Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol TRIM28 contributors: mct - updated : 05-04-2018
HGNC name tripartite motif-containing 28
HGNC id 16384
Location 19q13.43      Physical location : 59.055.835 - 59.062.082
Synonym name
  • transcriptional intermediary factor 1 beta
  • KRAB-associated protein 1
  • KRAB-interacting protein 1
  • KRAB-box-associated protein-1
  • nuclear corepressor KAP-1
  • RING finger protein 96
  • Krüppel-associated box domain-associated protein 1
    • Synonym symbol(s) KAP1, TIF1B, TF1B, FLJ29029, KAP-1, RNF96, PPP1R157
    DNA
    TYPE functioning gene
    STRUCTURE 6.25 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 2989 - 835 - 2001 11226167
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
    Lymphoid/Immunespleen    
     thymus   highly
    Reproductivefemale systemuteruscervix  
    Skin/Tegumentskin   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an N-terminal RING zinc finger
  • two B-box domains (one type 1 and one type 2)
  • a coiled-coil domain (RBCC) so called tripartite motif (TRIM)
  • a PHD (plant homeodomain) motif
  • a bromodomain
    • HOMOLOGY
    interspecies homolog to murine Trim 28
    intraspecies homolog to TIF1
    Homologene
    FAMILY
  • B box family, RBCC (TRIM family)
  • C-VI TRIM family
    • CATEGORY enzyme , regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,heterochromosome
    basic FUNCTION
  • retroviral silencer mediator of the transcriptional repression exerted by the KRAB domain
  • KRAB-binding corepressor of transcription with a KRAB domain transcription factor
  • repressing aldolase A gene transcription by interacting with ZNF224
  • functioning as corepressor with the Krüppel-associated box (KRAB) zinc finger DNA-binding proteins and acting by bridging the KRAB domain of the finger proteins to several known transcriptional corepressors
  • involved in the recruitment of proteins required for heritable gene silencing
  • may play an important role in early development, especially in embryonic stem cells and other pluripotent cells
  • may act as an endogenous regulator of the IFN/STAT1 signaling pathway
  • acting as a E3 ubiquitin ligase
  • universal corepressor protein for the Kruppel-associated box zinc-finger protein superfamily of transcriptional repressors
  • coactivator of the orphan nuclear receptor NR4A2, enhancing transcription mediated through the NR4A2 target, the Nur response element (NurRE)
  • may serve as a transcriptional regulator of the IL6/STAT3 signaling pathway
  • controls endogenous retroelements during early embryonic development
  • possesses an intrinsic silencing activity and also acts through chromatin via recruitment of chromatin modifiers
  • unique regulator of the pluripotency of embryonic stem cells and regulates POU5F1-dependent transcription in a phosphorylation-dependent manner
  • regulates the reprogramming process of somatic cells in a phosphorylation-dependent manner
  • together with ZNF350, may repress other genes critical for the DNA repair process as well as other physiological functions
  • acting as a positive regulator of NFE2L2, and participating in the oxidative stress response by maximizing NFE2L2-dependent transcription
  • poses a substantial barrier to DNA double-strand break (DSB) repair within heterochromatin that is alleviated by ATM-dependent TRIM28 phosphorylation
  • its function involves autoSUMOylation and recruitment of nucleosome deacetylation, methylation and remodeling activities
  • is an essential nuclear co-repressor for the KRAB zinc finger protein superfamily of transcriptional factors
  • is a unique regulator of thymocyte development
  • is critical for the silencing of endogenous retroviruses (ERVs) in embryonic stem (ES) cells
  • universal transcriptional corepressor that undergoes multiple posttranslational modifications (PTMs), including SUMOylation and Ser-824 phosphorylation
  • regulates senescence and affects the induction of the senescence-associated secretory phenotype
  • is a previously unappreciated interpreter of cell signaling, which modulates the ability of MYOD1 to drive myogenesis
  • transcription regulator, which forms a repressor complex containing heterochromatin protein 1 (CBX5)
  • plays unanticipated roles in transcriptional elongation
  • controls genomic imprinting through distinct mechanisms at different developmental stages
  • controls imprinting after early embryonic reprogramming through a mechanism other than the maintenance of germline imprints
