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Protein Tat



Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
Reviewed-Annotation score: -Experimental evidence at protein leveli


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.UniRule annotation6 Publications
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 annotation3 Publications


This truncated variant has a premature stop codon. It may have arose as a consequence of tissue culture passaging.UniRule annotation
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


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei11Essential for Tat translocation through the endosomal membraneUniRule annotation1
Metal bindingi22Zinc 1UniRule annotation2 Publications1
Metal bindingi25Zinc 2UniRule annotation2 Publications1
Metal bindingi27Zinc 2UniRule annotation2 Publications1
Metal bindingi30Zinc 2UniRule annotation2 Publications1
Metal bindingi33Zinc 1; via pros nitrogenUniRule annotation2 Publications1
Metal bindingi34Zinc 1UniRule annotation2 Publications1
Metal bindingi37Zinc 1UniRule annotation2 Publications1

GO - Molecular functioni

  • actinin binding Source: BHF-UCL
  • cyclin binding Source: ParkinsonsUK-UCL
  • metal ion binding Source: UniProtKB-KW
  • protein domain specific binding Source: CAFA
  • RNA binding transcription regulator activity Source: ParkinsonsUK-UCL
  • trans-activation response element binding Source: ParkinsonsUK-UCL

GO - Biological processi


Molecular functionActivator, RNA-binding
Biological processApoptosis, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Modulation of host chromatin by virus, Modulation of host PP1 activity by virus, Transcription, Transcription regulation, Viral immunoevasion
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-167200. Formation of HIV-1 elongation complex containing HIV-1 Tat.
R-HSA-167238. Pausing and recovery of Tat-mediated HIV elongation.
R-HSA-167243. Tat-mediated HIV elongation arrest and recovery.
R-HSA-167246. Tat-mediated elongation of the HIV-1 transcript.
R-HSA-176034. Interactions of Tat with host cellular proteins.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein TatUniRule annotation
Alternative name(s):
Transactivating regulatory proteinUniRule annotation
Gene namesi
Name:tatUniRule annotation
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
Taxonomic identifieri11706 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
  • UP000105453 Componenti: Genome
  • UP000002241 Componenti: Genome

Subcellular locationi

  • host nucleolus UniRule annotation1 Publication
  • Host cytoplasm UniRule annotation1 Publication
  • Secreted UniRule annotation1 Publication
  • 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.

GO - Cellular componenti

  • extracellular region Source: UniProtKB-SubCell
  • host cell cytoplasm Source: UniProtKB-SubCell
  • host cell nucleolus Source: UniProtKB-SubCell
  • host cell nucleus Source: ParkinsonsUK-UCL

Keywords - Cellular componenti

Host cytoplasm, Host nucleus, Secreted

Pathology & Biotechi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi50 – 51KK → AA: Reduced virus production. 1 Publication2

Keywords - Diseasei


Chemistry databases


PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000853641 – 86Protein TatAdd BLAST86

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei28N6-acetyllysine; by host PCAFUniRule annotation1
Modified residuei50N6-acetyllysine; by host EP300 and GCN5L2UniRule annotation1 Publication1
Modified residuei51N6-acetyllysine; by host EP300 and GCN5L2UniRule annotation1 Publication1
Modified residuei52Asymmetric dimethylarginine; by host PRMT6UniRule annotation1 Publication1
Modified residuei53Asymmetric dimethylarginine; by host PRMT6UniRule annotation1 Publication1
Cross-linki71Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)UniRule annotation

Post-translational modificationi

Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1.UniRule annotation1 Publication
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 annotation1 Publication
Polyubiquitination by host MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA.UniRule annotation1 Publication
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 annotation1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

PTM databases



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 annotation11 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • actinin binding Source: BHF-UCL
  • cyclin binding Source: ParkinsonsUK-UCL
  • protein domain specific binding Source: CAFA

Protein-protein interaction databases

BioGridi1205541. 315 interactors.
IntActiP04608. 34 interactors.

Chemistry databases



Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi10 – 12Combined sources3
Helixi30 – 32Combined sources3
Helixi35 – 40Combined sources6
Turni41 – 43Combined sources3

3D structure databases

Select the link destinations:
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum

Miscellaneous databases


Family & Domainsi


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


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi49 – 57Nuclear localization signal, RNA-binding (TAR), and protein transductionUniRule annotation9
Motifi78 – 80Cell attachment siteUniRule annotation3


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

Sequence similaritiesi

Belongs to the lentiviruses Tat family.UniRule annotation

Phylogenomic databases


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.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: P04608-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        10         20         30         40         50
60 70 80
Mass (Da):9,837
Last modified:July 15, 1999 - v2
Isoform Short (identifier: P04608-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     73-86: Missing.

Note: No experimental confirmation available. Expressed in the late stage of the infection cycle, when unspliced viral RNAs are exported to the cytoplasm by the viral Rev protein.
Show »
Mass (Da):8,389

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02230073 – 86Missing in isoform Short. Add BLAST14

Sequence databases

Select the link destinations:
Links Updated
K03455 Genomic RNA. Translation: AAB50256.1.
AF033819 Genomic RNA. Translation: AAC82591.1.
RefSeqiNP_057853.1. NC_001802.1.

Genome annotation databases


Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTAT_HV1H2
AccessioniPrimary (citable) accession number: P04608
Secondary accession number(s): O09778
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: July 15, 1999
Last modified: February 28, 2018
This is version 136 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program


Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome