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CITED2 (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2)

Written2010-01Matthias Haase, Holger S Willenberg
Department of Endocrinology, Diabetes, Rheumatology, University Hospital Duesseldorf, 40225 Duesseldorf, Germany

(Note : for Links provided by Atlas : click)

Identity

Alias_namesCbp/p300-interacting transactivator
Alias_symbol (synonym)MRG1
Other aliasMRG-1
p35srj
HGNC (Hugo) CITED2
LocusID (NCBI) 10370
Atlas_Id 40087
Location 6q24.1  [Link to chromosome band 6q24]
Location_base_pair Starts at 139372255 and ends at 139374362 bp from pter ( according to hg19-Feb_2009)  [Mapping CITED2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CITED2 (6q24.1) / PRDM10 (11q24.3)CITED2 (6q24.1) / UHMK1 (1q23.3)VGLL2 (6q22.1) / CITED2 (6q24.1)
Note CITED2 was mapped to 6q23.3 by fluorescence in situ hybridization, a weaker signal was detected at 1q22 (Leung et al., 1999).
The MRG1 isoform was isolated in 1996 from human melanocyte cDNA based on the homology to the melanocyte-specific gene 1 (MSG1, Shioda et al., 1996). The p35srj isoform has been identified in 1999 (Bhattacharya et al., 1999). The CITED2 gene that encodes p35srj and MRG1 has been cloned in 1999 (Leung et al., 1999).

DNA/RNA

Description The CITED2-Gene is composed of three exons and two introns. The gene encompasses 9,39 kb of DNA. The promoter contains hypoxia response elements, SP1 binding sites, STAT binding sites and a NFkappaB binding site (Leung et al., 1999).
Transcription By splicing processes two different transcripts are generated: in the p35srj-transcript there is only one intron spliced out and it still contains the intron 2 coding for a serine rich junction (srj). In the MRG1-transcript both introns are spliced out (Leung et al., 1999).

Protein

Description Isoform p35srj: 270 aa, 28,5 kDa (molecular weight calculated by amino acid sequence).
Isoform MRG1: 213 aa, 23,73 kDa (molecular weight calculated by amino acid sequence).
Expression Widely expressed, developmental regulated.
Localisation Predominantly nuclear.
Function Transcriptional co-regulator. The CITED2 isoform p35srj binds to p300/CBP and inhibits HIF-1alpha transactivation (Bhattacharya et al., 1999). CITED2 competes with HIF-1alpha for an overlapping binding site on the cysteine-histidine-rich 1 domain of p300 (Freedman et al., 2003). CITED2 was identified as a co-activator of all isoforms of the transcription factor AP-2 (TFAP2, Bamforth et al., 2001; Braganca et al., 2003). Overexpression of MRG1 resulted in tumor formation in nude mice (Sun et al., 1998). CITED2 controls fibroblast proliferation by the regulation of the proliferation inhibitors INK4a/ARF and the polycomb-group genes BMI1/Mel18 (Kranc et al., 2003). CITED2 is a co-regulator of the peroxisome proliferator-activated receptor alpha (PPARalpha) and increases proliferation in hepatocytes (Tien et al., 2004). CITED2 regulates the Nodal-Pitx2c pathway and controls developmental processes (Bamforth et al., 2004). CITED2 is a co-activator of Smad3/p300 transcription and modulates metalloproteinase 9 expression in a transforming growth factor beta (TGF-beta) dependent pathway (Chou et al., 2006).

Mutations

Germinal Amino acid changing mutations (p.Ser170_Gly178del, p.Gly178_Ser179ins9 and p.Ser198_Gly199del) in the serine-glycine-rich junction of the protein. The mutants show decreased transrepression of HIF-1a or decreased coactivation of TFAP2. The mutations mentioned above have been detected in patients suffering from congenital heart defects (cardiac septal defects) but not in normal individuals (Sperling et al., 2005).

Implicated in

Note
  
Entity Adrenocortical carcinoma
Note CITED2 is expressed in adrenocortical carcinomas as well as in the adrenocortical carcinoma cell line NCI-H295R. CITED2 is upregulated by bFGF, Forskolin, endothelial cell products and Angiotensin II in NCI-H295R cells (Haase et al., 2007; Romero et al., 2007; Haase et al., 2009). In part, CITED2-expression in adrenocortical carcinomas could be observed in close proximity to blood vessels (Haase et al., 2009).
  
