KAT5
entrez
10524
canonical
uniprot
Q92993
canonical
ensembl
ENSG00000172977
resolver
ensp
ENSP00000340330
resolver
ensp
ENSP00000344955
resolver
ensp
ENSP00000366245
resolver
ensp
ENSP00000434765
resolver
genesymbol
KAT5
resolver
genesymbol_syn
HTATIP
resolver
genesymbol_syn
TIP60
resolver
hgnc
HGNC:5275
resolver
uniprot
B4E3C7
resolver
uniprot
C9JL99
resolver
uniprot
O95624
resolver
uniprot
Q13430
resolver
uniprot
Q17RW5
resolver
uniprot
Q561W3
resolver
uniprot
Q6GSE8
resolver
uniprot
Q9BWK7
resolver
uniprot_entry
KAT5_HUMAN
resolver
uniprot_sec
B4E3C7
resolver
uniprot_sec
C9JL99
resolver
uniprot_sec
O95624
resolver
uniprot_sec
Q13430
resolver
uniprot_sec
Q17RW5
resolver
uniprot_sec
Q561W3
resolver
uniprot_sec
Q6GSE8
resolver
uniprot_sec
Q9BWK7
resolver
activity_regulation
ACTIVITY REGULATION: Acyltransferase and acetyltransferase activities are activated by phosphorylation and autoacetylation (PubMed:20100829, PubMed:30704899). Autoacetylation activates the histone acetyltransferase activity (PubMed:20100829, PubMed:25865756, PubMed:30704899). {ECO:0000269|PubMed:20100829, ECO:0000269|PubMed:25865756, ECO:0000269|PubMed:30704899}.
uniprot
proteins
amino_acid_sequence
MAEVGEIIEGCRLPVLRRNQDNEDEWPLAEILSVKDISGRKLFYVHYIDFNKRLDEWVTHERLDLKKIQFPKKEAKTPTKNGLPGSRPGSPEREVPASAQASGKTLPIPVQITLRFNLPKEREAIPGGEPDQPLSSSSCLQPNHRSTKRKVEVVSPATPVPSETAPASVFPQNGAARRAVAAQPGRKRKSNCLGTDEDSQDSSDGIPSAPRMTGSLVSDRSHDDIVTRMKNIECIELGRHRLKPWYFSPYPQELTTLPVLYLCEFCLKYGRSLKCLQRHLTKCDLRHPPGNEIYRKGTISFFEIDGRKNKSYSQNLCLLAKCFLDHKTLYYDTDPFLFYVMTEYDCKGFHIVGYFSKEKESTEDYNVACILTLPPYQRRGYGKLLIEFSYELSKVEGKTGTPEKPLSDLGLLSYRSYWSQTILEILMGLKSESGERPQITINEISEITSIKKEDVISTLQYLNLINYYKGQYILTLSEDIVDGHERAMLKRLLRIDSKCLHFTPKDWSKRGKW
uniprot
proteins
disease_involvement
DISEASE: Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities (NEDFASB) [MIM:619103]: A neurodevelopmental disorder characterized by severe global developmental delay, intellectual disability, poor or absent language, behavioral abnormalities, severe sleep disturbance, seizures, cerebral malformations, and craniofacial dysmorphism. Progressive cerebellar atrophy is also observed. Additional features may include genitourinary tract anomalies, hearing loss, and mild distal skeletal defects. {ECO:0000269|PubMed:32822602}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.3.1.-
uniprot
proteins
ec_number
2.3.1.48
uniprot
proteins
function
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:14966270, PubMed:15042092, PubMed:15121871, PubMed:15310756, PubMed:16387653, PubMed:19909775, PubMed:25865756, PubMed:27153538, PubMed:29174981, PubMed:29335245, PubMed:32822602, PubMed:33076429). Histone acetylation alters nucleosome-DNA interactions and promotes interaction of the modified histones with other proteins which positively regulate transcription (PubMed:12776177, PubMed:14966270, PubMed:15042092, PubMed:15121871, PubMed:15310756). 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 (By similarity). 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 (By similarity). 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, TP53/p53, NDC80/HEC1, NR1D2, RAN, SOX4, FOXP3, SQSTM1, ULK1 and RUBCNL/Pacer (PubMed:16141325, PubMed:17189187, PubMed:17360565, PubMed:17996965, PubMed:24835996, PubMed:26829474, PubMed:29040603, PubMed:30409912, PubMed:30704899, PubMed:31857589, 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 (By similarity). 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), S-lactoyl-CoA (lactyl-CoA) and 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), and is able to mediate protein crotonylation, lactylation and 2-hydroxyisobutyrylation, respectively (PubMed:29192674, PubMed:34608293, PubMed:38961290). 