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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''C-terminal-binding protein 2''' also known as '''CtBP2''' is a [[protein]] that in humans is encoded by the ''CTBP2'' [[gene]].<ref name="pmid9724649">{{cite journal | vauthors = Turner J, Crossley M | title = Cloning and characterization of mCtBP2, a co-repressor that associates with basic Krüppel-like factor and other mammalian transcriptional regulators | journal = EMBO J. | volume = 17 | issue = 17 | pages = 5129–40 |date=September 1998 | pmid = 9724649 | pmc = 1170841 | doi = 10.1093/emboj/17.17.5129 }}</ref><ref name="pmid11864595">{{cite journal | author = Chinnadurai G | title = CtBP, an unconventional transcriptional corepressor in development and oncogenesis | journal = Mol. Cell | volume = 9 | issue = 2 | pages = 213–24 |date=February 2002 | pmid = 11864595 | doi = 10.1016/S1097-2765(02)00443-4  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CTBP2 C-terminal binding protein 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1488| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
The CtBPs - [[CTBP1|CtBP1]] and CtBP2 in mammals - are among the best characterized transcriptional [[corepressor]]s.<ref name="pmid11494316">{{cite journal | vauthors = Turner J, Crossley M | title = The CtBP family: enigmatic and enzymatic transcriptional co-repressors | journal = BioEssays | volume = 23 | issue = 8 | pages = 683–90 |date=August 2001 | pmid = 11494316 | doi = 10.1002/bies.1097 }}</ref> They typically turn their target genes off. They do this by binding to sequence-specific DNA-binding proteins that carry a short motif of the general form Proline-Isoleucine-Aspartate-Leucine-Serine (the PIDLS motif). They then recruit histone modifying enzymes, [[histone deacetylase]]s, histone [[methylase]]s and histone [[demethylase]]s. These enzymes are thought to work together to remove activating and add repressive histone marks. For example, histone deacetylase 1 ([[HDAC1]]) and [[HDAC2]] can remove the activating mark histone 3 acetyl lysine 9 (H3K9Ac), then the histone methylase [[EHMT2|G9a]] can add methyl groups, while the histone demethylase lysine specific demethylase 1 ([[LSD1]]) can remove the activating mark H3K4me.<ref name="pmid15620353">{{cite journal | vauthors = Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y | title = Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 | journal = Cell | volume = 119 | issue = 7 | pages = 941–53 |date=December 2004 | pmid = 15620353 | doi = 10.1016/j.cell.2004.12.012 }}</ref>
| image = PBB_Protein_CTBP2_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 2ome.
| PDB = {{PDB2|2ome}}
| Name = C-terminal binding protein 2
| HGNCid = 2495
| Symbol = CTBP2
| AltSymbols =;
| OMIM = 602619
| ECnumber = 
| Homologene = 75187
| MGIid = 1201686
| Function = {{GNF_GO|id=GO:0016491 |text = oxidoreductase activity}} {{GNF_GO|id=GO:0016616 |text = oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor}} {{GNF_GO|id=GO:0051287 |text = NAD binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006564 |text = L-serine biosynthetic process}} {{GNF_GO|id=GO:0008152 |text = metabolic process}} {{GNF_GO|id=GO:0008285 |text = negative regulation of cell proliferation}} {{GNF_GO|id=GO:0019079 |text = viral genome replication}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1488
    | Hs_Ensembl = 
    | Hs_RefseqProtein = NP_001320
    | Hs_RefseqmRNA = NM_001329
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 
    | Hs_GenLoc_start = 
    | Hs_GenLoc_end = 
    | Hs_Uniprot = 
    | Mm_EntrezGene = 13017
    | Mm_Ensembl = ENSMUSG00000030970
    | Mm_RefseqmRNA = NM_009980
    | Mm_RefseqProtein = NP_034110
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 7
    | Mm_GenLoc_start = 132825906
    | Mm_GenLoc_end = 132961691
    | Mm_Uniprot = Q3UGL5
  }}
}}
'''C-terminal binding protein 2''', also known as '''CTBP2''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CTBP2 C-terminal binding protein 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1488| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
The CtBPs bind to many different DNA-binding proteins and also bind to co-repressors that are themselves bound to DNA-binding proteins, such as Friend of GATA ([[ZFPM1|Fog]]).<ref name="pmid10329627">{{cite journal | vauthors = Fox AH, Liew C, Holmes M, Kowalski K, Mackay J, Crossley M | title = Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers | journal = EMBO J. | volume = 18 | issue = 10 | pages = 2812–22 |date=May 1999 | pmid = 10329627 | pmc = 1171362 | doi = 10.1093/emboj/18.10.2812 }}</ref> CtBPs can also dimerize and multimerize to bridge larger transcriptional complexes. They appear to be primarily scaffold proteins that allow the assembly of gene repression complexes.
{{PBB_Summary
 
