From: Roles and functions of HIV-1 Tat protein in the CNS: an overview
Protein name | Protein Acc | Ref PMID | Interaction description |
---|---|---|---|
Activated RNA polymerase II transcriptional coactivator p15 | NP_006704.3 |  | Through amino acids 22–91, PC4 binds to the basic TAR binding domain of HIV-1 Tat (amino acids 49–57) and enhances activation of the HIV-1 LTR promoter in a Tat dependent manner |
Adenylate kinase isoenzyme 6 | NP_003178.1 |  | HIV-1 Tat binds, through amino acids 36–50, directly to the TBP subunit of the TFIID holoenzyme complex (which includes at least TFIID subunits p250, p125, p70, TBP, and p30), and increases the interaction of TFIID with the HIV-1 LTR promoter |
Aggrecan core protein isoform 1 precursor | NP_001126.3 | Â | HIV-Tat peptide interferes with polyamine uptake via competition for proteoglycan binding sites rather than a putative downstream transporter in human carcinoma cells |
AT-rich interactive domain-containing protein 1A isoform a | NP_006006.3 | Â | Acetylated HIV-1 Tat binds efficiently to BRG1 and BAF200 (component of PBAF complex) and weakly to BAF250 (component of BAF complex). BAF250 has a preference to bind to unmodified Tat |
AT-rich interactive domain-containing protein 2 | NP_689854.2 | Â | Acetylated HIV-1 Tat binds efficiently to BRG1 and BAF200 (component of PBAF complex) and weakly to BAF250 (component of BAF complex) |
B-cell lymphoma/leukemia 11B isoform 1 | NP_612808.1 |  | CTIP2 harbors two HIV-1 Tat interaction interfaces (amino acids 145–434 and 717–813) and binds to the N-terminus (amino acids 1–48) of Tat |
Bone marrow proteoglycan isoform 1 preproprotein | NP_002719.3 | Â | HIV-Tat peptide interferes with polyamine uptake via competition for proteoglycan binding sites rather than a putative downstream transporter in human carcinoma cells |
C-C chemokine receptor type 2 isoform A | NP_001116513.2 | Â | HIV-1 Tat binds to CCR2 and displaces MCP-1 from this beta-chemokine receptor, an effect mediated by Tat amino acids 24-51 |
C-C chemokine receptor type 3 isoform 1 | NP_001828.1 | Â | |
CCAAT/enhancer-binding protein beta | NP_005185.2 | 9169458 | HIV-1 Tat induces an increase in C/EBPbeta binding activity through a direct binding interaction between Tat and C/EBPbeta that is mediated through the N-terminal, cysteine rich, and core regions of Tat (amino acids 1–47) |
CDK-activating kinase assembly factor MAT1 isoform 1 | NP_002422.1 |  | Amino acids 1–48 of HIV-1 Tat, which includes the Tat activation domain, mediate the binding of Tat to CAK and the TFIIH complex through a direct interaction with CDK7 and possibly other TFIIH subunits, including p62 and ERCC3 |
Cellular tumor antigen p53 isoform a | NP_000537.3 |  | HIV-1 Tat binds to p53, an interaction mediated by the basic region of Tat (amino acids 49–57) and the acidic O2 domain of p53 (amino acids 341-354 |
NP_000537.3 | The p53 tetramerization domain (residues 326–355) binds directly to residues 1–35 and 47–57 in HIV-1 Tat as evidenced by using peptide mapping, fluorescence anisotropy, and NMR spectroscopy | ||
Complement component 1 Q subcomponent-binding protein, mitochondrial precursor | NP_001203.1 | 7778269 | Using a yeast two-hybrid system, the splicing factor SF2-associated protein p32 has been shown to bind to the basic domain of HIV-1 Tat (amino acids 47–59), suggesting a role for p32 in mediating the biological activity of Tat during HIV-1 replication |
