Transcriptional repressor CTCF

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• chromatin binding Source: RGDInferred from sequence orthologyⁱ
  • "Genome-wide and parental allele-specific analysis of CTCF and cohesin DNA binding in mouse brain reveals a tissue-specific binding pattern and an association with imprinted differentially methylated regions."
    Prickett A.R., Barkas N., McCole R.B., Hughes S., Amante S.M., Schulz R., Oakey R.J.
    Genome Res. 23:1624-1635(2013) [PubMed] [Europe PMC] [Abstract]
  • "Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors."
    Wajapeyee N., Malonia S.K., Palakurthy R.K., Green M.R.
    Genes Dev. 27:2221-2226(2013) [PubMed] [Europe PMC] [Abstract]
• chromatin insulator sequence binding Source: RGDInferred from sequence orthologyⁱ
  • "Critical DNA binding interactions of the insulator protein CTCF: a small number of zinc fingers mediate strong binding, and a single finger-DNA interaction controls binding at imprinted loci."
    Renda M., Baglivo I., Burgess-Beusse B., Esposito S., Fattorusso R., Felsenfeld G., Pedone P.V.
    J. Biol. Chem. 282:33336-33345(2007) [PubMed] [Europe PMC] [Abstract]
• DNA binding Source: RGDInferred from sequence orthologyⁱ
  • "CTCF, a candidate trans-acting factor for X-inactivation choice."
    Chao W., Huynh K.D., Spencer R.J., Davidow L.S., Lee J.T.
    Science 295:345-347(2002) [PubMed] [Europe PMC] [Abstract]
  • "CTCF maintains differential methylation at the Igf2/H19 locus."
    Schoenherr C.J., Levorse J.M., Tilghman S.M.
    Nat. Genet. 33:66-69(2003) [PubMed] [Europe PMC] [Abstract]
  • "Role of CTCF binding sites in the Igf2/H19 imprinting control region."
    Szabo P.E., Tang S.H., Silva F.J., Tsark W.M., Mann J.R.
    Mol. Cell. Biol. 24:4791-4800(2004) [PubMed] [Europe PMC] [Abstract]
  • "An antisense RNA regulates the bidirectional silencing property of the Kcnq1 imprinting control region."
    Thakur N., Tiwari V.K., Thomassin H., Pandey R.R., Kanduri M., Gondor A., Grange T., Ohlsson R., Kanduri C.
    Mol. Cell. Biol. 24:7855-7862(2004) [PubMed] [Europe PMC] [Abstract]
• DNA-binding transcription activator activity, RNA polymerase II-specific Source: RGDInferred from sequence orthologyⁱ
  • "Cohesin regulates tissue-specific expression by stabilizing highly occupied cis-regulatory modules."
    Faure A.J., Schmidt D., Watt S., Schwalie P.C., Wilson M.D., Xu H., Ramsay R.G., Odom D.T., Flicek P.
    Genome Res. 22:2163-2175(2012) [PubMed] [Europe PMC] [Abstract]
• DNA-binding transcription factor activity Source: RGDInferred from sequence orthologyⁱ
  • "An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes."
    Filippova G.N., Fagerlie S., Klenova E.M., Myers C., Dehner Y., Goodwin G., Neiman P.E., Collins S.J., Lobanenkov V.V.
    Mol. Cell. Biol. 16:2802-2813(1996) [PubMed] [Europe PMC] [Abstract]
  • "A widely expressed transcription factor with multiple DNA sequence specificity, CTCF, is localized at chromosome segment 16q22.1 within one of the smallest regions of overlap for common deletions in breast and prostate cancers."
    Filippova G.N., Lindblom A., Meincke L.J., Klenova E.M., Neiman P.E., Collins S.J., Doggett N.A., Lobanenkov V.V.
    Genes Chromosomes Cancer 22:26-36(1998) [PubMed] [Europe PMC] [Abstract]
• DNA-binding transcription repressor activity, RNA polymerase II-specific Source: RGDInferred from sequence orthologyⁱ
  • "An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes."
    Filippova G.N., Fagerlie S., Klenova E.M., Myers C., Dehner Y., Goodwin G., Neiman P.E., Collins S.J., Lobanenkov V.V.
    Mol. Cell. Biol. 16:2802-2813(1996) [PubMed] [Europe PMC] [Abstract]
• metal ion binding Source: UniProtKB-KW
• RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: RGDInferred from sequence orthologyⁱ
  • "An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes."
    Filippova G.N., Fagerlie S., Klenova E.M., Myers C., Dehner Y., Goodwin G., Neiman P.E., Collins S.J., Lobanenkov V.V.
    Mol. Cell. Biol. 16:2802-2813(1996) [PubMed] [Europe PMC] [Abstract]
• sequence-specific DNA binding Source: RGDInferred from sequence orthologyⁱ
  • "An evolutionarily conserved putative insulator element near the 3' boundary of the imprinted Igf2/H19 domain."
    Ishihara K., Sasaki H.
    Hum. Mol. Genet. 11:1627-1636(2002) [PubMed] [Europe PMC] [Abstract]
  • "Critical DNA binding interactions of the insulator protein CTCF: a small number of zinc fingers mediate strong binding, and a single finger-DNA interaction controls binding at imprinted loci."
    Renda M., Baglivo I., Burgess-Beusse B., Esposito S., Fattorusso R., Felsenfeld G., Pedone P.V.
    J. Biol. Chem. 282:33336-33345(2007) [PubMed] [Europe PMC] [Abstract]
• transcription regulatory region DNA binding Source: RGDInferred from sequence orthologyⁱ
  • "DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation."
    Sun L., Huang L., Nguyen P., Bisht K.S., Bar-Sela G., Ho A.S., Bradbury C.M., Yu W., Cui H., Lee S., Trepel J.B., Feinberg A.P., Gius D.
    Cancer Res. 68:2726-2735(2008) [PubMed] [Europe PMC] [Abstract]

