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FLASH GENE
Symbol MED12 contributors: mct - updated : 09-07-2018
HGNC name mediator complex subunit 12
HGNC id 11957
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrainhindbrainmedulla oblongata highly
 brainforebraincerebral cortex highly
 brainhindbraincerebellum highly
 brainforebraincerebral lobefrontal lobehighly
 brainforebraincerebral lobeoccipital lobehighly
 braindiencephalonhypothalamus highly
 spinal cord   highly
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo, fetal
Text fetal brain,lung, liver and kidney
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal nuclear localization signal and N-terminally truncated protein is unable to enter the nucleus due to the lack of identified nuclear localization signal (NLS)
  • a dodecamer repeat
  • two overlapping ligand-dependent nuclear hormone receptor signature recognition motifs
  • a highly glutamine-rich C-terminal region resulting from the CAG repeats
  • HOMOLOGY
    interspecies ortholog to Med12, Mus musculus
    ortholog to MED12, Pan troglodytes
    homolog to SRB8, Saccharomyces cerevisiae
    Homologene
    FAMILY
  • mediator complex subunit 12 family
  • CATEGORY regulatory , transcription factor , receptor nuclear
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    text
  • in part cytoplasmic where it negatively regulates TGFBR2 through physical interaction
  • basic FUNCTION
  • involved in the regulated transcription of nearly all RNA polymerase II-dependent genes
  • acts as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and general transcription factors
  • coactivator for nuclear receptors
  • playing a regulatory role in vertebrate neuronal development
  • regulates the homeobox transcription factor NANOG fonctions
  • Med12-Med13-Cdk8-CycC subcomplex may be involved in
  • both positive and negative transcriptional regulation of all RNAPII promoters
  • essential for Nanog signaling and maintenance of ES cell pluripotency
  • Med12 and Nanog function together to regulate Nanog target gene promoters
  • has possible roles in development
  • controls the response to multiple cancer drugs through regulation of TGFBR signaling
  • involved in transcriptional regulation by conveying information from gene-specific regulatory elements to the RNA polymerase II transcription machinery
  • MED12 and KAT6B are chromatin-modifying enzymes implicated in Ohdo syndrome and the development of uterine leiomyomata and other tumors strongly suggests that both genes are functionally related
  • is an essential regulator of hematopoietic stem cell (HSC) homeostasis
  • alterations in MED12-dependent enhancer regulation may control both physiological and malignant hematopoiesis
  • MED12 plays a key role in the regulation of uterine fibroid cell line (HuLM) cell proliferation through the modulation of WNT/CTNNB1, cell cycle-associated, and fibrosis-associated protein expression
  • is an important molecular regulator of tumor dormancy in epithelial ovarian cancer (EOC)
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text
  • neurogenesis
  • transcription co-activator
  • PATHWAY
    metabolism
    signaling
    Wnt/beta-catenin pathway
    a component
  • subunit of TRAP thyroid hormone receptor-associated protein complex
  • component and a potential therapeutic target in the Wnt/beta-catenin pathway
  • part of CDK8 subcomplex” (containing CDK8, cyclin C, MED12, and MED13), functioning as a simple switch that controls the Mediator–pol II interaction to help regulate transcription initiation and reinitiation events (Knuesel 2009)
  • is a key component of the transcription-regulating Mediator complex
  • INTERACTION
    DNA
    RNA Homeobox transcription factor nanog Promoter
    small molecule
    protein
  • SOX9
  • CTNNB1 and GLI3
  • HOMEOBOX TRANSCRIPTION FACTOR NANOG; NANOG
  • Med13 (TRAP240)
  • Cdk8 (SRB10)
  • CycC (SRB11)
  • Med12-Med13-Cdk8-CycC subcomplex interact with RNAPII
  • enzymatically active CDK8 is responsible for suppression of GLI3 transactivation activity, and further, MED12 most likely contributes to this suppression through its role as an anchor for CDK8 in Mediator
  • SOX10 functions during terminal differentiation of myelinating glia, at least in part by MED12-dependent recruitment of the Mediator complex
  • CDK8 and its paralog CDK19, in complex with CCNC, MED12 and MED13, are transcriptional regulators that mediate several carcinogenic pathways and the chemotherapy-induced tumor-supporting paracrine network
  • MED12 operates together with PRC1 to silence key developmental genes in pluripotency
  • JMJD6 is found to interact with MED12 in the mediator complex to regulate its recruitment
  • JMJD6 is necessary for MED12 to interact with CARM1, which methylates MED12 at multiple arginine sites and regulates its chromatin binding
  • JMJD6 is necessary for MED12 to interact with CARM1, which methylates MED12 at multiple arginine sites and regulates its chromatin binding
  • MED12 plays an important role in regulating dormancy of EOC (epithelial ovarian cancer) through regulation of EGFR
  • cell & other
    REGULATION
    Other under tissue- or developmental-specific control
    ASSOCIATED DISORDERS
    corresponding disease(s) FGS1 , LJFS1 , OHDOX
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in uterine leiomyomas
    tumoral somatic mutation      
    in prostate cancer
    tumoral germinal mutation      
    may likely contribute to chronic lymphocytic leukaemia (CLL) pathogenesis by activating NOTCH signalling
    tumoral somatic mutation      
    in 60p100 of breast fibroadenomas (FAs)
    Susceptibility
    Variant & Polymorphism
    Candidate gene for schizophrenia
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativealzheimer
    potential therapeutic target in Alzheimer disease
    ANIMAL & CELL MODELS
  • med12-deficient zebrafish embryos showed defects in brain, neural crest, and kidney development and do not survive beyond 1 week after fertilization