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

Article 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
362080532023Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2- rearranged salivary gland tumours.6
363442582023Malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements: A clinicopathologic study of seven cases demonstrating a heterogenous entity.3
366752342023Establishment of Mucoepidermoid Carcinoma Cell Lines from Surgical and Recurrence Biopsy Specimens.0
368988412023Pathogenic variations in MAML2 and MAMLD1 contribute to congenital hypothyroidism due to dyshormonogenesis by regulating the Notch signalling pathway.0
374895942023Significance of YAP1-MAML2 rearrangement and GTF2I mutation in the diagnosis and differential diagnosis of metaplastic thymoma.2
362080532023Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2- rearranged salivary gland tumours.6
363442582023Malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements: A clinicopathologic study of seven cases demonstrating a heterogenous entity.3
366752342023Establishment of Mucoepidermoid Carcinoma Cell Lines from Surgical and Recurrence Biopsy Specimens.0
368988412023Pathogenic variations in MAML2 and MAMLD1 contribute to congenital hypothyroidism due to dyshormonogenesis by regulating the Notch signalling pathway.0
374895942023Significance of YAP1-MAML2 rearrangement and GTF2I mutation in the diagnosis and differential diagnosis of metaplastic thymoma.2
345506332022KMT2A-MAML2 rearrangement emerged and regressed during neuroblastoma therapy without leukemia after 12.8-year follow-up.0
346573062022Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3-MAML2 fusions, and clinicopathological features.8
354571382022Diagnostic Value of MAML2 Rearrangements in Mucoepidermoid Carcinoma.1
355466362022Recurrent YAP1::MAML2 fusions in "nodular necrotizing" variants of myxoinflammatory fibroblastic sarcoma: a comprehensive study of 7 cases.6
359255632022MAML2 Gene Rearrangement Occurs in Nearly All Hidradenomas: A Reappraisal in a Series of 20 Cases.1

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-(mastermind-like-2)

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