GO - Biological processⁱ

• chromosome segregation Source: UniProtKB-KW
• DNA methylation Source: RGDInferred from sequence orthologyⁱ
  • "CTCF maintains differential methylation at the Igf2/H19 locus."
    Schoenherr C.J., Levorse J.M., Tilghman S.M.
    Nat. Genet. 33:66-69(2003) [PubMed] [Europe PMC] [Abstract]
  • "Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors."
    Wajapeyee N., Malonia S.K., Palakurthy R.K., Green M.R.
    Genes Dev. 27:2221-2226(2013) [PubMed] [Europe PMC] [Abstract]
• maintenance of DNA methylation Source: RGDInferred from sequence orthologyⁱ
  • "Transgenic RNAi reveals essential function for CTCF in H19 gene imprinting."
    Fedoriw A.M., Stein P., Svoboda P., Schultz R.M., Bartolomei M.S.
    Science 303:238-240(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cell population proliferation Source: UniProtKB
• negative regulation of gene expression Source: RGDInferred from sequence orthologyⁱ
  • "Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development."
    Wan L.-B., Pan H., Hannenhalli S., Cheng Y., Ma J., Fedoriw A., Lobanenkov V., Latham K.E., Schultz R.M., Bartolomei M.S.
    Development 135:2729-2738(2008) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription, DNA-templated Source: RGDInferred from sequence orthologyⁱ
  • "DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation."
    Sun L., Huang L., Nguyen P., Bisht K.S., Bar-Sela G., Ho A.S., Bradbury C.M., Yu W., Cui H., Lee S., Trepel J.B., Feinberg A.P., Gius D.
    Cancer Res. 68:2726-2735(2008) [PubMed] [Europe PMC] [Abstract]
  • "An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes."
    Filippova G.N., Fagerlie S., Klenova E.M., Myers C., Dehner Y., Goodwin G., Neiman P.E., Collins S.J., Lobanenkov V.V.
    Mol. Cell. Biol. 16:2802-2813(1996) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription by RNA polymerase II Source: RGDInferred from sequence orthologyⁱ
  • "Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors."
    Wajapeyee N., Malonia S.K., Palakurthy R.K., Green M.R.
    Genes Dev. 27:2221-2226(2013) [PubMed] [Europe PMC] [Abstract]
  • "An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes."
    Filippova G.N., Fagerlie S., Klenova E.M., Myers C., Dehner Y., Goodwin G., Neiman P.E., Collins S.J., Lobanenkov V.V.
    Mol. Cell. Biol. 16:2802-2813(1996) [PubMed] [Europe PMC] [Abstract]
• nucleosome positioning Source: RGDInferred from sequence orthologyⁱ
  • "The insulator binding protein CTCF positions 20 nucleosomes around its binding sites across the human genome."
    Fu Y., Sinha M., Peterson C.L., Weng Z.
    PLoS Genet. 4:E1000138-E1000138(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of gene expression Source: RGDInferred from sequence orthologyⁱ
  • "The insulator factor CTCF controls MHC class II gene expression and is required for the formation of long-distance chromatin interactions."
    Majumder P., Gomez J.A., Chadwick B.P., Boss J.M.
    J. Exp. Med. 205:785-798(2008) [PubMed] [Europe PMC] [Abstract]
  • "Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development."
    Wan L.-B., Pan H., Hannenhalli S., Cheng Y., Ma J., Fedoriw A., Lobanenkov V., Latham K.E., Schultz R.M., Bartolomei M.S.
    Development 135:2729-2738(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of pri-miRNA transcription by RNA polymerase II Source: BHF-UCL <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Identification of miR-34 regulatory networks in settings of disease and antimiR-therapy: Implications for treating cardiac pathology and other diseases."