| section_title =  
One interesting aspect of CtBPs is their ability to bind to [[Nicotinamide adenine dinucleotide|NADH]] and to a lesser extent NAD<sup>+</sup>. It has been proposed that this will enable them to sense the metabolic status of the cell and to regulate genes in response to changes in the NADH/NAD<sup>+</sup> ratio. Accordingly, CtBPs have been found to be important in fat biology, binding to key proteins such as [[PRDM16]], [[NRIP1|NRIP]], and [[ZFPM2|FOG2]].<ref name="pmid21281737">{{cite journal | vauthors = Jack BH, Pearson RC, Crossley M | title = C-terminal binding protein: A metabolic sensor implicated in regulating adipogenesis | journal = Int. J. Biochem. Cell Biol. | volume = 43 | issue = 5 | pages = 693–6 |date=May 2011 | pmid = 21281737 | doi = 10.1016/j.biocel.2011.01.017 }}</ref>
| summary_text = This gene produces alternative transcripts encoding two distinct proteins. One protein is a transcriptional repressor, while the other isoform is a major component of specialized synapses known as synaptic ribbons. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. A portion of the 3' untranslated region was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10.<ref name="entrez">{{cite web | title = Entrez Gene: CTBP2 C-terminal binding protein 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1488| accessdate = }}</ref>
 
}}
The full functional roles of CtBP proteins in mammals have been difficult to evaluate because of partial redundancy between CtBP1 and CtBP2.<ref name="pmid12101226">{{cite journal | vauthors = Hildebrand JD, Soriano P | title = Overlapping and unique roles for C-terminal binding protein 1 (CtBP1) and CtBP2 during mouse development | journal = Mol. Cell. Biol. | volume = 22 | issue = 15 | pages = 5296–307 |date=August 2002 | pmid = 12101226 | pmc = 133942 | doi =  10.1128/mcb.22.15.5296-5307.2002}}</ref> Similarly, the early lethality of the CtBP2 knockout and of double knockout mice has precluded detailed analysis of the cellular effects of deleting these proteins. Important results have emerged from model organisms where there is only a single CtBP gene. In ''[[Drosophila]]'' CtBP is involved in development and in [[circadian rhythm]]s.<ref name="pmid23646183">{{cite journal | vauthors = Itoh TQ, Matsumoto A, Tanimura T | title = C-terminal binding protein (CtBP) activates the expression of E-box clock genes with CLOCK/CYCLE in Drosophila | journal = PLoS ONE | volume = 8 | issue = 4 | pages = e63113 | year = 2013 | pmid = 23646183 | pmc = 3640014 | doi = 10.1371/journal.pone.0063113 }}</ref> In the worm ''[[Caenorhabditis elegans|C. elegans]]'' CtBP is involved in life span.<ref name="pmid19164523">{{cite journal | vauthors = Chen S, Whetstine JR, Ghosh S, Hanover JA, Gali RR, Grosu P, Shi Y | title = The conserved NAD(H)-dependent corepressor CTBP-1 regulates Caenorhabditis elegans life span | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 106 | issue = 5 | pages = 1496–501 |date=February 2009 | pmid = 19164523 | pmc = 2635826 | doi = 10.1073/pnas.0802674106 }}</ref> Both circadian rhythms and life span appear to be linked to metabolism supporting the role for CtBPs in metabolic sensing.
 
