The protein encoded by this gene inhibits transactivation of HIF1A-induced genes by competing with binding of hypoxia-inducible factor 1-alpha to p300-CH1. Mutations in this gene are a cause of cardiac septal defects. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012] See more...

Aliases for CITED2 Gene

Aliases for CITED2 Gene

  • Cbp/P300 Interacting Transactivator With Glu/Asp Rich Carboxy-Terminal Domain 2 2 3 5
  • Cbp/P300-Interacting Transactivator 2 3 4
  • MSG-Related Protein 1 3 4
  • MRG-1 3 4
  • MRG1 3 4
  • Cbp/P300-Interacting Transactivator, With Glu/Asp Rich Carboxy-Terminal Domain, 2 2
  • Melanocyte-Specific Gene 1-Related Gene 1 3
  • MSG1-Related Gene 1 3
  • P35SRJ 3
  • P35srj 4
  • ASD8 3
  • VSD2 3

External Ids for CITED2 Gene

Previous GeneCards Identifiers for CITED2 Gene

  • GC06M139316
  • GC06M139540
  • GC06M139673
  • GC06M139735
  • GC06M137254

Summaries for CITED2 Gene

Entrez Gene Summary for CITED2 Gene

  • The protein encoded by this gene inhibits transactivation of HIF1A-induced genes by competing with binding of hypoxia-inducible factor 1-alpha to p300-CH1. Mutations in this gene are a cause of cardiac septal defects. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

GeneCards Summary for CITED2 Gene

CITED2 (Cbp/P300 Interacting Transactivator With Glu/Asp Rich Carboxy-Terminal Domain 2) is a Protein Coding gene. Diseases associated with CITED2 include Atrial Septal Defect 8 and Ventricular Septal Defect 2. Among its related pathways are Gene Expression and CDK-mediated phosphorylation and removal of Cdc6. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription coactivator activity. An important paralog of this gene is CITED1.

UniProtKB/Swiss-Prot Summary for CITED2 Gene

  • Transcriptional coactivator of the p300/CBP-mediated transcription complex. Acts as a bridge, linking TFAP2 transcription factors and the p300/CBP transcriptional coactivator complex in order to stimulate TFAP2-mediated transcriptional activation. Positively regulates TGF-beta signaling through its association with the SMAD/p300/CBP-mediated transcriptional coactivator complex. Stimulates the peroxisome proliferator-activated receptors PPARA transcriptional activity. Enhances estrogen-dependent transactivation mediated by estrogen receptors. Acts also as a transcriptional corepressor; interferes with the binding of the transcription factors HIF1A or STAT2 and the p300/CBP transcriptional coactivator complex. Participates in sex determination and early gonad development by stimulating transcription activation of SRY. Plays a role in controlling left-right patterning during embryogenesis; potentiates transcriptional activation of NODAL-mediated gene transcription in the left lateral plate mesoderm (LPM). Plays an essential role in differentiation of the adrenal cortex from the adrenogonadal primordium (AGP); stimulates WT1-mediated transcription activation thereby up-regulating the nuclear hormone receptor NR5A1 promoter activity. Associates with chromatin to the PITX2 P1 promoter region.

Gene Wiki entry for CITED2 Gene

Additional gene information for CITED2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CITED2 Gene