  • requirement of TRIM28 after genome-wide reprogramming for interpreting germline imprints and regulating DNA methylation at imprinted gene promoters
  • RNF4 and TRIM28 play critical roles in the response to DNA double-strand breaks (DSBs)
  • combined effect of dynamic recruitment of RNF4 to TRIM28 regulates likely the relative occupancy of TP53BP1 and BRCA1 at DSB sites to direct DSB repair in a cell cycle-dependent manner
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • SRY, ZNF208/KRAB, and TRIM28 proteins formed a stable ternary protein complex
  • TRIM24 exists in a major complex with TRIM33 and a lesser abundant complex with TRIM33 and TRIM28
  • LCOR and TRIM28 form a complex with ZNF350 on an intronic binding site in GADD45A gene and a novel site in the fibroblast growth factor 2 (FGF2) gene
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting and repressing with KRAB domain of ZNF10 factor
  • with ZNF224
  • interacting with FES (FES-TRIM28 interaction, with a dual role for TRIM28 as both a FES activator and downstream effector)
  • physical and functional interactions between STAT3 and TRIM28
  • interacts directly with NR4A2 and with other Nur family members
  • interacting with TP53BP1 (phosphorylation is critical for TP53BP1-mediated repair, overall phosphorylated TRIM28 levels are only modestly affected by TP53BP1 loss)
  • physically interacted with PAX3 and KAP1 in a ternary complex and maintained PAX3 and TRIM28 in a deacetylated state
  • transcriptional co-repressor that is susceptible to phosphorylation at Ser(824) by ATM and to modification by small ubiquitin-like modifying (SUMO) proteins
  • PPP1CB interacted with TRIM28 only in response to genotoxic stress
  • PPP1CA directly interacted with TRIM28 under basal conditions
  • ZNF274 binding sites co-localize with SETDB1, TRIM28, and H3K9me3 at the 3prime ends of zinc finger genes
  • NFE2L2-interacting protein (facilitates NFE2L2 transactivation activity in a dose-dependent manner)
  • SMARCAD1 modulates the interaction of HDAC1 and TRIM28 with heterochromatin
  • ZFP57 and its cofactor TRIM28 are associated with DNMTs and hemimethylated DNA-binding UHRF1
  • TRIM28 is a novel protein-protein interaction partner of IRF5, and is an inhibitor of IRF5 function in inflammatory macrophages
  • TRIM28 has anti-proliferative activity in lung cancers via repression of E2F3, E2F4 that are critical for cell proliferation
  • MAGEC2 binds TRIM28, a scaffolding protein that regulates DNA repair
  • ZNF268 with its KRAB (Krüppel-associated box) at the N terminus, reinforces nuclear localization by interacting with TRIM28
  • TRIM28 and PRC1 bound cooperatively at the promoters of differentiation-inducible genes and repressed their transcription
  • ARM domain is required for RNF4 to efficiently target Ser(P)-824-SUMO-TRIM28, conferring ubiquitin Lys-48-mediated proteasomal degradation in the context of double strand breaks
  • TRIM28 as a new factor that modulates Pol II pausing and transcriptional elongation at a large number of mammalian genes
  • is a key regulator of MYOD1 function
  • TRIM28 is the major binding partner for nuclear AMER1 (AMER1 interacted with the coiled coil domain of TRIM28 required for its binding to Krüppel-associated box domains of transcription factors)
  • TRIM28 deacetylation by SIRT1 promotes non-homologous end-joining repair
  • BRDT has novel interactions with the histone deacetylase HDAC1, the arginine-specific histone methyltransferase 5 PRMT5, and the Tripartite motif-containing 28 protein TRIM28, and functions in transcriptional repression during spermatogenesis
  • TRIM17 stabilizes BCL2A1 by blocking TRIM28 from binding and ubiquitinating BCL2A1, and GSK3B is involved in the phosphorylation-mediated inhibition of BCL2A1 degradation
  • TRIM28 is necessary for MAGEE1 expression in cancer cells
  • TRIM28 binds NLRP3, promotes SUMO1, SUMO2 and SUMO3 modification of NLRP3, and thereby inhibits NLRP3 ubiquitination and proteasomal degradation
    • cell & other
    REGULATION
    Other TRIM28 Ser-473 phosphorylation was required for efficient DNA repair and cell survival in response to DNA damage
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colorectal cancer tissue compared with normal colorectal mucosa
    Susceptibility
    Variant & Polymorphism
    Candidate gene attractive candidate as a component of the repressor binding site silencer complex
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    TRIM28 may serve as a new potential target for immunotherapy of cancer
    ANIMAL & CELL MODELS