The mammalian CtBP2 gene produces alternative transcripts encoding two distinct proteins. In addition to the transcriptional repressor ([[corepressor]]) discussed above, there is a longer isoform that is a major component of specialized synapses known as [[ribbon synapse|synaptic ribbon]]s. Both proteins contain a NAD<sup>+</sup> binding domain similar to [[L-2-hydroxycarboxylate dehydrogenase (NAD+)|NAD<sup>+</sup>-dependent 2-hydroxyacid dehydrogenases]]. A portion of the [[three prime untranslated region|3'-untranslated region]] was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10.<ref name="entrez" />
 
==Interactions==
CTBP2 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[FHL3]],<ref name = pmid12556451>{{cite journal | vauthors = Turner J, Nicholas H, Bishop D, Matthews JM, Crossley M | title = The LIM protein FHL3 binds basic Krüppel-like factor/Krüppel-like factor 3 and its co-repressor C-terminal-binding protein 2 | journal = J. Biol. Chem. | volume = 278 | issue = 15 | pages = 12786–95 | year = 2003 | pmid = 12556451 | doi = 10.1074/jbc.M300587200 }}</ref>
* [[KLF3]],<ref name = pmid9724649 /><ref name = pmid12556451/>
* [[KLF8]],<ref name = pmid10756197>{{cite journal | vauthors = van Vliet J, Turner J, Crossley M | title = Human Krüppel-like factor 8: a CACCC-box binding protein that associates with CtBP and represses transcription | journal = Nucleic Acids Res. | volume = 28 | issue = 9 | pages = 1955–62 | year = 2000 | pmid = 10756197 | pmc = 103308 | doi = 10.1093/nar/28.9.1955}}</ref>
* [[Mdm2]],<ref name = pmid12867035>{{cite journal | vauthors = Mirnezami AH, Campbell SJ, Darley M, Primrose JN, Johnson PW, Blaydes JP | title = Hdm2 recruits a hypoxia-sensitive corepressor to negatively regulate p53-dependent transcription | journal = Curr. Biol. | volume = 13 | issue = 14 | pages = 1234–9 | year = 2003 | pmid = 12867035 | doi = 10.1016/S0960-9822(03)00454-8}}</ref>
* [[NRIP1]],<ref name = pmid16189514>{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | year = 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}</ref><ref name = pmid15060175>{{cite journal | vauthors = Castet A, Boulahtouf A, Versini G, Bonnet S, Augereau P, Vignon F, Khochbin S, Jalaguier S, Cavaillès V | title = Multiple domains of the Receptor-Interacting Protein 140 contribute to transcription inhibition | journal = Nucleic Acids Res. | volume = 32 | issue = 6 | pages = 1957–66 | year = 2004 | pmid = 15060175 | pmc = 390375 | doi = 10.1093/nar/gkh524 }}</ref>
* [[SOX6]],<ref name = pmid11504872>{{cite journal | vauthors = Murakami A, Ishida S, Thurlow J, Revest JM, Dickson C | title = SOX6 binds CtBP2 to repress transcription from the Fgf-3 promoter | journal = Nucleic Acids Res. | volume = 29 | issue = 16 | pages = 3347–55 | year = 2001 | pmid = 11504872 | pmc = 55854 | doi = 10.1093/nar/29.16.3347}}</ref>  and
* [[ZFPM2]].<ref name = pmid10438528>{{cite journal | vauthors = Holmes M, Turner J, Fox A, Chisholm O, Crossley M, Chong B | title = hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation | journal = J. Biol. Chem. | volume = 274 | issue = 33 | pages = 23491–8 | year = 1999 | pmid = 10438528 | doi = 10.1074/jbc.274.33.23491}}</ref>  
{{Div col end}}