Genomics for CITED2 Gene

GeneHancer (GH) Regulatory Elements for CITED2 Gene

Promoters and enhancers for CITED2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J139366 Promoter/Enhancer 2.5 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 521.6 +2.3 2344 11.4 EP300 HNRNPK FOXK2 ZNF217 CTCF TCF12 SIN3A MYC POLR2G USF1 CITED2 ENSG00000231329 ENSG00000226571 REPS1 HEBP2 lnc-HECA-11 lnc-CITED2-5
GH06J138986 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 11.5 +387.5 387524 3.9 HNRNPK EP300 CTCF SIN3A POLR2G GTF2E2 PHF8 ZFX ZIC2 POLR2A REPS1 CITED2 HEBP2 HSALNG0053853
GH06J138403 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 10.4 +969.8 969803 3.7 HNRNPK ZNF217 EP300 CTCF TCF12 ZSCAN5C MYC NRF1 POLR2G SP1 HEBP2 MARCKSL1P2 lnc-NHSL1-3 CITED2 lnc-HEBP2-2
GH06J138496 Promoter/Enhancer 1.9 FANTOM5 Ensembl ENCODE dbSUPER 11.5 +868.0 868022 20.3 EP300 FOXK2 CTCF POLR2G NCOR1 KDM6A TCF7 TRIM28 REST KLF4 NHSL1 CITED2 PERP ENSG00000225177 REPS1 piR-31937-222 ENSG00000274594
GH06J139576 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 12.7 -204.4 -204351 5.6 EP300 FOS REST ZNF623 TRIM28 MEF2C TOE1 TRIM22 ZEB1 RAD51 CITED2 piR-56037-040 LOC105378024 ENSG00000226571
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CITED2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CITED2

Top Transcription factor binding sites by QIAGEN in the CITED2 gene promoter:
  • AML1a

Genomic Locations for CITED2 Gene

Genomic Locations for CITED2 Gene
chr6:139,371,807-139,374,650
(GRCh38/hg38)
Size:
2,844 bases
Orientation:
Minus strand
chr6:139,693,393-139,695,785
(GRCh37/hg19)
Size:
2,393 bases
Orientation:
Minus strand

Genomic View for CITED2 Gene

Genes around CITED2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CITED2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CITED2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CITED2 Gene

Proteins for CITED2 Gene

  • Protein details for CITED2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99967-CITE2_HUMAN
    Recommended name:
    Cbp/p300-interacting transactivator 2
    Protein Accession:
    Q99967
    Secondary Accessions:
    • O95426
    • Q5VTF4

    Protein attributes for CITED2 Gene

    Size:
    270 amino acids
    Molecular mass:
    28497 Da
    Quaternary structure:
    • Interacts (via C-terminus) with SMAD2. Interacts (via C-terminus) with SMAD3 (via MH2 domain). Interacts with LHX2 (via LIM domains). Interacts with WT1 (By similarity). Interacts (via C-terminus) with EP300 (via CH1 domain); the interaction is stimulated in response to hypoxia. Interacts with PPARA. Interacts (via C-terminus) with TFAP2A, TFAP2B and TFAP2C.

    Three dimensional structures from OCA and Proteopedia for CITED2 Gene

    Alternative splice isoforms for CITED2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CITED2 Gene

Post-translational modifications for CITED2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for CITED2 Gene

No data available for DME Specific Peptides for CITED2 Gene

Domains & Families for CITED2 Gene

Gene Families for CITED2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for CITED2 Gene

Blocks:
  • CITED
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CITED2 Gene

GenScript: Design optimal peptide antigens:
  • P35srj (CITE2_HUMAN)
  • Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2, isoform CRA_d (D9ZGF1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q99967

UniProtKB/Swiss-Prot:

CITE2_HUMAN :
  • Belongs to the CITED family.
Family:
  • Belongs to the CITED family.
genes like me logo Genes that share domains with CITED2: view

