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KAT6A (MYST histone acetyltransferase (monocytic leukemia) 3

Identity

Other namesMYST3
MOZ (monocytic leukemia zinc finger)
ZNF220
RUNXBP2
HGNC (Hugo) KAT6A
LocusID (NCBI) 7994
Location 8p11.21
Location_base_pair Starts at 41786997 and ends at 41909505 bp from pter ( according to hg19-Feb_2009)

DNA/RNA

Description The gene spans121 kb on minus strand; 17 exons;
Transcription 7.85 kb

Protein

 
Description 2004 amino acids; 225 kDa; composed from N-term of: a NEMM domain (N-term region of ENOK, MOZ or MORF) including a H15 (linker H1 and H5 like) nuclear localization domain, 2 PHD (plant homeodomain, also known as LAP (leukemia associated protein)) Zn fingers (C4HC3), a C2HC Zn finger, essential part of the histone acyl transferase domain (HAT MOZ-SAS), an acidic (Glu-Asp) domain, localisation of breakpoints in the inv(8) and in the t(8;22) in 1118, and a Ser-(Pro-Glu)-Met rich domain, localisation of the t(8;16) breakpoint in 1547.
Localisation Nucleus
Function Lysine acetyltransferase activity (histone acyl transferase); MYST3 (MOZ) and MYST4 (MORF) possess both transcription activation and transcription repression domains; transcriptional regulators; interact with RUNX1 and RUNX2; Moz, the zebrafish ortholog of MYST3, was also found to regulate Hox expression; Moz behaves like a trithorax group factor.
Homology with MYST4 (MORF) (monocytic leukemia zinc finger protein-related factor), a transcription regulator with positive and negative domains and activities.

Implicated in

Entity t(2;8)(p23;p11) in therapy related myelodysplastic syndrome --> MYST3 / ?
Disease Only 1 case to date, a boy aged 6 years.
  
Entity inv(8)(p11q13) in acute myelomonocytic or monocytic leukaemia (M4 or M5 AML) --> MYST3 / NCOA2
Disease Erythrophagocytosis; very rare: less than 10 cases; young age, and female sex.
Prognosis likely to be poor
Hybrid/Mutated Gene 5' MYST3 - 3' NCOA2
Abnormal Protein The fusion product retains the zinc fingers, the the histone acetyl transferase (HAT) domain of MYST3 and the HAT domains and CREBBP interacting domain of NCOA2.
  
Entity t(8;16)(p11;p13) in acute myelomonocytic or monocytic leukaemia (M4 or M5 AML) and therapy related AML (t-AML) --> MYST3 / CREBBP
Disease Erythrophagocytosis; rare: less than 1% of AML; found in children and young adults of both sex.
Prognosis poor
Hybrid/Mutated Gene 5' MYST3 - 3' CREBBP
Abnormal Protein The fusion product retains the zinc fingers, the HAT domain of MYST3 and most of CREBBP, including the CREBBP interacting domain and the HAT domain; the fusion protein may repress RUNX1-dependant gene expression.
  
Entity t(8;22) (p11; q13) in acute myelomonocytic or monocytic leukaemia (M4 or M5 AML) --> MYST3 / EP300
Disease Erythrophagocytosis; very rare: less than 5 cases.
Prognosis likely to be poor
Oncogenesis EP300 is very similar to CRBBP (see above), the breakpoints on these 2 genes are on homologous regions; the breakpoint on MYST3 is more proximal in the t(8;22).
  

Breakpoints

 

To be noted

MYST3 and MLL share: a common dual transcription activation / repression activity; probable or certain HOX genes expression regulation; 2 common translocation partners: CREBBP and EP300 giving rise to AML and t-AML with poor prognoses.

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615 11q23ID1030 11q23secondLeukID1131 t1119ELLID1029 t0812q24q22ID2057
t0814ID1050

