{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q13309","secondaryAccessions":["A8K5E0","B4DJT4","Q8TDZ0","Q8TDZ1","Q9BV69"],"uniProtkbId":"SKP2_HUMAN","entryAudit":{"firstPublicDate":"2003-10-03","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2003-10-03","entryVersion":232,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"S-phase kinase-associated protein 2"}},"alternativeNames":[{"fullName":{"value":"Cyclin-A/CDK2-associated protein p45"}},{"fullName":{"value":"F-box protein Skp2"}},{"fullName":{"value":"F-box/LRR-repeat protein 1"}},{"fullName":{"value":"p45skp2"}}]},"genes":[{"geneName":{"value":"SKP2"},"synonyms":[{"value":"FBXL1"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9Z0Z3"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11931757"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12435635"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12769844"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12840033"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15342634"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15668399"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15949444"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16103164"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16262255"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16581786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16951159"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17908926"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17962192"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22464731"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22770219"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32267835"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9736735"}],"value":"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:9736735, 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:22464731, 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 (By similarity). Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, NBN, 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:16581786, PubMed:16951159, PubMed:17908926, PubMed:17962192, PubMed:22464731, PubMed:32267835). Degradation of TAL1 also requires STUB1 (PubMed:17962192). Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2 (PubMed:9736735, PubMed:16262255). Promotes ubiquitination and destruction of CDH1 in a CK1-dependent manner, thereby regulating cell migration (PubMed:22770219). Following phosphorylation in response to DNA damage, mediates 'Lys-63'-linked ubiquitination of NBN, promoting ATM recruitment to DNA damage sites and DNA repair via homologous recombination (PubMed:22464731)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27194766"}],"value":"Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22464731"}],"value":"Protein modification; protein ubiquitination"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9Z0Z3"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11099048"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11931757"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11961546"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12435635"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12769844"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12840033"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15342634"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15668399"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15949444"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16581786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16880511"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16951159"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17908926"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17962192"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21119685"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27194766"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7553852"}],"value":"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)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27194766"}],"value":"(Microbial infection) Interacts with hepatitis C virus/HCV non-structural protein NS5A; promotes the ubiquitin-mediated proteasomal degradation of 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NBN"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21571647"}],"value":"Ubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Deubiquitinated by USP13"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22770219"}],"value":"Acetylation at Lys-68 and Lys-71 increases stability through impairment of APC/C-mediated proteolysis and promotes cytoplasmic retention. 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