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MAML2 (mastermind-like 2)

Written2007-10Kazumi Suzukawa, Jean-Loup Huret
Department of Hematology, Institute of Clinical Medicine, University of Tsukuba (KS); Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH)
This article is an update of :
2003-07Goran Stenman
Lundberg Laboratory for Cancer Research, Department of Pathology, Goteborg University, Sahlgrenska University Hospital, SE-413 45 Goteborg, Sweden

(Note : for Links provided by Atlas : click)


Alias (NCBI)hMam-3
HGNC Alias symbKIAA1819
HGNC Previous namemastermind (Drosophila)-like 2
 mastermind-like 2 (Drosophila)
LocusID (NCBI) 84441
Atlas_Id 472
Location 11q21  [Link to chromosome band 11q21]
Location_base_pair Starts at 95976600 and ends at 96343195 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping MAML2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ACADL (2q34)::MAML2 (11q21)C11orf95 (11q13.1)::MAML2 (11q21)CHD6 (20q12)::MAML2 (11q21)
CRTC1 (19p13.11)::MAML2 (11q21)CRTC3 (15q26.1)::MAML2 (11q21)CXCR4 (2q22.1)::MAML2 (11q21)
KMT2A (11q23.3)::MAML2 (11q21)MALAT1 (11q13.1)::MAML2 (11q21)MAML2 (11q21)::CEP57 (11q21)
MAML2 (11q21)::CNTN5 (11q22.1)MAML2 (11q21)::CRTC1 (19p13.11)MAML2 (11q21)::CRTC3 (15q26.1)
MAML2 (11q21)::EPHB2 (1p36.12)MAML2 (11q21)::KMT2A (11q23.3)MAML2 (11q21)::MAML2 (11q21)
MAML2 (11q21)::MYO5A (15q21.2)MAML2 (11q21)::PATJ (1p31.3)MAML2 (11q21)::RTKN (2p13.1)
MTMR2 (11q21)::MAML2 (11q21)MYB (6q23.3)::MAML2 (11q21)TANC1 (2q24.2)::MAML2 (11q21)
YAP1 (11q22.1)::MAML2 (11q21)


Description Spans 365 kb; 5 exons.
Transcription A major transcript of 7.5 kb.


Description 1153 aa, 125 kDa; conserved N-terminal basic domain (aa 29-92) which binds to the ankyrin repeat domain of Notch receptors; two acidic domains (aa 263-360 and 1124-1153) and a C-terminal transcriptional activation domain.
Expression Widely expressed.
Localisation Nuclear granules.
Function Mastermind-like coactivator for all four Notch receptors; forms a complex with the Notch intracellular domain (Notch ICD) and the CSL family of transcription factors (CSL: , Suppressor of Hairless, LAG1), resulting in activation of the Notch target genes and HES5; functions as a CSL-dependent transcriptional coactivator for ligand-stimulated Notch.
Homology MAML1 and MAML3.

Implicated in

Disease - Most common type of malignant salivary gland tumor;
- Second most frequent lung tumor of bronchial gland origin;
- Rare tumour in the thyroid.
The t(11;19) was found in samples from the three different sites.
Prognosis - Mucoepidermoid carcinomas have an unpredictable behaviour.
- The CRTC1-MAML2 fusion transcript was found equally in low, intermediate and high grade tumours; however, tumours lacking the fusion transcript were significantly associated with metastases; they may represent a subset of aggressive tumours.
- In another study, the median survival for fusion-positive patients was greater than 10 years compared to 1.6 years for fusion-negative patients.
Hybrid/Mutated Gene CRTC1-MAML2; exon 1 of CRTC1 fused to exons 2-5 of MAML2. Note: CRTC1 is also known as MECT1, or WAMTP1.
Abnormal Protein CRTC1-MAML2. In the fusion protein, the first 171 aa including the basic domain of MAML2 are replaced by 42 aa of CRTC1; there are no sequence similarities in the N-terminal domains of MAML2 and CRTC1. The fusion protein activates transcription of the Notch target gene HES1 independently of both Notch ligand and CSL.
Transforming activity of CRTC1-MAML2 fusion oncoprotein is mediated by mimicking constitutive activation of cAMP signaling, by activating CREB directly.
Entity .
Note In rare instances mucoepidermoid carcinoma may arise from or coexist with Warthin's tumors.
Disease Warthin's tumor is a salivary gland neoplasm consisting of benign epithelial and lymphoid components; malignant transformation is extremely rare.
Hybrid/Mutated Gene CRTC1-MAML2
Disease Clear Cell Hidradenomas of the skin are benign sweat gland tumors of eccrine duct origin.
Hybrid/Mutated Gene CRTC1-MAML2; exon 1 of CRTC1 fused to exons 2 of MAML2.
Disease therapy-related acute leukemia and MDS.
Hybrid/Mutated Gene MLL-MAML2; exon 1-7 of MLL fused to exons 2-5 of MAML2.
Abnormal Protein Hybrid transcript MLL/MAML2 contains the following domains: from MLL: AT-hook, DNA-Methyltransferase; from MAML2: Q rich domain, acidic domain.



To be noted

It is amazing that a similar fusion transcript (CRTC1-MAML2) can be seen both in a benign and in a malignant tumour of the same organ: Warthin's tumor, a benign salivary gland neoplasm, and mucoepidermoid carcinoma of the salivary gland: either another event differentiate the two, or the genetic event takes place in different cell types or in a given cell type at different states of differenciation.
It has been hypothezised that CRTC1-MAML2 fusion is etiologically linked to benign and low-grade malignant tumors originating from diverse exocrine glands rather than being linked to a separate tumor entity.


Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene.
Behboudi A, Enlund F, Winnes M, Andrén Y, Nordkvist A, Leivo I, Flaberg E, Szekely L, Mäkitie A, Grenman R, Mark J, Stenman G
Genes, chromosomes & cancer. 2006 ; 45 (5) : 470-481.
PMID 16444749
Translocation t(11;19)(q21;p13.1) as the sole chromosome abnormality in a cystadenolymphoma (Warthin's tumor) of the parotid gland.
Bullerdiek J, Haubrich J, Meyer K, Bartnitzke S
Cancer genetics and cytogenetics. 1988 ; 35 (1) : 129-132.
PMID 3180001
Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors.
Enlund F, Behboudi A, Andrén Y, Oberg C, Lendahl U, Mark J, Stenman G
Experimental cell research. 2004 ; 292 (1) : 21-28.
PMID 14720503
Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands.
Jhappan C, Gallahan D, Stahle C, Chu E, Smith GH, Merlino G, Callahan R
Genes & development. 1992 ; 6 (3) : 345-355.
PMID 1372276
Identification of new human mastermind proteins defines a family that consists of positive regulators for notch signaling.
Lin SE, Oyama T, Nagase T, Harigaya K, Kitagawa M
The Journal of biological chemistry. 2002 ; 277 (52) : 50612-50620.
PMID 12386158
Chromosomal patterns in Warthin's tumor. A second type of human benign salivary gland neoplasm.
Mark J, Dahlenfors R, Stenman G, Nordquist A
Cancer genetics and cytogenetics. 1990 ; 46 (1) : 35-39.
PMID 2331681
A study of MECT1-MAML2 in mucoepidermoid carcinoma and Warthin's tumor of salivary glands.
Martins C, Cavaco B, Tonon G, Kaye FJ, Soares J, Fonseca I
The Journal of molecular diagnostics : JMD. 2004 ; 6 (3) : 205-210.
PMID 15269296
Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23).
Nemoto N, Suzukawa K, Shimizu S, Shinagawa A, Takei N, Taki T, Hayashi Y, Kojima H, Kawakami Y, Nagasawa T
Genes, chromosomes & cancer. 2007 ; 46 (9) : 813-819.
PMID 17551948
Recurrent rearrangements of 11q14-22 in mucoepidermoid carcinoma.
Nordkvist A, Gustafsson H, Juberg-Ode M, Stenman G
Cancer genetics and cytogenetics. 1994 ; 74 (2) : 77-83.
PMID 8019965
A child with a t(11;19)(q14-21;p12) in a pulmonary mucoepidermoid carcinoma.
Stenman G, Petursdottir V, Mellgren G, Mark J
Virchows Archiv : an international journal of pathology. 1998 ; 433 (6) : 579-581.
PMID 9870694
CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin's tumors: implications for histogenesis and biologic behavior.
Tirado Y, Williams MD, Hanna EY, Kaye FJ, Batsakis JG, El-Naggar AK
Genes, chromosomes & cancer. 2007 ; 46 (7) : 708-715.
PMID 17437281
t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway.
Tonon G, Modi S, Wu L, Kubo A, Coxon AB, Komiya T, O'Neil K, Stover K, El-Naggar A, Griffin JD, Kirsch IR, Kaye FJ
Nature genetics. 2003 ; 33 (2) : 208-213.
PMID 12539049
Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants of cutaneous hidradenomas.
Winnes M, Mölne L, Suurküla M, Andrén Y, Persson F, Enlund F, Stenman G
Genes, chromosomes & cancer. 2007 ; 46 (6) : 559-563.
PMID 17334997
MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors.
Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD
Nature genetics. 2000 ; 26 (4) : 484-489.
PMID 11101851
Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation.
Wu L, Liu J, Gao P, Nakamura M, Cao Y, Shen H, Griffin JD
The EMBO journal. 2005 ; 24 (13) : 2391-2402.
PMID 15961999
Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors.
Wu L, Sun T, Kobayashi K, Gao P, Griffin JD
Molecular and cellular biology. 2002 ; 22 (21) : 7688-7700.
PMID 12370315
Conservation of the Notch signalling pathway in mammalian neurogenesis.
de la Pompa JL, Wakeham A, Correia KM, Samper E, Brown S, Aguilera RJ, Nakano T, Honjo T, Mak TW, Rossant J, Conlon RA
Development (Cambridge, England). 1997 ; 124 (6) : 1139-1148.
PMID 9102301


