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S-phase kinase-associated protein 2 (p45)

PDB rendering based on 1fqv.
Available structures
1fqv, 1fs1, 1ldk, 2ass, 2ast
Symbols SKP2; FBL1; FBXL1; FLB1; MGC1366
External IDs OMIM601436 MGI1351663 HomoloGene55942 GeneCards: SKP2 Gene
RNA expression pattern
PBB GE SKP2 210567 s at tn.png
PBB GE SKP2 203625 x at tn.png
PBB GE SKP2 211042 x at tn.png
More reference expression data
Species Human Mouse
Entrez 6502 27401
Ensembl ENSG00000145604 ENSMUSG00000054115
UniProt Q13309 Q4KMS0
RefSeq (mRNA) NM_005983 NM_013787
RefSeq (protein) NP_005974 NP_038815
Location (UCSC) Chr 5:
36.19 - 36.22 Mb
Chr 15:
9.04 - 9.07 Mb
PubMed search [1] [2]

S-phase kinase-associated protein 2 is an enzyme that in humans is encoded by the SKP2 gene.[1][2]

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box[3]. 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[4]. 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)[5][6]. In addition, this gene is established as a protooncogene causally involved in the pathogenesis of lymphomas[7]. Alternative splicing of this gene generates 2 transcript variants encoding different isoforms.


SKP2 has been shown to interact with ORC1L,[8] Cyclin A2,[9][10] E2F1,[10] DNA replication factor CDT1,[11] SKP1A,[12][13][14][15][16][10] Cyclin-dependent kinase 2,[9][10][17] CKS1B,[18][19][20][21] CUL1[11][12][22][10][23][24] and CDKN1B.[18][19][25]


