NCOA2 (nuclear receptor coactivator 2)
- symbol:
- NCOA2
- locus group:
- protein-coding gene
- location:
- 8q13.3
- gene_family:
- Basic helix-loop-helix proteins|K(lysine) acetyltransferases
- alias symbol:
- TIF2|GRIP1|NCoA-2|KAT13C|bHLHe75
- alias name:
- glucocorticoid receptor interact...
- entrez id:
- 10499
- ensembl gene id:
- ENSG00000140396
- ucsc gene id:
- uc003xyn.2
- refseq accession:
- NM_001321703
- hgnc_id:
- HGNC:7669
- approved reserved:
- 1999-12-17
NCOA2（核受体共激活因子2），也称为SRC-2或TIF2，属于核受体共激活因子（SRC）家族，该家族包括NCOA1、NCOA2和NCOA3。这些共激活因子通过与核受体（如雌激素受体、雄激素受体和甲状腺激素受体）结合，增强靶基因的转录活性，从而调控细胞增殖、分化、代谢和生殖等生理过程。NCOA2在多种组织中表达，尤其在乳腺、前列腺和卵巢等激素敏感组织中发挥重要作用。它通过招募组蛋白乙酰转移酶（如CBP/p300）和其他转录辅助因子，改变染色质结构，促进基因表达。NCOA2的突变或异常表达与多种疾病相关，例如某些癌症（如乳腺癌和前列腺癌）中常见NCOA2的过表达，这可能通过过度激活激素信号通路促进肿瘤生长。此外，NCOA2的融合基因（如NCOA2-RET）在某些甲状腺癌中被发现，导致组成性激活下游信号通路。降低NCOA2表达可能影响激素依赖性基因的调控，导致代谢紊乱或生殖功能障碍。在动物模型中，NCOA2敲除小鼠表现出能量代谢异常和生育能力下降。NCOA2还参与炎症反应和免疫调节，其表达水平变化可能影响免疫相关疾病的发展。该基因的调控异常还与肥胖和糖尿病等代谢性疾病有关。NCOA2作为转录共激活因子的核心功能使其成为多种信号通路的关键节点，其表达或活性的改变可能广泛影响细胞行为和组织稳态。
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]
的NCOA2基因编码核受体辅活化子2，这有助于核激素受体的功能。核激素受体是有条件的转录因子，它通过控制特定基因的表达在细胞的生长，发育和体内稳态的各个方面的重要作用。 N末端转录激活区，中央的DNA结合结构域，和C：核激素受体超家族，它包括5类固醇激素受体和II类核受体（见下文），在结构上其特征在于，3个不同的域的成员末端激素结合结构域。激素的结合之前，类固醇受体，它有时被称为核激素受体家族的I类，保持与热休克蛋白90（MIM 140571）和其他应力家族蛋白的复合非活动状态。激素的结合诱导在这使得它们在从抑制复合离解，结合作为同二聚体与靶基因有关的特定DNA的增强子元件，??并调节该基因的转录类固醇受体临界的构象变化。结合增强子元件后，转录因子需要转录共激活剂蛋白质介导其转录起始的刺激（Hong等人，1997 [搜索PubMed 9111344]）。[由OMIM，2010年11月供给]
基因本体信息
NCOA2基因（以及对应的蛋白质）的细胞分布位置：
- 质膜
- 细胞质
- 细胞外
- 高尔基体
- 囊泡
- 细胞骨架
- 内质网
- 细胞核
- 内体
- 溶酶体
- 线粒体
NCOA2基因的本体（GO）信息：
| 名称 |
|---|
| 4919 Thyroid hormone signaling pathway [PATH:hsa04919] |
| 名称 |
|---|
| Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 |
| Activation of gene expression by SREBF (SREBP) |
| Bile acid and bile salt metabolism |
| Biological oxidations |
| BMAL1:CLOCK,NPAS2 activates circadian gene expression |
| Chromatin modifying enzymes |
| Chromatin organization |
| Circadian Clock |
| Cytochrome P450 - arranged by substrate type |
| Developmental Biology |
| Endogenous sterols |
| Fatty acid, triacylglycerol, and ketone body metabolism |
| Gene Expression |
| Generic Transcription Pathway |
| HATs acetylate histones |
| Metabolism |
| Metabolism of lipids and lipoproteins |
| Mitochondrial biogenesis |
| Organelle biogenesis and maintenance |
| Phase 1 - Functionalization of compounds |
| PPARA activates gene expression |
| Recycling of bile acids and salts |
| Regulation of cholesterol biosynthesis by SREBP (SREBF) |
| Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) |
| RHO GTPase Effectors |
| RHO GTPases activate PKNs |
| RORA activates gene expression |
| Signaling by Rho GTPases |
| Synthesis of bile acids and bile salts |
| Synthesis of bile acids and bile salts via 27-hydroxycholesterol |
| Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol |
| Transcriptional activation of mitochondrial biogenesis |
| Transcriptional regulation of white adipocyte differentiation |
| YAP1- and WWTR1 (TAZ)-stimulated gene expression |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Mammary Neoplasms | 0.122995792 | 3 | 0 | BeFree_CTD_human_LHGDN |
| Prostatic Neoplasms | 0.12272435 | 2 | 0 | CTD_human_LHGDN |
| Pregnancy Complications | 0.08 | 1 | 0 | RGD |
| Leukemia, Myelocytic, Acute | 0.005167327 | 9 | 0 | BeFree_LHGDN |
| leukemia | 0.00408156 | 5 | 0 | BeFree_LHGDN |
| Malignant neoplasm of prostate | 0.003452799 | 5 | 0 | BeFree_GAD |
| Malignant neoplasm of breast | 0.003452799 | 5 | 0 | BeFree_GAD |
| Carotid Stenosis | 0.002367032 | 1 | 1 | GAD |
| Bone necrosis | 0.002367032 | 1 | 0 | GAD |
| Tobacco Use Disorder | 0.002367032 | 1 | 0 | GAD |
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