This gene encodes a hormone inducible transcriptional repressor. Repression of transcription by this gene product can occur through interactions with other repressors, by the recruitment of proteins involved in histone deacetylation, or through sequestration of transcriptional activators. The product of this gene contains a carboxy-terminal domain that permits binding to other ... See more...

Aliases for SPEN Gene

Aliases for SPEN Gene

  • Spen Family Transcriptional Repressor 2 3 5
  • SMART/HDAC1-Associated Repressor Protein 3 4
  • Msx2-Interacting Protein 3 4
  • SHARP 3 4
  • MINT 3 4
  • SPEN Homolog, Transcriptional Regulator (Drosophila) 2
  • Spen Homolog, Transcriptional Regulator (Drosophila) 2
  • Msx2 Interacting Nuclear Target (MINT) Homolog 3
  • Nuclear Receptor Transcription Cofactor 3
  • Spen Homolog, Transcriptional Regulator 3
  • SPEN Homolog 4
  • HIAA0929 3
  • KIAA0929 4
  • RBM15C 3

External Ids for SPEN Gene

Previous GeneCards Identifiers for SPEN Gene

  • GC01P015920
  • GC01P016047
  • GC01P016174
  • GC01P014692

Summaries for SPEN Gene

Entrez Gene Summary for SPEN Gene

  • This gene encodes a hormone inducible transcriptional repressor. Repression of transcription by this gene product can occur through interactions with other repressors, by the recruitment of proteins involved in histone deacetylation, or through sequestration of transcriptional activators. The product of this gene contains a carboxy-terminal domain that permits binding to other corepressor proteins. This domain also permits interaction with members of the NuRD complex, a nucleosome remodeling protein complex that contains deacetylase activity. In addition, this repressor contains several RNA recognition motifs that confer binding to a steroid receptor RNA coactivator; this binding can modulate the activity of both liganded and nonliganded steroid receptors. [provided by RefSeq, Jul 2008]

GeneCards Summary for SPEN Gene

SPEN (Spen Family Transcriptional Repressor) is a Protein Coding gene. Diseases associated with SPEN include Acneiform Dermatitis and Bartter Syndrome, Type 3. Among its related pathways are Notch Signaling Pathway (WikiPathways) and Notch-mediated HES/HEY network. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and DNA-binding transcription factor activity. An important paralog of this gene is RBM15.

UniProtKB/Swiss-Prot Summary for SPEN Gene

  • May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA.

Gene Wiki entry for SPEN Gene

Additional gene information for SPEN Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SPEN Gene

Genomics for SPEN Gene

GeneHancer (GH) Regulatory Elements for SPEN Gene

Promoters and enhancers for SPEN Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SPEN on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SPEN gene promoter:
  • aMEF-2
  • HNF-1
  • HNF-1A
  • HSF2
  • MEF-2A
  • p53
  • Pax-4a
  • Pax-5
  • ZIC2

Genomic Locations for SPEN Gene

Genomic Locations for SPEN Gene
chr1:15,847,707-15,940,456
(GRCh38/hg38)
Size:
92,750 bases
Orientation:
Plus strand
chr1:16,174,359-16,266,955
(GRCh37/hg19)
Size:
92,597 bases
Orientation:
Plus strand

Genomic View for SPEN Gene

Genes around SPEN on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SPEN Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SPEN Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SPEN Gene

Proteins for SPEN Gene

  • Protein details for SPEN Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96T58-MINT_HUMAN
    Recommended name:
    Msx2-interacting protein
    Protein Accession:
    Q96T58
    Secondary Accessions:
    • Q9H9A8
    • Q9NWH5
    • Q9UQ01
    • Q9Y556

    Protein attributes for SPEN Gene

    Size:
    3664 amino acids
    Molecular mass:
    402248 Da
    Quaternary structure:
    • Interacts with MSX2 and HIPK3 (By similarity). Interacts with NCOR2, HDAC1, HDAC2, RBBP4, MBD3 and MTA1L1. Interacts with RBPSUH; this interaction may prevent the interaction between RBPSUH and NOTCH1. Interacts with the nuclear receptors RAR and PPARD. Interacts with RAR in absence of ligand. Binds to the steroid receptor RNA coactivator SRA.
    • (Microbial infection) Interacts with Epstein-Barr virus BSFL2/BMLF1.
    SequenceCaution:
    • Sequence=BAA91405.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAB14324.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAB51072.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for SPEN Gene

neXtProt entry for SPEN Gene

Post-translational modifications for SPEN Gene

  • Ubiquitination at Lys1293, Lys1308, Lys1361, Lys1430, Lys1445, Lys1864, Lys2617, Lys2680, Lys2967, and Lys2971
  • Modification sites at PhosphoSitePlus