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). Catalyzes lactylation of NBN/NBS1 in response to DNA damage, thereby promoting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38961290). {ECO:0000250|UniProtKB:Q8CHK4, ECO:0000269|PubMed:12776177, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15121871, ECO:0000269|PubMed:15310756, ECO:0000269|PubMed:16141325, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:17189187, ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:17709392, ECO:0000269|PubMed:17996965, ECO:0000269|PubMed:19783983, ECO:0000269|PubMed:19909775, ECO:0000269|PubMed:24463511, ECO:0000269|PubMed:24835996, ECO:0000269|PubMed:25865756, ECO:0000269|PubMed:26291311, ECO:0000269|PubMed:26438602, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:29040603, ECO:0000269|PubMed:29174981, ECO:0000269|PubMed:29192674, ECO:0000269|PubMed:29335245, ECO:0000269|PubMed:29765047, ECO:0000269|PubMed:30409912, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:31857589, ECO:0000269|PubMed:32034146, ECO:0000269|PubMed:32817552, ECO:0000269|PubMed:32822602, ECO:0000269|PubMed:32832608, ECO:0000269|PubMed:33076429, ECO:0000269|PubMed:33938178, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:34608293, ECO:0000269|PubMed:38961290}.; FUNCTION: (Microbial infection) Catalyzes the acetylation of flavivirus NS3 protein to modulate their RNA-binding and -unwinding activities leading to facilitate viral replication. {ECO:0000269|PubMed:37478852}.
uniprot
proteins
mass_dalton
58582
uniprot
proteins
mutagenesis
MUTAGEN 86; /note="S->A: Reduced phosphorylation. Abolishes phosphorylation; when associated with A-90. Reduced histone acetyltransferase activity. Abolished phosphorylation by GSK3 and decreased acetyltransferase activity."; /evidence="ECO:0000269|PubMed:12468530, ECO:0000269|PubMed:22539723, ECO:0000269|PubMed:30704899"; MUTAGEN 90; /note="S->A: Reduced phosphorylation, leading to reduced protein acetyltransferase activity. Abolishes phosphorylation; when associated with A-86. Reduced histone acetyltransferase activity. Abolished phosphorylation by GSK3 at S-86."; /evidence="ECO:0000269|PubMed:12468530, ECO:0000269|PubMed:22539723, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:29335245"; MUTAGEN 90; /note="S->D: Mimics phosphorylation, promoting protein acetyltransferase activity."; /evidence="ECO:0000269|PubMed:26829474"; MUTAGEN 104; /note="K->R: Impaired acetylation, leading to reduced histone acetyltransferase activity. In K6R; abolished autoacetylation; when associated with R-120, R-148, R-150, R-187 and R-189."; /evidence="ECO:0000269|PubMed:25301942, ECO:0000269|PubMed:29174981"; MUTAGEN 120; /note="K->R: In K6R; abolished autoacetylation; when associated with R-104, R-148, R-150, R-187 and R-189."; /evidence="ECO:0000269|PubMed:25301942"; MUTAGEN 148; /note="K->R: In K6R; abolished autoacetylation; when associated with R-104, R-120, R-150, R-187 and R-189."; /evidence="ECO:0000269|PubMed:25301942"; MUTAGEN 150; /note="K->R: In K6R; abolished autoacetylation; when associated with R-104, R-120, R-148, R-187 and R-189."; /evidence="ECO:0000269|PubMed:25301942"; MUTAGEN 187; /note="K->R: In K6R; abolished autoacetylation; when associated with R-104, R-120, R-148, R-150 and R-189."; /evidence="ECO:0000269|PubMed:25301942"; MUTAGEN 189; /note="K->R: In K6R; abolished autoacetylation; when associated with R-104, R-120, R-148, R-150 and R-187."; /evidence="ECO:0000269|PubMed:25301942"; MUTAGEN 254; /note="L->A: Does not affect phosphorylation; when associated with A-257."; /evidence="ECO:0000269|PubMed:12468530"; MUTAGEN 257; /note="L->A: Does not affect phosphorylation; when associated with A-254."; /evidence="ECO:0000269|PubMed:12468530"; MUTAGEN 327; /note="K->Q: Mimics acetylation; promoting interaction with FOXP3 and subsequent acetylation."; /evidence="ECO:0000269|PubMed:24835996"; MUTAGEN 327; /note="K->R: Decreased autoacetylation; leading to decreased acetyltransferase