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 (PubMed:11931757, PubMed:12435635, PubMed:12769844, PubMed:12840033, PubMed:15342634, PubMed:15668399, PubMed:15949444, PubMed:16103164, PubMed:16262255, PubMed:16581786, PubMed:16951159, PubMed:17908926, PubMed:17962192, PubMed:22770219, PubMed:32267835). Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition (By similarity). Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, YTHDF2, and probably MYC, TOB1 and TAL1 (PubMed:11931757, PubMed:12435635, PubMed:12769844, PubMed:12840033, PubMed:15342634, PubMed:15668399, PubMed:15949444, PubMed:16103164, PubMed:17962192, PubMed:16581786, PubMed:16951159, PubMed:17908926, PubMed:32267835). Degradation of TAL1 also requires STUB1 (PubMed:17962192). Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2 (PubMed:16262255). Promotes ubiquitination and destruction of CDH1 in a CK1-dependent manner, thereby regulating cell migration (PubMed:22770219). Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus. Protein modification; protein ubiquitination. Part 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 ASB2 which is the substrate-recognition component of a probable ECS E3 ubiquitin-protein ligase complex; ASB2 is likely to bridge the formation of dimeric E3-ubiquitin-protein ligase complexes composed of an ECS complex and an SCF(SKP2) complex (PubMed:21119685). 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. Interacts with cyclin-E (By similarity). Interacts with IFI27; promotes the ubiquitin-mediated proteasomal degradation of hepatitis C virus/HCV non-structural protein NS5A (PubMed:27194766). Interacts with CARM1 (By similarity). (Microbial infection) Interacts with hepatitis C virus/HCV non-structural protein NS5A; promotes the ubiquitin-mediated proteasomal degradation of NS5A. Ubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Deubiquitinated by USP13. Acetylation at Lys-68 and Lys-71 increases stability through impairment of APC/C-mediated proteolysis and promotes cytoplasmic retention. Deacetylated by SIRT3. Extended N-terminus. Probable cloning artifact.