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KAT6B (MYST histone acetyltransferase (monocytic leukemia) 4)

Written2006-05José Luis Vizmanos
Departamento de Genética, Facultad de Ciencias, Universidad de Navarra, 31008 Pamplona, Navarra, Espana

(Note : for Links provided by Atlas : click)

Identity

Other namesGTPTS
MORF
MOZ2
MYST4
ZC2HC6B
qkf
querkopf
HGNC (Hugo) KAT6B
LocusID (NCBI) 23522
Atlas_Id 41488
Location 10q22.2
Location_base_pair Starts at 76586171 and ends at 76792380 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order ADK (adenosine kinase isoform a) is more centromeric. DUPD1 (dual specificity phosphatase and pro isomerase) is more telomeric.
 
  Genomic structure of MYST4. Black boxes indicate exons.
Fusion genes
(updated 2016)
AFAP1 (4p16.1) / KAT6B (10q22.2)ANP32E (1q21.2) / KAT6B (10q22.2)AURKAIP1 (1p36.33) / KAT6B (10q22.2)
CREBBP (16p13.3) / KAT6B (10q22.2)KAT6B (10q22.2) / ADK (10q22.2)KAT6B (10q22.2) / CCDC172 (10q25.3)
KAT6B (10q22.2) / CORO7 (16p13.3)KAT6B (10q22.2) / CREBBP (16p13.3)KAT6B (10q22.2) / DDX4 (5q11.2)
KAT6B (10q22.2) / DDX50 (10q22.1)KAT6B (10q22.2) / FGFR1 (8p11.23)KAT6B (10q22.2) / GCNT1 (9q21.13)
KAT6B (10q22.2) / KANSL1 (17q21.31)KAT6B (10q22.2) / LYN (8q12.1)KAT6B (10q22.2) / NRDC (1p32.3)
KAT6B (10q22.2) / PCBP4 (3p21.2)KAT6B (10q22.2) / RTKN2 (10q21.2)KAT6B (10q22.2) / SDF4 (1p36.33)
KAT6B (10q22.2) / SH3BP5L (1q44)KAT6B (10q22.2) / STARD9 (15q15.2)LMAN2 (5q35.3) / KAT6B (10q22.2)
RRP7BP (22q13.2) / KAT6B (10q22.2)SAMD8 (10q22.2) / KAT6B (10q22.2)TMEM57 (1p36.11) / KAT6B (10q22.2)

DNA/RNA

Description 18 exons spanning 206.0 Kb on 10q22.2. Transcription is from centromere to telomere.
Transcription 1 transcript

Protein

Note MYST4_HUMAN; Histone acetyltransferase MYST4, MYST protein 4, MOZ, YBF2/SAS3, SAS2 and TIP60 protein 4, Histone acetyltransferase MOZ2, Monocytic leukemia zinc finger protein-related factor, or Histone acetyltransferase MORF.
 
  Schematic representation of MYST4 protein. H15 domain: domain in histone families 1 and 5; PHD zinc fingers: plant homeodomain (PHD) with a C4HC3-type motif, this domain is widely distributed in eukaryotes and it has been found in many chromatin regulatory factors; MOZ-SAS family region: this region has been suggested to be homologous to acetyltransferases but this similarity is not supported by sequence analysis.
Description Histone acetyltransferase MYST4.
Localisation Nucleous (probable).
Function It is a histone acetyltransferase probably involved in both positive (N-terminus) and negative (C-terminus) regulation of transcription, maybe involved in cerebral cortex development, required for RUNX2-dependent transcriptional activation and ubiquitously expressed in adult human tissues.