NP_001203.1 | Â | Splicing factor SF2-associated protein p32 preferentially binds acetylated HIV-1 Tat and co-localizes with Tat in HIV-1 infected cells | |
Core histone macro-H2A.1 isoform 1 | NP_613075.1 |  | HIV-1 Tat peptides bind core histones H2A, H2B, H3 and H4, and Tat protein recruits histone acetyltransferases to the HIV-1 LTR promoter leading to acetylation of histones H3 and H4, de-repressing chromatin structure and increasing NF-κB responsiveness |
Core histone macro-H2A.2 | NP_061119.1 | Â | |
CREB-binding protein isoform a | NP_004371.2 |  | HIV-1 Tat binds to the minimal histone acetyltransferase domain of the CBP/p300 complex (amino acids 1253–1710 of p300) and E1a binding domain (amino acids 1542–1710) of p300, an effect mediated by the basic domain (amino acids 48–57) of Tat |
The N-terminal 24 amino acids of HIV-1 Tat mediate its binding to the KIX domain (amino acids 589–679) of CBP | |||
C-X-C chemokine receptor type 4 isoform b | NP_003458.1 |  | HIV-1 Tat binds to CXCR4, competes with the natural ligand of CXCR4, SDF-1alpha, and selectively inhibits the entry and replication of ×4-tropic HIV-1 in peripheral blood mononuclear cells (PBMCs), indicating a role for Tat in selecting against ×4 virus |
Cyclin-dependent kinase 2 isoform 1 | NP_001789.2 | Â | HIV-1 Tat 41/44 peptide TAALS from the core domain of Tat inhibits Tat-mediated HIV-1 gene expression and replication by binding the Cdk2/Cyclin E complex and inhibiting the phosphorylation of serine 5 of RNAPII |
Cyclin-dependent kinase 7 | NP_001790.1 |  | Amino acids 1–48 of HIV-1 Tat, which includes the Tat activation domain, mediate the binding of Tat to CAK and the TFIIH complex through a direct interaction with CDK7 and possibly other TFIIH subunits, including p62 and ERCC3 |
TFIIH subunits CDK7 and cyclin H have been identified as two components associated with the Tat-associated CTD kinase (TTK) that binds to HIV-1 Tat | |||
Cyclin-dependent kinase 9 | NP_001252.1 | 7853496 | The N-terminus (amino acids 1–48, including activation domain) of HIV-1 Tat binds to P-TEFb through a direct interaction with the N-terminus (amino acids 1–290) of cyclin T1 during Tat-mediated transactivation of the HIV-1 LTR promoter |
8676484 | |||
 | 9356449 | ||
Cyclin-H isoform 1 | NP_001230.1 |  | Amino acids 1–48 of HIV-1 Tat, which includes the Tat activation domain, mediate the binding of Tat to CAK and the TFIIH complex through a direct interaction with CDK7 and possibly other TFIIH subunits, including p62 and ERCC3 |
NP_001230.1 | Â | TFIIH subunits CDK7 and cyclin H have been identified as two components associated with the Tat-associated CTD kinase (TTK) that binds to HIV-1 Tat | |
Cyclin-T1 | NP_001231.2 | 7853496 | The N-terminus (amino acids 1–48, including activation domain) of HIV-1 Tat binds to P-TEFb through a direct interaction with the N-terminus (amino acids 1–290) of cyclin T1 during Tat-mediated transactivation of the HIV-1 LTR promoter |
8676484 | |||
 | 9356449 | ||
Cyclin-T2 isoform a | NP_001232.1 |  | Amino acids 260–263 of cyclin T1 are critical for HIV-1 Tat-mediated transcriptional activation, and site-directed mutations in this region of cyclin T2 (asparagine to cysteine at residue 260) allow it to bind Tat and stimulate transcription |
Dipeptidyl peptidase 4 | NP_001926.2 | Â | The N-terminal nine amino acids of HIV-1 Tat mediate the binding of Tat to CD26 |
DNA-dependent protein kinase catalytic subunit isoform 1 | NP_008835.5 | 9525578 | Amino acids 56–101 of HIV-1 Tat mediate Tat binding to DNA-PK, an effect that augments DNA-PK-mediated phosphorylation of Sp1 during Tat transactivation of the HIV-1 LTR promoter |
