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Protein

Cbp/p300-interacting transactivator 2

Gene

CITED2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • histone acetyltransferase binding Source: BHF-UCL
  • LBD domain binding Source: UniProtKB
  • 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
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein, Repressor

Keywords - Biological processi

Differentiation, Stress response, Transcription, Transcription regulation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164442-MONOMER.
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

HGNCiHGNC:1987. CITED2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nuclear chromatin Source: BHF-UCL
  • nucleus Source: UniProtKB
Complete GO annotation...

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.

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.

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

WithEntry#Exp.IntActNotes
EP300Q094723EBI-937732,EBI-447295
HNF4AP412353EBI-937732,EBI-1049011
TFAP2CQ927542EBI-937732,EBI-937309

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi115649. 13 interactors.
IntActiQ99967. 7 interactors.
MINTiMINT-112487.
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.
PhylomeDBiQ99967.
TreeFamiTF331915.

Family and domain databases

InterProiIPR007576. CITED.
[Graphical view]
PANTHERiPTHR17045. PTHR17045. 2 hits.
PfamiPF04487. CITED. 1 hit.
[Graphical view]

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. Translation: CAH70354.1.
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

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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. Translation: CAH70354.1.
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.

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...

Protein-protein interaction databases

BioGridi115649. 13 interactors.
IntActiQ99967. 7 interactors.
MINTiMINT-112487.
STRINGi9606.ENSP00000356623.

PTM databases

iPTMnetiQ99967.
PhosphoSitePlusiQ99967.

Polymorphism and mutation databases

BioMutaiCITED2.
DMDMi21542403.

Proteomic databases

PaxDbiQ99967.
PeptideAtlasiQ99967.
PRIDEiQ99967.

Protocols and materials databases

DNASUi10370.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi10370.
DisGeNETi10370.
GeneCardsiCITED2.
H-InvDBHIX0006261.
HGNCiHGNC:1987. CITED2.
HPAiCAB016157.
MalaCardsiCITED2.
MIMi602937. gene.
614431. phenotype.
614433. phenotype.
neXtProtiNX_Q99967.
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.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IH9P. Eukaryota.
ENOG410Y09Y. LUCA.
GeneTreeiENSGT00530000063624.
HOGENOMiHOG000231079.
HOVERGENiHBG075182.
InParanoidiQ99967.
PhylomeDBiQ99967.
TreeFamiTF331915.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164442-MONOMER.
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.

Miscellaneous databases

ChiTaRSiCITED2. human.
EvolutionaryTraceiQ99967.
GeneWikiiCITED2.
GenomeRNAii10370.
PROiQ99967.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164442.
CleanExiHS_CITED2.
ExpressionAtlasiQ99967. baseline and differential.
GenevisibleiQ99967. HS.

Family and domain databases

InterProiIPR007576. CITED.
[Graphical view]
PANTHERiPTHR17045. PTHR17045. 2 hits.
PfamiPF04487. CITED. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCITE2_HUMAN
AccessioniPrimary (citable) accession number: Q99967
Secondary accession number(s): O95426, Q5VTF4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: June 20, 2002
Last modified: November 2, 2016
This is version 158 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.