MAML2 (mastermind-like 2)

2007-10-01 Kazumi Suzukawa , Jean-Loup Huret Affiliation

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

MAML2

LOCATION

11q21

LOCUSID

84441

ALIAS

MAM-3,MAM2,MAM3,MLL-MAML2

FUSION GENES

Show Gene Fusions

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.

Entity name

inv(11)(q21q23) in therapy related leukemias

Disease

therapy-related acute leukemia and MDS.

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.

Breakpoints

Article Bibliography

Pubmed ID	Last Year	Title	Authors
16444749	2006	Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene.	Behboudi A et al
3180001	1988	Translocation 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
14720503	2004	Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors.	Enlund F et al
1372276	1992	Expression 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
12386158	2002	Identification of new human mastermind proteins defines a family that consists of positive regulators for notch signaling.	Lin SE et al
2331681	1990	Chromosomal patterns in Warthin's tumor. A second type of human benign salivary gland neoplasm.	Mark J et al
15269296	2004	A study of MECT1-MAML2 in mucoepidermoid carcinoma and Warthin's tumor of salivary glands.	Martins C et al
17551948	2007	Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23).	Nemoto N et al
8019965	1994	Recurrent rearrangements of 11q14-22 in mucoepidermoid carcinoma.	Nordkvist A et al
9870694	1998	A child with a t(11;19)(q14-21;p12) in a pulmonary mucoepidermoid carcinoma.	Stenman G et al
17437281	2007	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 et al
12539049	2003	t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway.	Tonon G et al
17334997	2007	Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants of cutaneous hidradenomas.	Winnes M et al
11101851	2000	MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors.	Wu L et al
15961999	2005	Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation.	Wu L et al
12370315	2002	Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors.	Wu L et al
9102301	1997	Conservation 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 ID	Transcript ID	Uniprot
ENSG00000184384	ENST00000524717	Q8IZL2
ENSG00000184384	ENST00000618849	A0A087X0G5

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Notch signaling pathway	KEGG	ko04330
Notch signaling pathway	KEGG	hsa04330
Disease	REACTOME	R-HSA-1643685
Diseases of signal transduction	REACTOME	R-HSA-5663202
Signaling by NOTCH1 in Cancer	REACTOME	R-HSA-2644603
Signaling by NOTCH1 PEST Domain Mutants in Cancer	REACTOME	R-HSA-2644602
Constitutive Signaling by NOTCH1 PEST Domain Mutants	REACTOME	R-HSA-2644606
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	REACTOME	R-HSA-2894858
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	REACTOME	R-HSA-2894862
Signal Transduction	REACTOME	R-HSA-162582
Signaling by NOTCH	REACTOME	R-HSA-157118
Pre-NOTCH Expression and Processing	REACTOME	R-HSA-1912422
Pre-NOTCH Transcription and Translation	REACTOME	R-HSA-1912408
Signaling by NOTCH1	REACTOME	R-HSA-1980143
NOTCH1 Intracellular Domain Regulates Transcription	REACTOME	R-HSA-2122947
Signaling by NOTCH2	REACTOME	R-HSA-1980145
NOTCH2 intracellular domain regulates transcription	REACTOME	R-HSA-2197563
Gene Expression	REACTOME	R-HSA-74160
Generic Transcription Pathway	REACTOME	R-HSA-212436
Notch-HLH transcription pathway	REACTOME	R-HSA-350054
Th1 and Th2 cell differentiation	KEGG	ko04658
Th1 and Th2 cell differentiation	KEGG	hsa04658

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
36208053	2023	Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2- rearranged salivary gland tumours.	6
36344258	2023	Malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements: A clinicopathologic study of seven cases demonstrating a heterogenous entity.	3
36675234	2023	Establishment of Mucoepidermoid Carcinoma Cell Lines from Surgical and Recurrence Biopsy Specimens.	0
36898841	2023	Pathogenic variations in MAML2 and MAMLD1 contribute to congenital hypothyroidism due to dyshormonogenesis by regulating the Notch signalling pathway.	0
37489594	2023	Significance of YAP1-MAML2 rearrangement and GTF2I mutation in the diagnosis and differential diagnosis of metaplastic thymoma.	2
36208053	2023	Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2- rearranged salivary gland tumours.	6
36344258	2023	Malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements: A clinicopathologic study of seven cases demonstrating a heterogenous entity.	3
36675234	2023	Establishment of Mucoepidermoid Carcinoma Cell Lines from Surgical and Recurrence Biopsy Specimens.	0
36898841	2023	Pathogenic variations in MAML2 and MAMLD1 contribute to congenital hypothyroidism due to dyshormonogenesis by regulating the Notch signalling pathway.	0
37489594	2023	Significance of YAP1-MAML2 rearrangement and GTF2I mutation in the diagnosis and differential diagnosis of metaplastic thymoma.	2
34550633	2022	KMT2A-MAML2 rearrangement emerged and regressed during neuroblastoma therapy without leukemia after 12.8-year follow-up.	0
34657306	2022	Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3-MAML2 fusions, and clinicopathological features.	8
35457138	2022	Diagnostic Value of MAML2 Rearrangements in Mucoepidermoid Carcinoma.	1
35546636	2022	Recurrent YAP1::MAML2 fusions in "nodular necrotizing" variants of myxoinflammatory fibroblastic sarcoma: a comprehensive study of 7 cases.	6
35925563	2022	MAML2 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/gene-explorer/css/lib/case-report-explorer/

Historical Card

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

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