MAML2 (mastermind-like 2)

2007-10-01   Kazumi 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)

Identity

HGNC
LOCATION
11q21
LOCUSID
ALIAS
MAM-3,MAM2,MAM3,MLL-MAML2
FUSION GENES

DNA/RNA

Description

Spans 365 kb; 5 exons.

Transcription

A major transcript of 7.5 kb.

Proteins

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: CBF1/RBP-jk, Suppressor of Hairless, LAG1), resulting in activation of the Notch target genes HES1 and HES5; functions as a CSL-dependent transcriptional coactivator for ligand-stimulated Notch.

Homology

MAML1 and MAML3.

Implicated in

Entity name
mucoepidermoid carcinoma with t(11;19)(q21-22;p13).
Disease
- Most common type of malignant salivary gland tumor;
The t(11;19) was found in samples from the three different sites. - Rare tumour in the thyroid.
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 gene
CRTC1-MAML2; exon 1 of CRTC1 fused to exons 2-5 of MAML2. Note: CRTC1 is also known as MECT1, or WAMTP1.
Fusion 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 name
Warthins tumor with t(11;19)(q21-22;p13).
Note
In rare instances mucoepidermoid carcinoma may arise from or coexist with Warthins tumors.
Disease
Warthins tumor is a salivary gland neoplasm consisting of benign epithelial and lymphoid components; malignant transformation is extremely rare.
Hybrid gene
CRTC1-MAML2
Entity name
Clear Cell Hidradenomas of the skin with t(11;19)(q21-22;p13)
Disease
Clear Cell Hidradenomas of the skin are benign sweat gland tumors of eccrine duct origin.
Hybrid gene
CRTC1-MAML2; exon 1 of CRTC1 fused to exons 2 of MAML2.
Hybrid gene
MLL-MAML2; exon 1-7 of MLL fused to exons 2-5 of MAML2.
Fusion protein
Hybrid transcript MLL/MAML2 contains the following domains: from MLL: AT-hook, DNA-Methyltransferase; from MAML2: Q rich domain, acidic domain.
Atlas Image

Breakpoints

Atlas Image

Bibliography

Pubmed IDLast YearTitleAuthors
164447492006Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene.Behboudi A et al
31800011988Translocation t(11;19)(q21;p13.1) as the sole chromosome abnormality in a cystadenolymphoma (Warthin's tumor) of the parotid gland.Bullerdiek J et al
147205032004Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors.Enlund F et al
13722761992Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands.Jhappan C et al
123861582002Identification of new human mastermind proteins defines a family that consists of positive regulators for notch signaling.Lin SE et al
23316811990Chromosomal patterns in Warthin's tumor. A second type of human benign salivary gland neoplasm.Mark J et al
152692962004A study of MECT1-MAML2 in mucoepidermoid carcinoma and Warthin's tumor of salivary glands.Martins C et al
175519482007Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23).Nemoto N et al
80199651994Recurrent rearrangements of 11q14-22 in mucoepidermoid carcinoma.Nordkvist A et al
98706941998A child with a t(11;19)(q14-21;p12) in a pulmonary mucoepidermoid carcinoma.Stenman G et al
174372812007CRTC1/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 et al
125390492003t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway.Tonon G et al
173349972007Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants of cutaneous hidradenomas.Winnes M et al
111018512000MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors.Wu L et al
159619992005Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation.Wu L et al
123703152002Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors.Wu L et al
91023011997Conservation of the Notch signalling pathway in mammalian neurogenesis.de la Pompa JL et al

Other Information

Locus ID:

NCBI: 84441
MIM: 607537
HGNC: 16259
Ensembl: ENSG00000184384

Variants:

dbSNP: 84441
ClinVar: 84441
TCGA: ENSG00000184384
COSMIC: MAML2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000184384ENST00000524717Q8IZL2
ENSG00000184384ENST00000618849A0A087X0G5

Expression (GTEx)

0
5
10
15
20
25

Pathways

PathwaySourceExternal ID
Notch signaling pathwayKEGGko04330
Notch signaling pathwayKEGGhsa04330
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by NOTCH1 in CancerREACTOMER-HSA-2644603
Signaling by NOTCH1 PEST Domain Mutants in CancerREACTOMER-HSA-2644602
Constitutive Signaling by NOTCH1 PEST Domain MutantsREACTOMER-HSA-2644606
Signaling by NOTCH1 HD+PEST Domain Mutants in CancerREACTOMER-HSA-2894858
Constitutive Signaling by NOTCH1 HD+PEST Domain MutantsREACTOMER-HSA-2894862
Signal TransductionREACTOMER-HSA-162582
Signaling by NOTCHREACTOMER-HSA-157118
Pre-NOTCH Expression and ProcessingREACTOMER-HSA-1912422
Pre-NOTCH Transcription and TranslationREACTOMER-HSA-1912408
Signaling by NOTCH1REACTOMER-HSA-1980143
NOTCH1 Intracellular Domain Regulates TranscriptionREACTOMER-HSA-2122947
Signaling by NOTCH2REACTOMER-HSA-1980145
NOTCH2 intracellular domain regulates transcriptionREACTOMER-HSA-2197563
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Notch-HLH transcription pathwayREACTOMER-HSA-350054
Th1 and Th2 cell differentiationKEGGko04658
Th1 and Th2 cell differentiationKEGGhsa04658

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
125390492003t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway.99
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
205881782010A reappraisal of the MECT1/MAML2 translocation in salivary mucoepidermoid carcinomas.42
168186852006MECT1-MAML2 fusion transcript defines a favorable subset of mucoepidermoid carcinoma.33
174372812007CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin's tumors: implications for histogenesis and biologic behavior.31
123861582002Identification of new human mastermind proteins defines a family that consists of positive regulators for notch signaling.30
147205032004Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors.22
239754342014Aberrantly activated AREG-EGFR signaling is required for the growth and survival of CRTC1-MAML2 fusion-positive mucoepidermoid carcinoma cells.22
211195972011High-level expression of Mastermind-like 2 contributes to aberrant activation of the NOTCH signaling pathway in human lymphomas.17

Citation

Kazumi Suzukawa ; Jean-Loup Huret

MAML2 (mastermind-like 2)

Atlas Genet Cytogenet Oncol Haematol. 2007-10-01

Online version: http://atlasgeneticsoncology.org/gene/472/maml2

Historical Card

2003-07-01 MAML2 (mastermind-like 2) by  Goran Stenman 

Lundberg Laboratory for Cancer Research, Department of Pathology, Goteborg University, Sahlgrenska University Hospital, SE-413 45 Goteborg, Sweden