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FLASH GENE
Symbol SAFB contributors: mct/npt/pgu - updated : 30-11-2018
HGNC name scaffold attachment factor B
HGNC id 10520
DNA
TYPE functioning gene
SPECIAL FEATURE head to head
text
  • separated from SAFB2 by a short GC rich intergenic region that can be a bidirectional promoter containing a SP1 transcription factor binding site
  • STRUCTURE 45.44 kb     21 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (TATA box)
    Binding site   HRE
    text structure
  • imperfect estrogen response element and a TATA box
  • MAPPING cloned Y linked   status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 3018 - 915 - 2006 17081983
    21 - 3121 - 917 - 2006 17081983
    21 - 3118 - 916 - 2006 17081983
    20 - 2914 - 848 - 2006 17081983
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Endocrineparathyroid   highly
    Lymphoid/Immunethymus   highly
    Nervousbrain   moderately Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • rich in charged residues,containing two putative bipartite nuclear localization signals (NLS)
  • SAP domain
  • RNA recognition motif
  • DNA-binding (bihelical) motif
  • C-terminal repression domain (RD)
  • mono polymer monomer
    HOMOLOGY
    intraspecies paralog to SAFB2
    Homologene
    FAMILY
    CATEGORY chaperone/stress , DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • functioning as ESR1 corepressors (they directly interact with ESR1, and repress transcription via repression domains)
  • nuclear matrix protein that may couple chromatin structure, transcription, and RNA processing
  • may direct the reorganization and segregation of nuclear RNA and DNA prior to endonuclease-mediated DNA cleavage
  • like SAFB acts as a negative regulator of a TRA2B variable exon)
  • regulator of SRPK1 and SRPK2 activity underlining the importance of the assembly of transient intranuclear complexes in cellular regulation
  • major role in the activation of SREBF1 through its interaction with RBMX
  • involved in cell cycle regulation, apoptosis, differentiation, and stress response
  • role for SAFB1 in the regulation of immune genes and in estrogen-mediated repression of genes
  • nuclear matrix-associated protein that binds the scaffold or matrix attachment regions (S/MARs) of genomic DNA, as a novel TP53-interacting protein
  • multifunctional protein that binds both nucleic acids and is involved in the attachment of chromatin to the nuclear matrix, transcription, and stress response
  • SAFB and SAFB2 are nuclear matrix binding proteins that have been characterized as ESR1 corepressors
  • SAFB and SAFB2 are crucial repressors for ESR1 dynamics in association with the nuclear matrix and that their synergistic regulation of ESR1 mobility is sufficient for inhibiting ESR1 function
  • primarily associated with transcriptional repression, functions as a positive regulator of myogenic differentiation
  • contributes to the activation of skeletal muscle gene expression during myogenic differentiation by facilitating the transition of promoter sequences from a repressive chromatin structure to one that is transcriptionally permissive
  • undergoing a highly dynamic exchange at damaged chromatin in a PARP1- and poly(ADP-ribose)-dependent manner and is required for unperturbed cell-cycle checkpoint activation and guarding cells against replicative stress
  • chromatin scaffold protein SAFB1 renders chromatin permissive for DNA damage signaling
  • in addition to a role in basal cellular function in the brain, SAFB and SAFB2 proteins may serve as ESR1 corepressors in hormone-sensitive regions
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the DNA damage response
  • formed a complex with the histone methyltransferase EZH2 at AR-interacting chromatin sites in association with other polycomb repressive complex 2 (PRC2) proteins
  • INTERACTION
    DNA binding to HSP27 promoter
    RNA
    small molecule
    protein
  • POLR2A
  • interact with the nuclear receptor corepressor NCOR1, NCOR2
  • interaction with RBMX
  • associate with TP53 through its C-terminal domain
  • ESR1 interacts with both SAFB1 and SAFB2 in the presence of E2
  • bound to AR and phosphorylated by MST1, previously shown to be an AR repressor, and MST1 localization to AR-dependent promoters was inhibited by SAFB depletion
  • cooperates with histone acetylation to allow for efficient gamma H2AX spreading and genotoxic stress signaling
  • ERH interacts directly in the nucleus with the C-terminal Arg-Gly-rich region of SAFB1/2 and co-localizes with it in the insoluble nuclear fraction
  • SAFB and its paralogue, SAFB2, are nuclear matrix-binding proteins that negatively modulate ESR1-mediated transcription
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in breast tumor
    tumoral     --low  
    in prostate carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • intact Wrn protein is required for immortalization and tumorigenesis in Safb1-null mice