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FLASH GENE
Symbol SPEN contributors: mct/npt - updated : 06-04-2021
HGNC name spen homolog, transcriptional regulator (Drosophila)
HGNC id 17575
Corresponding disease
DDHSVD developmental delay, hypotonia, seizures, visuel anomalies, deafness
Location 1p36.21      Physical location : 16.174.358 - 16.266.950
Genatlas name Split Ends (SPEN) protein
Synonym name
  • MSX2 interacting nuclear target (MINT) homolog
  • SMRT/HDAC1 associated repressor protein
  • nuclear receptor transcription cofactor
  • SPEN homolog
    • Synonym symbol(s) MINT, KIAA0929, SHARP, RP1-134O19.1, RBM15C
    DNA
    TYPE functioning gene
    STRUCTURE 92.60 kb     15 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 12227 402 3664 - 2007 17474147
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three predicted RNA recognition motifs (RRMs) in the N-terminal region of the protein
  • a repression domain is necessary and sufficient to repress transcription and absence of this domain causes a dominant negative Notch-like phenotype (Oswald 2005)
  • C terminal domain permiting binding to other corepressor protein, and a highly conserved C-terminal SPOC (Spen Paralog and Ortholog C-terminal) domain that, in the case of SPEN, has been shown to interact with SMRT/NCoR corepressors (Hiriart 2005)
    • HOMOLOGY
    Homologene
    FAMILY
  • RNA recognition motif (RRM) split end family of proteins
    • CATEGORY RNA associated , transcription factor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text
  • mislocalization of SPEN in DM1 (myotonic dystrophy), is consistent with increased CRM1-mediated export of SPEN to the cytoplasm
    • basic FUNCTION
  • potent transcriptionnal repressor whose repression domain (RD) interacts directly with NCOR2
  • regulate the expression of key transcriptional effectors in diverse signaling pathways and play an essential role in the repression complex (Ariyoshi 2003)
  • novel component of the HDAC corepressor complex, recruited by RBPJ to repress transcription of target genes in the absence of activated Notch (Oswald 2002)
  • PAK1-SPEN interaction plays an essential role in enhancing the corepressor functions of SPEN, thereby modulating Notch signaling in cancer cells (Vadlamudi 2005)
  • having a a new function related to mRNA export and splicing (Hiriart 2005)
  • important positive regulator of Wnt signaling in cancers with beta-catenin dysregulation (Feng 2007)
  • performs its function as a coactivator by regulating chromatin modification
  • coactivating role for SPEN in activating Notch-dependent genes in differentiating cells
  • antagonize NOTCH1 signaling
  • recruits histone deacetylases
  • is thought to function in processes involving steroid hormone responses and the Notch signaling pathway
  • co-regulator of the nuclear receptors
  • is a key regulator of energy balance
  • role for SPEN in the regulation of primary cilia formation and cell migration in breast cancer cells, which may collectively explain why its expression is associated with time to metastasis in cohorts of patients with ESR1-negative breast cancers )
  • is a nucleic acid-binding protein putatively involved in repression of gene expression
  • SPEN acts as a molecular integrator for the initiation of X-chromosome inactivation (XCI), bridging XIST RNA with the transcription machinery-as well as with nucleosome remodellers and histone deacetylases-at active enhancers and promoters
  • is required for multiple developmental processes
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • SPEN forms a high affinity complex with RBPJ
    • INTERACTION
    DNA
    RNA
    small molecule other,
    protein
  • NCOR2
  • HDAC1
  • HDAC2
  • PAK1-interacting protein (interaction enhancing SPEN-mediated repression of Notch target genes)(Vadlamudi 2005)
  • interaction with the Epstein-Barr virus mRNA export factor EB2 (Hiriart 2005)
  • interacting with AML1/ETO (RUNX1/RUNX1T1) directly (ETO, but not AML1/ETO, augments SPEN-mediated repression in an histone deacetylase-dependent manner) (Salat 2008)
  • phosphorylation of the CSNK2A1 site on NCOR2 significantly increased affinity for SPEN
  • SPEN association with SRA1 relies on both single- and double-stranded RNA sequences
  • SPEN is required for gene repression by XIST
  • associations of SPEN with MTA1 (metastasis-associated 1), a member of the nucleosome remodeling complex with histone deacetylase activity, which might contribute to interactions of SPEN with chromatin
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DDHSVD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colon and ovarian endometrioid adenocarcinomas (Feng 2007)
    constitutional     --other  
    mislocalization of SPEN in DM1 (myotonic dystrophy), is consistent with increased CRM1-mediated export of SPEN to the cytoplasm
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • SPEN is likely a novel tumor-suppressor gene that may be clinically useful as a predictive biomarker of tamoxifen response in ESR1-positive breast cancers
    • Therapy target
    ANIMAL & CELL MODELS