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FLASH GENE
Symbol CTBP1 contributors: mct - updated : 11-06-2015
HGNC name C-terminal binding protein 1
HGNC id 2494
DNA
TYPE functioning gene
STRUCTURE 37.68 kb     10 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 2288 - 440 - 2008 18361917
10 - 2483 - 429 - 2008 18361917
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrinepancreas    
Hearing/Equilibriumearinnercochlea highly
Lymphoid/Immunelymph node   highly
Nervousnervecranial nerve  highly
Reproductivemale systemprostate   
Respiratorylung    
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a PXDLS-binding site, involved in the interaction between CTBP1 and SIMC1
  • conjugated PhosphoP
    mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine Ctbp1 (98.9pc)
    homolog to C.elegans F49e10.5
    homolog to rattus Ctbp1 (98.6pc)
    intraspecies homolog to CTBP2
    Homologene
    FAMILY
  • d-isomer specific 2-hydroxyacid dehydrogenases family
  • CATEGORY transcription factor , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,chromatin/chromosome
    text
  • restricted to nuclear speckles and co-localized with GLIS2
  • LCOR and CTBP1 colocalize in nuclear bodies
  • basic FUNCTION
  • transcriptional repressor in a histone acetylase dependent or independent manner
  • playing a role during cellular proliferation, adenovirus replication and oncogenic transformation
  • negative control of cell proliferation
  • involved in controlling the equilibrium between tubular and stacked structures in the Golgi complex
  • dehydrogenase activity
  • attenuates KLF4-mediated transcriptional activation through the physical interaction with KLF4
  • can interact with a polycomb group protein complex which participates in regulation of gene expression during development
  • acts in the nucleus as transcriptional corepressor and in the cytoplasm as regulators of Golgi apparatus fission
  • promotes cell survival through the maintenance of mitotic fidelity
  • corepressor that regulates transcription of the CYP17 gene by periodically interacting with steroidogenic factor-1 in response to ACTH signaling
  • transcriptional corepressor with tumorigenic potential that targets the promoter of the tumor suppressor gene E-cadherin
  • can recruit PNN to CTBP-associated complexes, resulting in Pnn-dependent chromatin remodeling at the E-cadherin promoter
  • is required for macropinocytic internalization and infection of ectovirus 1
  • target of PAK1 and is bifunctionally involved in membrane traffic and transcriptional repression of cell cycle, cancer, and innate immunity pathways
  • role for LCOR and CTBP1 as attenuators of progesterone-regulated transcription, suggesting that LCOR and CTBP1 can act to enhance transcription of some genes
  • central role to control the actions of many transcriptional factors, in large part, by recruitment and activation of a range of chromatin remodeling enzymes
  • transcriptional co-repressor and metabolic sensory protein, which often represses tumor suppressor genes
  • required for the ability of BCL3 to repress gene transcription, CTBP1 is also required for the oncogenic potential of BCL3 and for its ability to inhibit UV-mediated cell apoptosis in keratinocytes)
  • with TBL1XR1, are key regulators of different properties of the BCL3 oncoprotein
  • ZFPM1, ZFPM2, and CTBP1 and CTBP2 are partners of GATA2, GATA3 proteins in the control of adipocyte proliferation and differentiation
  • key transcriptional coregulator in adipose tissue
  • transcriptional repressor which plays a significant role in the regulation of cell proliferation and tumor progression
  • AMPK and CTBP1 act as energy sensors and cause cell death upon glucose deprivation
  • CTBP1, CTBP2 are essential pro-survival proteins in neurons and their downregulation contributes significantly to neuronal apoptosis via the de-repression of pro-apoptotic genes
  • potential functions and transcriptional activities of CTBP1 in the context of epithelial-mesenchymal interplay, suggesting that CTBP1 has a pathogenic role in hair follicle morphogenesis and differentiation
  • CTBP1 and CTBP2 are closely related and act as transcriptional corepressors when activated by nicotinamide adenine dinucleotide binding to their dehydrogenase domains
  • role of CTBP1, a transcriptional co-repressor enriched in presynapses and nuclei, in the activity-driven reconfiguration of gene expression in neurons
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • homo or heterodimer of CTBP1 and CTBP2
  • RB1/RBBP8/CTBP1/E2F1 complex plays a critical role in ZNF350 transcriptional repression, and loss of this repression may contribute to cellular sensitivity of DNA damage, ultimately leading to carcinogenesis
  • INTERACTION
    DNA
    RNA
    small molecule cofactor,
  • binds to NAD(+)/NADH and may respond to the metabolic state of the cell, thereby linking changes in nutrient levels to transcriptional outcomes
  • protein
  • corepressor interacting with KLF3, KLF12
  • the C terminus of adenovirus E1A protein, ELK3, CTIP (BCL11X) CTBP2
  • interacting with HD
  • interact with GLIS2 (repressed transcriptional activation induced by GLIS2)
  • interacting with KLF4
  • interacts with FOXP2, HDAC4, HDAC5, HDAC9, FOXP1, HIPK2, PNN, NRIP1, ZFHX1B, WIZ, EBNA3, EBNA6
  • CBX4 might coordinate multiple enzymatic activities to regulate CTBP1 function
  • represses BRCA1 transcription by binding to the E2F4 site of the BRCA1 promoter
  • ETV6 orchestrates endothelial sprouting by binding to the generic co-repressor, CTBP1
  • interaction of CTBPs with transcriptional regulators and/or chromatin-modifying enzymes in the cell nucleus, rather than their role in Golgi fission, which is critical for the maintenance of mitotic fidelity
  • CTBP1 interacts with Ikaros and modulates pituitary tumor cell survival and response to hypoxia
  • 1180 AA regions of CTBP1 are responsible for binding with AMPK, and interaction with AMPK serves as a phosphorylation target of AMPK under the condition of glucose deprivation
  • SIMC1 interacts with CTBP1 (C-terminal binding protein 1), a transcriptional co-regulator
  • CTBP1 is targeted and/or anchored to presynapses by direct interaction with the active zone scaffolding proteins BSN and PCLO
  • CTBP1 have an essential role in promoting glutaminolysis by directly repressing the expression of SIRT4, a repressor of glutaminolysis by enzymatically modifying glutamate dehydrogenase in mitochondria, in cancer cells
  • cell & other
    REGULATION
    Other the level of phosphorylation appears to be regulated during the cell cycle
    phosphorylated upon DNA damage
    ADP-ribosylated when cells are exposed to Brefeldin A
    sumoylated by CBX4
    Sumoylation of CTBP1 has an effect on its subcellular localization and thus attenuates the corepressive function
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    reduction of CTBP1 expression is correlated with migratory, invasive potential of melanoma cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhead and neck 
    potential chemo preventative or therapeutic strategy for head and neck squamous cell carcinomas (HNSCCs) by blocking NADH-dependent CTBP1 activity at early stages of HNSCC carcinogenesis
    cancer  
    potential target for therapeutic strategies for the treatment of cancer in general, and breast cancer in particular
    cancerdigestiveliver
    potential therapeutic target in human disease
    ANIMAL & CELL MODELS