MAP2K3 (mitogen-activated protein kinase kinase 3)
- symbol:
- MAP2K3
- locus group:
- protein-coding gene
- location:
- 17p11.2
- gene_family:
- Mitogen-activated protein kinase kinases
- alias symbol:
- MEK3|MKK3|MAPKK3
- alias name:
- MAPK/ERK kinase 3|MAP kinase kinas…
- entrez id:
- 5606
- ensembl gene id:
- ENSG00000034152
- ucsc gene id:
- uc002gys.4
- refseq accession:
- NM_145109
- hgnc_id:
- HGNC:6843
- approved reserved:
- 1997-11-11
MAP2K3（丝裂原活化蛋白激酶激酶3）是MAPK信号通路中的关键激酶，属于MAP2K基因家族成员。该家族共性是通过磷酸化激活下游MAPK（如p38 MAPK），调控细胞应激反应、增殖、分化及凋亡等过程。MAP2K3特异性激活p38 MAPK通路，参与炎症、免疫应答及环境压力（如氧化应激、渗透压变化）的传导。其表达产物为一种丝/苏氨酸蛋白激酶，通过磷酸化p38的苏氨酸和酪氨酸残基使其活化。突变可能导致p38通路异常，例如功能丧失突变会削弱细胞应对应激的能力，而激活突变可能促进慢性炎症或肿瘤发生。研究发现MAP2K3与自身免疫疾病（如类风湿关节炎）相关，其过度激活会加剧促炎细胞因子（如TNF-α、IL-1β）的释放。在癌症中，MAP2K3可能发挥双重作用：在某些肿瘤（如乳腺癌）中过表达促进转移，而在其他情境下（如神经母细胞瘤）低表达反而与不良预后相关。该基因表达异常还会影响相关通路交叉调控，例如下调可能减弱JNK通路的抑制作用，导致细胞凋亡抵抗。MAP2K家族包含7个成员（如MAP2K1/2/4/6等），均具有保守的激酶结构域和类似的上下游分子相互作用模式，但各自激活不同的MAPK亚群以实现信号特异性。
The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene. [provided by RefSeq, Jul 2008]
由该基因编码的蛋白是属于MAP激酶激酶家族的双特异性蛋白激酶。这种激酶被促有丝分裂和环境压力激活，并且在MAP激酶介导的信号传导级联参与。它磷酸化，从而激活MAP??K14 / P38-MAPK。这种激酶可通过胰岛素被激活，是必需的葡萄糖转运的表达。被发现的RAS癌基因的??表达以导致这种激酶，这从而导致MAPK14的组成性活化的活性形式的积累，并赋予初级细胞的致癌性转化。这种激酶的抑制是参与假耶尔森的发病机制。编码不同同种型的多个可变剪接转录物变体已经报道了这个基因。 [由RefSeq的，2008年7月提供]
基因本体信息
MAP2K3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
MAP2K3基因的本体（GO）信息：
| 名称 |
|---|
| 4015 Rap1 signaling pathway [PATH:hsa04015] |
| 4010 MAPK signaling pathway [PATH:hsa04010] |
| 4668 TNF signaling pathway [PATH:hsa04668] |
| 4620 Toll-like receptor signaling pathway [PATH:hsa04620] |
| 4664 Fc epsilon RI signaling pathway [PATH:hsa04664] |
| 4912 GnRH signaling pathway [PATH:hsa04912] |
| 4750 Inflammatory mediator regulation of TRP channels [PATH:hsa04750] |
| 5014 Amyotrophic lateral sclerosis (ALS) [PATH:hsa05014] |
| 5164 Influenza A [PATH:hsa05164] |
| 5169 Epstein-Barr virus infection [PATH:hsa05169] |
| 5145 Toxoplasmosis [PATH:hsa05145] |
| 名称 |
|---|
| activated TAK1 mediates p38 MAPK activation |
| Activated TLR4 signalling |
| Cellular responses to stress |
| Cellular Senescence |
| Disease |
| Immune System |
| Infectious disease |
| Innate Immune System |
| MAP kinase activation in TLR cascade |
| MyD88 cascade initiated on plasma membrane |
| MyD88 dependent cascade initiated on endosome |
| MyD88-independent TLR3/TLR4 cascade |
| MyD88:Mal cascade initiated on plasma membrane |
| Oxidative Stress Induced Senescence |
| Toll Like Receptor 10 (TLR10) Cascade |
| Toll Like Receptor 2 (TLR2) Cascade |
| Toll Like Receptor 3 (TLR3) Cascade |
| Toll Like Receptor 4 (TLR4) Cascade |
| Toll Like Receptor 5 (TLR5) Cascade |
| Toll Like Receptor 7/8 (TLR7/8) Cascade |
| Toll Like Receptor 9 (TLR9) Cascade |
| Toll Like Receptor TLR1:TLR2 Cascade |
| Toll Like Receptor TLR6:TLR2 Cascade |
| Toll-Like Receptors Cascades |
| TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation |
| TRAF6 Mediated Induction of proinflammatory cytokines |
| TRIF-mediated TLR3/TLR4 signaling |
| Uptake and actions of bacterial toxins |
| Uptake and function of anthrax toxins |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Retinal Diseases | 0.08 | 1 | 0 | RGD |
| Myocardial Ischemia | 0.08 | 1 | 0 | RGD |
| Diabetes Mellitus, Experimental | 0.08 | 1 | 0 | RGD |
| Mammary Neoplasms | 0.00272435 | 1 | 0 | LHGDN |
| Rheumatoid Arthritis | 0.002367032 | 1 | 0 | GAD |
| Tumor Progression | 0.000542884 | 2 | 0 | BeFree |
| Liver carcinoma | 0.000271442 | 1 | 0 | BeFree |
| Congestive heart failure | 0.000271442 | 1 | 0 | BeFree |
| Neutrophilia (disorder) | 0.000271442 | 1 | 0 | BeFree |
| Breast Carcinoma | 0.000271442 | 1 | 0 | BeFree |
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