Function for CITED2 Gene

Molecular function for CITED2 Gene

UniProtKB/Swiss-Prot Function:
Transcriptional coactivator of the p300/CBP-mediated transcription complex. Acts as a bridge, linking TFAP2 transcription factors and the p300/CBP transcriptional coactivator complex in order to stimulate TFAP2-mediated transcriptional activation. Positively regulates TGF-beta signaling through its association with the SMAD/p300/CBP-mediated transcriptional coactivator complex. Stimulates the peroxisome proliferator-activated receptors PPARA transcriptional activity. Enhances estrogen-dependent transactivation mediated by estrogen receptors. Acts also as a transcriptional corepressor; interferes with the binding of the transcription factors HIF1A or STAT2 and the p300/CBP transcriptional coactivator complex. Participates in sex determination and early gonad development by stimulating transcription activation of SRY. Plays a role in controlling left-right patterning during embryogenesis; potentiates transcriptional activation of NODAL-mediated gene transcription in the left lateral plate mesoderm (LPM). Plays an essential role in differentiation of the adrenal cortex from the adrenogonadal primordium (AGP); stimulates WT1-mediated transcription activation thereby up-regulating the nuclear hormone receptor NR5A1 promoter activity. Associates with chromatin to the PITX2 P1 promoter region.
UniProtKB/Swiss-Prot Induction:
By hypoxia and deferoxamine.
GENATLAS Biochemistry:
CBP/p300 interactive transactivator with ED rich tail 2,with two isoforms p35srj,ubiquitously expressed,involved in the recruitement of p300/CBP by hypoxia-inducible factor HIF1A and mrg1 (MSG1-related gene),cytokine-inducible transcription factor with transformation activity

Phenotypes From GWAS Catalog for CITED2 Gene

Gene Ontology (GO) - Molecular Function for CITED2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001102 RNA polymerase II activating transcription factor binding IEA --
GO:0003682 chromatin binding ISS --
GO:0003700 DNA-binding transcription factor activity ISS --
GO:0003713 transcription coactivator activity IBA,IDA 11581164
GO:0003714 transcription corepressor activity IMP 17906695
genes like me logo Genes that share ontologies with CITED2: view
genes like me logo Genes that share phenotypes with CITED2: view

Human Phenotype Ontology for CITED2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CITED2 Gene

MGI Knock Outs for CITED2:

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CITED2 Gene

Localization for CITED2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CITED2 Gene

Nucleus. Note=Colocalizes with EP300 in dot-like structures.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CITED2 gene
Compartment Confidence
nucleus 5
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
cytosol 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CITED2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISS --
GO:0005634 nucleus IBA,IDA 9434189
GO:0005654 nucleoplasm TAS --
GO:0032991 protein-containing complex IMP 14594809
genes like me logo Genes that share ontologies with CITED2: view

Pathways & Interactions for CITED2 Gene

genes like me logo Genes that share pathways with CITED2: view

Pathways by source for CITED2 Gene

SIGNOR curated interactions for CITED2 Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for CITED2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IMP 17906695
GO:0001568 blood vessel development IEA --
GO:0001570 vasculogenesis IEA --
GO:0001666 response to hypoxia IMP 17906695
GO:0001701 in utero embryonic development IEA --
genes like me logo Genes that share ontologies with CITED2: view

Drugs & Compounds for CITED2 Gene

No Compound Related Data Available

Transcripts for CITED2 Gene

mRNA/cDNA for CITED2 Gene

3 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CITED2 Gene

No ASD Table

Relevant External Links for CITED2 Gene

GeneLoc Exon Structure for
CITED2

Expression for CITED2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CITED2 Gene

Protein differential expression in normal tissues from HIPED for CITED2 Gene

This gene is overexpressed in Fetal heart (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CITED2 Gene



Protein tissue co-expression partners for CITED2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CITED2

SOURCE GeneReport for Unigene cluster for CITED2 Gene:

Hs.82071

Evidence on tissue expression from TISSUES for CITED2 Gene

  • Pancreas(4.3)
  • Heart(3.2)
  • Kidney(2.8)
  • Muscle(2.8)
  • Liver(2.7)
  • Nervous system(2.7)
  • Adrenal gland(2.6)
  • Intestine(2.5)
  • Lung(2.5)
  • Skin(2.1)
  • Bone marrow(2)
  • Thyroid gland(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CITED2 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • cardiovascular
  • integumentary
  • nervous
  • reproductive
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • lip
  • nose
  • outer ear
  • skull
Thorax:
  • heart
  • heart valve
Pelvis:
  • testicle
Limb:
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • toe
  • upper limb
General:
  • skin
genes like me logo Genes that share expression patterns with CITED2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for CITED2 Gene