Other Protein References for SPEN Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SPEN Gene

Domains & Families for SPEN Gene

Gene Families for SPEN Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Plasma proteins
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for SPEN Gene

GenScript: Design optimal peptide antigens:
  • SPEN homolog (MINT_HUMAN)
  • Spen homolog, transcriptional regulator (Drosophila) (Q5VVE2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96T58

UniProtKB/Swiss-Prot:

MINT_HUMAN :
  • The RID domain mediates the interaction with nuclear receptors.
  • Belongs to the RRM Spen family.
Domain:
  • The RID domain mediates the interaction with nuclear receptors.
  • The SPOC domain, which mediates the interaction with NCOR2, is essential for the repressive activity.
Family:
  • Belongs to the RRM Spen family.
genes like me logo Genes that share domains with SPEN: view

Function for SPEN Gene

Molecular function for SPEN Gene

UniProtKB/Swiss-Prot Function:
May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA.
UniProtKB/Swiss-Prot Induction:
By 17-beta-estradiol.

Phenotypes From GWAS Catalog for SPEN Gene

Gene Ontology (GO) - Molecular Function for SPEN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001085 RNA polymerase II transcription factor binding IPI 16287852
GO:0003676 nucleic acid binding IEA --
GO:0003677 DNA binding IEA --
GO:0003714 transcription corepressor activity IDA 16287852
GO:0003723 RNA binding IEA,HDA 22658674
genes like me logo Genes that share ontologies with SPEN: view
genes like me logo Genes that share phenotypes with SPEN: view

Animal Models for SPEN Gene

MGI Knock Outs for SPEN:

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SPEN Gene

Localization for SPEN Gene

Subcellular locations from UniProtKB/Swiss-Prot for SPEN Gene

Nucleus. Note=Associates with chromatin.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SPEN gene
Compartment Confidence
nucleus 5
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for SPEN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm IDA --
GO:0017053 transcriptional repressor complex IDA 16287852
GO:0070062 extracellular exosome HDA 19056867
genes like me logo Genes that share ontologies with SPEN: view

Pathways & Interactions for SPEN Gene

genes like me logo Genes that share pathways with SPEN: view

Pathways by source for SPEN Gene

1 R&D Systems pathway for SPEN Gene

SIGNOR curated interactions for SPEN Gene

Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for SPEN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 16287852
GO:0007219 Notch signaling pathway IEA --
GO:0016032 viral process IEA --
GO:0045892 negative regulation of transcription, DNA-templated IDA 16129689
GO:0050769 positive regulation of neurogenesis IMP 16287852
genes like me logo Genes that share ontologies with SPEN: view

Drugs & Compounds for SPEN Gene

(1) Additional Compounds for SPEN Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with SPEN: view

Transcripts for SPEN Gene

mRNA/cDNA for SPEN Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SPEN Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b · 4c ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19a · 19b
SP1: - -
SP2: - -
SP3:
SP4: -
SP5: - -
SP6:
SP7:

Relevant External Links for SPEN Gene

GeneLoc Exon Structure for
SPEN
ECgene alternative splicing isoforms for
SPEN

Expression for SPEN Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SPEN Gene

Protein differential expression in normal tissues from HIPED for SPEN Gene

This gene is overexpressed in Urinary Bladder (30.7), Gallbladder (10.7), and Cervix (8.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SPEN Gene



NURSA nuclear receptor signaling pathways regulating expression of SPEN Gene:

SPEN

SOURCE GeneReport for Unigene cluster for SPEN Gene:

Hs.744843

mRNA Expression by UniProt/SwissProt for SPEN Gene:

Q96T58-MINT_HUMAN
Tissue specificity: Expressed at high level in brain, testis, spleen and thymus. Expressed at intermediate level in kidney, liver, mammary gland and skin.

Evidence on tissue expression from TISSUES for SPEN Gene

  • Nervous system(4.6)
  • Liver(4.5)
  • Blood(2.4)
  • Heart(2.3)
  • Intestine(2.3)
  • Lung(2.2)
  • Skin(2.1)
  • Muscle(2)
genes like me logo Genes that share expression patterns with SPEN: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for SPEN Gene

Orthologs for SPEN Gene

This gene was present in the common ancestor of animals.

