DegronMD - O95251(KAT7)

FUNCTION: Catalytic subunit of histone acetyltransferase HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), thereby regulating various processes, such as gene transcription, protein ubiquitination, immune regulation, stem cell pluripotent and self-renewal maintenance and embryonic development (PubMed:16387653, PubMed:21753189, PubMed:24065767, PubMed:26620551, PubMed:31767635, PubMed:31827282). Some complexes also catalyze acetylation of histone H4 at 'Lys-5', 'Lys-8' and 'Lys-12' (H4K5ac, H4K8ac and H4K12ac, respectively), regulating DNA replication initiation, regulating DNA replication initiation (PubMed:10438470, PubMed:19187766, PubMed:20129055, PubMed:24065767). Specificity of the HBO1 complexes is determined by the scaffold subunit: complexes containing BRPF scaffold (BRPF1, BRD1/BRPF2 or BRPF3) direct KAT7/HBO1 specificity towards H3K14ac, while complexes containing JADE (JADE1, JADE2 and JADE3) scaffold direct KAT7/HBO1 specificity towards histone H4 (PubMed:19187766, PubMed:20129055, PubMed:24065767, PubMed:26620551). H3K14ac promotes transcriptional elongation by facilitating the processivity of RNA polymerase II (PubMed:31827282). Acts as a key regulator of hematopoiesis by forming a complex with BRD1/BRPF2, directing KAT7/HBO1 specificity towards H3K14ac and promoting erythroid differentiation (PubMed:21753189). H3K14ac is also required for T-cell development (By similarity). KAT7/HBO1-mediated acetylation facilitates two consecutive steps, licensing and activation, in DNA replication initiation: H3K14ac facilitates the activation of replication origins, and histone H4 acetylation (H4K5ac, H4K8ac and H4K12ac) facilitates chromatin loading of MCM complexes, promoting DNA replication licensing (PubMed:10438470, PubMed:11278932, PubMed:18832067, PubMed:19187766, PubMed:20129055, PubMed:21856198, PubMed:24065767, PubMed:26620551). Acts as a positive regulator of centromeric CENPA assembly: recruited to centromeres and mediates histone acetylation, thereby preventing centromere inactivation mediated by SUV39H1, possibly by increasing histone turnover/exchange (PubMed:27270040). Involved in nucleotide excision repair: phosphorylation by ATR in response to ultraviolet irradiation promotes its localization to DNA damage sites, where it mediates histone acetylation to facilitate recruitment of XPC at the damaged DNA sites (PubMed:28719581). Acts as an inhibitor of NF-kappa-B independently of its histone acetyltransferase activity (PubMed:16997280). {ECO:0000250|UniProtKB:Q5SVQ0, ECO:0000269|PubMed:10438470, ECO:0000269|PubMed:11278932, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:16997280, ECO:0000269|PubMed:18832067, ECO:0000269|PubMed:19187766, ECO:0000269|PubMed:20129055, ECO:0000269|PubMed:21753189, ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:24065767, ECO:0000269|PubMed:26620551, ECO:0000269|PubMed:27270040, ECO:0000269|PubMed:28719581, ECO:0000269|PubMed:31767635, ECO:0000269|PubMed:31827282}.; FUNCTION: Plays a central role in the maintenance of leukemia stem cells in acute myeloid leukemia (AML) (PubMed:31827282). Acts by mediating acetylation of histone H3 at 'Lys-14' (H3K14ac), thereby facilitating the processivity of RNA polymerase II to maintain the high expression of key genes, such as HOXA9 and HOXA10 that help to sustain the functional properties of leukemia stem cells (PubMed:31827282). {ECO:0000269|PubMed:31827282}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R172H	TCGA-AG-3892	READ	TCGA	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1944
p.R172H	TCGA-AJ-A3EK	UCEC	TCGA	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1944
p.R172H	DO36394	READ	ICGC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1944
p.R172H	DO41584	UCEC	ICGC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1944
p.R172H	SIDM01588	Endometrial Carcinoma	GDSC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1944
p.R172H	ACH-000993	Endometrial/Uterine Cancer	CCLE	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1944
p.G9D	TCGA-AP-A1DK	UCEC	TCGA	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation altering degron motif	0.6087
p.G9D	DO42033	UCEC	ICGC	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation altering degron motif	0.6087
p.D17Y	TCGA-AP-A1DV	UCEC	TCGA	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation rewiring degron network	0.1944
