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FLASH GENE
Symbol MED1 contributors: mct/npt/pgu - updated : 17-03-2014
HGNC name mediator complex subunit 1
HGNC id 9234
Location 17q12      Physical location : 37.560.539 - 37.607.527
Synonym name
  • thyroid hormone receptor interactor 2
  • peroxisome proliferator-activated receptor-binding protein
  • vitamin D receptor-interacting protein 230 kD
  • PPAR binding protein
  • thyroid hormone receptor-associated protein complex component TRAP220
  • p53 regulatory protein RB18A
  • Synonym symbol(s) PPARBP, MGC71488, PBP, RB18A, TRIP2, CRSP1, DRIP230, PPARGBP, TRAP220, CRSP200, DRIP205
    DNA
    TYPE pseudogene
    STRUCTURE 46.99 kb     17 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 8148 - 1581 - 1997 9325263
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestivepharynx   highly
    Endocrineparathyroid   highly
    Reproductivefemale systembreastmammary gland highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularexocrinehighly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductiveepithelial cell
    Skin/Tegumentkeratinocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text
  • critical for placental and cardiac development during embryogenesis
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal domain consisting of about 600 AAs, required for the assembly of MED1 into Mediator complex ,
  • two classical LXXLL motifs
  • two nuclear receptor interaction motifs necessary and sufficient for stable association with the TRAP/Mediator complex, and playing a role in mammary luminal epithelial cell differentiation and progenitor/stem cell determination
  • potential nuclear localization signal (NLS)
  • a C2 domain
  • three or four WW domains, and a ubiquitin ligase HECT domain
  • thirteen potential glycosylation sites
  • HOMOLOGY
    interspecies homolog to murine Pparbp
    Homologene
    FAMILY
  • mediator complex subunit 1 family
  • CATEGORY transcription factor , protooncogene , receptor nuclear
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • global coactivator for the nuclear receptor family
  • estrogen receptor coactivator playing a role in mammary epithelial cell differentiation and breast carcinogenesis
  • essential role for embryonic fibroblast differentiation pathway (adipogenesis,but not myogenesis)
  • essential for normal development of vital organ systems
  • acting as a coactivator of FXR and underscore the importance of DRIP205 in modulating the bile acid response of NR1H4 target genes
  • catalyzing PTEN polyubiquitination that negatively regulates PTEN stability
  • plays a key role in facilitating ligand-dependent interactions of this multisubunit coactivator complex with nuclear receptors through their ligand binding domains
  • dispensable for the regulation of PTEN stability and localization
  • via interactions with GGA3 and cargo (LAPTM5), regulates cargo trafficking to the lysosome without requiring cargo ubiquitination
  • core Mediator subunits MED1 and MED17 are recruited to the CDKN1A locus
  • general coactivator complex connecting transcription activators and RNA polymerase II
  • mediator subunit regulating peroxisome proliferator-activated receptor gamma-stimulated adipogenesis by alternative mechanisms
  • mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of ADRB2
  • is capable of binding to SPY1A and the dominant negative forms and knockdown of NEDD4 reduce ubiquitination and further degradation of SPY1A
  • cofactor involved in not only the regulation of nuclear receptors but also the activation of GATA6 transcription
  • required for proper heart development and likely vasculature development as well
  • differentially expressed in mammary epithelial cells and plays a role in luminal lineage determination
  • plays a broad role in nuclear receptor-mediated transcription by anchoring the Mediator complex to diverse promoter-bound nuclear receptors
  • strong suppressive function of MED1 on energy expenditure pathways in muscle
  • may be acting in the muscle to regulate glucose and energy metabolism
  • NEDD4 and ARRB1 as key regulators of SLC9A1 ubiquitylation, endocytosis, and function
  • E3 ubiquitin ligase responsible for GRIA1 ubiquitination, a modification that regulates multiple aspects of GRIA1 molecular biology including trafficking, localization and stability
  • ARGLU1 and MED1 colocalize on the same estrogen receptor target gene promoter upon estrogen induction
  • is a key regulator of FGFR1 endocytosis and signalling during neuronal differentiation and embryonic development
