S-phase kinase-associated protein 1

Details

Name
S-phase kinase-associated protein 1
Synonyms
  • Cyclin-A/CDK2-associated protein p19
  • EMC19
  • OCP-2
  • OCP-II
  • OCP2
  • Organ of Corti protein 2
  • Organ of Corti protein II
  • p19A
  • p19skp1
  • RNA polymerase II elongation factor-like protein
  • SIII
  • SKP1A
  • TCEB1L
  • Transcription elongation factor B polypeptide 1-like
Gene Name
SKP1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0007229|S-phase kinase-associated protein 1
MPSIKLQSSDGEIFEVDVEIAKQSVTIKTMLEDLGMDDEGDDDPVPLPNVNAAILKKVIQ
WCTHHKDDPPPPEDDENKEKRTDDIPVWDQEFLKVDQGTLFELILAANYLDIKGLLDVTC
KTVANMIKGKTPEEIRKTFNIKNDFTEEEEAQVRKENQWCEEK
Number of residues
163
Molecular Weight
18657.86
Theoretical pI
4.15
GO Classification
Functions
ubiquitin-protein transferase activity
Processes
anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process / circadian rhythm / Fc-epsilon receptor signaling pathway / G1/S transition of mitotic cell cycle / G2/M transition of mitotic cell cycle / histone H2A monoubiquitination / innate immune response / mitotic cell cycle / MyD88-dependent toll-like receptor signaling pathway / MyD88-independent toll-like receptor signaling pathway / NIK/NF-kappaB signaling / Notch signaling pathway / positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition / protein ubiquitination / regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / stimulatory C-type lectin receptor signaling pathway / stress-activated MAPK cascade / T cell receptor signaling pathway / toll-like receptor 10 signaling pathway / toll-like receptor 2 signaling pathway / toll-like receptor 3 signaling pathway / toll-like receptor 4 signaling pathway / toll-like receptor 5 signaling pathway / toll-like receptor 9 signaling pathway / toll-like receptor signaling pathway / toll-like receptor TLR1 / toll-like receptor TLR6 / TRIF-dependent toll-like receptor signaling pathway / tumor necrosis factor-mediated signaling pathway / viral process
Components
Cul7-RING ubiquitin ligase complex / cytosol / extracellular exosome / nucleoplasm / SCF ubiquitin ligase complex
General Function
Ubiquitin-protein transferase activity
Specific Function
Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5, CEP68 and probably NFKB2 (PubMed:25704143). SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO11) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0017221|S-phase kinase-associated protein 1 (SKP1)
ATGCCTTCAATTAAGTTGCAGAGTTCTGATGGAGAGATATTTGAAGTTGATGTGGAAATT
GCCAAACAATCTGTGACTATTAAGACCATGTTGGAAGATTTGGGAATGGATGATGAAGGA
GATGATGACCCAGTTCCTCTACCAAATGTGAATGCAGCAATATTAAAAAAGGTCATTCAG
TGGTGCACCCACCACAAGGATGACCCTCCTCCTCCTGAAGATGATGAGAACAAAGAAAAG
CGAACAGATGATATCCCTGTTTGGGACCAAGAATTCCTGAAAGTTGACCAAGGAACACTT
TTTGAACTCATTCTGGCTGCAAACTACTTAGACATCAAAGGTTTGCTTGATGTTACATGC
AAGACTGTTGCCAATATGATCAAGGGGAAAACTCCTGAGGAGATTCGCAAGACCTTCAAT
ATCAAAAATGACTTTACTGAAGAGGAGGAAGCCCAGGTAGGTAGCACACAGTTTTGTCTT
TGA
Chromosome Location
5
Locus
5q31
External Identifiers
ResourceLink
UniProtKB IDP63208
UniProtKB Entry NameSKP1_HUMAN
GenBank Protein ID995824
GenBank Gene IDU33760
HGNC IDHGNC:10899
General References
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  2. Sowden J, Morrison K, Schofield J, Putt W, Edwards Y: 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. 1995 Sep 1;29(1):145-51. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  5. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  6. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
