UniProt Accession

 SKP2_HUMAN; Q13309; A8K5E0; B4DJT4; Q8TDZ0; Q8TDZ1; Q9BV69 

Genbank Protein ID

 U33761; AB050979; AB050980; AB050981; AY029177; AK291255; AK296223; AC008942; CH471119; BC001441; BC007441 

Genbank Nucleotide ID

 AAC50242.1; BAB87200.1; BAB87201.1; BAB87202.1; AAK31593.1; BAF83944.1; BAG58946.1; EAW55936.1; AAH01441.1; AAH07441.1 

Protein Name

 S-phase kinase-associated protein 2 

Protein Synonyms/Alias

 Cyclin-A/CDK2-associated protein p45; F-box protein Skp2; F-box/LRR-repeat protein 1; p45skp2 

Gene Name

 SKP2 

Gene Synonyms/Alias

 FBXL1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
68	HPESPPRKRLKSKGS	acetylation	[1]
71	SPPRKRLKSKGSDKD	acetylation	[1]
73	PRKRLKSKGSDKDFV	ubiquitination	[2]
77	LKSKGSDKDFVIVRR	ubiquitination	[2]
145	QTLDLTGKNLHPDVT	ubiquitination	[2, 3, 4, 5]
207	GILSQCSKLQNLSLE	ubiquitination	[6]
228	PIVNTLAKNSNLVRL	ubiquitination	[2, 4, 6, 7, 8, 9]
299	GYRKNLQKSDLSTLV	ubiquitination	[2, 6, 9]
405	RPTIGNKKNQEIWGI	ubiquitination	[2]
413	NQEIWGIKCRLTLQK	ubiquitination	[2]
420	KCRLTLQKPSCL***	ubiquitination	[2]

Reference

 [1] Acetylation-dependent regulation of Skp2 function.
 Inuzuka H, Gao D, Finley LW, Yang W, Wan L, Fukushima H, Chin YR, Zhai B, Shaik S, Lau AW, Wang Z, Gygi SP, Nakayama K, Teruya-Feldstein J, Toker A, Haigis MC, Pandolfi PP, Wei W.
 Cell. 2012 Jul 6;150(1):179-93. [PMID: 22770219]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [6] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [7] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [8] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [9] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 

Functional Description

 Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration. 

Sequence Annotation

 DOMAIN 94 140 F-box.
 REPEAT 151 176 LRR 1.
 REPEAT 177 204 LRR 2.
 REPEAT 210 234 LRR 3.
 REPEAT 235 257 LRR 4.
 REPEAT 258 284 LRR 5.
 REPEAT 286 308 LRR 6.
 REPEAT 309 330 LRR 7.
 REPEAT 334 356 LRR 8.
 REPEAT 359 378 LRR 9.
 REPEAT 380 401 LRR 10.
 MOTIF 67 73 Nuclear localization signal.
 MOD_RES 64 64 Phosphoserine.
 MOD_RES 68 68 N6-acetyllysine; by p300/EP300.
 MOD_RES 71 71 N6-acetyllysine; by p300/EP300.
 MOD_RES 179 179 Phosphoserine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; Leucine-rich repeat; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 424 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IEA:Compara.
 GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0071460; P:cellular response to cell-matrix adhesion; IEA:Compara.
 GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome.
 GO:0000086; P:G2/M transition of mitotic cell cycle; IEA:Compara.
 GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; IEA:Compara.
 GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Compara.
 GO:0000209; P:protein polyubiquitination; IEA:Compara.
 GO:0051726; P:regulation of cell cycle; IEA:Compara. 

Interpro

 IPR001810; F-box_dom_cyclin-like. 

Pfam

  

SMART

 SM00256; FBOX 

PROSITE

 PS50181; FBOX 

PRINTS