SKP1A
S-phase kinase-associated protein 1 |
PDB rendering based on 1fs1. |
Available structures |
PDB |
1FQV, 1FS1, 1FS2, 1LDK, 1P22, 2ASS, 2AST, 2E31, 2E32, 2OVP, 2OVQ, 2OVR, 3L2O |
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Identifiers |
Symbols |
SKP1; EMC19; MGC34403; OCP-II; OCP2; SKP1A; TCEB1L; p19A |
External IDs |
OMIM: 601434 MGI: 103575 HomoloGene: 38775 GeneCards: SKP1 Gene |
EC number |
3.1.1.3 |
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RNA expression pattern |
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More reference expression data |
Orthologs |
Species |
Human |
Mouse |
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Entrez |
6500 |
21402 |
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Ensembl |
ENSG00000113558 |
ENSMUSG00000036309 |
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UniProt |
P63208 |
Q3TL58 |
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RefSeq (mRNA) |
NM_006930.3 |
NM_011543.4 |
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RefSeq (protein) |
NP_008861.2 |
NP_035673.3 |
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Location (UCSC) |
Chr 5:
133.49 – 133.56 Mb |
Chr 11:
52.05 – 52.06 Mb |
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PubMed search |
[1] |
[2] |
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S-phase kinase-associated protein 1 is an enzyme that in humans is encoded by the SKP1 gene.[1][2][3]
This gene encodes a protein that is a member of the SCF ubiquitin ligase protein complex. It binds to F-box proteins (proteins containing an F-box motif), such as cyclin F, S-phase kinase-associated protein 2, and other regulatory proteins involved in ubiquitin dependent proteolysis.[4] The encoded protein also collaborates with a network of proteins to control beta-catenin levels and affects the activity level of beta-catenin dependent TCF transcription factors. Studies have also characterized the protein as an RNA polymerase II elongation factor. Alternative splicing of this gene results in two transcript variants. A related pseudogene has been identified on chromosome 7.
Interactions
SKP1A has been shown to interact with FBXL3,[5] FBXO5,[5] FBXO4,[5][6] FBXO7,[5] SKP2,[5][7][8][9][10][11] CDK9,[12] CUL1,[7][13][14][15][16] CDCA3,[17] CACYBP,[18] BTRC,[5][7][8][19][20] FBXW2[5] and FBXW7.[13][21]
References
- ^ Zhang H, Kobayashi R, Galaktionov K, Beach D (Oct 1995). "p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase". Cell 82 (6): 915–25. doi:10.1016/0092-8674(95)90271-6. PMID 7553852.
- ^ 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. doi:10.1159/000134318. PMID 8646875.
- ^ "Entrez Gene: SKP1A S-phase kinase-associated protein 1A (p19A)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6500.
- ^ Bai et al.; Sen, P; Hofmann, K; Ma, L; Goebl, M; Harper, JW; Elledge, SJ (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. PMID 8706131.
- ^ a b c d e f g 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.
- ^ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1847948.
- ^ a b c 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.
- ^ a b 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.
- ^ 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. doi:10.1016/S0014-5793(98)01299-X. ISSN 0014-5793. PMID 9827542.
- ^ 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.
- ^ 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 10559858.
- ^ Kiernan, R E; Emiliani S, Nakayama K, Castro A, Labbé J C, Lorca T, Nakayama Ki K, Benkirane M (Dec. 2001). "Interaction between cyclin T1 and SCF(SKP2) targets CDK9 for ubiquitination and degradation by the proteasome". Mol. Cell. Biol. (United States) 21 (23): 7956–70. doi:10.1128/MCB.21.23.7956-7970.2001. ISSN 0270-7306. PMC 99964. PMID 11689688. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=99964.
- ^ a b Staropoli, John F; McDermott Caroline, Martinat Cécile, Schulman Brenda, Demireva Elena, Abeliovich Asa (Mar. 2003). "Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity". Neuron (United States) 37 (5): 735–49. doi:10.1016/S0896-6273(03)00084-9. ISSN 0896-6273. PMID 12628165.