    Ooi J.Y.Y., Bernardo B.C., Singla S., Patterson N.L., Lin R.C.Y., McMullen J.R.
    RNA Biol 14:500-513(2017) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription, DNA-templated Source: RGDInferred from sequence orthologyⁱ
  • "Architectural roles of multiple chromatin insulators at the human apolipoprotein gene cluster."
    Mishiro T., Ishihara K., Hino S., Tsutsumi S., Aburatani H., Shirahige K., Kinoshita Y., Nakao M.
    EMBO J. 28:1234-1245(2009) [PubMed] [Europe PMC] [Abstract]
  • "The zinc finger protein CTCF binds to the APBbeta domain of the amyloid beta-protein precursor promoter. Evidence for a role in transcriptional activation."
    Vostrov A.A., Quitschke W.W.
    J. Biol. Chem. 272:33353-33359(1997) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription by RNA polymerase II Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• protein localization to chromosome, centromeric region Source: UniProtKB
• regulation of gene expression, epigenetic Source: RGDInferred from sequence orthologyⁱ
  • "CTCF binding at the H19 imprinting control region mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to Igf2."
    Kurukuti S., Tiwari V.K., Tavoosidana G., Pugacheva E., Murrell A., Zhao Z., Lobanenkov V., Reik W., Ohlsson R.
    Proc. Natl. Acad. Sci. U.S.A. 103:10684-10689(2006) [PubMed] [Europe PMC] [Abstract]
• regulation of gene expression by genetic imprinting Source: RGDInferred from sequence orthologyⁱ
  • "CTCF maintains differential methylation at the Igf2/H19 locus."
    Schoenherr C.J., Levorse J.M., Tilghman S.M.
    Nat. Genet. 33:66-69(2003) [PubMed] [Europe PMC] [Abstract]
  • "Transgenic RNAi reveals essential function for CTCF in H19 gene imprinting."
    Fedoriw A.M., Stein P., Svoboda P., Schultz R.M., Bartolomei M.S.
    Science 303:238-240(2004) [PubMed] [Europe PMC] [Abstract]
  • "Role of CTCF binding sites in the Igf2/H19 imprinting control region."
    Szabo P.E., Tang S.H., Silva F.J., Tsark W.M., Mann J.R.
    Mol. Cell. Biol. 24:4791-4800(2004) [PubMed] [Europe PMC] [Abstract]
• regulation of histone acetylation Source: RGDInferred from sequence orthologyⁱ
  • "CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus."
    Splinter E., Heath H., Kooren J., Palstra R.-J., Klous P., Grosveld F., Galjart N., de Laat W.
    Genes Dev. 20:2349-2354(2006) [PubMed] [Europe PMC] [Abstract]
• regulation of histone methylation Source: RGDInferred from sequence orthologyⁱ
  • "CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus."
    Splinter E., Heath H., Kooren J., Palstra R.-J., Klous P., Grosveld F., Galjart N., de Laat W.
    Genes Dev. 20:2349-2354(2006) [PubMed] [Europe PMC] [Abstract]
• regulation of molecular function, epigenetic Source: RGDInferred from sequence orthologyⁱ
  • "CTCF binding at the H19 imprinting control region mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to Igf2."
    Kurukuti S., Tiwari V.K., Tavoosidana G., Pugacheva E., Murrell A., Zhao Z., Lobanenkov V., Reik W., Ohlsson R.
    Proc. Natl. Acad. Sci. U.S.A. 103:10684-10689(2006) [PubMed] [Europe PMC] [Abstract]
• regulation of transcription, DNA-templated Source: RGDInferred from sequence orthologyⁱ
  • "Role of CTCF binding sites in the Igf2/H19 imprinting control region."
    Szabo P.E., Tang S.H., Silva F.J., Tsark W.M., Mann J.R.
    Mol. Cell. Biol. 24:4791-4800(2004) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

