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S-phase kinase-associated protein 2; F-box protein Skp2; cyclin-A/CDK2-associated protein p45; p45skp2; F-box/LRR-repeat protein 1 (SKP2 FBXL1)
Function:
- substrate recognition component of a SCF complex which mediates ubiquitination & subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction & transcription
- specifically recognizes phosphorylated CDKN1B/p27kip
- role in regulation of G1/S transition
- degradation of CDKN1B/p27kip also requires CKS1 recognizes target proteins ORC1L, CDT1, RBL2, MLL, CDK9, RAG2, FOXO1A, UBP43, & probably MYC, TOB1 & TAL1
- degradation of TAL1 also requires STUB1
- recognizes CDKN1A in association with CCNE1 or CCNE2 & CDK2
- interacts directly with CUL1 & SKP1
- interacts with CKS1
- interacts with the cyclin-A-CDK2 complex
- interacts with ORC1L, phosphorylated CDT1, phosphorylated RBL2, ELF4, phosphorylated RAG2, FOXO1A, UBP43, MYC, TOB1, TAL1 & MLL
Structure:
- contains 1 F-box domain
- contains 8 LRR repeats (leucine-rich repeats)
Alternative splicing: named isoforms=2
General
leucine-rich repeat-containing protein (LRRC)
phosphoprotein
Skp (S phase kinase associated protein) family protein
Properties
SIZE: entity length = 424 aa
MW = 48 kD
MOTIF: Ser phosphorylation site {S64}
F-box domain {94-140}
Ser phosphorylation site {S179}
leucine-rich repeat
SITE: 180-204
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 210-234
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 258-284
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 286-308
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 309-330
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 334-356
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 359-378
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 380-403
MOTIF: leucine residue (SEVERAL)
Database Correlations
OMIM 601436
UniProt Q13309
Pfam PF00646
Entrez Gene 6502
Kegg hsa:6502
References
- UniProt :accession Q13309
- Zhang et al.
p19Skp1 and p45Skp2 are essential elements of the cyclin A-
CDK2 S phase kinase.
Cell 82:915-25 1995
PMID: 7553852
Component-of
SKP1-CUL1-F-box protein (SCF) complex; SCF(FBXW11) E3 ligase complex; CF(SKP2) E3 ligase complex