CHEK2 (checkpoint kinase 2)
- symbol:
- CHEK2
- locus group:
- protein-coding gene
- location:
- 22q12.1
- gene_family:
- alias symbol:
- CDS1|CHK2|HuCds1|PP1425|bA444G7
- alias name:
- None
- entrez id:
- 11200
- ensembl gene id:
- ENSG00000183765
- ucsc gene id:
- uc003adu.2
- refseq accession:
- NM_001005735
- hgnc_id:
- HGNC:16627
- approved reserved:
- 2001-09-19
CHEK2（Checkpoint Kinase 2）是一种重要的抑癌基因，属于丝氨酸/苏氨酸蛋白激酶家族，主要参与DNA损伤修复和细胞周期调控。当DNA发生损伤时，CHEK2被ATM（共济失调毛细血管扩张突变基因）激活，通过磷酸化下游靶蛋白（如p53、BRCA1和CDC25）来阻滞细胞周期，促进DNA修复或诱导凋亡，防止受损DNA传递到子代细胞。CHEK2的功能特点是作为细胞周期检查点（checkpoint）的关键调控分子，确保基因组稳定性。若CHEK2发生功能丧失性突变（如移码突变或无义突变），其抑癌能力会下降，导致DNA错误积累，增加乳腺癌、卵巢癌、前列腺癌等遗传性癌症风险。某些人群携带的CHEK2突变（如1100delC）已被明确列为癌症易感因素。当CHEK2过表达时，可能过度激活细胞周期阻滞或凋亡通路，引起细胞生长抑制；而低表达则削弱DNA损伤应答，导致基因组不稳定性增强。CHEK2属于CHECKPOINT KINASE家族，该家族成员（如CHEK1）均通过磷酸化调控细胞周期进程和DNA修复。CHEK2与CHEK1功能部分冗余，但CHEK2更倾向于响应电离辐射等双链断裂损伤，而CHEK1主要应对复制压力。目前针对CHEK2突变携带者的临床管理包括加强癌症筛查，而抑制CHEK2激酶活性也成为某些癌症治疗的潜在策略。
In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
响应于DNA损伤和复制块，细胞周期进展通过临界细胞周期调节的控制停止。由该基因编码的蛋白质是细胞周期关卡调节器和推定的肿瘤抑制基因。它包含了活化所必需的一个叉头相关的蛋白质相互作用域DNA损伤反应，是应对复制块和DNA损伤迅速磷酸化。当激活时，所编码的蛋白质是已知的抑制CDC25C磷酸酶，防止进入有丝分裂，并且已经显示出稳定的肿瘤抑制蛋白p53，导致细胞周期停滞在G1期。此外，此蛋白质与相互作用和磷酸BRCA1，允许BRCA1 DNA损伤后恢复存活。在这种基因突变与李弗劳明综合征，通常与TP53遗传突变相关联的高度渗透剂家族性癌症表型相关。此外，在该基因的突变被认为赋予易感性肉瘤，乳癌，脑肿瘤。此核蛋白质是丝氨酸/苏氨酸蛋白激酶的CDS1亚科的成员。已发现该基因编码不同亚型的几个抄本变形。 [由RefSeq的，2012年4月提供]
基因本体信息
CHEK2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
CHEK2基因的本体（GO）信息：
| 名称 |
|---|
| 4110 Cell cycle [PATH:hsa04110] |
| 4115 p53 signaling pathway [PATH:hsa04115] |
| 5166 HTLV-I infection [PATH:hsa05166] |
| 名称 |
|---|
| Cell Cycle |
| Cell Cycle Checkpoints |
| G1/S DNA Damage Checkpoints |
| G2/M Checkpoints |
| G2/M DNA damage checkpoint |
| p53-Independent DNA Damage Response |
| p53-Independent G1/S DNA damage checkpoint |
| Ubiquitin Mediated Degradation of Phosphorylated Cdc25A |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Osteosarcoma | 0.363267234 | 2 | 2 | BeFree_CLINVAR_CTD_human_LHGDN_ORPHANET |
| Li-Fraumeni Syndrome 2 | 0.36 | 1 | 2 | CLINVAR_CTD_human_UNIPROT |
| Li-Fraumeni Syndrome | 0.250334654 | 19 | 0 | BeFree_CTD_human_LHGDN_ORPHANET |
| Prostate cancer, familial | 0.240814326 | 3 | 0 | BeFree_CTD_human_ORPHANET |
| Malignant neoplasm of breast | 0.236916095 | 151 | 4 | BeFree_GAD_UNIPROT |
| Mammary Neoplasms | 0.212182547 | 53 | 1 | BeFree_CTD_human_GAD_LHGDN |
| Prostatic Neoplasms | 0.144347399 | 9 | 1 | BeFree_CTD_human_GAD_LHGDN |
| Colorectal Neoplasms | 0.141437484 | 8 | 0 | CTD_human_GAD_LHGDN |
| Malignant neoplasm of prostate | 0.138349765 | 25 | 6 | BeFree_GAD_UNIPROT |
| Malignant neoplasm of lung | 0.129815515 | 11 | 2 | BeFree_GAD_GWASCAT |
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