  1. ^ Demetrick DJ, Zhang H, Beach DH (Jul 1996). "Chromosomal mapping of the genes for the human CDK2/cyclin A-associated proteins p19 (SKP1A and SKP1B) and p45 (SKP2)". Cytogenet Cell Genet 73 (1-2): 104–7. PMID 8646875.  
  2. ^ "Entrez Gene: SKP2 S-phase kinase-associated protein 2 (p45)".  
  3. ^ Bai et al. (1996). "SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box.". Cell 86 (2): 263–74. doi:10.1016/S0092-8674(00)80098-7.  
  4. ^ Kipreos ET, Pagano M. (2000). The F-box protein family. Genome Biol 1(5):REVIEWS3002. PMID 11178263
  5. ^ Carrano et al. (1999). "SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.". Nat Cell Biol 1 (4): 193–9. doi:10.1038/12013.  
  6. ^ Tsvetkov et al.. "p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27.". Curr Biol 9 (12): 661–4.  
  7. ^ Latres et al. (2001). "Role of the F-box protein Skp2 in lymphomagenesis.". Proc Natl Acad Sci USA 98 (5): 2515–20. doi:10.1073/pnas.041475098.  
  8. ^ Méndez, Juan; Zou-Yang X Helena, Kim So-Young, Hidaka Masumi, Tansey William P, Stillman Bruce (Mar. 2002). "Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication". Mol. Cell (United States) 9 (3): 481–91. ISSN 1097-2765. PMID 11931757.  
  9. ^ a b Rosner, Margit; Hengstschläger Markus (Nov. 2004). "Tuberin binds p27 and negatively regulates its interaction with the SCF component Skp2". J. Biol. Chem. (United States) 279 (47): 48707–15. doi:10.1074/jbc.M405528200. ISSN 0021-9258. PMID 15355997.  
  10. ^ a b c d e Marti, A; Wirbelauer C, Scheffner M, Krek W (May. 1999). "Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation". Nat. Cell Biol. (ENGLAND) 1 (1): 14–9. doi:10.1038/8984. ISSN 1465-7392. PMID 10559870.  
  11. ^ a b Li, Xianghong; Zhao Qiping, Liao Rong, Sun Peiqing, Wu Xiaohua (Aug. 2003). "The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation". J. Biol. Chem. (United States) 278 (33): 30854–8. doi:10.1074/jbc.C300251200. ISSN 0021-9258. PMID 12840033.  
  12. ^ a b Min, Kyoeng-Woo; Hwang Ji-Won, Lee Jong-Sik, Park Yoon, Tamura Taka-aki, Yoon Jong-Bok (May. 2003). "TIP120A associates with cullins and modulates ubiquitin ligase activity". J. Biol. Chem. (United States) 278 (18): 15905–10. doi:10.1074/jbc.M213070200. ISSN 0021-9258. PMID 12609982.  
  13. ^ Strack, P; Caligiuri M, Pelletier M, Boisclair M, Theodoras A, Beer-Romero P, Glass S, Parsons T, Copeland R A, Auger K R, Benfield P, Brizuela L, Rolfe M (Jul. 2000). "SCF(beta-TRCP) and phosphorylation dependent ubiquitinationof I kappa B alpha catalyzed by Ubc3 and Ubc4". Oncogene (ENGLAND) 19 (31): 3529–36. doi:10.1038/sj.onc.1203647. ISSN 0950-9232. PMID 10918611.  
  14. ^ Ng, R W; Arooz T, Yam C H, Chan I W, Lau A W, Poon R Y (Nov. 1998). "Characterization of the cullin and F-box protein partner Skp1". FEBS Lett. (NETHERLANDS) 438 (3): 183–9. ISSN 0014-5793. PMID 9827542.  
  15. ^ Schulman, B A; Carrano A C, Jeffrey P D, Bowen Z, Kinnucan E R, Finnin M S, Elledge S J, Harper J W, Pagano M, Pavletich N P (Nov. 2000). "Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex". Nature (ENGLAND) 408 (6810): 381–6. doi:10.1038/35042620. ISSN 0028-0836. PMID 11099048.  
  16. ^ Cenciarelli, C; Chiaur D S, Guardavaccaro D, Parks W, Vidal M, Pagano M (Oct. 1999). "Identification of a family of human F-box proteins". Curr. Biol. (ENGLAND) 9 (20): 1177–9. doi:10.1016/S0960-9822(00)80020-2. ISSN 0960-9822. PMID 10531035.  
  17. ^ Yam, C H; Ng R W, Siu W Y, Lau A W, Poon R Y (Jan. 1999). "Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein Skp2". Mol. Cell. Biol. (UNITED STATES) 19 (1): 635–45. ISSN 0270-7306. PMID 9858587.  
  18. ^ a b Wang, Wei; Ungermannova Dana, Chen Lin, Liu Xuedong (Aug. 2003). "A negatively charged amino acid in Skp2 is required for Skp2-Cks1 interaction and ubiquitination of p27Kip1". J. Biol. Chem. (United States) 278 (34): 32390–6. doi:10.1074/jbc.M305241200. ISSN 0021-9258. PMID 12813041.  
  19. ^ a b Sitry, Danielle; Seeliger Markus A, Ko Tun K, Ganoth Dvora, Breward Sadie E, Itzhaki Laura S, Pagano Michele, Hershko Avram (Nov. 2002). "Three different binding sites of Cks1 are required for p27-ubiquitin ligation". J. Biol. Chem. (United States) 277 (44): 42233–40. doi:10.1074/jbc.M205254200. ISSN 0021-9258. PMID 12140288.  
  20. ^ Ganoth, D; Bornstein G, Ko T K, Larsen B, Tyers M, Pagano M, Hershko A (Mar. 2001). "The cell-cycle regulatory protein Cks1 is required for SCF(Skp2)-mediated ubiquitinylation of p27". Nat. Cell Biol. (England) 3 (3): 321–4. doi:10.1038/35060126. ISSN 1465-7392. PMID 11231585.  
  21. ^ Calvisi, Diego F; Pinna Federico, Meloni Floriana, Ladu Sara, Pellegrino Rossella, Sini Marcella, Daino Lucia, Simile Maria M, De Miglio Maria R, Virdis Patrizia, Frau Maddalena, Tomasi Maria L, Seddaiu Maria A, Muroni Maria R, Feo Francesco, Pascale Rosa M (Jun. 2008). "Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human hepatocellular carcinoma". Cancer Res. (United States) 68 (11): 4192–200. doi:10.1158/0008-5472.CAN-07-6157. PMID 18519678.  
  22. ^ Lisztwan, J; Marti A, Sutterlüty H, Gstaiger M, Wirbelauer C, Krek W (Jan. 1998). "Association of human CUL-1 and ubiquitin-conjugating enzyme CDC34 with the F-box protein p45(SKP2): evidence for evolutionary conservation in the subunit composition of the CDC34-SCF pathway". EMBO J. (ENGLAND) 17 (2): 368–83. doi:10.1093/emboj/17.2.368. ISSN 0261-4189. PMID 9430629.  
  23. ^ Zheng, Ning; Schulman Brenda A, Song Langzhou, Miller Julie J, Jeffrey Philip D, Wang Ping, Chu Claire, Koepp Deanna M, Elledge Stephen J, Pagano Michele, Conaway Ronald C, Conaway Joan W, Harper J Wade, Pavletich Nikola P (Apr. 2002). "Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex". Nature (England) 416 (6882): 703–9. doi:10.1038/416703a. ISSN 0028-0836. PMID 11961546.  
  24. ^ Menon, Suchithra; Tsuge Tomohiko, Dohmae Naoshi, Takio Koji, Wei Ning (2008). "Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome". BMC Biochem. (England) 9: 1. doi:10.1186/1471-2091-9-1. PMID 18173839.  
  25. ^ Fujita, Naoya; Sato Saori, Katayama Kazuhiro, Tsuruo Takashi (Aug. 2002). "Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization". J. Biol. Chem. (United States) 277 (32): 28706–13. doi:10.1074/jbc.M203668200. ISSN 0021-9258. PMID 12042314.  


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