SKP2 (S-phase kinase associated protein 2)
- symbol:
- SKP2
- locus group:
- protein-coding gene
- location:
- 5p13.2
- gene_family:
- F-box and leucine-rich repeat proteins
- alias symbol:
- FBXL1|FBL1|p45
- alias name:
- None
- entrez id:
- 6502
- ensembl gene id:
- ENSG00000145604
- ucsc gene id:
- uc003jkc.3
- refseq accession:
- NM_005983
- hgnc_id:
- HGNC:10901
- approved reserved:
- 1995-12-18
SKP2（S期激酶相关蛋白2，S-phase kinase-associated protein 2）属于F-box蛋白家族，是SCF（Skp1-Cul1-F-box蛋白）泛素连接酶复合体的关键组分，负责通过泛素-蛋白酶体途径调控靶蛋白的降解。其表达产物主要功能是识别并结合磷酸化的底物蛋白（如细胞周期蛋白依赖性激酶抑制剂p27、p21等），促进它们的泛素化标记并降解，从而调控细胞周期进程（尤其是G1/S期转换）和细胞增殖。SKP2的作用位点集中在细胞核内，其活性依赖于与其他SCF复合体成员（如Skp1、Cul1）的相互作用。突变或功能丧失可能导致p27等蛋白异常积累，引发细胞周期阻滞或增殖抑制；而过表达则常见于多种癌症（如乳腺癌、前列腺癌、肺癌），与肿瘤细胞无限增殖、侵袭转移及不良预后相关。SKP2的异常表达还影响其他通路，如通过降解FOXO1（一种抑癌转录因子）促进肿瘤存活，或通过调控E2F1（细胞周期转录因子）影响DNA修复。若SKP2表达降低，细胞可能停滞在G1期，抑制肿瘤生长，但正常组织中过度抑制可能导致再生障碍。F-box蛋白家族的共性是通过保守的F-box结构域与Skp1结合，并利用可变底物识别域选择性靶向特定蛋白进行泛素化降解，从而广泛参与细胞周期、信号转导和代谢调控。目前针对SKP2的抗癌策略包括小分子抑制剂或基因沉默，但其全身性抑制可能带来毒性，需进一步研究组织特异性调控。
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class; in addition to an F-box, this protein contains 10 tandem leucine-rich repeats. This protein is an essential element of the cyclin A-CDK2 S-phase kinase. It specifically recognizes phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S phase and interacts with S-phase kinase-associated protein 1 (SKP1 or p19). In addition, this gene is established as a protooncogene causally involved in the pathogenesis of lymphomas. Alternative splicing of this gene generates three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2011]
该基因编码在F-box蛋白家族，其特征是一个约40个氨基酸基序，在F-盒的成员。在F-box蛋白组成四个亚基蛋白泛素连接酶复合体称为SCFS（SKP1-滞-F-箱）中的其中一个功能的磷酸化依赖泛素化。在F-box蛋白被分为3类：Fbws含WD-40结构域，含有Fbls富含亮氨酸的重复序列，以及含有任一不同的蛋白质 - 蛋白质相互作用的模块或没有可识别的图案Fbxs。由该基因编码的蛋白质属于Fbls类;除了一架F-中，这种蛋白质包含10个串联富含亮氨酸重复。这种蛋白质是细胞周期蛋白A-CDK2 S期激酶的一个重要因素。它特异性识别磷酸化细胞周期蛋白依赖性激酶抑制剂1B（CDKN1B，也被称为p27蛋白或KIP1）主要在S期，并与S相激酶相关蛋白1（SKP1或P19）相互作用。另外，作为原癌因果涉及淋巴瘤的发病该基因被建立。该基因的可变剪接产生编码不同亚型3转录变异体。 [由RefSeq的，2011年7月提供]
基因本体信息
SKP2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
SKP2基因的本体（GO）信息：
| 名称 |
|---|
| 4120 Ubiquitin mediated proteolysis [PATH:hsa04120] |
| 4068 FoxO signaling pathway [PATH:hsa04068] |
| 4110 Cell cycle [PATH:hsa04110] |
| 5200 Pathways in cancer [PATH:hsa05200] |
| 5203 Viral carcinogenesis [PATH:hsa05203] |
| 5222 Small cell lung cancer [PATH:hsa05222] |
| 5168 Herpes simplex infection [PATH:hsa05168] |
| 5169 Epstein-Barr virus infection [PATH:hsa05169] |
| 名称 |
|---|
| Adaptive Immune System |
| Antigen processing: Ubiquitination & Proteasome degradation |
| APC/C-mediated degradation of cell cycle proteins |
| APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 |
| Cell Cycle |
| Cell Cycle, Mitotic |
| Class I MHC mediated antigen processing & presentation |
| Cyclin A:Cdk2-associated events at S phase entry |
| Cyclin D associated events in G1 |
| Cyclin E associated events during G1/S transition |
| G1 Phase |
| G1/S Transition |
| Mitotic G1-G1/S phases |
| Regulation of mitotic cell cycle |
| S Phase |
| SCF(Skp2)-mediated degradation of p27/p21 |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Liver carcinoma | 0.206524536 | 15 | 0 | BeFree_CTD_human_LHGDN_RGD |
| ovarian neoplasm | 0.122995792 | 3 | 0 | BeFree_CTD_human_LHGDN |
| Diffuse Large B-Cell Lymphoma | 0.120542884 | 2 | 0 | BeFree_CTD_human |
| Medulloblastoma | 0.12 | 1 | 0 | CTD_human |
| Mammary Neoplasms | 0.019341894 | 8 | 0 | BeFree_LHGDN |
| Squamous cell carcinoma | 0.018789078 | 13 | 0 | BeFree_LHGDN |
| melanoma | 0.01225461 | 7 | 1 | BeFree_LHGDN |
| Neoplasm Metastasis | 0.011973237 | 16 | 0 | BeFree_LHGDN |
| Lung Neoplasms | 0.011168843 | 5 | 0 | BeFree_LHGDN |
| Malignant neoplasm of breast | 0.010434343 | 23 | 0 | BeFree_GAD |
联系方式
山东省济南市章丘区文博路2号 齐鲁师范学院 genelibs生信实验室
山东省济南市高新区舜华路750号大学科技园北区F座4单元2楼
电话： 0531-88819269
E-mail: product@genelibs.com
微信公众号
关注微信订阅号，实时查看信息，关注医学生物学动态。
版权所有 © 2025.Genelibs 济南弘晖生物技术有限公司 鲁ICP备13024435号-2