==References==
==References==
{{reflist|2}}
{{reflist|35em}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin|35em}}
{{PBB_Further_reading
* {{cite journal | vauthors = Schaeper U, Boyd JM, Verma S, Uhlmann E, Subramanian T, Chinnadurai G | title = Molecular cloning and characterization of a cellular phosphoprotein that interacts with a conserved C-terminal domain of adenovirus E1A involved in negative modulation of oncogenic transformation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 92 | issue = 23 | pages = 10467–71 |date=November 1995 | pmid = 7479821 | pmc = 40632 | doi = 10.1073/pnas.92.23.10467 }}
| citations =
* {{cite journal | vauthors = Sewalt RG, Gunster MJ, van der Vlag J, Satijn DP, Otte AP | title = C-Terminal binding protein is a transcriptional repressor that interacts with a specific class of vertebrate Polycomb proteins | journal = Mol. Cell. Biol. | volume = 19 | issue = 1 | pages = 777–87 |date=January 1999 | pmid = 9858600 | pmc = 83934 | doi =  }}
*{{cite journal | author=Chinnadurai G |title=CtBP, an unconventional transcriptional corepressor in development and oncogenesis. |journal=Mol. Cell |volume=9 |issue= 2 |pages= 213-24 |year= 2002 |pmid= 11864595 |doi=  }}
* {{cite journal | vauthors = Furusawa T, Moribe H, Kondoh H, Higashi Y | title = Identification of CtBP1 and CtBP2 as corepressors of zinc finger-homeodomain factor deltaEF1 | journal = Mol. Cell. Biol. | volume = 19 | issue = 12 | pages = 8581–90 |date=December 1999 | pmid = 10567582 | pmc = 84984 | doi = 10.1128/mcb.19.12.8581}}
*{{cite journal  | author=Schaeper U, Boyd JM, Verma S, ''et al.'' |title=Molecular cloning and characterization of a cellular phosphoprotein that interacts with a conserved C-terminal domain of adenovirus E1A involved in negative modulation of oncogenic transformation. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=92 |issue= 23 |pages= 10467-71 |year= 1995 |pmid= 7479821 |doi= }}
* {{cite journal | vauthors = Yu X, Baer R | title = Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor | journal = J. Biol. Chem. | volume = 275 | issue = 24 | pages = 18541–9 |date=June 2000 | pmid = 10764811 | doi = 10.1074/jbc.M909494199 }}
*{{cite journal  | author=Katsanis N, Fisher EM |title=A novel C-terminal binding protein (CTBP2) is closely related to CTBP1, an adenovirus E1A-binding protein, and maps to human chromosome 21q21.3. |journal=Genomics |volume=47 |issue= 2 |pages= 294-9 |year= 1998 |pmid= 9479502 |doi= 10.1006/geno.1997.5115 }}
* {{cite journal | vauthors = Schmitz F, Königstorfer A, Südhof TC | title = RIBEYE, a component of synaptic ribbons: a protein's journey through evolution provides insight into synaptic ribbon function | journal = Neuron | volume = 28 | issue = 3 | pages = 857–72 |date=December 2000 | pmid = 11163272 | doi = 10.1016/S0896-6273(00)00159-8 }}
*{{cite journal  | author=Turner J, Crossley M |title=Cloning and characterization of mCtBP2, a co-repressor that associates with basic Krüppel-like factor and other mammalian transcriptional regulators. |journal=EMBO J. |volume=17 |issue= 17 |pages= 5129-40 |year= 1998 |pmid= 9724649 |doi= 10.1093/emboj/17.17.5129 }}
* {{cite journal | vauthors = Valenta T, Lukas J, Korinek V | title = HMG box transcription factor TCF-4's interaction with CtBP1 controls the expression of the Wnt target Axin2/Conductin in human embryonic kidney cells | journal = Nucleic Acids Res. | volume = 31 | issue = 9 | pages = 2369–80 |date=May 2003 | pmid = 12711682 | pmc = 154232 | doi = 10.1093/nar/gkg346 }}
*{{cite journal | author=Sewalt RG, Gunster MJ, van der Vlag J, ''et al.'' |title=C-Terminal binding protein is a transcriptional repressor that interacts with a specific class of vertebrate Polycomb proteins. |journal=Mol. Cell. Biol. |volume=19 |issue= 1 |pages= 777-87 |year= 1999 |pmid= 9858600 |doi=  }}