External links

Nomenclature
HGNC (Hugo)KAT6A   13013
Cards
AtlasMYST3ID25ch8p11
Entrez_Gene (NCBI)KAT6A  7994  K(lysine) acetyltransferase 6A
GeneCards (Weizmann)KAT6A
Ensembl (Hinxton)ENSG00000083168 [Gene_View]  chr8:41786997-41909505 [Contig_View]  KAT6A [Vega]
ICGC DataPortalENSG00000083168
AceView (NCBI)KAT6A
Genatlas (Paris)KAT6A
WikiGenes7994
SOURCE (Princeton)NM_001099412 NM_001099413 NM_006766
Genomic and cartography
GoldenPath (UCSC)KAT6A  -  8p11.21   chr8:41786997-41909505 -  8p11   [Description]    (hg19-Feb_2009)
EnsemblKAT6A - 8p11 [CytoView]
Mapping of homologs : NCBIKAT6A [Mapview]
OMIM601408   
Gene and transcription
Genbank (Entrez)AK027361 AK128323 BC018011 BC142659 BC142959
RefSeq transcript (Entrez)NM_001099412 NM_001099413 NM_006766
RefSeq genomic (Entrez)AC_000140 NC_000008 NC_018919 NT_167187 NW_001839130 NW_004929337
Consensus coding sequences : CCDS (NCBI)KAT6A
Cluster EST : UnigeneHs.491577 [ NCBI ]
CGAP (NCI)Hs.491577
Alternative Splicing : Fast-db (Paris)GSHG0029548
Alternative Splicing GalleryENSG00000083168
Gene ExpressionKAT6A [ NCBI-GEO ]     KAT6A [ SEEK ]   KAT6A [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ92794 (Uniprot)
NextProtQ92794  [Medical]
With graphics : InterProQ92794
Splice isoforms : SwissVarQ92794 (Swissvar)
Catalytic activity : Enzyme2.3.1.48 [ Enzyme-Expasy ]   2.3.1.482.3.1.48 [ IntEnz-EBI ]   2.3.1.48 [ BRENDA ]   2.3.1.48 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)H15 (PS51504)    ZF_PHD_1 (PS01359)    ZF_PHD_2 (PS50016)   
Domains : Interpro (EBI)Acyl_CoA_acyltransferase    Histone_H1/H5_H15    MOZ_SAS    Znf_FYVE_PHD    Znf_PHD    Znf_PHD-finger    Znf_RING    Znf_RING/FYVE/PHD   
Related proteins : CluSTrQ92794
Domain families : Pfam (Sanger)MOZ_SAS (PF01853)    PHD (PF00628)   
Domain families : Pfam (NCBI)pfam01853    pfam00628   
Domain families : Smart (EMBL)H15 (SM00526)  PHD (SM00249)  RING (SM00184)  
DMDM Disease mutations7994
Blocks (Seattle)Q92794
PDB (SRS)1M36    2LN0    2OZU    2RC4    3V43    4LJN    4LK9    4LKA    4LLB   
PDB (PDBSum)1M36    2LN0    2OZU    2RC4    3V43    4LJN    4LK9    4LKA    4LLB   
PDB (IMB)1M36    2LN0    2OZU    2RC4    3V43    4LJN    4LK9    4LKA    4LLB   
PDB (RSDB)1M36    2LN0    2OZU    2RC4    3V43    4LJN    4LK9    4LKA    4LLB   
Human Protein AtlasENSG00000083168
Peptide AtlasQ92794
HPRD03244
IPIIPI00023340   IPI00747970   IPI00878877   IPI00980404   
Protein Interaction databases
DIP (DOE-UCLA)Q92794
IntAct (EBI)Q92794
FunCoupENSG00000083168
BioGRIDKAT6A
InParanoidQ92794
Interologous Interaction database Q92794
IntegromeDBKAT6A
STRING (EMBL)KAT6A
Ontologies - Pathways
Ontology : AmiGOnucleosome  heart morphogenesis  DNA binding  chromatin binding  transcription coactivator activity  histone acetyltransferase activity  protein binding  nucleus  nucleoplasm  nucleolus  Golgi apparatus  DNA packaging  chromatin organization  nucleosome assembly  transcription, DNA-templated  protein acetylation  transcription factor binding  zinc ion binding  acetyltransferase activity  histone acetylation  PML body  myeloid cell differentiation  somatic stem cell maintenance  embryonic hemopoiesis  aorta morphogenesis  negative regulation of sequence-specific DNA binding transcription factor activity  histone H3 acetylation  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  face morphogenesis  MOZ/MORF histone acetyltransferase complex  cellular senescence  
Ontology : EGO-EBInucleosome  heart morphogenesis  DNA binding  chromatin binding  transcription coactivator activity  histone acetyltransferase activity  protein binding  nucleus  nucleoplasm  nucleolus  Golgi apparatus  DNA packaging  chromatin organization  nucleosome assembly  transcription, DNA-templated  protein acetylation  transcription factor binding  zinc ion binding  acetyltransferase activity  histone acetylation  PML body  myeloid cell differentiation  somatic stem cell maintenance  embryonic hemopoiesis  aorta morphogenesis  negative regulation of sequence-specific DNA binding transcription factor activity  histone H3 acetylation  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  face morphogenesis  MOZ/MORF histone acetyltransferase complex  cellular senescence  
REACTOMEQ92794 [protein]
REACTOME PathwaysREACT_172623 Chromatin organization [pathway]
Protein Interaction DatabaseKAT6A
Wikipedia pathwaysKAT6A
Gene fusion - rearrangments
Rearrangement : TICdbKAT6A [8p11.21]  -  ASXL2 [14q32.33]
Rearrangement : TICdbKAT6A [8p11.21]  -  CREBBP [16p13.3]
Rearrangement : TICdbKAT6A [8p11.21]  -  NCOA2 [9q33.2]
Rearrangement : TICdbKAT6A [8p11.21]  -  NCOA3 [3q21.3]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)KAT6A
SNP (GeneSNP Utah)KAT6A
SNP : HGBaseKAT6A
Genetic variants : HAPMAPKAT6A
1000_GenomesKAT6A 
ICGC programENSG00000083168 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
Mutations and Diseases : HGMDKAT6A
OMIM601408   
MedgenKAT6A
GENETestsKAT6A
Disease Genetic AssociationKAT6A
Huge Navigator KAT6A [HugePedia]  KAT6A [HugeCancerGEM]
Genomic VariantsKAT6A  KAT6A [DGVbeta]
Exome VariantKAT6A
dbVarKAT6A
ClinVarKAT6A
snp3D : Map Gene to Disease7994
General knowledge
Homologs : HomoloGeneKAT6A
Homology/Alignments : Family Browser (UCSC)KAT6A
Phylogenetic Trees/Animal Genes : TreeFamKAT6A
Chemical/Protein Interactions : CTD7994
Chemical/Pharm GKB GenePA37592
Clinical trialKAT6A
Cancer Resource (Charite)ENSG00000083168
Other databases
Probes
Litterature
PubMed50 Pubmed reference(s) in Entrez
CoreMineKAT6A
iHOPKAT6A