E3 ubiquitin-protein ligase TRIM32 | NP_036342.2 | 7778269 | HT2A specifically and precisely binds to the activation domain of HIV-1 Tat (amino acids 1–48), suggesting a role for HT2A in mediating the biological activity of Tat during HIV-1 replication |
Early growth response protein 1 | NP_001955.1 | Â | HIV-1 Tat binds to Egr-1, an interaction that is mediated through Tat amino acids 30-40 |
G1/S-specific cyclin-E1 | NP_001229.1 | Â | HIV-1 Tat 41/44 peptide TAALS from the core domain of Tat inhibits Tat-mediated HIV-1 gene expression and replication by binding the Cdk2/Cyclin E complex and inhibiting the phosphorylation of serine 5 of RNAPII |
G2/mitotic-specific cyclin-B1 | NP_114172.1 |  | HIV-1 Tat stimulates polyubiquitination-mediated degradation of cyclin B1 through binding to the N-terminal of cyclin B1 (amino acids 61–129) that is just downstream of the D box |
General transcription factor IIH subunit | NP_005307.1 |  | Amino acids 1–48 of HIV-1 Tat, which includes the Tat activation domain, mediate the binding of Tat to CAK and the TFIIH complex through a direct interaction with CDK7 and possibly other TFIIH subunits, including p62 and ERCC3 |
Granulins precursor | NP_002078.1 |  | The cysteine rich region of HIV-1 Tat (amino acids 21–37) mediates the binding of Tat to granulin amino acids 206–337 (granulin regions B + A) suggesting a role for granulin growth factors as biologically important extracellular Tat co-factors |
Growth factor receptor-bound protein 2 isoform 1 | NP_002077.1 |  | The binding between HIV-1 Tat and Grb2 is mediated by the proline-rich sequence (residues 1–18) of Tat and the SH3 domain (residues 160–212) of Grb2, which impairs activation of the Raf/MAPK pathway and increases the PKA/Raf inhibitory pathway |
Histone acetyltransferase KAT2A | NP_066564.2 |  | Binding of HIV-1 Tat to hGCN5 is mediated by amino acids 20–48 of Tat (includes cysteine rich, core, and minimal activation domains of Tat) and by amino acids 111–151 (histone acetyltransferase domain) and 389–476 (bromodomain) of hGCN5 |
Histone acetyltransferase KAT2B | NP_003875.3 |  | The bromodomain (amino acids 712–832) of P/CAF mediates its binding to amino acids 20–40 of non-acetylated HIV-1 Tat, to amino acids 48–57 in the arginine rich motif of Lys50 acetylated Tat, while Lys28 acetylation of Tat abrogates P/CAF binding to Tat |
Histone acetyltransferase KAT5 isoform 1 | NP_874369.1 | Â | Tip60 is a nuclear histone acetyltransferase that binds to the N-terminal 31 amino acids of HIV-1 Tat |
Histone acetyltransferase p300 | NP_001420.2 |  | HIV-1 Tat binds to the minimal histone acetyltransferase domain (amino acids 1253–1710) and E1a binding domain (amino acids 1542–1710) of p300, an effect mediated by the basic domain (amino acids 48–57) of Tat |
Histone H2A/H2B/H3/H4 | NP_003500.1 | Â | HIV-1 Tat peptides bind core histones H2A, H2B, H3 and H4, and Tat protein recruits histone acetyltransferases to the HIV-1 LTR promoter leading to acetylation of histones H3 and H4, derepressing chromatin structure and increasing NFkappaB responsiveness |
Histone-lysine N-methyltransferase SETD7 | NP_085151.1 | Â | SET7/9-KMT7 binds directly to HIV-1 Tat and enhances recruitment of the Tat/P-TEFb complex to HIV-1 TAR RNA |
Importin subunit alpha-2 | NP_002257.1 |  | HIV-1 Tat peptide (amino-acids 47–57) binds to importin alpha and beta receptors |