- ^ 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. PMC 1170388. PMID 9430629. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170388.
- ^ 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.
- ^ Ohta, T; Michel J J, Schottelius A J, Xiong Y (Apr. 1999). "ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity". Mol. Cell (UNITED STATES) 3 (4): 535–41. doi:10.1016/S1097-2765(00)80482-7. ISSN 1097-2765. PMID 10230407.
- ^ Ayad, Nagi G; Rankin Susannah, Murakami Monica, Jebanathirajah Judith, Gygi Steven, Kirschner Marc W (Apr. 2003). "Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC". Cell (United States) 113 (1): 101–13. doi:10.1016/S0092-8674(03)00232-0. ISSN 0092-8674. PMID 12679038.
- ^ Matsuzawa, S I; Reed J C (May. 2001). "Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses". Mol. Cell (United States) 7 (5): 915–26. doi:10.1016/S1097-2765(01)00242-8. ISSN 1097-2765. PMID 11389839.
- ^ Suzuki, H; Chiba T, Suzuki T, Fujita T, Ikenoue T, Omata M, Furuichi K, Shikama H, Tanaka K (Jan. 2000). "Homodimer of two F-box proteins betaTrCP1 or betaTrCP2 binds to IkappaBalpha for signal-dependent ubiquitination". J. Biol. Chem. (UNITED STATES) 275 (4): 2877–84. doi:10.1074/jbc.275.4.2877. ISSN 0021-9258. PMID 10644755.
- ^ Margottin, F; Bour S P, Durand H, Selig L, Benichou S, Richard V, Thomas D, Strebel K, Benarous R (Mar. 1998). "A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif". Mol. Cell (UNITED STATES) 1 (4): 565–74. doi:10.1016/S1097-2765(00)80056-8. ISSN 1097-2765. PMID 9660940.
- ^ Wu, G; Lyapina S, Das I, Li J, Gurney M, Pauley A, Chui I, Deshaies R J, Kitajewski J (Nov. 2001). "SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation". Mol. Cell. Biol. (United States) 21 (21): 7403–15. doi:10.1128/MCB.21.21.7403-7415.2001. ISSN 0270-7306. PMC 99913. PMID 11585921. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=99913.
Further reading
- Chen H, Thalmann I, Adams JC, et al. (1995). "cDNA cloning, tissue distribution, and chromosomal localization of Ocp2, a gene encoding a putative transcription-associated factor predominantly expressed in the auditory organs.". Genomics 27 (3): 389–98. doi:10.1006/geno.1995.1068. PMID 7558018.
- Sowden J, Morrison K, Schofield J, et al. (1996). "A novel cDNA with homology to an RNA polymerase II elongation factor maps to human chromosome 5q31 (TCEB1L) and to mouse chromosome 11 (Tceb1l).". Genomics 29 (1): 145–51. doi:10.1006/geno.1995.1225. PMID 8530064.
- Bai C, Sen P, Hofmann K, 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. PMID 8706131.
- Brown KA, Leek JP, Lench NJ, et al. (1996). "Human sequences homologous to the gene for the cochlear protein Ocp-II do not map to currently known non-syndromic hearing loss loci.". Ann. Hum. Genet. 60 (Pt 5): 385–9. doi:10.1111/j.1469-1809.1996.tb00436.x. PMID 8912791.
- Liang Y, Chen H, Asher JH, et al. (1997). "Human inner ear OCP2 cDNA maps to 5q22-5q35.2 with related sequences on chromosomes 4p16.2-4p14, 5p13-5q22, 7pter-q22, 10 and 12p13-12qter.". Gene 184 (2): 163–7. doi:10.1016/S0378-1119(96)00590-2. PMID 9031623.
- Lisztwan J, Marti A, Sutterlüty H, et al. (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. 17 (2): 368–83. doi:10.1093/emboj/17.2.368. PMC 1170388. PMID 9430629. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170388.
