Gene/Proteome Database (LMPD)
LMPD ID
LMP004097
Gene ID
Species
Homo sapiens (Human)
Gene Name
nuclear receptor coactivator 2
Gene Symbol
Synonyms
GRIP1; KAT13C; NCoA-2; SRC2; TIF2; bHLHe75
Alternate Names
nuclear receptor coactivator 2; hTIF2; transcriptional intermediary factor 2; class E basic helix-loop-helix protein 75; glucocorticoid receptor-interacting protein-1
Chromosome
8
Map Location
8q13.3
Summary
The NCOA2 gene encodes nuclear receptor coactivator 2, which aids in the function of nuclear hormone receptors. Nuclear hormone receptors are conditional transcription factors that play important roles in various aspects of cell growth, development, and homeostasis by controlling expression of specific genes. Members of the nuclear hormone receptor superfamily, which includes the 5 steroid receptors and class II nuclear receptors (see below), are structurally characterized by 3 distinct domains: an N-terminal transcriptional activation domain, a central DNA-binding domain, and a C-terminal hormone-binding domain. Before the binding of hormone, steroid receptors, which are sometimes called class I of the nuclear hormone receptor family, remain inactive in a complex with heat-shock protein-90 (MIM 140571) and other stress family proteins. Binding of hormone induces critical conformational changes in steroid receptors that cause them to dissociate from the inhibitory complex, bind as homodimers to specific DNA enhancer elements associated with target genes, and modulate that gene's transcription. After binding to enhancer elements, transcription factors require transcriptional coactivator proteins to mediate their stimulation of transcription initiation (Hong et al., 1997 [PubMed 9111344]).[supplied by OMIM, Nov 2010]
Orthologs
Proteins
| nuclear receptor coactivator 2 | |
|---|---|
| Refseq ID | NP_006531 |
| Protein GI | 5729858 |
| UniProt ID | Q15596 |
| mRNA ID | NM_006540 |
| Length | 1464 |
| RefSeq Status | VALIDATED |
| MSGMGENTSDPSRAETRKRKECPDQLGPSPKRNTEKRNREQENKYIEELAELIFANFNDIDNFNFKPDKCAILKETVKQIRQIKEQEKAAAANIDEVQKSDVSSTGQGVIDKDALGPMMLEALDGFFFVVNLEGNVVFVSENVTQYLRYNQEELMNKSVYSILHVGDHTEFVKNLLPKSIVNGGSWSGEPPRRNSHTFNCRMLVKPLPDSEEEGHDNQEAHQKYETMQCFAVSQPKSIKEEGEDLQSCLICVARRVPMKERPVLPSSESFTTRQDLQGKITSLDTSTMRAAMKPGWEDLVRRCIQKFHAQHEGESVSYAKRHHHEVLRQGLAFSQIYRFSLSDGTLVAAQTKSKLIRSQTTNEPQLVISLHMLHREQNVCVMNPDLTGQTMGKPLNPISSNSPAHQALCSGNPGQDMTLSSNINFPINGPKEQMGMPMGRFGGSGGMNHVSGMQATTPQGSNYALKMNSPSQSSPGMNPGQPTSMLSPRHRMSPGVAGSPRIPPSQFSPAGSLHSPVGVCSSTGNSHSYTNSSLNALQALSEGHGVSLGSSLASPDLKMGNLQNSPVNMNPPPLSKMGSLDSKDCFGLYGEPSEGTTGQAESSCHPGEQKETNDPNLPPAVSSERADGQSRLHDSKGQTKLLQLLTTKSDQMEPSPLASSLSDTNKDSTGSLPGSGSTHGTSLKEKHKILHRLLQDSSSPVDLAKLTAEATGKDLSQESSSTAPGSEVTIKQEPVSPKKKENALLRYLLDKDDTKDIGLPEITPKLERLDSKTDPASNTKLIAMKTEKEEMSFEPGDQPGSELDNLEEILDDLQNSQLPQLFPDTRPGAPAGSVDKQAIINDLMQLTAENSPVTPVGAQKTALRISQSTFNNPRPGQLGRLLPNQNLPLDITLQSPTGAGPFPPIRNSSPYSVIPQPGMMGNQGMIGNQGNLGNSSTGMIGNSASRPTMPSGEWAPQSSAVRVTCAATTSAMNRPVQGGMIRNPAASIPMRPSSQPGQRQTLQSQVMNIGPSELEMNMGGPQYSQQQAPPNQTAPWPESILPIDQASFASQNRQPFGSSPDDLLCPHPAAESPSDEGALLDQLYLALRNFDGLEEIDRALGIPELVSQSQAVDPEQFSSQDSNIMLEQKAPVFPQQYASQAQMAQGSYSPMQDPNFHTMGQRPSYATLRMQPRPGLRPTGLVQNQPNQLRLQLQHRLQAQQNRQPLMNQISNVSNVNLTLRPGVPTQAPINAQMLAQRQREILNQHLRQRQMHQQQQVQQRTLMMRGQGLNMTPSMVAPSGMPATMSNPRIPQANAQQFPFPPNYGISQQPDPGFTGATTPQSPLMSPRMAHTQSPMMQQSQANPAYQAPSDINGWAQGNMGGNSMFSQQSPPHFGQQANTSMYSNNMNINVSMATNTGGMSSMNQMTGQISMTSVTSVPTSGLSSMGPEQVNDPALRGGNLFPNQLPGMDMIKQEGDTTRKYC | |