This paper should be referenced as such :
Suzukawa, K ; Huret, JL
MAML2 (mastermind-like 2)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(3):220-222.
Free journal version : [ pdf ]   [ DOI ]
History of this paper:
Stenman, G. MAML2 (mastermind-like 2). Atlas Genet Cytogenet Oncol Haematol. 2003;7(3):170-171.

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 3 ]
  inv(11)(q21q23) KMT2A::MAML2 in therapy related leukemias
Therapy-Related Hematopoietic Neoplasia
t(2;11)(q22;q21) CXCR4::MAML2

External links


HGNC (Hugo)MAML2   16259
Atlas Explorer : (Salamanque)MAML2
Entrez_Gene (NCBI)MAML2    mastermind like transcriptional coactivator 2
AliasesMAM-3; MAM2; MAM3; MLL-MAML2
GeneCards (Weizmann)MAML2
Ensembl hg19 (Hinxton)ENSG00000184384 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000184384 [Gene_View]  ENSG00000184384 [Sequence]  chr11:95976600-96343195 [Contig_View]  MAML2 [Vega]
ICGC DataPortalENSG00000184384
TCGA cBioPortalMAML2
Genatlas (Paris)MAML2
SOURCE (Princeton)MAML2
Genetics Home Reference (NIH)MAML2
Genomic and cartography
GoldenPath hg38 (UCSC)MAML2  -     chr11:95976600-96343195 -  11q21   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MAML2  -     11q21   [Description]    (hg19-Feb_2009)
GoldenPathMAML2 - 11q21 [CytoView hg19]  MAML2 - 11q21 [CytoView hg38]
Genome Data Viewer NCBIMAML2 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB058722 AK308157 AW513171 AY040322 BC143529
RefSeq transcript (Entrez)NM_032427
Consensus coding sequences : CCDS (NCBI)MAML2
Gene ExpressionMAML2 [ NCBI-GEO ]   MAML2 [ EBI - ARRAY_EXPRESS ]   MAML2 [ SEEK ]   MAML2 [ MEM ]
Gene Expression Viewer (FireBrowse)MAML2 [ Firebrowse - Broad ]
GenevisibleExpression of MAML2 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)84441
GTEX Portal (Tissue expression)MAML2
Human Protein AtlasENSG00000184384-MAML2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8IZL2   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8IZL2  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8IZL2
Domains : Interpro (EBI)Neuroggenic_mastermind-like_N   
Domain families : Pfam (Sanger)MamL-1 (PF09596)   
Domain families : Pfam (NCBI)pfam09596   
Domain families : Smart (EMBL)MamL-1 (SM01275)  
Conserved Domain (NCBI)MAML2
AlphaFold pdb e-kbQ8IZL2   
Human Protein Atlas [tissue]ENSG00000184384-MAML2 [tissue]
Protein Interaction databases
IntAct (EBI)Q8IZL2
Ontologies - Pathways
Ontology : AmiGOtranscription coactivator activity  transcription coactivator activity  protein binding  nucleus  nucleoplasm  nucleoplasm  Notch signaling pathway  positive regulation of transcription of Notch receptor target  nuclear speck  positive regulation of transcription by RNA polymerase II  
Ontology : EGO-EBItranscription coactivator activity  transcription coactivator activity  protein binding  nucleus  nucleoplasm  nucleoplasm  Notch signaling pathway  positive regulation of transcription of Notch receptor target  nuclear speck  positive regulation of transcription by RNA polymerase II  
