Q75005 - TAT_HV1ET
- Names & Taxonomy
- Subcellular locationSubcell. location
- Pathology & BiotechPathol./Biotech
- PTM / Processing
- Family & Domains
- Sequences (2)
- Entry information
- Similar proteins
- BLAST>sp|Q75005|TAT_HV1ET Protein Tat OS=Human immunodeficiency virus type 1 group M subtype C (isolate ETH2220) PE=3 SV=1 MEPVDPNLEPWNHPGSQPKTACNQCYCKKCSYHCLVCFLTKA
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- HistoryEntry version 68 (11 Jun 2014)
Sequence version 1 (01 Nov 1996)
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Select a section on the left to see content.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. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat protein exerts as well a positive feedback on the translation of its cognate mRNA. 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 By similarity.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 cell dysfunctions 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 to inhibit 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 By similarity.
Feature key Position(s) Length Description Graphical view Feature identifier Actions <p>Describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.</p><p><a href='../manual/site' target='_top'>More...</a></p>Sitei 11 – 11 1 Essential for Tat's translocation through the endosomal membrane By similarity
- RNA binding Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- sequence-specific DNA binding transcription factor activity Source: InterPro
Recommended name:Protein TatAlternative name(s):Transactivating regulatory protein
- apoptotic process Source: UniProtKB-KW
- modulation by virus of host PP1 activity Source: UniProtKB-KW
- modulation by virus of host chromatin organization Source: UniProtKB-KW
- suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
- transcription, DNA-templated Source: UniProtKB-KW
Human immunodeficiency virus type 1 group M subtype C (isolate ETH2220) (HIV-1) 388796 [NCBI] Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Primate lentivirus group › Human immunodeficiency virus 1 › HIV-1 group M › HIV-1 M:C <p>Only exists in viral entries and indicates the host(s) either as a specific organism or taxonomic group of organisms that are susceptible to be infected by a virus.</p><p><a href='../manual/virus_host' target='_top'>More...</a></p>Virus hosti Homo sapiens (Human) [TaxID: 9606] UP000007694: GenomeHost 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 By similarity.
<p>Provides information on the disease(s) and phenotype(s) associated with the deficiency of a protein.</p><p><a href='../manual/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi
<div> <p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - DiseaseiAIDS
Feature key Position(s) Length Description Graphical view Feature identifier Actions 1 – 42 42 Protein Tat PRO_0000244851 Add
Amino acid modifications
Feature key Position(s) Length Description Graphical view Feature identifier Actions 28 – 28 1 N6-acetyllysine; by host PCAF By similarity
<p>Describes post-translational modifications (PTMs). This subsection complements the information provided at the sequence level or describes modifications for which position-specific data is not yet available.</p><p><a href='../manual/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationiAcetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the transactivation activity of Tat. PCAF-mediated acetylation of Lys-28 enhances Tat's binding to CCNT1 By similarity.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 By similarity.Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1 By similarity.Polyubiquitination by MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA By similarity.
<div> <p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - PTMiAcetylation, Methylation, Phosphoprotein, Ubl conjugationInteracts 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 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 By similarity.
3D structure databases
Q75005. SWISS-MODEL Repository - a database of annotated 3D protein structure models<br/><a href='/database/98'>More..</a>SMRi Q75005. Positions 1-42.
Feature key Position(s) Length Description Graphical view Feature identifier Actions 1 – 24 24 Interaction with human CREBBP By similarity Add
22 – 37 16 Cysteine-rich By similarity Add
<p>Provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.</p><p><a href='../manual/domain_cc' target='_top'>More...</a></p>DomainiThe transactivation domain mediates the interaction with CCNT1, GCN5L2, and MDM2 By similarity.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 By similarity.The Cys-rich region may bind 2 zinc ions Reviewed prediction. This region is involved in binding to KAT5 By similarity.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 By similarity.Belongs to the lentiviruses Tat family.
Family and domain databases
Gene3D Structural and Functional Annotation of Protein Families<br/><a href='/database/29'>More..</a>Gene3Di 188.8.131.52. 1 hit. IPR001831. IV_Tat.
Pfam protein domain database<br/><a href='/database/73'>More..</a>Pfami PF00539. Tat. 1 hit.
<p>Displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.</p><p><a href='../manual/sequences_section' target='_top'>More...</a></p>Sequences (2)i
This entry describes 2<p>Lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.</p><p><a href='../manual/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignIsoform Long (identifier: Q75005-1) [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.
MEPVDPNLEP WNHPGSQPKT ACNQCYCKKC SYHCLVCFLT KA 42Length:42Mass (Da):4,786Last modified:November 1, 1996 - v1<div> <p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> </div> Checksum:i583F4346E07C007BIsoform Short (identifier: Q75005-2)Sequence is not available
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.Length:–Mass (Da):–
Sequence databasesSelect the link destinations:
U46016 Genomic DNA. Translation: AAB36504.1.
<div> <p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Coding sequence diversityiAlternative splicing
Sequence databasesSelect the link destinations:
U46016 Genomic DNA. Translation: AAB36504.1 .
3D structure databases
Q75005. SWISS-MODEL Repository - a database of annotated 3D protein structure models<br/><a href='/database/98'>More..</a> SMRi Q75005. Positions 1-42. Database of comparative protein structure models<br/><a href='/database/63'>More..</a> ModBasei Search... Search...
Protocols and materials databases
Structural Biology Knowledgebase Search...
Family and domain databases
Gene3D Structural and Functional Annotation of Protein Families<br/><a href='/database/29'>More..</a> Gene3Di 184.108.40.206. 1 hit. IPR001831. IV_Tat.
[Graphical view ]
Pfam protein domain database<br/><a href='/database/73'>More..</a> Pfami PF00539. Tat. 1 hit.
[Graphical view ]
- "Full-length sequence of an ethiopian human immunodeficiency virus type 1 (HIV-1) isolate of genetic subtype C."
Salminen M.O., Johansson B., Sonnerborg A., Ayehunie S., Gotte D., Leinikki P., Burke D.S., McCutchan F.E.
AIDS Res. Hum. Retroviruses 12:1329-1339(1996) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
- "Decoding Tat: the biology of HIV Tat posttranslational modifications."
Hetzer C., Dormeyer W., Schnolzer M., Ott M.
Microbes Infect. 7:1364-1369(2005) [PubMed] [Europe PMC] [Abstract]Cited for: REVIEW, ALTERNATIVE SPLICING.
- "The multiple functions of HIV-1 Tat: proliferation versus apoptosis."
Front. Biosci. 11:708-717(2006) [PubMed] [Europe PMC] [Abstract]Cited for: REVIEW.
- "HIV tat and neurotoxicity."
King J.E., Eugenin E.A., Buckner C.M., Berman J.W.
Microbes Infect. 8:1347-1357(2006) [PubMed] [Europe PMC] [Abstract]Cited for: REVIEW.
TAT_HV1ET Q75005Primary (citable) accession number: Q75005 Integrated into UniProtKB/Swiss-Prot: July 11, 2006 Last sequence update: November 1, 1996 Last modified: June 11, 2014 This is version 68 of the entry and version 1 of the sequence. [Complete history] Reviewed (UniProtKB/Swiss-Prot) Annotation program Viral Protein Annotation Program
MiscellaneousHIV-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).This truncated variant has a premature stop codon. It may have arose as a consequence of tissue culture passaging.
- SIMILARITY commentsIndex of protein domains and families
External DataDasty 3