  
Entity Breast cancer
Note CITED2 is highly expressed in MDA-MB-231 invasive breast cancer cells which are resistant to TGF-beta mediated growth arrest. TGF-beta induced MDA-MB-231 cell invasion could be reduced by downregulation of CITED2 as an enhancer of metalloproteinase 9 (MMP9)-expression, suggesting a role for CITED2 during tumor invasion (Chou et al., 2005). In Fibroblasts and in breast cancer cells FOXO3a inhibits HIF-1 induced apoptosis via upregulation of CITED2 (Bakker et al., 2007). CITED2 was especially expressed in human breast cancer cell lines that form osteolytic metastases in animal models. Elevated expression of CITED2 could also be observed in invasive ductal carcinoma tissue samples and in breast cancer bone metastases in comparison to normal mammary epithelial tissues (Lau et al., 2010). A study from Agthoven et al., observed that high levels of CITED2 mRNA in oestrogen receptor-alpha positive breast tumors of lymph-node negative patients were associated with prolonged metastasis-free-survival. In the same study high levels of CITED2 mRNA were also associated with a favourable outcome in patients that have received Tamoxifen as a first line therapy (van Agthoven et al., 2009).
  
  
Entity Colorectal cancer
Note In a human colorectal carcinoma cell line CITED2 is downregulated by Rac1, a protein that has been associated with tumor growth (Gomez del Pulgar et al., 2007). In the human colon cancer cell line RKO downregulation of CITED2 increased colon cancer cell invasivness and upregulated MMP-13 expression (Bai et al., 2007).
  
  
Entity Esophageal cancer
Note CITED2 was downregulated in a well and a poorly differentiated esophageal cancer cell line after treatment with up to 8 Gy irradiation (Bo et al., 2004).
  
  
Entity Leiomyoma
Note GnRHa therapy increased CITED2 expression in leiomyoma and myometrium. GnRHa therapy had a biphasic effect on CITED2 expression in primary cultures of myometrial smooth muscle cells and inhibits expression in primary cultures of leiomyoma smooth muscle cells (Luo et al., 2005b). Expression of CITED2 was downregulated by TGF-beta in primary cultures of myometrial and leiomyoma smooth muscle cells (Luo et al., 2005a).
  
  
Entity Osteosarcoma
Note CITED2 is downregulated in radiation-induced rat osteosarcoma as compared with normal osteoblasts (Daino et al., 2009). The analysis of radiation-induced rat osteosarcoma showed reduced mRNA and protein expression and suggests a role for CITED2 as a tumor supressor gene in osteosarcoma (Daino et al., 2009).
  
  
Entity Ovarian carcinoma
Note CITED2 expression was significantly downregulated after silencing of the tumor susceptibility gene 101 protein (TSG101) in SKOV-3 ovarian cancer cells with elevated RAS activity. The downregulation of CITED2 went along with a decrease of cell viability (Young et al., 2007). Expression of CITED2 was elevated in the oxaliplatin resistant cell line KFR as compared with the oxaliplatin sensitive cell line KF-1. The downregulation of CITED2 in the platinum-resistent ovarian cancer cell line KFR enhances the cytotoxicity of platinum compounds to the KFR cell line (Yanangie et al., 2009).
  
  
Entity Sarcoma
Note Ewing's-Sarcoma show a 6-fold increase in CITED2-expression as compared with rhabdomyosarcoma (Baer et al., 2004).
  
  
Entity Adrenal development and adrenocortical physiology
Note CITED2-null mice show adrenal agenesis indicating a role for CITED2 within adrenal development (Bamforth et al., 2001). At 8 weeks of gestation CITED2 could be detected especially within the definitive zone of the developing adrenal cortex (Haase et al., 2007). Following studies confirmed the expression of CITED2 during early human fetal adrenal gland development at 7 and 10 weeks of gestation (Ferraz-de-Souza et al., 2009). In mice CITED2 was expressed in the coelomic epithelium and in the nephrogenic mesenchyme at E10. At E12 CITED2 was highly expressed in the adrenal primordium and remained highly expressed in adrenocortical cells at E13.5 and later (Val et al., 2007). In mice CITED2 acts as a WT-1 co-factor to increase SF-1 levels in the adrenogonadal primordium to initiate adrenal development (Val et al., 2007). Other studies applying human NCI-H295R adrenal carcinoma cells demonstrate that SF-1 activates the CITED2-promoter (Ferraz-de-Souza et al., 2009). In human NCI-H295R cells CITED2-expression is regulated by basic fibroblast growth factor, endothelial cell products and is dependent on the MAPK-pathway (Haase et al., 2007; Haase et al., 2009). Forskolin could also be identified as a positive regulator of CITED2-expression in NCI-H295R cells (Haase et al., 2007; Romero et al., 2007). Angiotensin II upregulates CITED2-expression in NCI-H295R cells and CITED2 enhances the expression of steroidogenic enzymes such as 11-beta-Hydroxylase and Aldosterone-Synthase (Romero et al., 2007).
  