Importin subunit beta-1 | NP_002256.2 | 9891055 | The binding of HIV-1 Tat with importin beta is inhibited by RanGTP; HIV-1 Tat peptide (amino-acids 47–57) binds to importin alpha and beta receptors |
Insulin-like growth factor-binding protein 4 precursor | NP_001543.2 | 7778269 | Using a yeast two-hybrid system, HIV-1 Tat has been shown to bind the human insulin-like growth factor binding protein 4, suggesting a role for this protein in mediating the biological activity of Tat during HIV-1 replication |
Integrin alpha | NP_002196.2 | Â | The arginine-glycine-aspartic acid (RGD) sequence present at the carboxy-terminal of HIV-1 Tat mediates vascular cell and monocyte migration and invasion by binding to the alpha-5-beta-1 and alpha-v-beta-3 integrins |
Interferon regulatory factor 1 | NP_002189.1 | Â | HIV-1 Tat represses transcription of the LMP2 gene by competing with STAT1 (signal transducer and activator of transcription 1) for binding to IRF-1 (interferon-regulatory factor-1) at the LMP2 promoter |
Interferon-induced, double-stranded RNA-activated protein kinase isoform a | NP_002750.1 |  | Binding of HIV-1 Tat to PKR has been mapped to residues 40–58 of Tat, overlapping the hydrophobic core and basic region of Tat |
Lamin isoform A | NP_733821.1 | Â | Purified HIV-1 Tat has been shown to bind with high affinity to the nuclear matrix from H9 cells and to link viral RNAs to the nuclear matrix |
Lediator of RNA polymerase II transcription subunit 6 | NP_005457.2 | Â | The interaction of HIV-1 Tat with MED21 hypothetically induces the binding of Tat to MED6 |
mRNA-capping enzyme | NP_003791.3 |  | HIV-1 Tat binding to mammalian capping enzyme (Mce1) is mediated through the C-terminal domain of Tat (amino acids 49–86) and amino acids 211–597 of Mce1 |
myoD family inhibitor | NP_005577.1 | Â | I-mfa (inhibitor of MyoD family a) and HIC (human I-mfa-domain-containing) proteins serve as substrates for P-TEFb. Their I-mfa domains bind the activation domain of HIV-1 Tat and inhibit Tat- and P-TEFb-dependent HIV-1 transcription |
NAD-dependent protein deacetylase sirtuin-1 isoform a | NP_036370.2 |  | HIV-1 Tat binds the deacetylase domain (amino acids 341–512) of SIRT1 and inhibits SIRT1 deacetylase activity, which results in the induction of NF-kappaB hyperacetylation |
NF-kappa-B inhibitor alpha | NP_065390.1 |  | Amino acids 72 to 287 of IkappaB-alpha are required for Tat inhibition. Amino acids 263 to 269 within the sixth ankrin of IκB-alpha are required for the binding to Tat |
Nuclear factor NF-κB p100 subunit isoform b | NP_002493.3 |  | HIV-1 Tat has been shown to bind NFkappaB in vitro in gel shift, GST-pull down and affinity matrix assays |
Nuclear factor of activated T-cells, cytoplasmic 2 isoform B | NP_036472.2 |  | HIV-1 Tat binds to NFAT1, an interaction mediated by the N-terminus of Tat (amino acids 1–26) and the transactivation domain of NFAT1 (amino acids 1–96) |
Nuclear inhibitor of protein phosphatase 1 isoform alpha | NP_054829.2 | Â | PP1 interacts with Tat in part through the binding of Val (36) and Phe (38) of Tat to PP1, and Tat is involved in the nuclear and subnuclear targeting of PP1 |
Nuclease-sensitive element-binding protein 1 | NP_004550.2 |  | Binding of YB-1 to HIV-1 Tat is mediated through the C-terminal region of Tat (amino acids 48–72) and through amino acids 75–203 of YB-1 |
nucleophosmin isoform 1 | NP_002511.1 | Â | The nucleolar shuttle protein B23 binds to HIV-1 Tat and data indicates B23 is necessary for the nucleolar localization of Tat |