* {{cite journal | vauthors = Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW | title = Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation | journal = Nat. Biotechnol. | volume = 22 | issue = 6 | pages = 707–16 |date=June 2004 | pmid = 15146197 | doi = 10.1038/nbt971 }}
*{{cite journal  | author=Holmes M, Turner J, Fox A, ''et al.'' |title=hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation. |journal=J. Biol. Chem. |volume=274 |issue= 33 |pages= 23491-8 |year= 1999 |pmid= 10438528 |doi=  }}
* {{cite journal | vauthors = Alpatov R, Munguba GC, Caton P, Joo JH, Shi Y, Shi Y, Hunt ME, Sugrue SP | title = Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene | journal = Mol. Cell. Biol. | volume = 24 | issue = 23 | pages = 10223–35 |date=December 2004 | pmid = 15542832 | pmc = 529029 | doi = 10.1128/MCB.24.23.10223-10235.2004 }}
*{{cite journal | author=Furusawa T, Moribe H, Kondoh H, Higashi Y |title=Identification of CtBP1 and CtBP2 as corepressors of zinc finger-homeodomain factor deltaEF1. |journal=Mol. Cell. Biol. |volume=19 |issue= 12 |pages= 8581-90 |year= 2000 |pmid= 10567582 |doi= }}
*{{cite journal  | author=van Vliet J, Turner J, Crossley M |title=Human Krüppel-like factor 8: a CACCC-box binding protein that associates with CtBP and represses transcription. |journal=Nucleic Acids Res. |volume=28 |issue= 9 |pages= 1955-62 |year= 2000 |pmid= 10756197 |doi=  }}
*{{cite journal | author=Yu X, Baer R |title=Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor. |journal=J. Biol. Chem. |volume=275 |issue= 24 |pages= 18541-9 |year= 2000 |pmid= 10764811 |doi= 10.1074/jbc.M909494199 }}
*{{cite journal | author=Schmitz F, Königstorfer A, Südhof TC |title=RIBEYE, a component of synaptic ribbons: a protein's journey through evolution provides insight into synaptic ribbon function. |journal=Neuron |volume=28 |issue= 3 |pages= 857-72 |year= 2001 |pmid= 11163272 |doi=  }}
*{{cite journal  | author=Murakami A, Ishida S, Thurlow J, ''et al.'' |title=SOX6 binds CtBP2 to repress transcription from the Fgf-3 promoter. |journal=Nucleic Acids Res. |volume=29 |issue= 16 |pages= 3347-55 |year= 2001 |pmid= 11504872 |doi=  }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Turner J, Nicholas H, Bishop D, ''et al.'' |title=The LIM protein FHL3 binds basic Krüppel-like factor/Krüppel-like factor 3 and its co-repressor C-terminal-binding protein 2. |journal=J. Biol. Chem. |volume=278 |issue= 15 |pages= 12786-95 |year= 2003 |pmid= 12556451 |doi= 10.1074/jbc.M300587200 }}
*{{cite journal | author=Valenta T, Lukas J, Korinek V |title=HMG box transcription factor TCF-4's interaction with CtBP1 controls the expression of the Wnt target Axin2/Conductin in human embryonic kidney cells. |journal=Nucleic Acids Res. |volume=31 |issue= 9 |pages= 2369-80 |year= 2003 |pmid= 12711682 |doi=  }}
*{{cite journal  | author=Mirnezami AH, Campbell SJ, Darley M, ''et al.'' |title=Hdm2 recruits a hypoxia-sensitive corepressor to negatively regulate p53-dependent transcription. |journal=Curr. Biol. |volume=13 |issue= 14 |pages= 1234-9 |year= 2004 |pmid= 12867035 |doi=  }}
*{{cite journal  | author=Castet A, Boulahtouf A, Versini G, ''et al.'' |title=Multiple domains of the Receptor-Interacting Protein 140 contribute to transcription inhibition. |journal=Nucleic Acids Res. |volume=32 |issue= 6 |pages= 1957-66 |year= 2004 |pmid= 15060175 |doi= 10.1093/nar/gkh524 }}
*{{cite journal | author=Brandenberger R, Wei H, Zhang S, ''et al.'' |title=Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. |journal=Nat. Biotechnol. |volume=22 |issue= 6 |pages= 707-16 |year= 2005 |pmid= 15146197 |doi= 10.1038/nbt971 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | author=Alpatov R, Munguba GC, Caton P, ''et al.'' |title=Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene. |journal=Mol. Cell. Biol. |volume=24 |issue= 23 |pages= 10223-35 |year= 2005 |pmid= 15542832 |doi= 10.1128/MCB.24.23.10223-10235.2004 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
==External links==
{{WikiDoc Sources}}
*{{FactorBook|CtBP2}}
* {{UCSC gene info|CTBP2}}
 