Gene Information
Entrez Gene ID
Gene Name
nuclear receptor coactivator 2
Gene Symbol
Species
Homo sapiens
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005737 | IEA:Ensembl | C | cytoplasm |
| GO:0005654 | TAS:Reactome | C | nucleoplasm |
| GO:0003682 | IEA:Ensembl | F | chromatin binding |
| GO:0004402 | IEA:InterPro | F | histone acetyltransferase activity |
| GO:0016922 | IPI:UniProtKB | F | ligand-dependent nuclear receptor binding |
| GO:0030374 | IDA:BHF-UCL | F | ligand-dependent nuclear receptor transcription coactivator activity |
| GO:0035257 | IPI:UniProtKB | F | nuclear hormone receptor binding |
| GO:0004871 | IEA:InterPro | F | signal transducer activity |
| GO:0030375 | IEA:Ensembl | F | thyroid hormone receptor coactivator activity |
| GO:0003713 | ISS:UniProtKB | F | transcription coactivator activity |
| GO:0044255 | TAS:Reactome | P | cellular lipid metabolic process |
| GO:0000122 | IEA:Ensembl | P | negative regulation of transcription from RNA polymerase II promoter |
| GO:0045944 | IEA:Ensembl | P | positive regulation of transcription from RNA polymerase II promoter |
| GO:0010906 | IEA:Ensembl | P | regulation of glucose metabolic process |
| GO:0006355 | NAS:UniProtKB | P | regulation of transcription, DNA-templated |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
| GO:0006351 | IEA:UniProtKB-KW | P | transcription, DNA-templated |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| hsa04919 | Thyroid hormone signaling pathway |
REACTOME Pathway Links
| REACTOME Pathway ID | Description |
|---|---|
| REACT_200608 | Transcriptional activation of mitochondrial biogenesis |
Domain Information
InterPro Annotations
| Accession | Description |
|---|---|
| IPR010011 | Domain of unknown function DUF1518 |
| IPR011598 | Myc-type, basic helix-loop-helix (bHLH) domain |
| IPR017426 | Nuclear receptor coactivator |
| IPR028822 | Nuclear receptor coactivator 2 |
| IPR008955 | Nuclear receptor coactivator Src-1 |
| IPR014920 | Nuclear receptor coactivator, Ncoa-type, interlocking |
| IPR009110 | Nuclear receptor coactivator, interlocking |
| IPR001610 | PAC motif |
| IPR000014 | PAS domain |
| IPR013767 | PAS_fold |
| IPR014935 | Steroid receptor coactivator |
UniProt Annotations
Entry Information
Comments
| Comment Type | Description |
|---|---|
| Disease | Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N- terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation. |
| Domain | Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently. |
| Domain | Contains four Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors and are, at least in part, functionally redundant. |