  
Entity Congenital heart defects and cardiac septal defects
Note CITED2 -/- mice show cardiac malformations including ventricular and atrial septal defects, double-outlet right ventricle, overriding aorta, right sided aortic arches and persistent truncus arteriosus (Bamforth et al., 2001). Functional loss of CITED2 during transrepression of HIF-1 alpha has been suggested to be responsible for the observed phenotype (Yin et al., 2002). Aberrant signaling of the Nodal-Pitx2c pathway has also been linked to the cardiovascular defects observed in CITED2 -/- mice (Bamforth et al., 2004). Aberrant left-right patterning as well as direct loss of CITED2 in cardiac tissues has been associated with the defects in CITED2-null mice (Weninger et al., 2005). The cardiovascular defects seem to result from the disruption of left-right patterning in epiblast derivatives and from the malfunction of septation in the mesoderm (MacDonald et al., 2008).
Mutations of CITED2 in humans have been linked to cardiac septal defects and congenital heart defects (Sperling et al., 2005).
  
  
Entity Exencephaly, neural crest defects and neurologic implications
Note CITED2-null mice show exencephaly, abnormal cranial ganglia, neural crest defects and increased apoptosis in the midbrain region (Bamforth et al., 2001). Exencephaly seem to arise from defective closure of the midbrain and hindbrain region, associated with a defective closure of the neural tube (Barbera et al., 2002). Apoptosis around the Forebrain-Midbrain-junction in the dorsal neuroectoderm was increased in CITED2 -/- mice and CITED2 was necessary for the survival of neuroepithelial cells (Barbera et al., 2002). The administration of folic acid significantly reduced exencephaly in CITED2-null mice (Barbera et al., 2002). Transient forebrain ischemia induced CITED2-expression in different brain regions including the piriform cortex and the dentate gyrus of the hippocampal region and it has been speculated if CITED2 protects from neuronal death under hypoxic conditions (Sun et al., 2006). However, other studies also demonstrate that CITED2-overexpression can promote cell death in cortical neurons of the mouse (Gonzales et al., 2008). CITED2 expression is increased after olfactory bulbectomy and may contribute to the phenotype of basal progenitor cells of the olfactory sensory neuron lineage in the mouse (Shetty et al., 2005). CITED2 was also identified as a neural activity-dependent transcription-factor in vivo and in vitro in rat cortical neurons (Sun et al., 2007).
  
  
Entity Eye developement
Note CITED2 is necessary for the morphogenesis of the lens and for hyaloid vasculature formation (Chen et al., 2008). Selective deletion of CITED2 resulted in abnormal corneal epithelial differentiation, impaired wound healing and corneal neovascularization in older mice associated with decreased expression of Pax6 and Klf4 (Chen et al., 2009).
  
  
Entity Fracture healing
Note CITED2 was identified as a negative regulator of fracture healing in rats and was inversly related to the expression of metalloproteinases (MMP-2, MMP-3, MMP-9, MMP-13), HIF-1a, VEGF, RANK-L, M-CSF and OPG (Lee et al., 2009).
  
  
Entity Gonadal development
Note In CITED2 null mice XY-gonad development was delayed and testis structure was disorganized. In XX-gonads of CITED2 null mice cell migration was disturbed (Combes et al., 2009). CITED2 interacts with Wt1 and SF-1 in mice and increases Sry levels initiating testes development (Buaas et al., 2009).
  
  
Entity Hematopoiesis
Note CITED2 is required for the regulation of hematopoeisis during embryogenesis in the murine fetal liver (Chen et al., 2007). CITED2 controls adult hematopoietic stem cell function via Ink4a/Arf and Trp53 (Kranc et al., 2009).
  
  
Entity Liver development
Note CITED2 null mice show liver hypoplasia, increased apoptosis, disrupted sinusoidal architecture, disrupted cell-cell contacts, impaired lipid metabolism and gluconeogenesis. The observations have been linked to the role of CITED2 as a co-activator of HNF4alpha (Qu et al., 2007).
  
  
Entity Lung development
Note CITED2 is required for fetal lung maturation. Terminal sac space and differentiation of alveolar epithelial cells Typ 1 and 2 is altered in CITED2 null lungs in mice (Xu et al., 2008). CITED2 is developmentally regulated in pulmonary artery smooth muscle cells in sheep with higher expression in the fetus compared with the adult (Resnik et al., 2007).
  