{{PDB Gallery|geneid=1488}}
{{Transcription coregulators}}
 
[[Category:Transcription coregulators]]

Latest revision as of 10:09, 30 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
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View/Edit Human

C-terminal-binding protein 2 also known as CtBP2 is a protein that in humans is encoded by the CTBP2 gene.[1][2][3]

Function

The CtBPs - CtBP1 and CtBP2 in mammals - are among the best characterized transcriptional corepressors.[4] They typically turn their target genes off. They do this by binding to sequence-specific DNA-binding proteins that carry a short motif of the general form Proline-Isoleucine-Aspartate-Leucine-Serine (the PIDLS motif). They then recruit histone modifying enzymes, histone deacetylases, histone methylases and histone demethylases. These enzymes are thought to work together to remove activating and add repressive histone marks. For example, histone deacetylase 1 (HDAC1) and HDAC2 can remove the activating mark histone 3 acetyl lysine 9 (H3K9Ac), then the histone methylase G9a can add methyl groups, while the histone demethylase lysine specific demethylase 1 (LSD1) can remove the activating mark H3K4me.[5]

The CtBPs bind to many different DNA-binding proteins and also bind to co-repressors that are themselves bound to DNA-binding proteins, such as Friend of GATA (Fog).[6] CtBPs can also dimerize and multimerize to bridge larger transcriptional complexes. They appear to be primarily scaffold proteins that allow the assembly of gene repression complexes.

One interesting aspect of CtBPs is their ability to bind to NADH and to a lesser extent NAD+. It has been proposed that this will enable them to sense the metabolic status of the cell and to regulate genes in response to changes in the NADH/NAD+ ratio. Accordingly, CtBPs have been found to be important in fat biology, binding to key proteins such as PRDM16, NRIP, and FOG2.[7]

The full functional roles of CtBP proteins in mammals have been difficult to evaluate because of partial redundancy between CtBP1 and CtBP2.[8] Similarly, the early lethality of the CtBP2 knockout and of double knockout mice has precluded detailed analysis of the cellular effects of deleting these proteins. Important results have emerged from model organisms where there is only a single CtBP gene. In Drosophila CtBP is involved in development and in circadian rhythms.[9] In the worm C. elegans CtBP is involved in life span.[10] Both circadian rhythms and life span appear to be linked to metabolism supporting the role for CtBPs in metabolic sensing.

The mammalian CtBP2 gene produces alternative transcripts encoding two distinct proteins. In addition to the transcriptional repressor (corepressor) discussed above, there is a longer isoform that is a major component of specialized synapses known as synaptic ribbons. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. A portion of the 3'-untranslated region was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10.[3]

Interactions

CTBP2 has been shown to interact with:

References

  1. ↑ 1.0 1.1 Turner J, Crossley M (September 1998). "Cloning and characterization of mCtBP2, a co-repressor that associates with basic Krüppel-like factor and other mammalian transcriptional regulators". EMBO J. 17 (17): 5129–40. doi:10.1093/emboj/17.17.5129. PMC 1170841. PMID 9724649.
  2. ↑ Chinnadurai G (February 2002). "CtBP, an unconventional transcriptional corepressor in development and oncogenesis". Mol. Cell. 9 (2): 213–24. doi:10.1016/S1097-2765(02)00443-4. PMID 11864595.
  3. ↑ 3.0 3.1 "Entrez Gene: CTBP2 C-terminal binding protein 2".
  4. ↑ Turner J, Crossley M (August 2001). "The CtBP family: enigmatic and enzymatic transcriptional co-repressors". BioEssays. 23 (8): 683–90. doi:10.1002/bies.1097. PMID 11494316.
  5. ↑ Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y (December 2004). "Histone demethylation mediated by the nuclear amine oxidase homolog LSD1". Cell. 119 (7): 941–53. doi:10.1016/j.cell.2004.12.012. PMID 15620353.
  6. ↑ Fox AH, Liew C, Holmes M, Kowalski K, Mackay J, Crossley M (May 1999). "Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers". EMBO J. 18 (10): 2812–22. doi:10.1093/emboj/18.10.2812. PMC 1171362. PMID 10329627.
  7. ↑ Jack BH, Pearson RC, Crossley M (May 2011). "C-terminal binding protein: A metabolic sensor implicated in regulating adipogenesis". Int. J. Biochem. Cell Biol. 43 (5): 693–6. doi:10.1016/j.biocel.2011.01.017. PMID 21281737.
  8. ↑ Hildebrand JD, Soriano P (August 2002). "Overlapping and unique roles for C-terminal binding protein 1 (CtBP1) and CtBP2 during mouse development". Mol. Cell. Biol. 22 (15): 5296–307. doi:10.1128/mcb.22.15.5296-5307.2002. PMC 133942. PMID 12101226.
  9. ↑ Itoh TQ, Matsumoto A, Tanimura T (2013). "C-terminal binding protein (CtBP) activates the expression of E-box clock genes with CLOCK/CYCLE in Drosophila". PLoS ONE. 8 (4): e63113. doi:10.1371/journal.pone.0063113. PMC 3640014. PMID 23646183.
  10. ↑ Chen S, Whetstine JR, Ghosh S, Hanover JA, Gali RR, Grosu P, Shi Y (February 2009). "The conserved NAD(H)-dependent corepressor CTBP-1 regulates Caenorhabditis elegans life span". Proc. Natl. Acad. Sci. U.S.A. 106 (5): 1496–501. doi:10.1073/pnas.0802674106. PMC 2635826. PMID 19164523.
  11. ↑ 11.0 11.1 Turner J, Nicholas H, Bishop D, Matthews JM, Crossley M (2003). "The LIM protein FHL3 binds basic Krüppel-like factor/Krüppel-like factor 3 and its co-repressor C-terminal-binding protein 2". J. Biol. Chem. 278 (15): 12786–95. doi:10.1074/jbc.M300587200. PMID 12556451.
  12. ↑ van Vliet J, Turner J, Crossley M (2000). "Human Krüppel-like factor 8: a CACCC-box binding protein that associates with CtBP and represses transcription". Nucleic Acids Res. 28 (9): 1955–62. doi:10.1093/nar/28.9.1955. PMC 103308. PMID 10756197.
  13. ↑ Mirnezami AH, Campbell SJ, Darley M, Primrose JN, Johnson PW, Blaydes JP (2003). "Hdm2 recruits a hypoxia-sensitive corepressor to negatively regulate p53-dependent transcription". Curr. Biol. 13 (14): 1234–9. doi:10.1016/S0960-9822(03)00454-8. PMID 12867035.
  14. ↑ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
  15. ↑ Castet A, Boulahtouf A, Versini G, Bonnet S, Augereau P, Vignon F, Khochbin S, Jalaguier S, Cavaillès V (2004). "Multiple domains of the Receptor-Interacting Protein 140 contribute to transcription inhibition". Nucleic Acids Res. 32 (6): 1957–66. doi:10.1093/nar/gkh524. PMC 390375. PMID 15060175.
  16. ↑ Murakami A, Ishida S, Thurlow J, Revest JM, Dickson C (2001). "SOX6 binds CtBP2 to repress transcription from the Fgf-3 promoter". Nucleic Acids Res. 29 (16): 3347–55. doi:10.1093/nar/29.16.3347. PMC 55854. PMID 11504872.
  17. ↑ Holmes M, Turner J, Fox A, Chisholm O, Crossley M, Chong B (1999). "hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation". J. Biol. Chem. 274 (33): 23491–8. doi:10.1074/jbc.274.33.23491. PMID 10438528.

Further reading

External links

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