Mutations

Somatic MYST4 fusion genes in neoplasia t(10;16)(q22;p13) (see below) 5' MYST4-CREBBP 3' (previously known as MORF-CBP, MORF-CREBBP, or MYST4-CBP) fusion was first described in a 4-year-old girl with AML M5a without signs of erythrophagocytosis and several chromosome abnormalities. It was also described in an 84-year-old male without erythrophagocytosis and with this sole cytogenetic aberration. This suggested that the recurrent fusion gene could contribute directly to the development of the AML. This fusion gene was also described with a variant breakpoint in a 52-year-old japanese woman with a therapy-related myelodysplastic syndrome (t-MDS) and this sole translocation. A novel fusion variant was also described in an AML-M4 female patient with the t(10;16) (q22;p13) and a t(11;17)(q23;q21).

t(10;17)(q22;q21-q24). It has been observed that 5% of chromosomally abnormal uterine leiomyomata had rearrangements of 10q22, most of them with balanced translocations with a variety of partners in chromosomes 4, 6, or 12 in leiomyomata and chromosomes 7, 11, 17, or 18 in leiomyosarcomas. Previously the t(10;17) had been reported as the sole cytogenetic abnormality in one leiomyosarcoma and as part of a complex karyotype in another leiomyosarcoma.

FISH analysis of four uterine leiomyomata has revealed a breakpoint in the third intron of MYST4 after the H15 domain and before the PHD zinc finger domain. This disruption of MYST4 seems to be more 5' to the breakpoints reported in hematopoietic malignancies. In addition, in three of the four uterine leiomyomata, the10q22 rearrangement also involves a locus on 17q with probably the same breakpoint. This could suggest a cytogenetically distinct subgroup of uterine leiomyomata that could be also defined by a common phenotype.

Implicated in

Note
Entity t(10;16)(q22;p13)
Note The t(10;16)(q22;p13) fusing MYST4 and CREBBP to generate a chimeric protein MYST4-CREBBP (previously known as MORF-CBP, MORF-CREBBP, or MYST4-CBP) is a very rare cytogenetic abnormality only described in 4 cases to date with AML M4/M5a and therapy-related MDS without signs of erythrophagocytosis; most of them with bad prognosis.

This translocation is related to t(8;16)(p11;p13) that fuses MYST3 to CREBBP (previously also known as MOZ-CREBBP or MOZ-CBP) also described in cases with AML/M4-M5 and therapy-related AML with a poor response to chemotherapy and frequently displaying erythrophagocytosis.

Disease Described in two cases with AML M5, one case with AML M4 and one case with therapy-related MDS, all of them without signs of erythrophagocytosis (showed in the t(8;16), MYST3-CREBBP fusion).
Prognosis poor.
Cytogenetics t(10;16)(q22;p13), rarely as sole anomaly.
Hybrid/Mutated Gene 5' MYST4-CREBBP 3'
Abnormal Protein MYST4-CREBBP The putative MYST4-CREBBP fusion protein retains the zinc fingers, two nuclear localization signals, the HAT domain, and a portion of the acidic domain from MYST4, and most of the CREBBP protein, including its HAT domain.

  
Entity Rearrangements of 10q22 in uterine leiomyomata
Note Some of the chromosomally abnormal uterine leiomyomata had rearrangements of 10q22, most of them with balanced translocations with a variety of partners in chromosomes 4, 6, or 12 in leiomyomata and chromosomes 7, 11, 17, or 18 in leiomyosarcomas. FISH analysis of some uterine leiomyomata has revealed a disruption of MYST4 between the H15 domain and the PHD zinc finger domain. In three cases the partner gene was a locus on 17q with probably the same breakpoint. This could delimit a distinct subgroup of uterine leiomyomata.
Prognosis Unknown.
Cytogenetics Rearrangements of 10q22, most of them with balanced translocations with chromosomes 4, 6, or 12 in leiomyomata and chromosomes 7, 11, 17, or 18 in leiomyosarcomas.
Hybrid/Mutated Gene Several cases has shown disruption of MYST4, some of them with an unknown partner in 17q21-q24.
Abnormal Protein Unknown.
  