Bibliography

Profiling and functional annotation of mRNA gene expression in pediatric rhabdomyosarcoma and Ewing's sarcoma.
Baer C, Nees M, Breit S, Selle B, Kulozik AE, Schaefer KL, Braun Y, Wai D, Poremba C.
Int J Cancer. 2004 Jul 10;110(5):687-94.
PMID 15146558
 
A role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasion.
Bai L, Merchant JL.
FEBS Lett. 2007 Dec 22;581(30):5904-10. Epub 2007 Dec 3.
PMID 18054336
 
FOXO3a is activated in response to hypoxic stress and inhibits HIF1-induced apoptosis via regulation of CITED2.
Bakker WJ, Harris IS, Mak TW.
Mol Cell. 2007 Dec 28;28(6):941-53.
PMID 18158893
 
Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway.
Bamforth SD, Bragana J, Farthing CR, Schneider JE, Broadbent C, Michell AC, Clarke K, Neubauer S, Norris D, Brown NA, Anderson RH, Bhattacharya S.
Nat Genet. 2004 Nov;36(11):1189-96. Epub 2004 Oct 10.
PMID 15475956
 
Folic acid prevents exencephaly in Cited2 deficient mice.
Barbera JP, Rodriguez TA, Greene ND, Weninger WJ, Simeone A, Copp AJ, Beddington RS, Dunwoodie S.
Hum Mol Genet. 2002 Feb 1;11(3):283-93.
PMID 11823447
 
Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1.
Bhattacharya S, Michels CL, Leung MK, Arany ZP, Kung AL, Livingston DM.
Genes Dev. 1999 Jan 1;13(1):64-75.
PMID 9887100
 
Effect of ionizing irradiation on human esophageal cancer cell lines by cDNA microarray gene expression analysis.
Bo H, Ghazizadeh M, Shimizu H, Kurihara Y, Egawa S, Moriyama Y, Tajiri T, Kawanami O.
J Nippon Med Sch. 2004 Jun;71(3):172-80.
PMID 15226608
 
Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2.
Braganca J, Eloranta JJ, Bamforth SD, Ibbitt JC, Hurst HC, Bhattacharya S.
J Biol Chem. 2003 May 2;278(18):16021-9. Epub 2003 Feb 12.
PMID 12586840
 
The transcription co-factor CITED2 functions during sex determination and early gonad development.
Buaas FW, Val P, Swain A.
Hum Mol Genet. 2009 Aug 15;18(16):2989-3001. Epub 2009 May 20.
PMID 19457926
 
Conditional deletion of Cited2 results in defective corneal epithelial morphogenesis and maintenance.
Chen Y, Carlson EC, Chen ZY, Hamik A, Jain MK, Dunwoodie SL, Yang YC.
Dev Biol. 2009 Oct 1;334(1):243-52. Epub 2009 Jul 24.
PMID 19632219
 
Cited2 is required for the proper formation of the hyaloid vasculature and for lens morphogenesis.
Chen Y, Doughman YQ, Gu S, Jarrell A, Aota S, Cvekl A, Watanabe M, Dunwoodie SL, Johnson RS, van Heyningen V, Kleinjan DA, Beebe DC, Yang YC.
Development. 2008 Sep;135(17):2939-48. Epub 2008 Jul 24.
PMID 18653562
 
Cited2 is required for normal hematopoiesis in the murine fetal liver.
Chen Y, Haviernik P, Bunting KD, Yang YC.
Blood. 2007 Oct 15;110(8):2889-98. Epub 2007 Jul 20.
PMID 17644732
 
Cited2 modulates TGF-beta-mediated upregulation of MMP9.
Chou YT, Wang H, Chen Y, Danielpour D, Yang YC.
Oncogene. 2006 Sep 7;25(40):5547-60. Epub 2006 Apr 17.
PMID 16619037
 
Gonadal defects in Cited2 -mutant mice indicate a role for SF1 in both testis and ovary differentiation.
Combes AN, Spiller CM, Harley VR, Sinclair AH, Dunwoodie SL, Wilhelm D, Koopman P.
Int J Dev Biol. 2009 Jul 24.
PMID 19757380
 
Gene expression profiling of alpha-radiation-induced rat osteosarcomas: identification of dysregulated genes involved in radiation-induced tumorigenesis of bone.
Daino K, Ugolin N, Altmeyer-Morel S, Guilly MN, Chevillard S.
Int J Cancer. 2009 Aug 1;125(3):612-20.
PMID 19444910
 
