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FLASH GENE
Symbol PRDM1 contributors: mct/ - updated : 09-10-2015
HGNC name PR domain containing 1, with ZNF domain
HGNC id 9346
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a SET domain
  • five C2H2 type zinc finger DNA binding motifs
  • Krueppel-type zinc fingers
  • a PR domain
  • five C-terminal C2H2 Zn-finger domains, the first four of these highly evolutionarily conserved, and of these, the first two are necessary to confer DNA binding specificity , and this zinc finger domain mediates nuclear import, DNA binding, and recruitment of the corepressors G9a and HDAC1/2
    • HOMOLOGY
    interspecies homolog to rattus Prdm1 (88.7pc)
    homolog to murine Prdm1 (89.9pc)
    Homologene
    FAMILY Krueppel-like family
    CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • acting as a transcriptional repressor that binds specifically to the PRDI element in the promoter of the beta-interferon gene
  • driving the maturation of B lymphocytes into Ig secreting cells
  • binds to the TP53 promoter and represses TP53 transcription, and suppression of TP53 transcription is a crucial function of endogenous PRDM1 and is essential for normal cell growth
  • playing a crucial role in the control of cell proliferation and survival through the negative regulation of TP53 at the transcriptional level
  • involved in B cell differentiation and the development of B cell lymphomas
  • transcriptional repressor that plays an important role during plasmacytic differentiation and is expressed in normal and transformed plasma cells
  • involved in nuclear import and recruitment of histone modifying enzymes
  • acting specifically to repress BCL6 and thus blocks T follicular helper cell differentiation
  • functions as a global repressor of negative regulators of NFATC1 during osteoclastogenesis
  • acts as a global repressor of multiple anti-osteoclastogenic genes, and it is possible that inhibitors of PRDM1 function may serve as antiresorptive agents by inducing various factors affecting osteoclastogenesis
  • required both in B cells and T cells, but its major impact in B cells is on terminal differentiation of plasma cells, whereas in T cells it seems to be important in the regulation of immune response
  • its expression stabilizes immature photoreceptors by preventing bipolar cell induction
  • plays a crucial role in photoreceptor development by repressing genes involved in bipolar cell fate specification and retinal cell proliferation in differentiating photoreceptor precursors
  • transcriptional repressor required for the differentiation of plasma cells and short-lived effector T cells
  • required for NK-cell maturation and homeostasis and for regulating their proliferative potential
  • PRDM1 and IRF4 jointly control the differentiation and function of effector regulatory T cells
  • PRDM1 and FOXO3 are considered to play an important role in the pathogenesis of NK-cell neoplasms
  • plays important roles in developmental processes, such as of germ cells and hair follicle stem cell
  • key regulator of plasma cell differentiation in B cells and effector/memory function in T cells
  • critical role in the tolerogenic function of dendritic cells and a diminished expression in dendritic cells can result in aberrant activation of the adaptive immune system
  • is a master regulator of gene expression in diverse tissues of the developing embryo and adult organism
  • ETS1 and PRDM1 play opposite roles during plasma cell differentiation, with ETS1 suppressing but PRDM1 promoting the process
  • transcription factor necessary for the generation of plasma cells, and many essential functions of plasma cells are under the control of PRDM1
    • CELLULAR PROCESS cell life, differentiation
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text a pivotal role in plasma-cell differentiation
    PATHWAY
    metabolism
    signaling
  • SUMO pathway critically regulates PRDM1 function during plasma cell differentiation
    • a component
    INTERACTION
    DNA binding specifically to the PRDI (positive regulatory domain I) element in the promoter of the beta-interferon gene
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • PRMT5
  • interacting with BCL6 (BCL6 and PRDM1 are powerful antagonistic master regulators of germinal center B cell differentiation and plasma cell differentiation)
  • binds to IFN-responsive sites in the IDO1 promoter, represses IFN-dependent IDO1 activationand can act in a negative feedback loop to successfully balance the outcome of tolerance vs inflammation)
  • interacting with DNA motifs of interferon regulatory factors (IRFs), which respond to inflammatory/immune signals
  • downstream factor of OTX2, which plays an essential role in photoreceptor cell fate determination
  • can bind to the VSX2 enhancer and repress VSX2 enhancer activity
  • TNFRSF13B promotes sustained PRDM1 expression by B cells responding to antigen, which in turn limits B-cell clonal expansion and facilitates differentiation of long-lived antibody-secreting cells
  • MYC and TNFSF9 are targets of PRDM1 in NK cells
  • is a transcription repressor that is known to negatively regulate the expression of IL2
  • EBF1 acts as a powerful repressor of PRDM1 gene expression in immature B cells
  • multi-faceted role of IRF2 in the function of B cells, particularly B2 cells, through regulating proliferation in an IFNAR-dependent manner and antibody production via up-regulation of PRDM1
  • TNFRSF13B plays an important role in plasma cells and signals PRDM1 expression
  • ZFP36L1 negatively regulates plasmacytoid differentiation, at least in part, by targeting the expression of PRDM1
  • IL21 and CD40LG collaborate through at least two distinct mechanisms to synergistically promote PRDM1 activation and plasma cells (PCs) differentiation
  • very likely directly ETS1 suppresses the expression of PRDM1 in Th1 cells by binding to the EBS2 of the PRDM1 promoter
  • PRDM1-dependent recruitment of TLE4 to the IFNG locus causes epigenetic silencing of the expression of the IFNG gene in anergic TH1 cells
  • represses the expression of PRDM1 encoding BLIMP1 repressor and thereby inhibits terminal differentiation of B cells to plasma cells
  • PRDM1 induced the transcription of immunoglobulin genes and regulated the post-transcriptional expression switch from the membrane-bound form of the immunoglobulin heavy chain to its secreted form by activating ELL2
  • TAX1BP1 restricts ERK activation and PRDM1 expression and regulates germinal center formation
    • cell & other
    REGULATION
    induced by virus
    TNFSF11 through NFATC1
    repressed by BCL6
    Other SUMOylation of PRDM1 regulates its intracellular stability
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    deleted in several B-cell non Hodgkin lymphoma and other cancers
    tumoral somatic mutation      
    in B-cell lymphoma
    tumoral     --other  
    disruption of homeostatic control by PRDM1 may be an important pathogenetic mechanism for natural killer cell lymphoma
    Susceptibility
  • to systemic lupus erythematosus
  • to therapy-induced second malignancies after Hodgkin lymphoma
    • Variant & Polymorphism other
  • variant (rs6568431) identified in an intergenic region between PRDM1 and ATG5 (APG5 autophagy 5-like) associated to to systemic lupus erythematosus
  • variants implicated in the etiology of therapy-induced second malignancies after Hodgkin lymphoma
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • in the Prdm1 conditional knockout (CKO) retina, the number of photoreceptor cells was markedly reduced in the differentiated retina