POU domain, class 2, transcription factor 1 isoform 1 | NP_002688.3 | 7690421 | Oct binds to HIV-1 Tat affinity matrices and also confers Tat responsiveness on a basal HIV-1 promoter |
Prolow-density lipoprotein receptor-related pr otein 1 precursor | NP_002323.2 |  | LRP binds to the core domain of HIV-1 Tat (amino acids 37–48) and promotes the efficient uptake of Tat into neurons, suggesting Tat may mediate HIV-1 induced neuropathology through disruption of LRP ligands and activation of neuronal genes |
Proteasome subunit alpha type | NP_002778.1 | Â | HIV-1 Tat binds to the alpha2, alpha4, alpha6, alpha7, beta1, beta2, beta3, beta5, beta6, beta7, LMP7/beta5i, and MECL1/beta2i subunits of the proteasome 20Â S core structure and can inhibit cellular proteasome function |
Proteoglycan 3 precursor | NP_006084.2 | Â | HIV-Tat peptide interferes with polyamine uptake via competition for proteoglycan binding sites rather than a putative downstream transporter in human carcinoma cells |
Retinoblastoma-like protein 2 | NP_005602.3 | Â | HIV-1 Tat protein specifically binds to pRb2/p130 and data suggest this interaction results in the deregulation of the control exerted by pRb2/p130 on the cell cycle, indicating a potential role in AIDS-related oncogenesis |
RNA polymerase II subunit A C-terminal domain phosphatase isoform 1 | NP_004706.3 |  | FCP1 is required for Tat-mediated transactivation in vitro and amino acids 562–685 of FCP1 are necessary for binding to Tat in yeast two-hybrid studies |
Serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform 1 | NP_002699.1 | Â | PP1 interacts with Tat in part through the binding of Val (36) and Phe (38) of Tat to PP1, and Tat is involved in the nuclear and subnuclear targeting of PP1 |
Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial precursor | NP_002991.2 | 7778269 | Using a yeast two-hybrid system, HIV-1 Tat has been shown to bind the human succinate-ubiquinone oxidoreductase iron sulfur subunit, suggesting a role for this protein in mediating the biological activity of Tat during HIV-1 replication |
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 isoform a | NP_003064.2 | Â | Integrase interactor 1 (INI1)/hSNF5 binds to HIV-1 Tat and co-activates Tat-mediated transcription; both the repeat (Rpt) 1 and Rpt 2 domains of INI1 are required for efficient co-activation |
Syndecan-1 precursor | NP_002988.3 |  | Binding of HIV-1 Tat to heparan sulfate proteoglycans is competed out by the heparin-binding factor bFGF; Cell membrane heparin sulfate proteoglycans bind to the basic region of HIV-1 Tat (amino acids 49–57) and act as receptors for extracellular Tat uptake, an effect that may contribute to the angiogenic properties of Tat in promoting Kaposi's sarcoma |
TATA-binding protein-associated factor 172 | NP_003963.1 |  | HIV-1 Tat binds, through amino acids 36–50, directly to the TBP subunit of the TFIID holoenzyme complex (which includes at least TFIID subunits p250, p125, p70, TBP, and p30), and increases the interaction of TFIID with the HIV-1 LTR promoter |
TATA-box-binding protein isoform 1 | NP_003185.1 |  | Binding of HIV-1 Tat to TBP has been mapped to the cysteine rich and core domains (amino acids 20–50) of Tat and the H1 alpha helical and S2 domains (amino acids 163–220) of TBP |
TFIIH basal transcription factor complex helicase XPB subunit | NP_000113.1 |  | Amino acids 1–48 of HIV-1 Tat, which includes the Tat activation domain, mediate the binding of Tat to CAK and the TFIIH complex through a direct interaction with CDK7 and possibly other TFIIH subunits, including p62 and ERCC3 |