| Domain | The LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding. |
| Function | Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF- 2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues. Critical regulator of glucose metabolism regulation, acts as RORA coactivator to specifically modulate G6PC expression. Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3. {ECO |
| Interaction | P10275:AR; NbExp=2; IntAct=EBI-81236, EBI-608057; Q92841:DDX17; NbExp=2; IntAct=EBI-81236, EBI-746012; P03372:ESR1; NbExp=8; IntAct=EBI-81236, EBI-78473; |
| Similarity | Belongs to the SRC/p160 nuclear receptor coactivator family. |
| Similarity | Contains 1 PAS (PER-ARNT-SIM) domain. |
| Similarity | Contains 1 bHLH (basic helix-loop-helix) domain. |
| Subcellular Location | Nucleus. |
| Subunit | Present in a complex containing NCOA3, IKKA, IKKB, IKBKG and CREBBP. Interacts (via C-terminus) with CREBBP. Interacts with ESR1, HIF1A, NCOA1, APEX, NR3C1, NR3C2, CARM1, RARA, and RXRA. Present in a complex containing CARM1 and EP300/P300. Interacts with CASP8AP2 and TTLL5/STAMP. Interacts with PSMB9 and DDX5. Interacts (via LXXLL 1, 2 and 3 motifs) with RORA and RORC (via AF-2 motif). Interacts with RWDD3. {ECO |
Identical and Related Proteins
Unique RefSeq proteins for LMP004097 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 5729858 | RefSeq | NP_006531 | 1464 | nuclear receptor coactivator 2 |
Identical Sequences to LMP004097 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:5729858 | RefSeq | XP_009453760.1 | 1464 | PREDICTED: nuclear receptor coactivator 2 isoform X1 [Pan troglodytes] |
| GI:5729858 | RefSeq | XP_009453761.1 | 1464 | PREDICTED: nuclear receptor coactivator 2 isoform X1 [Pan troglodytes] |
| GI:5729858 | RefSeq | XP_009453762.1 | 1464 | PREDICTED: nuclear receptor coactivator 2 isoform X1 [Pan troglodytes] |
| GI:5729858 | RefSeq | XP_009453763.1 | 1464 | PREDICTED: nuclear receptor coactivator 2 isoform X1 [Pan troglodytes] |
| GI:5729858 | RefSeq | XP_009453764.1 | 1464 | PREDICTED: nuclear receptor coactivator 2 isoform X1 [Pan troglodytes] |
| GI:5729858 | RefSeq | XP_009453765.1 | 1464 | PREDICTED: nuclear receptor coactivator 2 isoform X1 [Pan troglodytes] |
Related Sequences to LMP004097 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:5729858 | DBBJ | BAG10541.1 | 1464 | nuclear receptor coactivator 2, partial [synthetic construct] |
| GI:5729858 | GenBank | AAI14384.1 | 1464 | Nuclear receptor coactivator 2 [Homo sapiens] |
| GI:5729858 | RefSeq | XP_003831386.1 | 1464 | PREDICTED: nuclear receptor coactivator 2 isoform X1 [Pan paniscus] |
| GI:5729858 | RefSeq | XP_004047182.1 | 1464 | PREDICTED: nuclear receptor coactivator 2 [Gorilla gorilla gorilla] |
| GI:5729858 | RefSeq | XP_008954950.1 | 1464 | PREDICTED: nuclear receptor coactivator 2 isoform X1 [Pan paniscus] |
| GI:5729858 | RefSeq | XP_008954951.1 | 1464 | PREDICTED: nuclear receptor coactivator 2 isoform X1 [Pan paniscus] |