CBP/p300-interacting transactivator, with Glu/Asp-rich C-terminal domain, 2, and pre-B-cell leukemia transcription factor 1 in human adrenal development and disease.
Ferraz-de-Souza B, Martin F, Mallet D, Hudson-Davies RE, Cogram P, Lin L, Gerrelli D, Beuschlein F, Morel Y, Huebner A, Achermann JC.
J Clin Endocrinol Metab. 2009 Feb;94(2):678-83. Epub 2008 Nov 4.
PMID 18984668
 
Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2.
Freedman SJ, Sun ZY, Kung AL, France DS, Wagner G, Eck MJ.
Nat Struct Biol. 2003 Jul;10(7):504-12.
PMID 12778114
 
Differential expression of Rac1 identifies its target genes and its contribution to progression of colorectal cancer.
Gomez del Pulgar T, Bandres E, Espina C, Valdes-Mora F, Perez-Palacios R, Garcia-Amigot F, Garcia-Foncillas J, Lacal JC.
Int J Biochem Cell Biol. 2007;39(12):2289-302. Epub 2007 Jul 4.
PMID 17766170
 
CITED2 signals through peroxisome proliferator-activated receptor-gamma to regulate death of cortical neurons after DNA damage.
Gonzalez YR, Zhang Y, Behzadpoor D, Cregan S, Bamforth S, Slack RS, Park DS.
J Neurosci. 2008 May 21;28(21):5559-69.
PMID 18495890
 
Evidence for the involvement of endothelial cell products in adrenal CITED2 expression.
Haase M, Ansurudeen I, Schinner S, Paramonova I, Schott M, Papewalis C, Bornstein SR, Scherbaum WA, Willenberg HS.
Cell Tissue Res. 2009 May;336(2):337-43. Epub 2009 Mar 25.
PMID 19319572
 
CITED2 is expressed in human adrenocortical cells and regulated by basic fibroblast growth factor.
Haase M, Schott M, Bornstein SR, Malendowicz LK, Scherbaum WA, Willenberg HS.
J Endocrinol. 2007 Feb;192(2):459-65.
PMID 17283246
 
Transcriptional coactivator Cited2 induces Bmi1 and Mel18 and controls fibroblast proliferation via Ink4a/ARF.
Kranc KR, Bamforth SD, Bragana J, Norbury C, van Lohuizen M, Bhattacharya S.
Mol Cell Biol. 2003 Nov;23(21):7658-66.
PMID 14560011
 
Cited2 is an essential regulator of adult hematopoietic stem cells.
Kranc KR, Schepers H, Rodrigues NP, Bamforth S, Villadsen E, Ferry H, Bouriez-Jones T, Sigvardsson M, Bhattacharya S, Jacobsen SE, Enver T.
Cell Stem Cell. 2009 Dec 4;5(6):659-65.
PMID 19951693
 
Identification of prospective factors promoting osteotropism in breast cancer: a potential role for CITED2.
Lau WM, Weber KL, Doucet M, Chou YT, Brady K, Kowalski J, Tsai HL, Yang J, Kominsky SL.
Int J Cancer. 2010 Feb 15;126(4):876-84.
PMID 19642106
 
Identification of CITED2 as a negative regulator of fracture healing.
Lee JY, Taub PJ, Wang L, Clark A, Zhu LL, Maharam ER, Leong DJ, Ramcharan M, Li Z, Liu Z, Ma YZ, Sun L, Zaidi M, Majeska RJ, Sun HB.
Biochem Biophys Res Commun. 2009 Oct 2;387(4):641-5. Epub 2009 Jul 14.
PMID 19607804
 
Molecular cloning and chromosomal localization of the human CITED2 gene encoding p35srj/Mrg1.
Leung MK, Jones T, Michels CL, Livingston DM, Bhattacharya S.
Genomics. 1999 Nov 1;61(3):307-13.
PMID 10552932
 
Leiomyoma and myometrial gene expression profiles and their responses to gonadotropin-releasing hormone analog therapy.
Luo X, Ding L, Xu J, Williams RS, Chegini N.
Endocrinology. 2005b Mar;146(3):1074-96. Epub 2004 Dec 16.
PMID 15604208
 
Epiblastic Cited2 deficiency results in cardiac phenotypic heterogeneity and provides a mechanism for haploinsufficiency.
MacDonald ST, Bamforth SD, Chen CM, Farthing CR, Franklyn A, Broadbent C, Schneider JE, Saga Y, Lewandoski M, Bhattacharya S.
Cardiovasc Res. 2008 Aug 1;79(3):448-57. Epub 2008 Apr 25.
PMID 18440989
 