Thrombospondin-1 precursor | NP_003237.2 | Â | Thrombospondin-1 (TSP) binds to HIV-1 Tat, an interaction that can be inhibited by heparin which can bind to both TSP and Tat |
Thyroid hormone receptor alpha isoform 2 | NP_003241.2 | 7609079 | Thyroid hormone (T3) receptor alpha (T3Ralpha) binds to HIV-1 Tat, an interaction mediated through the DNA-binding domain of T3Ralpha (amino acids 51–118) and the arginine-rich basic region (amino acids 49–57) and possibly amino acids 58–72 of Tat |
Transcription activator BRG1 isoform B | NP_003063.2 | Â | Acetylated HIV-1 Tat binds efficiently to BRG1 and BAF200 (component of PBAF complex) and weakly to BAF250 (component of BAF complex) |
Transcription factor AP-1 | NP_002219.1 | 7690421 | Crosslinking experiments suggest a direct binding interaction between HIV-1 Tat and AP1 that is relatively inefficient and that correlates with the ability of AP1 to support Tat transactivation |
Transcription factor p65 isoform 1 | NP_068810.3 | Â | HIV-1 Tat has been shown to bind NFkappaB in vitro in gel shift, GST-pull down and affinity matrix assays |
Transcription factor RelB | NP_006500.2 | Â | |
Transcription factor Sp1 isoform a | NP_612482.2 |  | HIV-1 Tat amino acids 30–55 mediate binding of Tat to Sp1, an effect that some reports indicate is a direct binding interaction, while other reports suggest it is indirect and possibly mediated through interaction with other cellular factors |
Transcription initiation factor TFIID subunit 1 isoform 1 | NP_004597.2 |  | HIV-1 Tat binds, through amino acids 36–50, directly to the TBP subunit of the TFIID holoenzyme complex (which includes at least TFIID subunits p250, p125, p70, TBP, and p30), and increases the interaction of TFIID with the HIV-1 LTR promoter; Amino acids (aa) 67–101 (C-term. domain) of HIV-1 Tat bind to aa 848–1279 of TAFII250, while Tat aa 18–36 (cysteine-rich domain) and 36–56 (includes basic domain) bind to TAFII250 aa 885–984 (AT domain) and 1120–1279 (Rap74 binding domain), respectively |
Transcriptional activator protein Pur-alpha | NP_005850.1 | Â | HIV-1 Tat downregulates the expression of p35, a neuron-specific activator of cdk5, and also binds to Puralpha, which associates with cdk5, leading to deregulation of neuronal differentiation and survival |
Transportin-1 isoform 1 | NP_002261.3 | 9891055 | The binding of HIV-1 Tat with importin beta is inhibited by RanGTP |
Tubulin alpha/beta | NP_006000.2 |  | HIV-1 Tat (amino acids 36–39) binds tubulin alpha/beta dimers and polymerized microtubules leading to the alteration of microtubule dynamics and activation of a mitochondria-dependent apoptotic pathway that is facilitated by the Bcl-2 relative Bim |
Tumor suppressor protein p73 isoform a | NP_005418.1 | Â | Association of tumor protein p73 with HIV-1 Tat prevents the acetylation of Tat on lysine 28 by PCAF, and requires the cysteine-rich domain (amino acids 30 to 40) of Tat, which binds to the N-terminal region (amino acids 1 to 120) of p73 |
Vascular endothelial growth factor receptor 1 isoform 1 precursor | NP_002010.2 | 9269752 | The mechanism of monocyte activation by HIV-1 Tat involves the binding of Tat to VEGFR-1/Flt-1 and activating signals through this receptor |
Zinc finger and BTB domain-containing protein 7A | NP_056982.1 |  | Binding of FBI-1 to HIV-1 Tat is mediated by the zinc finger (ZF) domain of FBI-1 (amino acids 377–584) and is diminished by point mutations in Tat at amino acids 18, 30, and 31 |