Human Gene CITED2 (ENST00000367651.4) from GENCODE V43
  Description: Homo sapiens Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2 (CITED2), transcript variant 1, mRNA. (from RefSeq NM_006079)
RefSeq Summary (NM_006079): 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].
Gencode Transcript: ENST00000367651.4
Gencode Gene: ENSG00000164442.10
Transcript (Including UTRs)
   Position: hg38 chr6:139,371,807-139,374,648 Size: 2,842 Total Exon Count: 2 Strand: -
Coding Region
   Position: hg38 chr6:139,373,132-139,373,944 Size: 813 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-02-17 13:02:02

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr6:139,371,807-139,374,648)mRNA (may differ from genome)Protein (270 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSCGAPEnsemblEntrez GeneExonPrimer

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Cbp/p300-interacting transactivator 2; AltName: Full=MSG-related protein 1; Short=MRG-1; AltName: Full=P35srj;
FUNCTION: Transcriptional coactivator of the p300/CBP-mediated trancription 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.
SUBUNIT: 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.
INTERACTION: Q09472:EP300; NbExp=3; IntAct=EBI-937732, EBI-447295; Q92754:TFAP2C; NbExp=2; IntAct=EBI-937732, EBI-937309;
SUBCELLULAR LOCATION: Nucleus. Note=Colocalizes with EP300 in dot- like structures.
INDUCTION: By hypoxia and deferoxamine.
DISEASE: Defects in CITED2 are a cause of ventricular septal defect type 2 (VSD2) [MIM:614431]. VSD2 is 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.
DISEASE: Defects in CITED2 are a cause of atrial septal defect type 8 (ASD8) [MIM:614433]. ASD8 is 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.
SIMILARITY: Belongs to the CITED family.

-  Primer design for this transcript

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Click here to load the transcript sequence and exon structure into Primer3Plus

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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3

-  MalaCards Disease Associations
  MalaCards Gene Search: CITED2
Diseases sorted by gene-association score: atrial septal defect 8* (1019), ventricular septal defect 2* (1019), atrial septal defect sinus venosus* (350), patent foramen ovale* (143), hypoxia (19), atrial septal defect 3 (11), tetralogy of fallot* (9), dextrocardia with situs inversus* (9), ventricular septal defect (8), exencephaly (8), char syndrome (7), heart septal defect (6), conotruncal heart malformations (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 256.26 RPKM in Cells - Cultured fibroblasts
Total median expression: 2254.74 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -90.40244-0.370 Picture PostScript Text
3' UTR -293.301325-0.221 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007576 - CITED

Pfam Domains:
PF04487 - CITED

Protein Data Bank (PDB) 3-D Structure
MuPIT help

ModBase Predicted Comparative 3D Structure on Q99967
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001105 RNA polymerase II transcription coactivator activity
GO:0001106 RNA polymerase II transcription corepressor activity
GO:0003682 chromatin binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0003713 transcription coactivator activity
GO:0003714 transcription corepressor activity
GO:0005515 protein binding
GO:0019904 protein domain specific binding
GO:0035035 histone acetyltransferase binding
GO:0050693 LBD domain binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001666 response to hypoxia
GO:0001889 liver development
GO:0003151 outflow tract morphogenesis
GO:0003156 regulation of animal organ formation
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
GO:0007275 multicellular organism development
GO:0007368 determination of left/right symmetry
GO:0007507 heart development
GO:0007530 sex determination
GO:0008283 cell proliferation
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0022409 positive regulation of cell-cell adhesion
GO:0030154 cell differentiation
GO:0030336 negative regulation of cell migration
GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway
GO:0034405 response to fluid shear stress
GO:0035360 positive regulation of peroxisome proliferator activated receptor signaling pathway
GO:0035802 adrenal cortex formation
GO:0043066 negative regulation of apoptotic process
GO:0043627 response to estrogen
GO:0045787 positive regulation of cell cycle
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048536 spleen development
GO:0060412 ventricular septum morphogenesis
GO:0060971 embryonic heart tube left/right pattern formation
GO:0060972 left/right pattern formation
GO:0061428 negative regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0070986 left/right axis specification
GO:1900164 nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
GO:2000020 positive regulation of male gonad development

Cellular Component:
GO:0000790 nuclear chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0032991 macromolecular complex

-  Descriptions from all associated GenBank mRNAs
  LF208705 - JP 2014500723-A/16208: Polycomb-Associated Non-Coding RNAs.
MA444282 - JP 2018138019-A/16208: Polycomb-Associated Non-Coding RNAs.
AF109161 - Homo sapiens p35srj (MRG1) mRNA, complete cds.
BC004377 - Homo sapiens Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2, mRNA (cDNA clone MGC:10574 IMAGE:3640855), complete cds.
JD450666 - Sequence 431690 from Patent EP1572962.
JD166852 - Sequence 147876 from Patent EP1572962.
JD286157 - Sequence 267181 from Patent EP1572962.
LF321905 - JP 2014500723-A/129408: Polycomb-Associated Non-Coding RNAs.
MA557482 - JP 2018138019-A/129408: Polycomb-Associated Non-Coding RNAs.
U65093 - Human msg1-related gene 1 (mrg1) mRNA, complete cds.
JD460505 - Sequence 441529 from Patent EP1572962.
DQ893296 - Synthetic construct clone IMAGE:100005926; FLH199490.01X; RZPDo839D1082D Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2 (CITED2) gene, encodes complete protein.
DQ896731 - Synthetic construct Homo sapiens clone IMAGE:100011191; FLH199396.01L; RZPDo839D1081D Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2 (CITED2) gene, encodes complete protein.
AB464473 - Synthetic construct DNA, clone: pF1KB9584, Homo sapiens CITED2 gene for Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2, without stop codon, in Flexi system.
LF321904 - JP 2014500723-A/129407: Polycomb-Associated Non-Coding RNAs.
MA557481 - JP 2018138019-A/129407: Polycomb-Associated Non-Coding RNAs.
LF321902 - JP 2014500723-A/129405: Polycomb-Associated Non-Coding RNAs.
MA557479 - JP 2018138019-A/129405: Polycomb-Associated Non-Coding RNAs.
JD204121 - Sequence 185145 from Patent EP1572962.
LF321900 - JP 2014500723-A/129403: Polycomb-Associated Non-Coding RNAs.
MA557477 - JP 2018138019-A/129403: Polycomb-Associated Non-Coding RNAs.
JD482765 - Sequence 463789 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_pparaPathway - Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha)

Reactome (by CSHL, EBI, and GO)

Protein Q99967 (Reactome details) participates in the following event(s):

R-HSA-8864718 TFAP2A,TFAP2C homodimers:CITED2 binds PITX2 gene promoter
R-HSA-8864307 TFAP2 homo- and heterodimers bind CITED and EP300/CREBBP
R-HSA-8866906 TFAP2 (AP-2) family regulates transcription of other transcription factors
R-HSA-8866907 Activation of the TFAP2 (AP-2) family of transcription factors
R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors
R-HSA-212436 Generic Transcription Pathway
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: CITE2_HUMAN, ENST00000367651.1, ENST00000367651.2, ENST00000367651.3, MRG1, NM_006079, O95426, Q5VTF4, Q99967, uc003qip.1, uc003qip.2, uc003qip.3, uc003qip.4
UCSC ID: ENST00000367651.4
RefSeq Accession: NM_006079
Protein: Q99967 (aka CITE2_HUMAN or CIT2_HUMAN)
CCDS: CCDS5195.1, CCDS75530.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.