  • functions in the endosomal-lysosomal pathway, and robustly ubiquitinates SNCA, unlike ligases previously implicated in its degradation
  • plays an essential role for the activation of the genetic program involved in the terminal maturation stage of invariant natural killer T-cell development
  • has a critical role in regulating hair/epidermal proliferation and differentiation
  • . has roles in maintaining quiescence of keratinocytes and preventing depletion of the follicular stem cells
  • is a context-dependent GATA1 coregulator, and also exerts specialized functions in erythroid cells to control GATA1-independent, cell-type-specific genes, which include candidate regulators of erythroid cell development and function
  • MED1 stimulated transcription from the TSHB gene promoter in a T3-dependent manner
  • functions as a coactivator of several transcription factors and is implicated in adipogenesis of the lipid and glucose metabolism
  • has an important affect on mitochondrial function
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text transcription coactivator
    PATHWAY
    metabolism
    signaling hormonal
    a component
  • component of the CRSP coactivation complex, mediating, import, activator-dependent recruitment of RNA PolII
  • subunit of the mediator complex
  • NEDD4-LAPTM5 complex recruits ubiquitinated GGA3, which binds the LAPTM5-UIM
  • pivotal component of the complex that binds to nuclear receptors and a broad array of other gene-specific activators
  • INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • estrogen receptor ESR1
  • thyroid hormone receptor
  • binding PPARG, PPARA and THRB and activating PPARG2 (for PPARG2 stimulated adipogenesis)
  • TP53 (regulation of p53 transactivating activity)
  • GATA2, GATA3, GATA4, GATA6
  • N4BP2
  • interacting physically with the erythroid master regulator GATA1 (acting as a pivotal coactivator for GATA1 in erythroid development)
  • PRRG2
  • binds NR1H4 in a ligand-dependent manner (required the presence of an intact LXXLL nuclear receptor box 1 (N-terminal motif)
  • interact with glucocorticoid receptor (GR) in a ligand-dependent manner (for optimal glucocorticoid receptor-mediated transcription activation)
  • binding to LAPTM5, not LAPTM5 ubiquitination, is required for targeting
  • able to ubiquitinate GGA3
  • directly binds to the MED7 subunit and ERK phosphorylation of MED1 enhances this interaction
  • with d GATA6 are key regulators of SULT2A1 expression, and they play important roles in adrenal androgen production
  • SPRY1 and SPRY2, associate with the HECT domain family E3 ubiquitin ligase, NEDD4 and NEDD4 ubiquitinates SPRY2
  • suppressor of THBS1
  • PTEN, a negative regulator of the PI3K pathway, is a key downstream target of NEDD4 (NEDD4-regulated PTEN is a key regulator of terminal arborization)
  • interacts with ARRDC3 through its conserved PPXY motifs
  • GRB10 can interact with the C2 domain of the E3 ubiquitin ligase NEDD4 through its Src homology 2 (SH2) domain
  • ARGLU1 is a MED1/Mediator-associated protein
  • E3 ubiquitin ligase regulating endocytosis and signalling of FGFR1
  • interplay between MED1 and VDR, and potential VDR-dependent regulation of TBX21
  • mitogen-activated protein kinase phosphorylation of MED1 enhances the AR-MED1 interaction in prostate cancer cells
  • MED1 and MED25, regulate a restricted cohort of genes that are predominantly not controlled by GATA1
  • IRAK1BP1 is found in p65-MED1 complexes where IRAK1BP1 enhances p65/MED1/IRAK1BP1 complex formation
  • MED1 is a ligand-dependent positive cofactor on TSHB pomoter
  • enhances nuclear receptor-dependent transcription of the brown fat-specific UCP1 gene through interactions with Mediator subunit MED1
  • cell & other
    REGULATION
    Phosphorylated by AMPK, and by its association with AMPK, MED1 regulates liver cell proliferation and fatty acid oxidation, most likely as a downstream effector of PPARA and AMPK
    Other reguklated by ERK phosphorylation which is a regulatory mechanism that promotes MED1 association with Mediator and, as such, may facilitate a novel feed-forward action of nuclear hormones
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    overexpressed and amplified in more than 40–50p 100 of human breast cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmune 
    VDR/MED1 interaction is of potential therapeutic interest
    ANIMAL & CELL MODELS
  • Med1 knockout mice show enhanced insulin sensitivity and improved glucose tolerance as well as resistance to high-fat diet–induced obesity