DegronMD - Q92993(KAT5)

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 (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 ARNTL/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 ARNTL/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) 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). {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: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: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}. 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GO - Biological processes (BP): cellular response to DNA damage stimulus [GO:0006974]; cellular response to estradiol stimulus [GO:0071392]; cellular response to glucose starvation [GO:0042149]; cellular senescence [GO:0090398]; chromatin organization [GO:0006325]; DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator [GO:0006978]; double-strand break repair [GO:0006302]; double-strand break repair via homologous recombination [GO:0000724]; establishment of mitotic spindle orientation [GO:0000132]; histone acetylation [GO:0016573]; histone H2A acetylation [GO:0043968]; histone H4 acetylation [GO:0043967]; lipid droplet disassembly [GO:1905691]; negative regulation of interleukin-2 production [GO:0032703]; negative regulation of transcription, DNA-templated [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; nucleotide-excision repair [GO:0006289]; peptidyl-lysine acetylation [GO:0018394]; positive regulation of attachment of mitotic spindle microtubules to kinetochore [GO:1902425]; positive regulation of autophagy [GO:0010508]; positive regulation of circadian rhythm [GO:0042753]; positive regulation of double-strand break repair via homologous recombination [GO:1905168]; positive regulation of histone exchange [GO:1900051]; positive regulation of mitotic sister chromatid segregation [GO:0062033]; positive regulation of myoblast differentiation [GO:0045663]; positive regulation of protein acetylation [GO:1901985]; positive regulation of regulatory T cell differentiation [GO:0045591]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of triglyceride biosynthetic process [GO:0010867]; proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161]; regulation of apoptotic process [GO:0042981]; regulation of cell cycle [GO:0051726]; regulation of double-strand break repair [GO:2000779]; regulation of growth [GO:0040008]; regulation of hematopoietic stem cell differentiation [GO:1902036]; response to ionizing radiation [GO:0010212]; spermatid development [GO:0007286] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.E154D	TCGA-86-8585	LUAD	TCGA	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.2778
p.G160S	TCGA-B5-A3FC	UCEC	TCGA	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation altering degron motif	0.6993
p.P142L	TCGA-FI-A2D5	UCEC	TCGA	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.1944
p.P142L	DO41331	UCEC	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.1944
p.R155L	TCGA-FS-A1ZR	SKCM	TCGA	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation blocking phosphorylation signal	0.75
p.S168F	TCGA-K4-A6MB	BLCA	TCGA	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.1667
p.S171F	TCGA-K4-A6MB	BLCA	TCGA	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.0833
p.S171F	DO44077	BLCA	ICGC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.0833
p.S135F	DO44077	BLCA	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation altering degron motif	0.7982
p.R168Q	DO3958	BRCA	ICGC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.1667
p.R125H	DO49950	CESC	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.1111
p.R125H	DO15543	HNSC	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.1111
p.R125H	DO42312	UCEC	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.1111
p.R125H	SNU-1040	large intestine	COSMIC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.1111
p.D171N	DO44377	CESC	ICGC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.0833
p.D171N	DO222601	ESCA	ICGC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.0833
p.D171N	DO13863	GBM	ICGC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.0833
p.R136Q	DO8312	COAD	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation altering degron motif	0.7329
p.E129K	DO222765	COCA	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.2222
p.R159H	DO222765	COCA	ICGC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation altering degron motif	0.8244
p.R159H	DO41331	UCEC	ICGC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation altering degron motif	0.8244
p.D146Y	DO22237	LGG	ICGC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.0556
p.D146Y	DO22237	LGG	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.0833
p.Q131H	DO228986	LICA	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.2778
p.Q131H	DO229032	LICA	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.2778
p.S163I	DO228986	LICA	ICGC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.3056
p.R145L	DO229006	LICA	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.1111
p.S138L	DO46657	PAAD	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.3056
p.R136P	DO47153	RECA	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation altering degron motif	0.7512
p.R159C	DO43338	UCEC	ICGC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation altering degron motif	0.8301
p.G127S	DO41871	UCEC	ICGC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.1667
p.G127S	ACH-000966	Ovarian Cancer	CCLE	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.1667
p.D172V	DO41235	UCEC	ICGC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.0556
p.D172N	DO41199	UCEC	ICGC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.0556
p.S131L	SIDM02010	Esophageal Carcinoma	GDSC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.2778
p.A134D	SIDM00572	Gastric Carcinoma	GDSC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation altering degron motif	0.7793
p.A134D	NUGC-3	stomach	COSMIC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation altering degron motif	0.7793
p.E125Q	SIDM01578	Bladder Carcinoma	GDSC	PLSSS	DEG_SPOP_SBC_1	133:137	Mutation rewiring degron network	0.1111
p.V169I	ACH-002263	Esophageal Cancer	CCLE	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.1389
p.V169I	KYSE-220	oesophagus	COSMIC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.1389
p.R158H	SNU-1040	large intestine	COSMIC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation altering degron motif	0.8244
p.V150I	KYSE-220	oesophagus	COSMIC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation substituting flanking lysine	0.2778
p.Y165N	NCI-H446	lung	COSMIC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.25
p.R159G	GI-1	central nervous system	COSMIC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation altering degron motif	0.7568
p.G171D	NCI-H630	large intestine	COSMIC	PATPVPS	DEG_SCF_FBW7_1	156:162	Mutation rewiring degron network	0.0833

DegronMD: protein-targeted degradation, mutation and drug response to degrons

KAT5

UniProt ID: Q92993

Entrez ID: 10524

External links: UniprotKB HGNC RefSeq COSMIC

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