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  8. Liang Y, Chen H, Asher JH Jr, Chang CC, Friedman TB: 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. 1997 Jan 15;184(2):163-7. [Article]
  9. Dias DC, Dolios G, Wang R, Pan ZQ: CUL7: A DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16601-6. Epub 2002 Dec 12. [Article]
  10. Matsuzawa SI, Reed JC: Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses. Mol Cell. 2001 May;7(5):915-26. [Article]
  11. Sabile A, Meyer AM, Wirbelauer C, Hess D, Kogel U, Scheffner M, Krek W: Regulation of p27 degradation and S-phase progression by Ro52 RING finger protein. Mol Cell Biol. 2006 Aug;26(16):5994-6004. [Article]
  12. Glenn KA, Nelson RF, Wen HM, Mallinger AJ, Paulson HL: Diversity in tissue expression, substrate binding, and SCF complex formation for a lectin family of ubiquitin ligases. J Biol Chem. 2008 May 9;283(19):12717-29. doi: 10.1074/jbc.M709508200. Epub 2008 Jan 18. [Article]
  13. D'Angiolella V, Donato V, Vijayakumar S, Saraf A, Florens L, Washburn MP, Dynlacht B, Pagano M: SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation. Nature. 2010 Jul 1;466(7302):138-42. doi: 10.1038/nature09140. [Article]
  14. Duan S, Cermak L, Pagan JK, Rossi M, Martinengo C, di Celle PF, Chapuy B, Shipp M, Chiarle R, Pagano M: FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature. 2012 Jan 5;481(7379):90-3. doi: 10.1038/nature10688. [Article]
  15. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  16. Man X, Megraw TL, Lim YP: Cep68 can be regulated by Nek2 and SCF complex. Eur J Cell Biol. 2015 Mar-Apr;94(3-4):162-72. doi: 10.1016/j.ejcb.2015.01.004. Epub 2015 Feb 4. [Article]
  17. Pagan JK, Marzio A, Jones MJ, Saraf A, Jallepalli PV, Florens L, Washburn MP, Pagano M: Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement and licensing. Nat Cell Biol. 2015 Jan;17(1):31-43. doi: 10.1038/ncb3076. Epub 2014 Dec 15. [Article]
  18. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  19. Schulman BA, Carrano AC, Jeffrey PD, Bowen Z, Kinnucan ER, Finnin MS, Elledge SJ, Harper JW, Pagano M, Pavletich NP: Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex. Nature. 2000 Nov 16;408(6810):381-6. [Article]
  20. Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP: Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature. 2002 Apr 18;416(6882):703-9. [Article]
  21. Wu G, Xu G, Schulman BA, Jeffrey PD, Harper JW, Pavletich NP: Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase. Mol Cell. 2003 Jun;11(6):1445-56. [Article]
  22. Hao B, Zheng N, Schulman BA, Wu G, Miller JJ, Pagano M, Pavletich NP: Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase. Mol Cell. 2005 Oct 7;20(1):9-19. [Article]
  23. Hao B, Oehlmann S, Sowa ME, Harper JW, Pavletich NP: Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol Cell. 2007 Apr 13;26(1):131-43. [Article]
  24. Mizushima T, Yoshida Y, Kumanomidou T, Hasegawa Y, Suzuki A, Yamane T, Tanaka K: Structural basis for the selection of glycosylated substrates by SCF(Fbs1) ubiquitin ligase. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5777-81. Epub 2007 Mar 26. [Article]
  25. Li Y, Hao B: Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase. J Biol Chem. 2010 Apr 30;285(18):13896-906. doi: 10.1074/jbc.M110.111518. Epub 2010 Feb 24. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB06980(2S)-2-(1H-indol-3-yl)hexanoic acidexperimentalunknownDetails
DB06981(2S)-2-(1H-indol-3-yl)pentanoic acidexperimentalunknownDetails
DB06982(2S)-8-[(tert-butoxycarbonyl)amino]-2-(1H-indol-3-yl)octanoic acidexperimentalunknownDetails
DB07950Indoleacetic acidexperimentalunknownDetails
DB017501-naphthaleneacetic acidexperimentalunknownDetails