Bibliography

t(10;17) as the sole chromosome change in a uterine leiomyosarcoma.
Dal Cin P, Boghosian L, Crickard K, Sandberg AA
Cancer genetics and cytogenetics. 1988 ; 32 (2) : 263-266.
PMID 3163264
 
Chromosome aberrations in uterine smooth muscle tumors: potential diagnostic relevance of cytogenetic instability.
Fletcher JA, Morton CC, Pavelka K, Lage JM
Cancer research. 1990 ; 50 (13) : 4092-4097.
PMID 2354458
 
Identification of a human histone acetyltransferase related to monocytic leukemia zinc finger protein.
Champagne N, Bertos NR, Pelletier N, Wang AH, Vezmar M, Yang Y, Heng HH, Yang XJ
The Journal of biological chemistry. 1999 ; 274 (40) : 28528-28536.
PMID 10497217
 
Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13).
Panagopoulos I, Fioretos T, Isaksson M, Samuelsson U, Billström R, Strömbeck B, Mitelman F, Johansson B
Human molecular genetics. 2001 ; 10 (4) : 395-404.
PMID 11157802
 
A novel fusion variant of the MORF and CBP genes detected in therapy-related myelodysplastic syndrome with t(10;16)(q22;p13).
Kojima K, Kaneda K, Yoshida C, Dansako H, Fujii N, Yano T, Shinagawa K, Yasukawa M, Fujita S, Tanimoto M
British journal of haematology. 2003 ; 120 (2) : 271-273.
PMID 12542485
 
Expression, purification, and analysis of MOZ and MORF histone acetyltransferases.
Pelletier N, Champagne N, Lim H, Yang XJ
Methods (San Diego, Calif.). 2003 ; 31 (1) : 24-32.
PMID 12893170
 
The MYST family of histone acetyltransferases.
Utley RT, Côté J
Current topics in microbiology and immunology. 2003 ; 274 : 203-236.
PMID 12596909
 
t(10;16)(q22;p13) and MORF-CREBBP fusion is a recurrent event in acute myeloid leukemia.
Vizmanos JL, Larr´yoz MJ, Lahortiga I, Florist´n F, Alvarez C, Odero MD, Novo FJ, Calasanz MJ
Genes, chromosomes & cancer. 2003 ; 36 (4) : 402-405.
PMID 12619164
 
Uterine leiomyomata with t(10;17) disrupt the histone acetyltransferase MORF.
Moore SD, Herrick SR, Ince TA, Kleinman MS, Cin PD, Morton CC, Quade BJ
Cancer research. 2004 ; 64 (16) : 5570-5577.
PMID 15313893
 
Variant MYST4-CBP gene fusion in a t(10;16) acute myeloid leukaemia.
Murati A, Adélaïde J, Mozziconacci MJ, Popovici C, Carbuccia N, Letessier A, Birg F, Birnbaum D, Chaffanet M
British journal of haematology. 2004 ; 125 (5) : 601-604.
PMID 15147375
 
Querkopf, a histone acetyltransferase, is essential for embryonic neurogenesis.
Thomas T, Voss AK
Frontiers in bioscience : a journal and virtual library. 2004 ; 9 : 24-31.
PMID 14766340
 
MOZ fusion proteins in acute myeloid leukaemia.
Troke PJ, Kindle KB, Collins HM, Heery DM
Biochemical Society symposium. 2006 : 23-39.
PMID 16626284
 

Citation

This paper should be referenced as such :
Vizmanos, JL
MYST4 (MYST histone acetyltransferase (monocytic leukemia) 4)
Atlas Genet Cytogenet Oncol Haematol. 2006;10(4):224-226.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MYST4ID41488ch10q22.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(10;16)(q22;p13) KAT6B/CREBBP