activity and ability to acetylate FOXP3."; /evidence="ECO:0000269|PubMed:24835996"; MUTAGEN 377..380; /note="QRRG->ERRE: In KAT5(QG/EE) mutant; abolished acetyltransferase activity. Impaired ability to activate CGAS."; /evidence="ECO:0000269|PubMed:24835996, ECO:0000269|PubMed:26291311, ECO:0000269|PubMed:32034146, ECO:0000269|PubMed:32817552, ECO:0000269|PubMed:33938178"; MUTAGEN 380; /note="G->A: Loss of function. Does not affect phosphorylation."; /evidence="ECO:0000269|PubMed:12468530"; MUTAGEN 430; /note="K->R: Abrogates sumoylation. Abolished sumoylation by PIAS4, promoting interaction with PRKDC, leading to decreased repair of DNA double-strand breaks (DSBs) via homologous recombination (HR)."; /evidence="ECO:0000269|PubMed:17704809, ECO:0000269|PubMed:32832608"; MUTAGEN 451; /note="K->R: Abrogates sumoylation."; /evidence="ECO:0000269|PubMed:17704809
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on Ser-86 and Ser-90; enhanced during G2/M phase (PubMed:12468530, PubMed:26829474, PubMed:29335245). The phosphorylated form has a higher activity (PubMed:12468530, PubMed:29335245). Phosphorylation at Ser-90 by CDK1 or CDK9 is a prerequisite for phosphorylation at Ser-86 by GSK3 (PubMed:26829474, PubMed:30704899). Phosphorylation at Ser-86 by GSK3 (GSK3A or GSK3B) activates acetyltransferase and acyltransferase activities (PubMed:30704899). Phosphorylation at Ser-90 by CDK9 promotes KAT5 recruitment to chromatin (PubMed:29335245). Phosphorylation by VRK1 following DNA damage promotes KAT5 association with chromatin and histone acetyltransferase activity (PubMed:33076429). {ECO:0000269|PubMed:12468530, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:29335245, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:33076429}.; PTM: Autoacetylated (PubMed:20100829, PubMed:24835996, PubMed:25301942, PubMed:26291311, PubMed:33938178). Autoacetylation is required for histone acetyltransferase activity (PubMed:20100829, PubMed:25865756). Autoacetylation at Lys-327 is facilitated by interaction with EP300/p300: it prevents ubiquitination and subsequent degradation by the proteasome and promotes acetylation of target proteins (PubMed:24835996). Deacetylated by HDAC3 and SIRT1 (PubMed:20100829, PubMed:25301942). Deacetylation by HDAC3 promotes its ubiquitination and cytoplasmic localization (PubMed:25301942). {ECO:0000269|PubMed:20100829, ECO:0000269|PubMed:24835996, ECO:0000269|PubMed:25301942, ECO:0000269|PubMed:25865756, ECO:0000269|PubMed:26291311, ECO:0000269|PubMed:33938178}.; PTM: Sumoylated by UBE2I at Lys-430 and Lys-451, leading to increase of its histone acetyltransferase activity in UV-induced DNA damage response, as well as its translocation to nuclear bodies (PubMed:17704809). Sumoylation with SUMO2 by PIAS4 at Lys-430 promotes repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:32832608). Sumoylation by PIAS4 impairs interaction with PRKDC, inhibiting non-homologous end joining (NHEJ)-mediated repair of DSBs, thereby facilitating HR (PubMed:32832608). Desumoylated by SENP3 (PubMed:32832608). {ECO:0000269|PubMed:17704809, ECO:0000269|PubMed:32832608}.; PTM: Ubiquitinated by MDM2, leading to its proteasome-dependent degradation (PubMed:11927554, PubMed:24835996). Ubiquitination is prevented by autoacetylation at Lys-327 (PubMed:24835996). Ubiquitinated following deacetylation by HDAC3, leading to cytoplasmic localization (PubMed:25301942). Deubiquitinated by USP7 following interaction with ATF3, promoting its stabilization (PubMed:25865756). {ECO:0000269|PubMed:11927554, ECO:0000269|PubMed:24835996, ECO:0000269|PubMed:25301942, ECO:0000269|PubMed:25865756}.; PTM: (Microbial infection) In case of HIV-1 infection, interaction with the viral Tat protein leads to KAT5 polyubiquitination and targets it to degradation. {ECO:0000269|PubMed:16001085}.