Keywords - Diseaseⁱ

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Compositional bias

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Zinc finger

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

        10         20         30         40         50
MEGEAVEAIV EESETFIKGK ERKTYQRRRE GGQEEDACHL PQNQTDGGEV 
        60         70         80         90        100
VQDVNSSVQM VMMEQLDPTL LQMKTEVMEG TVAPEAEAAV DDTQIITLQV 
       110        120        130        140        150
VNMEEQPINI GELQLVQVPV PVTVPVATTS VEELQGAYEN EVSKEGLAES 
       160        170        180        190        200
EPMICHTLPL PEGFQVVKVG ANGEVETLEQ GELPPQEDPS WQKDPDYQPP 
       210        220        230        240        250
AKKTKKTKKS KLRYTEEGKD VDVSVYDFEE EQQEGLLSEV NAEKVVGNMK 
       260        270        280        290        300
PPKPTKIKKK GVKKTFQCEL CSYTCPRRSN LDRHMKSHTD ERPHKCHLCG 
       310        320        330        340        350
RAFRTVTLLR NHLNTHTGTR PHKCPDCDMA FVTSGELVRH RRYKHTHEKP 
       360        370        380        390        400
FKCSMCDYAS VEVSKLKRHI RSHTGERPFQ CSLCSYASRD TYKLKRHMRT 
       410        420        430        440        450
HSGEKPYECY ICHARFTQSG TMKMHILQKH TENVAKFHCP HCDTVIARKS 
       460        470        480        490        500
DLGVHLRKQH SYIEQGKKCR YCDAVFHERY ALIQHQKSHK NEKRFKCDQC 
       510        520        530        540        550
DYACRQERHM IMHKRTHTGE KPYACSHCDK TFRQKQLLDM HFKRYHDPNF 
       560        570        580        590        600
VPAAFVCSKC GKTFTRRNTM ARHADNCAGP DGVEGENGGE TKKSKRGRKR 
       610        620        630        640        650
KMRSKKEDSS DSENAEPDLD DNEEEEEPAV EIEPEPEPQP QPQPQPQPQP 
       660        670        680        690        700
VAPAPPPAKK RRGRPPGRTN QPKQNQPTAI IQVEDQNTGA IENIIVEVKK 
       710        720        730 
EPDAEPAEGE EEEAQAAPAD APNGDLTPEM ILSMMDR               

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. SIMILARITY comments
   Index of protein domains and families