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Symbol CITED2 contributors: mct - updated : 25-02-2015
HGNC name Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2
HGNC id 1987
Corresponding disease
ASD8 atrial septal defect 8
Location 6q24.1      Physical location : 139.693.396 - 139.695.785
Synonym name
  • CREB-binding protein/p300-interacting transactivator with ED-rich tail 2
  • MSG-related protein 1
  • carboxy-terminal domain, 2
  • melanocyte-specific gene 1-related gene 1
  • Synonym symbol(s) D6S2114, MRG1, P35SRJ
    TYPE functioning gene
    STRUCTURE 2.39 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D6S292 - IFNGR1 - CITED2 - D6S311- D6S420 - OPRM1 - qter
    TRANSCRIPTS type messenger
    text all transcripts encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 1930 - 270 - 1999 10552932
    2 - 1776 - 270 - 1999 10552932
    2 - 1793 - 270 - 1999 10552932
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal glandcortex    Homo sapiens
    cell lineage
    cell lines adrenocortical cancer
    at STAGE
    physiological period embryo
    Text adrenal cortex , during gonad development
  • three conserved domains shared with other CITED family members and a unique Serine-Glycine Rich Junction (SRJ) that is highly conserved in placental mammals
  • a glutamic-aspartic (ED) rich C terminal region, with a functional motif (LPXL) within this domain necessary and sufficient for binding to the first cysteine/histidine-rich region of EP300, a EP300 binding motif with 32 AAs (D224-F255), required for competing with HIF1A in binding to EP300 to inhibit HIF1 mediated signaling
    interspecies homolog to rattus Cited2 (95.5 pc)
    homolog to murine Cited2 (95.2 pc)
  • CITED family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • cytokine-inducible transcription factor with transformation activity, involved in the recruitement of p300/CBP by hypoxia-inducible factor HIF1A and MRG1 (MSG1-related gene)
  • controlling left-right patterning and heart development through NODAL/PITX2 pathway
  • coactivator of PPARA and that both proteins may participate in signaling cascades of hypoxic response and angiogenesis
  • regulating colon cancer invasion and might be a target for HDAC inhibitor-based intervention of colon cancer
  • interfering with the binding of transcription factors HIF-1a and STAT2 to p300/CBP
  • involved in response to stress
  • implicated in control of cell growth and malignant transformation
  • important regulator of transforming growth factor (TGF)-beta signaling
  • functioning as a Smad3/p300-interacting transcriptional co-activator in modulating the expression of MMP9, which could affect tumor cell invasion mediated by TGF-beta
  • playing a role in adrenal growth and possibly in adrenal tumorigenesis
  • non-DNA binding protein that functions as a context dependent transcriptional co-activator or repressor
  • functions to ensure elevated NR5A1 and SRY levels which provide a robust activation of the male pathway as well as proper development
  • critical upstream regulator of fracture healing
  • may act as a mechanosensitive molecular switch regulating cartilage matrix breakdown
  • role in tissues of the embryo vital for left–right patterning (the node and lateral plate mesoderm)
  • role as a potentiator of bone morphogenetic protein (BMP) signalling, counteracting the initiation of NODAL expression in the lateral plate mesoderm
  • cardiac transcription factor, plays an important role in cardiac development
  • may play a role in the development of congenital heart disease (CHD)
  • plays a role in left–right patterning through the NODAL-PITX2C pathway
  • potential role of CITED2 in the remodeling of chromatin structures
  • critical role of CITED2 in cardiomyocyte differentiation by affecting the expression of NFATC4 leading to down-regulation of NKX2.5 and beta-MHC cardiomyocyte genes
  • functions as a molecular switch of cytokine-induced proliferation and quiescence
  • functions as a transcriptional co-activator of ESR1 in breast cancer cells and its increased expression in tumors may result in estrogen-independent ER activation, thereby reducing estrogen dependence and response to anti-estrogen therapy
  • is an essential regulator for HSC quiescence, apoptosis, and function
  • is a transcriptional co-factor with important roles in many organs of the developing mammalian embryo
  • its overexpression sustains ESC pluripotency
  • CELLULAR PROCESS cell cycle
    nucleotide, transcription, regulation
  • determination of left/right symmetry
  • heart development
  • positive regulation of cell cycle
    role during sex determination through a WT1/NR5A1 regulatory pathway
    a component
  • CITED2-TFAP2C complex controls lung maturation by regulating CEBPA expression
    small molecule
  • coactivator of TFAP2
  • interacting directly with PPARA in the presence or absence of ligand predominantly via the ligand binding domain of the nuclear receptor
  • binding to the CH1 region of p300/CBP
  • interacts with WT1 to stimulate the expression of NR5A1 in the adrenogonadal primordium to ensure adrenal development
  • role for transcription factor LMO4 in thymus development through genetic interaction with CITED2
  • may interact with both NODAL and BMP signalling in establishing laterality
  • EP300 interacting transcriptional modulator that functions as an important modulator in cardiac development
  • controls embryonic stem cells (ESCs) pluripotency and differentiation via direct regulation of POU5F1 gene expression.
  • SPI1 is a critical regulator of CITED2, as SPI1 repressed CITED2 expression in a DNMT3A/B-dependent manner in normal CD34+ cells
  • cell & other
    induced by hypoxia and deferoxamine
    corresponding disease(s) ASD8
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    mutation cluster in the serine-glycine rich junction, reducing the trans repression of HIF1A in congenital heart defect (VSD, ASD, malrotation of the great arteries)
    tumoral     --low  
    might act as a repressor of colon cancer progression
    constitutional     --over  
    enhanced TGF-beta-mediated MMP9 promoter reporter activity
    constitutional     --low  
    rapidly within 3 h after osteotomy, associated with a dramatic increase in matrix metalloproteinases, namely MMPs 2, 3, 9, and 13, as well as genes regulating angiogenesis and osteogenesis
    constitutional       loss of function
    in syncytiotrophoblasts results in the subcellular mislocalization of one of the major lactate transporters in the placenta, SLC16A3
    constitutional   deletion    
    deletion of CITED2 in mESCs results in abnormal mitochondrial morphology and impaired glucose metabolism, which correlates with a defective cell fate decision
    tumoral     --over  
    in breast cancer with poor survival
    Susceptibility to congenital heart defects
    Variant & Polymorphism SNP
  • missense mutations G184S and S192G, decreased cooperation between CITED2 and TFAP2C in the transactivation of the PITX2 gene, and are responsible for tetralogy of Fallot and aortic stenosis, respectively
  • Candidate gene
    Therapy target
    target for nutrition-based chemoprevention and chemotherapy for colon cancer
  • Cited2-null mice die during gestation with fully penetrant heart defects and partially penetrant laterality defects
  • mice lacking Cited2 die in utero, and they show various cardiac malformations including atrial and ventricular septal defects
  • loss of Cited2 in mice results in cardiac and aortic arch malformations, adrenal agenesis, neural tube and placental defects, and partially penetrant defects in left-right patterning
  • embryonic growth retardation observed in Cited2 null embryos is likely due in part to a disorganized embryonic capillary network, and in part due to abnormalities of the nutrient transport functions of the feto-maternal interface