domaini

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.UniRule annotation
The Cys-rich region may bind 2 zinc ions. This region is involved in binding to KAT5.UniRule annotation
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.UniRule annotation
The transactivation domain mediates the interaction with CCNT1, GCN5L2, and MDM2.UniRule annotation

Sequence similaritiesi

Belongs to the lentiviruses Tat family.UniRule annotationSAAS annotation

Family and domain databases

Gene3Di4.10.20.10. 1 hit.
HAMAPiMF_04079. HIV_TAT. 1 hit.
InterProiView protein in InterPro
IPR001831. IV_Tat.
IPR036963. Tat_dom_sf.
PfamiView protein in Pfam
PF00539. Tat. 1 hit.
PRINTSiPR00055. HIVTATDOMAIN.

Sequencei

Sequence statusi: Complete.

O41786-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEPVDPNLEP WNHPGSQPRT PCNKCYCKRC CYHCYVCFVT KGLGISYGRK
60 70 80
KRRPRRRTPP GGQANQDPVP KQPSSQPRGN PTGPKE
Length:86
Mass (Da):9,736
Last modified:January 1, 1998 - v1
Checksum:iB895FE4E382B074A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88824 Genomic DNA. Translation: AAC97577.1.

Similar proteinsi

Entry informationi

Entry nameiO41786_9HIV1
AccessioniPrimary (citable) accession number: O41786
Entry historyiIntegrated into UniProtKB/TrEMBL: January 1, 1998
Last sequence update: January 1, 1998
Last modified: January 31, 2018
This is version 70 of the entry and version 1 of the sequence. See complete history.
Entry statusiUnreviewed (UniProtKB/TrEMBL)

Miscellaneousi

Caution

Lacks conserved residue(s) required for the propagation of feature annotation.UniRule annotation

Keywords - Technical termi

Complete proteomeImported