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FLASH GENE
Symbol MAML1 contributors: mct/pgu - updated : 30-08-2013
HGNC name mastermind-like 1 (Drosophila)
HGNC id 13632
PROTEIN
PHYSICAL PROPERTIES basic
STRUCTURE
motifs/domains
  • an N terminal basic domain, directly interacts with both EP300 and histones, and the EP300-MAML1 complex specifically acetylates histone H3 and H4 tails in chromatin
  • a proline repeat motif (PXPAAPAP) present in TP53 and important for the EP300-TP53 interaction
  • two consensus sites for SUMOylation at Lysine217 and Lysine299
  • mono polymer complex
    HOMOLOGY
    interspecies homolog to rattus Maml1 (86.5 pc)
    homolog to murine Maml1 (86.5 pc)
    Homologene
    FAMILY
  • mastermind family
  • CATEGORY regulatory , transcription factor , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    text nuclear in a punctate manner
    basic FUNCTION
  • acting as a transcriptional coactivator for NOTCH-signaling
  • amplifying NOTCH-induced transcription of HES1
  • enhancing phosphorylation and proteolytic turnover of the NOTCH intracellular domain in the nucleus through interaction with CDK8
  • inducing phosphorylation and localization of CREBBP to nuclear foci
  • playing a role in hematopoietic development by regulating NOTCH-mediated lymphoid cell fate decisions
  • binding to CREBBP/CBP which promotes nucleosome acetylation at NOTCH enhancers and activates transcription
  • increasing the half-life of p53 protein
  • enhancing the TP53 phosphorylation/acetylation upon DNA damage of cells
  • specific coactivator for the Notch pathway, as a coactivator for beta-catenin and participates in the Wnt signaling by modulating the beta-catenin/TCF activity
  • in colonic carcinoma cells having a role in cell death by affecting beta-catenin-induced expression of cyclin D1 and c-Myc
  • plays an important role in Notch-regulated transcription, by direct interactions with Notch, EP300 and histone
  • novel modulator for NF-KB signaling and regulates cellular survival
  • engagement of Mastermind (Mam) is essential for Notch signaling, and MAML1, MAML2, MAML3 have distinct roles
  • MAML1 and RBPJ, which are components of the Notch transcription complex, enhance Notch acetylation and we suggest that MAML1 increases Notch acetylation by potentiating EP300 autoacetylation
  • may be a component of the transcriptional networks which regulate EGR1 target genes during nephrogenesis and could also have implications for the development of renal cell carcinoma
  • enhances the transcriptional activity of RUNX2, a transcription factor essential for osteoblastic differentiation and chondrocyte proliferation and maturation
  • might be a key regulator of Notch stability in the nucleus by interacting with either EP300, which leads to increased Notch receptor stability, or the recruitment of CDK8 for Notch degradation
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text
  • hematopoietic development
  • PATHWAY
    metabolism
    signaling signal transduction
    NOTCH signaling pathway
    a component
  • forming a DNA-binding complex with Notch proteins and
  • RBPSUH/RBP-J kappa/CBF1
    INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • NOTCH (intracellular domain 1) and recombination signal binding protein JK
  • binding to CDK8
  • binding to CREBBP/CBP
  • interacting through its N-terminal region with the ankyrin repeat region of the Notch proteins NOTCH1, NOTCH2, NOTCH3 and NOTCH4
  • interacting with TP53
  • also interact with other coregulator proteins, such as CDK8 and EP300, to modulate the activity of Notch (MAML1 recruits EP300 to Notch-regulated genes through direct interactions with the DNA-CSL-Notch complex and EP300)
  • interacting with HDAC7 (SUMOylation of MAML1 is a mechanism for repressing MAML1 activity by influencing its interaction with HDAC7)
  • plays a key role in recruiting CDK8 to phosphorylate Notch1 ICD(intracellular domain) and subsequent degradation via the FBXW7 ubiquitin ligase
  • DDX5 interacts with MAML1 and is associated with the endogenous NOTCH1 transcription activation complex in human T-ALL leukemic cells
  • SNAI1 inhibits NOTCH1 intracellular domain mediated transcriptional activation via competing with MAML1
  • cell & other
    REGULATION
    Other SUMOylation of MAML1 is a mechanism for repressing MAML1 activity by influencing its interaction with HDAC7
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • MamL1-deficient mice did not recapitulate total loss of Notch signaling, suggesting that other members could compensate for the loss or that Notch signaling could proceed in the absence of Mam in certain contexts