Orthologs for SPEN Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SPEN 33 32
  • 99.15 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SPEN 33 32
  • 87.41 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SPEN 33 32
  • 86.6 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SPEN 33
  • 82 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Spen 17 33 32
  • 81.01 (n)
rat
(Rattus norvegicus)
Mammalia LOC690911 32
  • 80.88 (n)
oppossum
(Monodelphis domestica)
Mammalia SPEN 33
  • 70 (a)
OneToOne
chicken
(Gallus gallus)
Aves SPEN 33
  • 69 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SPEN 33
  • 64 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii spen 33
  • 47 (a)
OneToMany
SPEN (2 of 2) 33
  • 42 (a)
OneToMany
-- 32
fruit fly
(Drosophila melanogaster)
Insecta spen 33
  • 10 (a)
OneToOne
Species where no ortholog for SPEN was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SPEN Gene

ENSEMBL:
Gene Tree for SPEN (if available)
TreeFam:
Gene Tree for SPEN (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SPEN: view image

Paralogs for SPEN Gene

Paralogs for SPEN Gene

(1) SIMAP similar genes for SPEN Gene using alignment to 3 proteins:

  • MINT_HUMAN
  • F6WRY4_HUMAN
  • H0Y5U7_HUMAN
genes like me logo Genes that share paralogs with SPEN: view

Variants for SPEN Gene

Sequence variations from dbSNP and Humsavar for SPEN Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs869312174 uncertain-significance, Ductal breast carcinoma 15,933,237(+) CAGAAAACAACCCGATCA/CA coding_sequence_variant, frameshift
VAR_035483 A breast cancer sample p.Asp990His
VAR_035484 A breast cancer sample p.Arg1488Ile
rs751475729 uncertain-significance, not provided 15,928,434(+) C/A/T coding_sequence_variant, stop_gained, synonymous_variant
rs374383017 uncertain-significance, not specified 15,935,971(+) CCCCC/CCCCCC/CCCCCCCCCCCCCC/CCCCCCCCCCCTCCCCC coding_sequence_variant, frameshift, inframe_insertion

Structural Variations from Database of Genomic Variants (DGV) for SPEN Gene

Variant ID Type Subtype PubMed ID
dgv37n100 CNV gain 25217958
dgv38n100 CNV gain 25217958
esv22591 CNV gain 19812545
esv2665696 CNV deletion 23128226
esv2668319 CNV deletion 23128226
esv2744352 CNV deletion 23290073
esv2764241 CNV loss 21179565
esv3585322 CNV loss 21293372
nsv1011969 CNV gain+loss 25217958
nsv1012917 CNV loss 25217958
nsv1133814 CNV deletion 24896259
nsv3409 CNV deletion 18451855
nsv478397 CNV novel sequence insertion 20440878
nsv508936 CNV insertion 20534489
nsv829559 CNV loss 20364138
nsv833647 CNV loss 17160897
nsv954843 CNV deletion 24416366

Variation tolerance for SPEN Gene

Residual Variation Intolerance Score: 0.428% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.96; 79.88% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SPEN Gene

Human Gene Mutation Database (HGMD)
SPEN
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SPEN

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SPEN Gene

Disorders for SPEN Gene

MalaCards: The human disease database

(2) MalaCards diseases for SPEN Gene - From: HGMD and DISEASES

Disorder Aliases PubMed IDs
acneiform dermatitis
  • dermatitis acneiform
bartter syndrome, type 3
  • barts3
- elite association - COSMIC cancer census association via MalaCards
Search SPEN in MalaCards View complete list of genes associated with diseases

Additional Disease Information for SPEN

genes like me logo Genes that share disorders with SPEN: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SPEN Gene

Publications for SPEN Gene

  1. Sharp, an inducible cofactor that integrates nuclear receptor repression and activation. (PMID: 11331609) Shi Y … Evans RM (Genes & development 2001) 2 3 4 23 56
  2. Interaction of the Epstein-Barr virus mRNA export factor EB2 with human Spen proteins SHARP, OTT1, and a novel member of the family, OTT3, links Spen proteins with splicing regulation and mRNA export. (PMID: 16129689) Hiriart E … Manet E (The Journal of biological chemistry 2005) 3 4 23 56
  3. A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling. (PMID: 12897056) Ariyoshi M … Schwabe JW (Genes & development 2003) 3 4 23 56
  4. The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling. (PMID: 11867749) Shi Y … Evans RM (Proceedings of the National Academy of Sciences of the United States of America 2002) 3 4 23 56
  5. Drosophila split ends homologue SHARP functions as a positive regulator of Wnt/beta-catenin/T-cell factor signaling in neoplastic transformation. (PMID: 17234755) Feng Y … Fearon ER (Cancer research 2007) 3 23 56

Products for SPEN Gene

Sources for SPEN Gene