Anti-TIP60

The protein encoded by this gene belongs to the MYST family of histone acetyl transferases (HATs) and was originally isolated as an HIV-1 TAT-interactive protein. HATs play important roles in regulating chromatin remodeling, transcription and other nuclear processes by acetylating histone and nonhistone proteins. This protein is a histone acetylase that has a role in DNA repair and apoptosis and is thought to play an important role in signal transduction. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008], Protein function: Catalytic subunit of the NuA4 histone acetyltransferase complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H2A and H4 (PubMed:12776177, PubMed:15042092, PubMed:15121871, PubMed:15310756, PubMed:14966270, PubMed:16387653, PubMed:19909775, PubMed:25865756, PubMed:27153538, PubMed:29335245, PubMed:29174981, PubMed:33076429, PubMed:32822602). Histone acetylation alters nucleosome-DNA interactions and promotes interaction of the modified histones with other proteins which positively regulate transcription (PubMed:12776177, PubMed:15042092, PubMed:15121871, PubMed:15310756, PubMed:14966270). The NuA4 histone acetyltransferase complex is required for the activation of transcriptional programs associated with proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:17709392, PubMed:19783983, PubMed:32832608). The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR): the complex inhibits TP53BP1 binding to chromatin via MBTD1, which recognizes and binds histone H4 trimethylated at 'Lys-20' (H4K20me), and KAT5 that catalyzes acetylation of 'Lys-15' of histone H2A (H2AK15ac), thereby blocking the ubiquitination mark required for TP53BP1 localization at DNA breaks (PubMed:27153538, PubMed:32832608). Also involved in DSB repair by mediating acetylation of 'Lys-5' of histone H2AX (H2AXK5ac), promoting NBN/NBS1 assembly at the sites of DNA damage (PubMed:17709392, PubMed:26438602). The NuA4 complex plays a key role in hematopoietic stem cell maintenance and is required to maintain acetylated H2A.Z/H2AZ1 at MYC target genes. The NuA4 complex is also required for spermatid development by promoting acetylation of histones: histone hyperacetylation is required for histone replacement during the transition from round to elongating spermatids. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Also acetylates non-histone proteins, such as BMAL1, ATM, AURKB, CHKA, CGAS, ERCC4/XPF, LPIN1, NDC80/HEC1, NR1D2, RAN, SOX4, FOXP3, ULK1 and RUBCNL/Pacer (PubMed:16141325, PubMed:17360565, PubMed:17996965, PubMed:24835996, PubMed:26829474, PubMed:29040603, PubMed:30409912, PubMed:30704899, PubMed:32034146, PubMed:32817552, PubMed:34077757). Directly acetylates and activates ATM (PubMed:16141325). Promotes nucleotide excision repair (NER) by mediating acetylation of ERCC4/XPF, thereby promoting formation of the ERCC4-ERCC1 complex (PubMed:32034146). Relieves NR1D2-mediated inhibition of APOC3 expression by acetylating NR1D2 (PubMed:17996965). Acts as a regulator of regulatory T-cells (Treg) by catalyzing FOXP3 acetylation, thereby promoting FOXP3 transcriptional repressor activity (PubMed:17360565, PubMed:24835996). Involved in skeletal myoblast differentiation by mediating acetylation of SOX4 (PubMed:26291311). Catalyzes acetylation of APBB1/FE65, increasing its transcription activator activity (PubMed:33938178). Promotes transcription elongation during the activation phase of the circadian cycle by catalyzing acetylation of BMAL1, promoting elongation of circadian transcripts. Together with GSK3 (GSK3A or GSK3B), acts as a regulator of autophagy: phosphorylated at Ser-86 by GSK3 under starvation conditions, leading to activate acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Acts as a regulator of the cGAS-STING innate antiviral response by catalyzing acetylation the N-terminus of CGAS, thereby promoting CGAS DNA-binding and activation (PubMed:32817552). Also regulates lipid metabolism by mediating acetylation of CHKA or LPIN1 (PubMed:34077757). Promotes lipolysis of lipid droplets following glucose deprivation by mediating acetylation of isoform 1 of CHKA, thereby promoting monomerization of CHKA and its conversion into a tyrosine-protein kinase (PubMed:34077757). Acts as a regulator of fatty-acid-induced triacylglycerol synthesis by catalyzing acetylation of LPIN1, thereby promoting the synthesis of diacylglycerol (PubMed:29765047). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA) and 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), and is able to mediate protein crotonylation and 2-hydroxyisobutyrylation, respectively (PubMed:29192674, PubMed:34608293). Acts as a key regulator of chromosome segregation and kinetochore-microtubule attachment during mitosis by mediating acetylation or crotonylation of target proteins (PubMed:26829474, PubMed:29040603, PubMed:30409912, PubMed:34608293). Catalyzes acetylation of AURKB at kinetochores, increasing AURKB activity and promoting accurate chromosome segregation in mitosis (PubMed:26829474). Acetylates RAN during mitosis, promoting microtubule assembly at mitotic chromosomes (PubMed:29040603). Acetylates NDC80/HEC1 during mitosis, promoting robust kinetochore- microtubule attachment (PubMed:30409912). Catalyzes crotonylation of MAPRE1/EB1, thereby ensuring accurate spindle positioning in mitosis (PubMed:34608293). [The UniProt Consortium] Recommended dilutions: WB 1:500-2000,IHC-p 1:50-300. Cellular localization: Nucleus . Chromosome . Cytoplasm . Chromosome, centromere, kinetochore . Cytoplasm, cytoskeleton, spindle pole . Nucleus, nucleolus . Cytoplasm, perinuclear region . Upon stimulation with EDN1, it is exported from the nucleus to the perinuclear region and UV irradiation induces translocation into punctuate subnuclear structures named nuclear bodies (PubMed:11262386). Transiently localizes to kinetochores in early mitosis (PubMed:26829474). Localizes to spindle poles when chromosomes align during metaphase (PubMed:34608293). Localizes in the cytoplasm and nucleus of round spermatids (By similarity). .