uniprot
proteins
protein_family
MYST (SAS/MOZ) family
uniprot
proteins
pubmed
10096020
uniprot
proteins
pubmed
10966108
uniprot
proteins
pubmed
11262386
uniprot
proteins
pubmed
11416127
uniprot
proteins
pubmed
11927554
uniprot
proteins
pubmed
12468530
uniprot
proteins
pubmed
12551922
uniprot
proteins
pubmed
12776177
uniprot
proteins
pubmed
12801643
uniprot
proteins
pubmed
12963728
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14966270
uniprot
proteins
pubmed
15042092
uniprot
proteins
pubmed
15121871
uniprot
proteins
pubmed
15196461
uniprot
proteins
pubmed
15310756
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15502158
uniprot
proteins
pubmed
16001085
uniprot
proteins
pubmed
16141325
uniprot
proteins
pubmed
16387653
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16835243
uniprot
proteins
pubmed
17189187
uniprot
proteins
pubmed
17360565
uniprot
proteins
pubmed
17704809
uniprot
proteins
pubmed
17709392
uniprot
proteins
pubmed
17996965
uniprot
proteins
pubmed
18397884
uniprot
proteins
pubmed
18451177
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19308289
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19783983
uniprot
proteins
pubmed
19909775
uniprot
proteins
pubmed
20100829
uniprot
proteins
pubmed
21858214
uniprot
proteins
pubmed
22539723
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24463511
uniprot
proteins
pubmed
24835996
uniprot
proteins
pubmed
25245946
uniprot
proteins
pubmed
25301942
uniprot
proteins
pubmed
25560918
uniprot
proteins
pubmed
25865756
uniprot
proteins
pubmed
26291311
uniprot
proteins
pubmed
26438602
uniprot
proteins
pubmed
26829474
uniprot
proteins
pubmed
26945015
uniprot
proteins
pubmed
27153538
uniprot
proteins
pubmed
29040603
uniprot
proteins
pubmed
29174981
uniprot
proteins
pubmed
29192674
uniprot
proteins
pubmed
29335245
uniprot
proteins
pubmed
29494751
uniprot
proteins
pubmed
29765047
uniprot
proteins
pubmed
30409912
uniprot
proteins
pubmed
30704899
uniprot
proteins
pubmed
31857589
uniprot
proteins
pubmed
32034146
uniprot
proteins
pubmed
32817552
uniprot
proteins
pubmed
32822602
uniprot
proteins
pubmed
32832608
uniprot
proteins
pubmed
33076429
uniprot
proteins
pubmed
33938178
uniprot
proteins
pubmed
34077757
uniprot
proteins
pubmed
34608293
uniprot
proteins
pubmed
37478852
uniprot
proteins
pubmed
38961290
uniprot
proteins
pubmed
8607265
uniprot
proteins
sequence_length
513
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11262386, ECO:0000269|PubMed:11416127, ECO:0000269|PubMed:12551922, ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:17704809, ECO:0000269|PubMed:17996965, ECO:0000269|PubMed:19308289, ECO:0000269|PubMed:25301942, ECO:0000269|PubMed:33938178}. Chromosome {ECO:0000269|PubMed:25560918, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:29335245, ECO:0000269|PubMed:33076429}. Cytoplasm {ECO:0000269|PubMed:25301942}. Chromosome, centromere, kinetochore {ECO:0000269|PubMed:26829474}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:34608293}. Nucleus, nucleolus {ECO:0000269|PubMed:16387653}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:11262386}. Note=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). {ECO:0000250|UniProtKB:Q8CHK4, ECO:0000269|PubMed:11262386, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:34608293}.; SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:37478852}. Note=(Microbial infection) Relocalizes from the nucleus to zika virus replication complexes in the cytoplasm. {ECO:0000269|PubMed:37478852}.
uniprot
proteins