- Ng RW, Arooz T, Yam CH, et al. (1998). "Characterization of the cullin and F-box protein partner Skp1.". FEBS Lett. 438 (3): 183–9. doi:10.1016/S0014-5793(98)01299-X. PMID 9827542.
- Yam CH, Ng RW, Siu WY, et al. (1999). "Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein Skp2.". Mol. Cell. Biol. 19 (1): 635–45. PMC 83921. PMID 9858587. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=83921.
- Henzl MT, Thalmann I, Thalmann R (1999). "OCP2 exists as a dimer in the organ of Corti.". Hear. Res. 126 (1-2): 37–46. doi:10.1016/S0378-5955(98)00148-8. PMID 9872132.
- Winston JT, Strack P, Beer-Romero P, et al. (1999). "The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro.". Genes Dev. 13 (3): 270–83. doi:10.1101/gad.13.3.270. PMC 316433. PMID 9990852. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316433.
- Ilyin GP, Rialland M, Glaise D, Guguen-Guillouzo C (1999). "Identification of a novel Skp2-like mammalian protein containing F-box and leucine-rich repeats.". FEBS Lett. 459 (1): 75–9. doi:10.1016/S0014-5793(99)01211-9. PMID 10508920.
- Cenciarelli C, Chiaur DS, Guardavaccaro D, et al. (1999). "Identification of a family of human F-box proteins.". Curr. Biol. 9 (20): 1177–9. doi:10.1016/S0960-9822(00)80020-2. PMID 10531035.
- Winston JT, Koepp DM, Zhu C, et al. (1999). "A family of mammalian F-box proteins.". Curr. Biol. 9 (20): 1180–2. doi:10.1016/S0960-9822(00)80021-4. PMID 10531037.
- Suzuki H, Chiba T, Suzuki T, et al. (2000). "Homodimer of two F-box proteins betaTrCP1 or betaTrCP2 binds to IkappaBalpha for signal-dependent ubiquitination.". J. Biol. Chem. 275 (4): 2877–84. doi:10.1074/jbc.275.4.2877. PMID 10644755.
- Read MA, Brownell JE, Gladysheva TB, et al. (2000). "Nedd8 modification of cul-1 activates SCF(beta(TrCP))-dependent ubiquitination of IkappaBalpha.". Mol. Cell. Biol. 20 (7): 2326–33. doi:10.1128/MCB.20.7.2326-2333.2000. PMC 85397. PMID 10713156. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85397.
- Schulman BA, Carrano AC, Jeffrey PD, et al. (2000). "Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex.". Nature 408 (6810): 381–6. doi:10.1038/35042620. PMID 11099048.
- Lyapina S, Cope G, Shevchenko A, et al. (2001). "Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome.". Science 292 (5520): 1382–5. doi:10.1126/science.1059780. PMID 11337588.
- Fukuchi M, Imamura T, Chiba T, et al. (2001). "Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of ROC1 and associated proteins.". Mol. Biol. Cell 12 (5): 1431–43. PMC 34595. PMID 11359933. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=34595.
PDB gallery
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1fs1: INSIGHTS INTO SCF UBIQUITIN LIGASES FROM THE STRUCTURE OF THE SKP1-SKP2 COMPLEX
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1fs2: INSIGHTS INTO SCF UBIQUITIN LIGASES FROM THE STRUCTURE OF THE SKP1-SKP2 COMPLEX
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1ldk: Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF Ubiquitin Ligase Complex
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2ass: Crystal structure of the Skp1-Skp2-Cks1 complex
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2ast: Crystal structure of Skp1-Skp2-Cks1 in complex with a p27 peptide
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2e31: Structural basis for selection of glycosylated substrate by SCFFbs1 ubiquitin ligase
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2e32: Structural basis for selection of glycosylated substrate by SCFFbs1 ubiquitin ligase
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