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Protein

Cbp/p300-interacting transactivator 2

Gene

CITED2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • DNA binding transcription factor activity Source: UniProtKB
  • histone acetyltransferase binding Source: BHF-UCL
  • LBD domain binding Source: UniProtKB
  • protein domain specific binding Source: CAFA
  • RNA polymerase II transcription coactivator activity Source: GO_Central
  • RNA polymerase II transcription corepressor activity Source: BHF-UCL
  • transcription coactivator activity Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionActivator, Developmental protein, Repressor
Biological processDifferentiation, Stress response, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-1234158 Regulation of gene expression by Hypoxia-inducible Factor
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
SIGNORiQ99967

Names & Taxonomyi

Protein namesi
Recommended name:
Cbp/p300-interacting transactivator 2
Alternative name(s):
MSG-related protein 1
Short name:
MRG-1
P35srj
Gene namesi
Name:CITED2
Synonyms:MRG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000164442.9
HGNCiHGNC:1987 CITED2
MIMi602937 gene
neXtProtiNX_Q99967

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Ventricular septal defect 2 (VSD2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:614431
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067583170 – 178Missing in VSD2; reduces coactivation of the TFAP2C gene to 50% of that obtained with wild-type and represses HIF1A with about 60% efficiency compared to wild-type. 1 Publication9
Atrial septal defect 8 (ASD8)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria.
See also OMIM:614433
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067584179S → GGSSTPGGS in ASD8; demonstrates only about 75% of the repressive activity of wild-type. 1
Natural variantiVAR_067585198 – 199Missing in ASD8; demonstrates only about 75% of the repressive activity of wild-type. 1 Publication2

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi243 – 246Missing : Inhibits transactivation activity. 1 Publication4
Mutagenesisi243L → E: Inhibits transactivation activity; when associated with E-246. 1 Publication1
Mutagenesisi246L → E: Inhibits transactivation activity; when associated with E-243. 1 Publication1

Keywords - Diseasei

Atrial septal defect, Disease mutation

Organism-specific databases

DisGeNETi10370
MalaCardsiCITED2
MIMi614431 phenotype
614433 phenotype
OpenTargetsiENSG00000164442
Orphaneti99103 Atrial septal defect, ostium secundum type
99105 Atrial septal defect, sinus venosus type
99097 Single ventricular septal defect
101063 Situs inversus totalis
3303 Tetralogy of Fallot
PharmGKBiPA26524

Polymorphism and mutation databases

BioMutaiCITED2
DMDMi21542403

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001447261 – 270Cbp/p300-interacting transactivator 2Add BLAST270

Proteomic databases

PaxDbiQ99967
PeptideAtlasiQ99967
PRIDEiQ99967
ProteomicsDBi78555
78556 [Q99967-2]

PTM databases

iPTMnetiQ99967
PhosphoSitePlusiQ99967

Expressioni

Inductioni

By hypoxia and deferoxamine.1 Publication

Gene expression databases

BgeeiENSG00000164442
CleanExiHS_CITED2
ExpressionAtlasiQ99967 baseline and differential
GenevisibleiQ99967 HS

Organism-specific databases

HPAiCAB016157
CAB069879

Interactioni

Subunit structurei

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.By similarity6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • histone acetyltransferase binding Source: BHF-UCL
  • LBD domain binding Source: UniProtKB
  • protein domain specific binding Source: CAFA

Protein-protein interaction databases

BioGridi115649, 13 interactors
IntActiQ99967, 7 interactors
MINTiQ99967
STRINGi9606.ENSP00000356623

Structurei

Secondary structure

1270
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi221 – 223Combined sources3
Helixi227 – 235Combined sources9
Beta strandi237 – 239Combined sources3
Helixi251 – 253Combined sources3
Helixi254 – 256Combined sources3
Helixi266 – 268Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1P4QNMR-A216-259[»]
1R8UNMR-A220-269[»]
DisProtiDP00356
ProteinModelPortaliQ99967
SMRiQ99967
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99967

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi21 – 57His-richAdd BLAST37
Compositional biasi162 – 199Gly-richAdd BLAST38
Compositional biasi219 – 258Asp/Glu-rich (acidic)Add BLAST40

Sequence similaritiesi

Belongs to the CITED family.Curated

Phylogenomic databases

eggNOGiENOG410IH9P Eukaryota
ENOG410Y09Y LUCA
GeneTreeiENSGT00530000063624
HOGENOMiHOG000231079
HOVERGENiHBG075182
InParanoidiQ99967
KOiK21361
PhylomeDBiQ99967
TreeFamiTF331915

Family and domain databases

InterProiView protein in InterPro
IPR007576 CITED
PANTHERiPTHR17045 PTHR17045, 1 hit
PfamiView protein in Pfam
PF04487 CITED, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99967-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MADHMMAMNH GRFPDGTNGL HHHPAHRMGM GQFPSPHHHQ QQQPQHAFNA
60 70 80 90 100
LMGEHIHYGA GNMNATSGIR HAMGPGTVNG GHPPSALAPA ARFNNSQFMG
110 120 130 140 150
PPVASQGGSL PASMQLQKLN NQYFNHHPYP HNHYMPDLHP AAGHQMNGTN
160 170 180 190 200
QHFRDCNPKH SGGSSTPGGS GGSSTPGGSG SSSGGGAGSS NSGGGSGSGN
210 220 230 240 250
MPASVAHVPA AMLPPNVIDT DFIDEEVLMS LVIEMGLDRI KELPELWLGQ
260 270
NEFDFMTDFV CKQQPSRVSC
Length:270
Mass (Da):28,497
Last modified:June 20, 2002 - v2
Checksum:i45DDE3A9E2B4C472
GO
Isoform 2 (identifier: Q99967-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     159-215: Missing.

Show »
Length:213
Mass (Da):23,732
Checksum:iC91FAABA3D2A9AD1
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067583170 – 178Missing in VSD2; reduces coactivation of the TFAP2C gene to 50% of that obtained with wild-type and represses HIF1A with about 60% efficiency compared to wild-type. 1 Publication9
Natural variantiVAR_067584179S → GGSSTPGGS in ASD8; demonstrates only about 75% of the repressive activity of wild-type. 1
Natural variantiVAR_067585198 – 199Missing in ASD8; demonstrates only about 75% of the repressive activity of wild-type. 1 Publication2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001089159 – 215Missing in isoform 2. 1 PublicationAdd BLAST57

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U65093 mRNA Translation: AAC51114.1
AF129290 Genomic DNA Translation: AAF01263.1
AF129290 Genomic DNA Translation: AAF01264.1
AF109161 mRNA Translation: AAD10055.1
AL592429 Genomic DNA No translation available.
BC004377 mRNA Translation: AAH04377.1
CCDSiCCDS5195.1 [Q99967-1]
RefSeqiNP_001161860.1, NM_001168388.2 [Q99967-1]
NP_001161861.2, NM_001168389.2
NP_006070.2, NM_006079.4 [Q99967-1]
UniGeneiHs.82071

Genome annotation databases

EnsembliENST00000367651; ENSP00000356623; ENSG00000164442 [Q99967-1]
ENST00000536159; ENSP00000442831; ENSG00000164442 [Q99967-1]
ENST00000618718; ENSP00000479918; ENSG00000164442 [Q99967-2]
GeneIDi10370
KEGGihsa:10370
UCSCiuc003qip.3 human [Q99967-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCITE2_HUMAN
AccessioniPrimary (citable) accession number: Q99967
Secondary accession number(s): O95426, Q5VTF4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: June 20, 2002
Last modified: June 20, 2018
This is version 168 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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