Cited2, a coactivator of HNF4alpha, is essential for liver development.
Qu X, Lam E, Doughman YQ, Chen Y, Chou YT, Lam M, Turakhia M, Dunwoodie SL, Watanabe M, Xu B, Duncan SA, Yang YC.
EMBO J. 2007 Oct 31;26(21):4445-56. Epub 2007 Oct 11.
PMID 17932483
 
Developmental regulation of hypoxia-inducible factor 1 and prolyl-hydroxylases in pulmonary vascular smooth muscle cells.
Resnik ER, Herron JM, Lyu SC, Cornfield DN.
Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18789-94. Epub 2007 Nov 13.
PMID 18000055
 
Adrenal transcription regulatory genes modulated by angiotensin II and their role in steroidogenesis.
Romero DG, Rilli S, Plonczynski MW, Yanes LL, Zhou MY, Gomez-Sanchez EP, Gomez-Sanchez CE.
Physiol Genomics. 2007 Jun 19;30(1):26-34. Epub 2007 Feb 27.
PMID 17327493
 
Transcriptional changes during neuronal death and replacement in the olfactory epithelium.
Shetty RS, Bose SC, Nickell MD, McIntyre JC, Hardin DH, Harris AM, McClintock TS.
Mol Cell Neurosci. 2005 Dec;30(4):583-600.
PMID 16456926
 
msg1, a novel melanocyte-specific gene, encodes a nuclear protein and is associated with pigmentation.
Shioda T, Fenner MH, Isselbacher KJ.
Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12298-303.
PMID 8901575
 
Identification and functional analysis of CITED2 mutations in patients with congenital heart defects.
Sperling S, Grimm CH, Dunkel I, Mebus S, Sperling HP, Ebner A, Galli R, Lehrach H, Fusch C, Berger F, Hammer S.
Hum Mutat. 2005 Dec;26(6):575-82.
PMID 16287139
 
MRG1, the product of a melanocyte-specific gene related gene, is a cytokine-inducible transcription factor with transformation activity.
Sun HB, Zhu YX, Yin T, Sledge G, Yang YC.
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13555-60.
PMID 9811838
 
Identification and characterization of novel activity-dependent transcription factors in rat cortical neurons.
Sun W, Choi SH, Park SK, Kim SJ, Noh MR, Kim EH, Kim HJ, Kim H.
J Neurochem. 2007 Jan;100(1):269-78. Epub 2006 Nov 20.
PMID 17116234
 
Induction of CITED2 expression in the rat hippocampus following transient global ischemia.
Sun W, Kim KH, Noh M, Hong S, Huh PW, Kim Y, Kim H.
Brain Res. 2006 Feb 9;1072(1):15-8. Epub 2006 Jan 24.
PMID 16434029
 
Identification of the CREB-binding protein/p300-interacting protein CITED2 as a peroxisome proliferator-activated receptor alpha coregulator.
Tien ES, Davis JW, Vanden Heuvel JP.
J Biol Chem. 2004 Jun 4;279(23):24053-63. Epub 2004 Mar 29.
PMID 15051727
 
Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage.
Val P, Martinez-Barbera JP, Swain A.
Development. 2007 Jun;134(12):2349-58.
PMID 17537799
 
Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development.
Weninger WJ, Lopes Floro K, Bennett MB, Withington SL, Preis JI, Barbera JP, Mohun TJ, Dunwoodie SL.
Development. 2005 Mar;132(6):1337-48.
PMID 15750185
 
Cited2 is required for fetal lung maturation.
Xu B, Qu X, Gu S, Doughman YQ, Watanabe M, Dunwoodie SL, Yang YC.
Dev Biol. 2008 May 1;317(1):95-105. Epub 2008 Feb 26.
PMID 18358466
 
Improvement of sensitivity to platinum compound with siRNA knockdown of upregulated genes in platinum complex-resistant ovarian cancer cells in vitro.
Yanagie H, Hisa T, Ogata A, Miyazaki A, Nonaka Y, Nishihira T, Osada I, Sairennji T, Sugiyama H, Furuya Y, Kidani Y, Takamoto S, Takahashi H, Eriguchi M.
Biomed Pharmacother. 2009 Sep;63(8):553-60. Epub 2008 May 27.
PMID 18571892
 
The essential role of Cited2, a negative regulator for HIF-1alpha, in heart development and neurulation.
Yin Z, Haynie J, Yang X, Han B, Kiatchoosakun S, Restivo J, Yuan S, Prabhakar NR, Herrup K, Conlon RA, Hoit BD, Watanabe M, Yang YC.
Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10488-93. Epub 2002 Jul 29.
PMID 12149478
 