REACTOMEQ8IZL2 [protein]
REACTOME PathwaysR-HSA-9013695 [pathway]   
NDEx NetworkMAML2
Atlas of Cancer Signalling NetworkMAML2
Wikipedia pathwaysMAML2
Orthology - Evolution
GeneTree (enSembl)ENSG00000184384
Phylogenetic Trees/Animal Genes : TreeFamMAML2
Homologs : HomoloGeneMAML2
Homology/Alignments : Family Browser (UCSC)MAML2
Gene fusions - Rearrangements
Fusion : MitelmanC11orf95::MAML2 [11q13.1/11q21]  
Fusion : MitelmanCRTC1::MAML2 [19p13.11/11q21]  
Fusion : MitelmanCRTC3::MAML2 [15q26.1/11q21]  
Fusion : MitelmanCXCR4::MAML2 [2q22.1/11q21]  
Fusion : MitelmanMAML2::CNTN5 [11q21/11q22.1]  
Fusion : MitelmanMYB::MAML2 [6q23.3/11q21]  
Fusion : MitelmanYAP1::MAML2 [11q22.1/11q21]  
Fusion : COSMICCRTC1 [19p13.11]  -  MAML2 [11q21]  [fusion_1102]  
Fusion : COSMICCRTC3 [15q26.1]  -  MAML2 [11q21]  [fusion_1104]  
Fusion : COSMICMAML2 [11q21]  -  CRTC1 [19p13.11]  [fusion_1106]  
Fusion : FusionHubACADL--MAML2    C11ORF80--MAML2    C11ORF95--MAML2    CACNA2D3--MAML2    CHD6--MAML2    CRTC1--MAML2    CRTC3--MAML2    CXCR4--MAML2    FAT3--MAML2    KMT2A--MAML2   
LRP5--MAML2    MALAT1--MAML2    MAML2--ANKMY2    MAML2--ARHGAP12    MAML2--ATG13    MAML2--ATXN3    MAML2--BCAS4    MAML2--CACHD1    MAML2--CCDC82    MAML2--CEP57   
MAML2--CNTN5    MAML2--CRTC1    MAML2--CRTC3    MAML2--CXCR4    MAML2--EED    MAML2--EEF2    MAML2--EPHB2    MAML2--EXOC2    MAML2--GFAP    MAML2--LOC401491   
MAML2--POMC    MAML2--RBM12    MAML2--RNF19B    MAML2--RTKN    MAML2--SIK3    MAML2--SLC25A37    MAML2--SMARCB1    MAML2--SUCLG2    MAML2--TMEM135    MAML2--TNFAIP3   
MAML2--YAP    MAML2--YAP1    MECT1--MAML2    MLL--MAML2    MTMR2--MAML2    PDIA5--MAML2    PEX5L--MAML2    PHF21A--MAML2    ROBO2--MAML2    TANC1--MAML2   
Fusion : QuiverMAML2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMAML2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MAML2
Exome Variant ServerMAML2
GNOMAD BrowserENSG00000184384
Varsome BrowserMAML2
ACMGMAML2 variants
Genomic Variants (DGV)MAML2 [DGVbeta]
DECIPHERMAML2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMAML2 
ICGC Data PortalMAML2 
TCGA Data PortalMAML2 
Broad Tumor PortalMAML2
OASIS PortalMAML2 [ Somatic mutations - Copy number]
Cancer Gene: CensusMAML2 
Somatic Mutations in Cancer : COSMICMAML2  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DMAML2
Mutations and Diseases : HGMDMAML2
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)MAML2
DoCM (Curated mutations)MAML2
CIViC (Clinical Interpretations of Variants in Cancer)MAML2
NCG (London)MAML2
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry MAML2
NextProtQ8IZL2 [Medical]
Target ValidationMAML2
Huge Navigator MAML2 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDMAML2
Pharm GKB GenePA134946327
Clinical trialMAML2
DataMed IndexMAML2
PubMed86 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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