External links

Nomenclature
HGNC (Hugo)KAT6B   17582
Cards
AtlasMYST4ID41488ch10q22
Entrez_Gene (NCBI)KAT6B  23522  lysine acetyltransferase 6B
GeneCards (Weizmann)KAT6B
Ensembl hg19 (Hinxton)ENSG00000156650 [Gene_View]  chr10:76586171-76792380 [Contig_View]  KAT6B [Vega]
Ensembl hg38 (Hinxton)ENSG00000156650 [Gene_View]  chr10:76586171-76792380 [Contig_View]  KAT6B [Vega]
ICGC DataPortalENSG00000156650
TCGA cBioPortalKAT6B
AceView (NCBI)KAT6B
Genatlas (Paris)KAT6B
WikiGenes23522
SOURCE (Princeton)KAT6B
Genomic and cartography
GoldenPath hg19 (UCSC)KAT6B  -     chr10:76586171-76792380 +  10q22.2   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)KAT6B  -     10q22.2   [Description]    (hg38-Dec_2013)
EnsemblKAT6B - 10q22.2 [CytoView hg19]  KAT6B - 10q22.2 [CytoView hg38]
Mapping of homologs : NCBIKAT6B [Mapview hg19]  KAT6B [Mapview hg38]
OMIM603736   605880   606170   
Gene and transcription
Genbank (Entrez)AA416904 AB002381 AF113514 AF119230 AF119231
RefSeq transcript (Entrez)NM_001256468 NM_001256469 NM_012330
RefSeq genomic (Entrez)NC_000010 NC_018921 NG_032048 NT_030059 NW_004929376 NW_009646202
Consensus coding sequences : CCDS (NCBI)KAT6B
Cluster EST : UnigeneHs.740873 [ NCBI ]
CGAP (NCI)Hs.740873
Alternative Splicing GalleryENSG00000156650
Gene ExpressionKAT6B [ NCBI-GEO ]   KAT6B [ EBI - ARRAY_EXPRESS ]   KAT6B [ SEEK ]   KAT6B [ MEM ]
Gene Expression Viewer (FireBrowse)KAT6B [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)23522
GTEX Portal (Tissue expression)KAT6B
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8WYB5 (Uniprot)
NextProtQ8WYB5  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8WYB5
Splice isoforms : SwissVarQ8WYB5 (Swissvar)
PhosPhoSitePlusQ8WYB5
Domaine pattern : Prosite (Expaxy)H15 (PS51504)    MYST_HAT (PS51726)    ZF_PHD_1 (PS01359)    ZF_PHD_2 (PS50016)   
Domains : Interpro (EBI)Acyl_CoA_acyltransferase    HAT_MYST-type    Histone_H1/H5_H15    WHTH_DNA-bd_dom    Znf_FYVE_PHD    Znf_PHD    Znf_PHD-finger    Znf_RING/FYVE/PHD   
Domain families : Pfam (Sanger)MOZ_SAS (PF01853)    PHD (PF00628)   
Domain families : Pfam (NCBI)pfam01853    pfam00628   
Domain families : Smart (EMBL)H15 (SM00526)  PHD (SM00249)  
DMDM Disease mutations23522
Blocks (Seattle)KAT6B
SuperfamilyQ8WYB5
Human Protein AtlasENSG00000156650
Peptide AtlasQ8WYB5
HPRD07065
IPIIPI00099433   IPI00384388   IPI00607795   
Protein Interaction databases
DIP (DOE-UCLA)Q8WYB5
IntAct (EBI)Q8WYB5
FunCoupENSG00000156650
BioGRIDKAT6B
STRING (EMBL)KAT6B
ZODIACKAT6B
Ontologies - Pathways
QuickGOQ8WYB5
Ontology : AmiGOnucleosome  DNA binding  histone acetyltransferase activity  protein binding  nucleus  nucleoplasm  nucleosome assembly  transcription, DNA-templated  regulation of transcription, DNA-templated  transcription factor binding  zinc ion binding  acetyltransferase activity  histone acetylation  protein complex binding  histone H3 acetylation  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  MOZ/MORF histone acetyltransferase complex  
Ontology : EGO-EBInucleosome  DNA binding  histone acetyltransferase activity  protein binding  nucleus  nucleoplasm  nucleosome assembly  transcription, DNA-templated  regulation of transcription, DNA-templated  transcription factor binding  zinc ion binding  acetyltransferase activity  histone acetylation  protein complex binding  histone H3 acetylation  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  MOZ/MORF histone acetyltransferase complex  