Up-regulation of tumor susceptibility gene 101 protein in ovarian carcinomas revealed by proteomics analyses.
Young TW, Mei FC, Rosen DG, Yang G, Li N, Liu J, Cheng X.
Mol Cell Proteomics. 2007 Feb;6(2):294-304. Epub 2006 Nov 16.
PMID 17110434
 
CITED2 and NCOR2 in anti-oestrogen resistance and progression of breast cancer.
van Agthoven T, Sieuwerts AM, Veldscholte J, Meijer-van Gelder ME, Smid M, Brinkman A, den Dekker AT, Leroy IM, van Ijcken WF, Sleijfer S, Foekens JA, Dorssers LC.
Br J Cancer. 2009 Dec 1;101(11):1824-32. Epub 2009 Nov 10.
PMID 19904269
 

Citation

This paper should be referenced as such :
Haase, M ; Willenberg, HS
CITED2 (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(10):937-941.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CITED2ID40087ch6q24.html


External links

Nomenclature
HGNC (Hugo)CITED2   1987
Cards
AtlasCITED2ID40087ch6q24
Entrez_Gene (NCBI)CITED2  10370  Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2
AliasesASD8; MRG-1; MRG1; P35SRJ; 
VSD2
GeneCards (Weizmann)CITED2
Ensembl hg19 (Hinxton)ENSG00000164442 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000164442 [Gene_View]  chr6:139372255-139374362 [Contig_View]  CITED2 [Vega]
ICGC DataPortalENSG00000164442
TCGA cBioPortalCITED2
AceView (NCBI)CITED2
Genatlas (Paris)CITED2
WikiGenes10370
SOURCE (Princeton)CITED2
Genetics Home Reference (NIH)CITED2
Genomic and cartography
GoldenPath hg38 (UCSC)CITED2  -     chr6:139372255-139374362 -  6q24.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CITED2  -     6q24.1   [Description]    (hg19-Feb_2009)
EnsemblCITED2 - 6q24.1 [CytoView hg19]  CITED2 - 6q24.1 [CytoView hg38]
Mapping of homologs : NCBICITED2 [Mapview hg19]  CITED2 [Mapview hg38]
OMIM602937   614431   614433   
Gene and transcription
Genbank (Entrez)AA400897 AA767624 AF109161 AI087283 BC004377
RefSeq transcript (Entrez)NM_001168388 NM_001168389 NM_006079
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CITED2
Cluster EST : UnigeneHs.82071 [ NCBI ]
CGAP (NCI)Hs.82071
Alternative Splicing GalleryENSG00000164442
Gene ExpressionCITED2 [ NCBI-GEO ]   CITED2 [ EBI - ARRAY_EXPRESS ]   CITED2 [ SEEK ]   CITED2 [ MEM ]
Gene Expression Viewer (FireBrowse)CITED2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10370
GTEX Portal (Tissue expression)CITED2
Human Protein AtlasENSG00000164442-CITED2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ99967   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ99967  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ99967
Splice isoforms : SwissVarQ99967
PhosPhoSitePlusQ99967
Domains : Interpro (EBI)CITED   
Domain families : Pfam (Sanger)CITED (PF04487)   
Domain families : Pfam (NCBI)pfam04487   
Conserved Domain (NCBI)CITED2
DMDM Disease mutations10370
Blocks (Seattle)CITED2
PDB (SRS)1P4Q    1R8U   
PDB (PDBSum)1P4Q    1R8U   
PDB (IMB)1P4Q    1R8U   
PDB (RSDB)1P4Q    1R8U   
Structural Biology KnowledgeBase1P4Q    1R8U   
SCOP (Structural Classification of Proteins)1P4Q    1R8U   
CATH (Classification of proteins structures)1P4Q    1R8U   
SuperfamilyQ99967
Human Protein Atlas [tissue]ENSG00000164442-CITED2 [tissue]
Peptide AtlasQ99967
HPRD04245
IPIIPI00019175   IPI00216547   
Protein Interaction databases
DIP (DOE-UCLA)Q99967
IntAct (EBI)Q99967
FunCoupENSG00000164442
BioGRIDCITED2
STRING (EMBL)CITED2
ZODIACCITED2
Ontologies - Pathways
QuickGOQ99967
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  nuclear chromatin  RNA polymerase II transcription coactivator activity  RNA polymerase II transcription corepressor activity  response to hypoxia  response to hypoxia  liver development  outflow tract morphogenesis  regulation of animal organ formation  chromatin binding  transcription factor activity, sequence-specific DNA binding  transcription coactivator activity  transcription corepressor activity  transcription corepressor activity  protein binding  nucleus  nucleoplasm  transcription, DNA-templated  determination of left/right symmetry  heart development  heart development  sex determination  sex determination  cell proliferation  positive regulation of gene expression  negative regulation of gene expression  protein domain specific binding  positive regulation of cell-cell adhesion  cell differentiation  negative regulation of cell migration  positive regulation of transforming growth factor beta receptor signaling pathway  response to fluid shear stress  histone acetyltransferase binding  positive regulation of peroxisome proliferator activated receptor signaling pathway  adrenal cortex formation  negative regulation