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KAT6B (MYST histone acetyltransferase (monocytic leukemia) 4)

Identity

Other namesMYST4
qkf
MORF
MOZ2
FLJ90335
KIAA0383
querkopf
DKFZp313G1618
EC 2.3.1.- EC 2.3.1.48
HGNC (Hugo) KAT6B
LocusID (NCBI) 23522
Location 10q22.2
Location_base_pair Starts at 76586171 and ends at 76792380 bp from pter ( according to hg19-Feb_2009)
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.

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

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.
  

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

Leukemias t0817q24q22ID1494

External links

Nomenclature
HGNC (Hugo)KAT6B   17582
Cards
AtlasMYST4ID41488ch10q22
Entrez_Gene (NCBI)KAT6B  23522  K(lysine) acetyltransferase 6B
GeneCards (Weizmann)KAT6B
Ensembl (Hinxton)ENSG00000156650 [Gene_View]  chr10:76586171-76792380 [Contig_View]  KAT6B [Vega]
ICGC DataPortalENSG00000156650
cBioPortalKAT6B
AceView (NCBI)KAT6B
Genatlas (Paris)KAT6B
WikiGenes23522
SOURCE (Princeton)NM_001256468 NM_001256469 NM_012330
Genomic and cartography
GoldenPath (UCSC)KAT6B  -  10q22.2   chr10:76586171-76792380 +  10q22.2   [Description]    (hg19-Feb_2009)
EnsemblKAT6B - 10q22.2 [CytoView]
Mapping of homologs : NCBIKAT6B [Mapview]
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)AC_000142 NC_000010 NC_018921 NG_032048 NT_030059 NW_001837987 NW_004929376
Consensus coding sequences : CCDS (NCBI)KAT6B
Cluster EST : UnigeneHs.740873 [ NCBI ]
CGAP (NCI)Hs.740873
Alternative Splicing : Fast-db (Paris)GSHG0003465
Alternative Splicing GalleryENSG00000156650
Gene ExpressionKAT6B [ NCBI-GEO ]     KAT6B [ SEEK ]   KAT6B [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8WYB5 (Uniprot)
NextProtQ8WYB5  [Medical]
With graphics : InterProQ8WYB5
Splice isoforms : SwissVarQ8WYB5 (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 [organisation]   Histone_H1/H5_H15 [organisation]   MOZ_SAS [organisation]   WHTH_DNA-bd_dom [organisation]   Znf_FYVE_PHD [organisation]   Znf_PHD [organisation]   Znf_PHD-finger [organisation]   Znf_RING/FYVE/PHD [organisation]  
Related proteins : CluSTrQ8WYB5
Domain families : Pfam (Sanger)Linker_histone (PF00538)    MOZ_SAS (PF01853)    PHD (PF00628)   
Domain families : Pfam (NCBI)pfam00538    pfam01853    pfam00628   
Domain families : Smart (EMBL)H15 (SM00526)  PHD (SM00249)  
DMDM Disease mutations23522
Blocks (Seattle)Q8WYB5
Human Protein AtlasENSG00000156650 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ8WYB5
HPRD07065
IPIIPI00099433   IPI00384388   IPI00607795   
Protein Interaction databases
DIP (DOE-UCLA)Q8WYB5
IntAct (EBI)Q8WYB5
FunCoupENSG00000156650
BioGRIDKAT6B
InParanoidQ8WYB5
Interologous Interaction database Q8WYB5
IntegromeDBKAT6B
STRING (EMBL)KAT6B
Ontologies - Pathways
Ontology : AmiGOnucleosome  DNA binding  histone acetyltransferase activity  protein binding  nucleus  nucleus  nucleosome assembly  transcription, DNA-templated  regulation of transcription, DNA-dependent  transcription factor binding  zinc ion binding  acetyltransferase activity  histone acetylation  histone H3 acetylation  negative regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  MOZ/MORF histone acetyltransferase complex  
Ontology : EGO-EBInucleosome  DNA binding  histone acetyltransferase activity  protein binding  nucleus  nucleus  nucleosome assembly  transcription, DNA-templated  regulation of transcription, DNA-dependent  transcription factor binding  zinc ion binding  acetyltransferase activity  histone acetylation  histone H3 acetylation  negative regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  MOZ/MORF histone acetyltransferase complex  
Protein Interaction DatabaseKAT6B
Wikipedia pathwaysKAT6B
Gene fusion - rearrangments
Rearrangement : TICdbKAT6B [10q22.2]  -  CREBBP [19p13.11]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)KAT6B
snp3D : Map Gene to Disease23522
SNP (GeneSNP Utah)KAT6B
SNP : HGBaseKAT6B
Genetic variants : HAPMAPKAT6B
Exome VariantKAT6B
1000_GenomesKAT6B 
ICGC programENSG00000156650 
Mutations and Diseases : HGMDKAT6B
Genomic VariantsKAT6B  KAT6B [DGVbeta]
dbVarKAT6B
ClinVarKAT6B
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM603736    605880    606170   
MedgenKAT6B
GENETestsKAT6B
Disease Genetic AssociationKAT6B
Huge Navigator KAT6B [HugePedia]  KAT6B [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneKAT6B
Homology/Alignments : Family Browser (UCSC)KAT6B
Phylogenetic Trees/Animal Genes : TreeFamKAT6B
Chemical/Protein Interactions : CTD23522
Chemical/Pharm GKB GenePA134880712
Clinical trialKAT6B
Cancer Resource (Charite)ENSG00000156650
Other databases
Probes
Litterature
PubMed33 Pubmed reference(s) in Entrez
CoreMineKAT6B
iHOPKAT6B

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, Billstrˆm R, Strˆmbeck 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, Cˆ¥tˆ© 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, Larrˆ°yoz MJ, Lahortiga I, Floristˆ°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, Adˆ©laˆØde 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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written05-2006José Luis Vizmanos
Departamento de Genética, Facultad de Ciencias, Universidad de Navarra, 31008 Pamplona, Navarra, Espana

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 online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/MYST4ID41488ch10q22.html

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indexed on : Fri Jul 11 17:11:18 CEST 2014

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