REACTOMEQ8WYB5 [protein]
REACTOME PathwaysR-HSA-3214847 HATs acetylate histones [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkKAT6B
Wikipedia pathwaysKAT6B
Orthology - Evolution
OrthoDB23522
GeneTree (enSembl)ENSG00000156650
Phylogenetic Trees/Animal Genes : TreeFamKAT6B
Homologs : HomoloGeneKAT6B
Homology/Alignments : Family Browser (UCSC)KAT6B
Gene fusions - Rearrangements
Fusion : MitelmanAFAP1/KAT6B [4p16.1/10q22.2]  [t(4;10)(p16;q22)]  
Fusion : MitelmanANP32E/KAT6B [1q21.2/10q22.2]  [t(1;10)(q21;q22)]  
Fusion : MitelmanKAT6B/ADK [10q22.2/10q22.2]  [t(10;10)(q22;q22)]  
Fusion : MitelmanKAT6B/CCDC172 [10q22.2/10q25.3]  [t(10;10)(q22;q25)]  
Fusion : MitelmanKAT6B/CORO7 [10q22.2/16p13.3]  [t(10;16)(q22;p13)]  
Fusion : MitelmanKAT6B/CREBBP [10q22.2/16p13.3]  [t(10;16)(q22;p13)]  
Fusion : MitelmanKAT6B/DDX4 [10q22.2/5q11.2]  [t(5;10)(q11;q22)]  
Fusion : MitelmanKAT6B/RTKN2 [10q22.2/10q21.2]  [t(10;10)(q21;q22)]  
Fusion : MitelmanKAT6B/SH3BP5L [10q22.2/1q44]  [t(1;10)(q44;q22)]  
Fusion : MitelmanSAMD8/KAT6B [10q22.2/10q22.2]  [t(10;10)(q22;q22)]  
Fusion: TCGAKAT6B 10q22.2 ADK 10q22.2 BRCA LUAD OV
Fusion: TCGAKAT6B 10q22.2 C10orf96 BRCA
Fusion: TCGAKAT6B 10q22.2 CORO7 16p13.3 PRAD
Fusion: TCGAKAT6B 10q22.2 DDX4 5q11.2 BRCA
Fusion: TCGAKAT6B 10q22.2 RTKN2 10q21.2 BRCA
Fusion: TCGAKAT6B 10q22.2 SH3BP5L 1q44 PRAD
Fusion: TCGASAMD8 10q22.2 KAT6B 10q22.2 LUAD
Fusion : TICdbKAT6B [10q22.2]  -  CREBBP [16p13.3]
Polymorphisms : SNP, variants
NCBI Variation ViewerKAT6B [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)KAT6B
dbVarKAT6B
ClinVarKAT6B
1000_GenomesKAT6B 
Exome Variant ServerKAT6B
ExAC (Exome Aggregation Consortium)KAT6B (select the gene name)
Genetic variants : HAPMAP23522
Genomic Variants (DGV)KAT6B [DGVbeta]
Mutations
ICGC Data PortalKAT6B 
TCGA Data PortalKAT6B 
Broad Tumor PortalKAT6B
OASIS PortalKAT6B [ Somatic mutations - Copy number]
Cancer Gene: CensusKAT6B 
Somatic Mutations in Cancer : COSMICKAT6B 
intOGen PortalKAT6B
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Baylor College of Medicine
BioMutasearch KAT6B
DgiDB (Drug Gene Interaction Database)KAT6B
DoCM (Curated mutations)KAT6B (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)KAT6B (select a term)
intoGenKAT6B
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)10:76586171-76792380  ENSG00000156650
CONAN: Copy Number AnalysisKAT6B 
Mutations and Diseases : HGMDKAT6B
OMIM603736    605880    606170   
MedgenKAT6B
Genetic Testing Registry KAT6B
NextProtQ8WYB5 [Medical]
TSGene23522
GENETestsKAT6B
Huge Navigator KAT6B [HugePedia]
snp3D : Map Gene to Disease23522
BioCentury BCIQKAT6B
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD23522
Chemical/Pharm GKB GenePA134880712
Clinical trialKAT6B
Miscellaneous
canSAR (ICR)KAT6B (select the gene name)
Probes
Litterature
PubMed40 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineKAT6B
EVEXKAT6B
GoPubMedKAT6B
iHOPKAT6B
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Sat Apr 30 13:55:11 CEST 2016

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