p.D17Y	DO43186	UCEC	ICGC	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation rewiring degron network	0.1944
p.R174H	TCGA-AP-A1DV	UCEC	TCGA	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1389
p.R174H	TCGA-B5-A3FC	UCEC	TCGA	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1389
p.R174H	DO43186	UCEC	ICGC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1389
p.R174H	DO41871	UCEC	ICGC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1389
p.R174H	SIDM00145	T-Lymphoblastic Leukemia	GDSC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1389
p.R174H	SIDM01608	Endometrial Carcinoma	GDSC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1389
p.R174H	ACH-000990	Endometrial/Uterine Cancer	CCLE	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1389
p.R174H	ACH-001127	Leukemia	CCLE	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1389
p.R174H	MOLT-4	haematopoietic and lymphoid tissue	COSMIC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1389
p.R172C	TCGA-B5-A3FC	UCEC	TCGA	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1944
p.R172C	DO41871	UCEC	ICGC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1944
p.R6S	TCGA-B9-4115	KIRP	TCGA	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation rewiring degron network	0.2778
p.R6S	DO20768	KIRP	ICGC	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation rewiring degron network	0.2778
p.D17H	TCGA-GD-A6C6	BLCA	TCGA	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation rewiring degron network	0.1944
p.D17H	DO48504	BLCA	ICGC	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation rewiring degron network	0.1944
p.S18F	TCGA-LP-A4AV	CESC	TCGA	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation blocking phosphorylation signal	0.6111
p.S18F	DO44275	CESC	ICGC	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation blocking phosphorylation signal	0.6111
p.P170S	DO224967	BRCA	ICGC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.25
p.P170S	DO227854	BRCA	ICGC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.25
p.D13Y	DO229034	LICA	ICGC	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation rewiring degron network	0.3056
p.G14V	DO229038	LICA	ICGC	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation rewiring degron network	0.2778
p.S158A	DO44798	LICA	ICGC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation blocking phosphorylation signal	0.6944
p.S21P	SIDM00541	Colorectal Carcinoma	GDSC	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation rewiring degron network	0.0833
p.S21P	ACH-000926	Colon/Colorectal Cancer	CCLE	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation rewiring degron network	0.0833
p.S21P	HT55	large intestine	COSMIC	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation rewiring degron network	0.0833
p.M157T	SIDM01545	Non-Small Cell Lung Carcinoma	GDSC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.2222
p.M157T	ACH-000511	Lung Cancer	CCLE	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.2222
p.A154D	SIDM01510	Non-Small Cell Lung Carcinoma	GDSC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1389
p.A154D	ACH-000925	Lung Cancer	CCLE	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1389
p.R175C	RCC-AB	kidney	COSMIC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1111
p.R18H	MOLT-4	haematopoietic and lymphoid tissue	COSMIC	AGSSS	DEG_SPOP_SBC_1	8:12	Mutation blocking phosphorylation signal	0.6111
p.R175Q	SK-MEL-2	skin	COSMIC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1111
p.R175W	HCT-15	large intestine	COSMIC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation rewiring degron network	0.1111
p.N166H	NCI-H322M	lung	COSMIC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation altering degron motif	0.7423
p.L158F	MZ7-mel	skin	COSMIC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation blocking phosphorylation signal	0.6944
p.R158C	RCC-AB	kidney	COSMIC	DSGSDLS	DEG_SCF_TRCP1_1	161:167	Mutation blocking phosphorylation signal	0.6944

Kaplan plot for KAT7 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

KAT7

UniProt ID: O95251

Entrez ID: 11143

Protein name: Histone acetyltransferase KAT7 (EC 2.3.1.48) (Histone acetyltransferase binding to ORC1) (Lysine acetyltransferase 7) (MOZ, YBF2/SAS3, SAS2 and TIP60 protein 2) (MYST-2)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for KAT7 in