Orthologs for CITED2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CITED2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CITED2 31 30
  • 94.91 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CITED2 31
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CITED2 31 30
  • 91.98 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Cited2 17 31 30
  • 91.82 (n)
rat
(Rattus norvegicus)
Mammalia Cited2 30
  • 91.45 (n)
cow
(Bos Taurus)
Mammalia CITED2 31 30
  • 90.74 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CITED2 31
  • 81 (a)
OneToOne
chicken
(Gallus gallus)
Aves CITED2 31 30
  • 80.28 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CITED2 31
  • 83 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia cited2 30
  • 74.67 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.25598 30
zebrafish
(Danio rerio)
Actinopterygii cited2 31 30
  • 69.71 (n)
OneToOne
idibd5008 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.10810 30
Species where no ortholog for CITED2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CITED2 Gene

ENSEMBL:
Gene Tree for CITED2 (if available)
TreeFam:
Gene Tree for CITED2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CITED2: view image

Paralogs for CITED2 Gene

Paralogs for CITED2 Gene

genes like me logo Genes that share paralogs with CITED2: view

Variants for CITED2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CITED2 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
560611 Uncertain Significance: not specified 139,373,466(-) T/A MISSENSE_VARIANT
668342 Likely Benign: not provided 139,373,371(-) T/C MISSENSE_VARIANT
rs1064797329 Uncertain Significance: not provided 139,373,151(-) G/GGCT INFRAME_INSERTION
rs1554233859 Uncertain Significance: not provided 139,373,871(-) G/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for CITED2 Gene

Variation tolerance for CITED2 Gene

Residual Variation Intolerance Score: 20.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.64; 31.47% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CITED2 Gene

Human Gene Mutation Database (HGMD)
CITED2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CITED2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for CITED2 Gene

Disorders for CITED2 Gene

MalaCards: The human disease database

(20) MalaCards diseases for CITED2 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
atrial septal defect 8
  • asd8
ventricular septal defect 2
  • vsd2
atrial septal defect sinus venosus
  • sinus venosus asd
patent foramen ovale
  • atrial septal defect within oval fossa
hypoxia
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

CITE2_HUMAN
  • Ventricular septal defect 2 (VSD2) [MIM:614431]: A common form of congenital cardiovascular anomaly that may occur alone or in combination with other cardiac malformations. It can affect any portion of the ventricular septum, resulting in abnormal communications between the two lower chambers of the heart. Classification is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect. Large defects that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death. {ECO:0000269 PubMed:16287139}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Atrial septal defect 8 (ASD8) [MIM:614433]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. {ECO:0000269 PubMed:16287139}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for CITED2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CITED2: view

No data available for Genatlas for CITED2 Gene

Publications for CITED2 Gene

  1. Molecular cloning and chromosomal localization of the human CITED2 gene encoding p35srj/Mrg1. (PMID: 10552932) Leung MK … Bhattacharya S (Genomics 1999) 2 3 4 23 54
  2. Identification and functional analysis of CITED2 mutations in patients with congenital heart defects. (PMID: 16287139) Sperling S … Hammer S (Human mutation 2005) 3 4 41 54
  3. Interaction of the TAZ1 domain of the CREB-binding protein with the activation domain of CITED2: regulation by competition between intrinsically unstructured ligands for non-identical binding sites. (PMID: 14594809) De Guzman RN … Wright PE (The Journal of biological chemistry 2004) 3 4 23 54
  4. Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1. (PMID: 9887100) Bhattacharya S … Livingston DM (Genes & development 1999) 3 4 23 54
  5. msg1, a novel melanocyte-specific gene, encodes a nuclear protein and is associated with pigmentation. (PMID: 8901575) Shioda T … Isselbacher KJ (Proceedings of the National Academy of Sciences of the United States of America 1996) 2 3 4 54

Products for CITED2 Gene

Sources for CITED2 Gene