of apoptotic process  protein complex  response to estrogen  positive regulation of cell cycle  negative regulation of transcription, DNA-templated  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  spleen development  LBD domain binding  ventricular septum morphogenesis  embryonic heart tube left/right pattern formation  left/right pattern formation  negative regulation of transcription from RNA polymerase II promoter in response to hypoxia  left/right axis specification  nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry  positive regulation of male gonad development  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  nuclear chromatin  RNA polymerase II transcription coactivator activity  RNA polymerase II transcription corepressor activity  response to hypoxia  response to hypoxia  liver development  outflow tract morphogenesis  regulation of animal organ formation  chromatin binding  transcription factor activity, sequence-specific DNA binding  transcription coactivator activity  transcription corepressor activity  transcription corepressor activity  protein binding  nucleus  nucleoplasm  transcription, DNA-templated  determination of left/right symmetry  heart development  heart development  sex determination  sex determination  cell proliferation  positive regulation of gene expression  negative regulation of gene expression  protein domain specific binding  positive regulation of cell-cell adhesion  cell differentiation  negative regulation of cell migration  positive regulation of transforming growth factor beta receptor signaling pathway  response to fluid shear stress  histone acetyltransferase binding  positive regulation of peroxisome proliferator activated receptor signaling pathway  adrenal cortex formation  negative regulation of apoptotic process  protein complex  response to estrogen  positive regulation of cell cycle  negative regulation of transcription, DNA-templated  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  spleen development  LBD domain binding  ventricular septum morphogenesis  embryonic heart tube left/right pattern formation  left/right pattern formation  negative regulation of transcription from RNA polymerase II promoter in response to hypoxia  left/right axis specification  nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry  positive regulation of male gonad development  
Pathways : BIOCARTAMechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) [Genes]   
REACTOMEQ99967 [protein]
REACTOME PathwaysR-HSA-8866907 [pathway]   
NDEx NetworkCITED2
Atlas of Cancer Signalling NetworkCITED2
Wikipedia pathwaysCITED2
Orthology - Evolution
OrthoDB10370
GeneTree (enSembl)ENSG00000164442
Phylogenetic Trees/Animal Genes : TreeFamCITED2
HOVERGENQ99967
HOGENOMQ99967
Homologs : HomoloGeneCITED2
Homology/Alignments : Family Browser (UCSC)CITED2
Gene fusions - Rearrangements
Tumor Fusion PortalCITED2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCITED2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CITED2
dbVarCITED2
ClinVarCITED2
1000_GenomesCITED2 
Exome Variant ServerCITED2
ExAC (Exome Aggregation Consortium)ENSG00000164442
GNOMAD BrowserENSG00000164442
Genetic variants : HAPMAP10370
Genomic Variants (DGV)CITED2 [DGVbeta]
DECIPHERCITED2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCITED2 
Mutations
ICGC Data PortalCITED2 
TCGA Data PortalCITED2 
Broad Tumor PortalCITED2
OASIS PortalCITED2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCITED2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCITED2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CITED2
DgiDB (Drug Gene Interaction Database)CITED2
DoCM (Curated mutations)CITED2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CITED2 (select a term)
intoGenCITED2
NCG5 (London)CITED2
Cancer3DCITED2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602937    614431    614433   
Orphanet820    14122    14120    14114    14774   
DisGeNETCITED2
MedgenCITED2
Genetic Testing Registry CITED2
NextProtQ99967 [Medical]
TSGene10370
GENETestsCITED2
Target ValidationCITED2
Huge Navigator CITED2 [HugePedia]
snp3D : Map Gene to Disease10370
BioCentury BCIQCITED2
ClinGenCITED2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD10370
Chemical/Pharm GKB GenePA26524
Clinical trialCITED2
Miscellaneous
canSAR (ICR)CITED2 (select the gene name)
Probes
Litterature
PubMed60 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCITED2
EVEXCITED2
GoPubMedCITED2
iHOPCITED2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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