Bibliography

Three cases of translocation (8;16)(p11;p13) observed in acute myelomonocytic leukemia: a new specific subgroup?
Lałě JL, Zandecki M, Jouet JP, Savary JB, Lambiliotte A, Bauters F, Cosson A, Deminatti M
Cancer genetics and cytogenetics. 1987 ; 27 (1) : 101-109.
PMID 3472640
 
The 8p11 anomaly in monoblastic leukaemia.
Brizard A, Guilhot F, Huret JL, Benz-Lemoine E, Tanzer J
Leukemia research. 1988 ; 12 (8) : 693-697.
PMID 3184987
 
The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein.
Borrow J, Stanton VP Jr, Andresen JM, Becher R, Behm FG, Chaganti RS, Civin CI, Disteche C, Dubłę I, Frischauf AM, Horsman D, Mitelman F, Volinia S, Watmore AE, Housman DE
Nature genetics. 1996 ; 14 (1) : 33-41.
PMID 8782817
 
Abnormalities of chromosome band 8p11 in leukemia: two clinical syndromes can be distinguished on the basis of MOZ involvement.
Aguiar RC, Chase A, Coulthard S, Macdonald DH, Carapeti M, Reiter A, Sohal J, Lennard A, Goldman JM, Cross NC
Blood. 1997 ; 90 (8) : 3130-3135.
PMID 9376594
 
A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia.
Carapeti M, Aguiar RC, Goldman JM, Cross NC
Blood. 1998 ; 91 (9) : 3127-3133.
PMID 9558366
 
Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11).
Imamura T, Kakazu N, Hibi S, Morimoto A, Fukushima Y, Ijuin I, Hada S, Kitabayashi I, Abe T, Imashuku S
Genes, chromosomes & cancer. 2003 ; 36 (4) : 413-419.
PMID 12619166
 
moz regulates Hox expression and pharyngeal segmental identity in zebrafish.
Miller CT, Maves L, Kimmel CB
Development (Cambridge, England). 2004 ; 131 (10) : 2443-2461.
PMID 15128673
 
The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases.
Yang XJ
Nucleic acids research. 2004 ; 32 (3) : 959-976.
PMID 14960713
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written12-2005Jean Loup Huret, Sylvie Senon

Citation

This paper should be referenced as such :
Huret, JL ; Senon, S
MYST3 (MYST histone acetyltransferase (monocytic leukemia) 3
Atlas Genet Cytogenet Oncol Haematol. 2006;10(3):151-153.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/MYST3ID25ch8p11.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Oct 13 13:30:49 CEST 2014

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