MGP Database

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MGP002843

UniProt Annotations

Entry Information
Gene NameS-phase kinase-associated protein 2, E3 ubiquitin protein ligase
Protein EntrySKP2_HUMAN
UniProt IDQ13309
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; Synonyms=SKP2-alpha; IsoId=Q13309-1; Sequence=Displayed; Name=2; Synonyms=SKP2-beta; IsoId=Q13309-2; Sequence=VSP_008432; Name=3; IsoId=Q13309-4; Sequence=VSP_044931, VSP_044932; Note=No experimental confirmation available.;
FunctionSubstrate 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. {ECO:0000269|PubMed:11931757, ECO:0000269|PubMed:12435635, ECO:0000269|PubMed:12769844, ECO:0000269|PubMed:12840033, ECO:0000269|PubMed:15342634, ECO:0000269|PubMed:15668399, ECO:0000269|PubMed:15949444, ECO:0000269|PubMed:16103164, ECO:0000269|PubMed:16262255, ECO:0000269|PubMed:16581786, ECO:0000269|PubMed:16951159, ECO:0000269|PubMed:17908926, ECO:0000269|PubMed:17962192, ECO:0000269|PubMed:22770219}.
InteractionSelf; NbExp=3; IntAct=EBI-456291, EBI-456291; Q4AE16:- (xeno); NbExp=3; IntAct=EBI-456291, EBI-7418293; A5D8W4:CDH1; NbExp=2; IntAct=EBI-456291, EBI-7793316; P09803:Cdh1 (xeno); NbExp=2; IntAct=EBI-456291, EBI-984420; P38936:CDKN1A; NbExp=2; IntAct=EBI-456291, EBI-375077; P46527:CDKN1B; NbExp=4; IntAct=EBI-456291, EBI-519280; P61024:CKS1B; NbExp=6; IntAct=EBI-456291, EBI-456371; Q13616:CUL1; NbExp=9; IntAct=EBI-456291, EBI-359390; P28562:DUSP1; NbExp=3; IntAct=EBI-456291, EBI-975493; Q09472:EP300; NbExp=3; IntAct=EBI-456291, EBI-447295; Q9UM11:FZR1; NbExp=2; IntAct=EBI-456291, EBI-724997; P01106:MYC; NbExp=2; IntAct=EBI-456291, EBI-447544; Q13415:ORC1; NbExp=2; IntAct=EBI-456291, EBI-374847; P35232:PHB; NbExp=2; IntAct=EBI-7791408, EBI-354213; P62877:RBX1; NbExp=3; IntAct=EBI-456291, EBI-398523; Q9NTG7:SIRT3; NbExp=5; IntAct=EBI-456291, EBI-724621; P63208:SKP1; NbExp=15; IntAct=EBI-456291, EBI-307486;
PathwayProtein modification; protein ubiquitination.
PtmAcetylation at Lys-68 and Lys-71 increases stability through impairment of APC/C-mediated proteolysis and promotes cytoplasmic retention. Deacetylated by SIRT3. {ECO:0000269|PubMed:22770219}.
PtmUbiquitinated by the APC/C complex, leading to its degradation by the proteasome. Deubiquitinated by USP13. {ECO:0000269|PubMed:21571647}.
Sequence CautionSequence=AAC50242.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=BAB87202.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
SimilarityContains 10 LRR (leucine-rich) repeats. {ECO:0000305}.
SimilarityContains 1 F-box domain. {ECO:0000255|PROSITE- ProRule:PRU00080}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:22770219}. Nucleus {ECO:0000269|PubMed:22770219}.
SubunitPart of a SCF(SKP2) complex consisting of CUL1, RBX1, SKP1 and SKP2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Interacts directly with CUL1 and SKP1. Interacts with CKS1. Interacts with the cyclin-A-CDK2 complex. Interacts with ORC1, phosphorylated CDT1, phosphorylated RBL2, ELF4, phosphorylated RAG2, FOXO1, UBP43, MYC, TOB1, TAL1 and KMT2A/MLL1. Interacts with TRIM21. {ECO:0000269|PubMed:11099048, ECO:0000269|PubMed:11931757, ECO:0000269|PubMed:11961546, ECO:0000269|PubMed:12435635, ECO:0000269|PubMed:12769844, ECO:0000269|PubMed:12840033, ECO:0000269|PubMed:15342634, ECO:0000269|PubMed:15668399, ECO:0000269|PubMed:15949444, ECO:0000269|PubMed:16581786, ECO:0000269|PubMed:16880511, ECO:0000269|PubMed:16951159, ECO:0000269|PubMed:17908926, ECO:0000269|PubMed:17962192, ECO:0000269|PubMed:7553852}.
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