UniProt functional annotation for Q13309



	UniProt functional annotation for Q13309

UniProt code: Q13309.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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). {ECO:0000250|UniProtKB:Q9Z0Z3, 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, ECO:0000269|PubMed:32267835}.

Function: Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus. {ECO:0000269|PubMed:27194766}.

Pathway: Protein modification; protein ubiquitination.

Subunit: 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 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 IFI27; promotes the ubiquitin-mediated proteasomal degradation of NS5A (PubMed:27194766). Interacts with hepatitis C virus/HCV non-structural protein NS5A; promotes the ubiquitin-mediated proteasomal degradation of NS5A (PubMed:27194766). {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:27194766, ECO:0000269|PubMed:7553852}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:22770219}. Nucleus {ECO:0000269|PubMed:22770219}.

Ptm: Ubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Deubiquitinated by USP13. {ECO:0000269|PubMed:21571647}.

Ptm: Acetylation 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}.

Sequence caution: Sequence=AAC50242.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB87202.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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). {ECO:0000250\|UniProtKB:Q9Z0Z3, 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, ECO:0000269\|PubMed:32267835}.



Function:		Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus. {ECO:0000269\|PubMed:27194766}.


Pathway:		Protein modification; protein ubiquitination.
Subunit:		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 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 IFI27; promotes the ubiquitin-mediated proteasomal degradation of NS5A (PubMed:27194766). Interacts with hepatitis C virus/HCV non-structural protein NS5A; promotes the ubiquitin-mediated proteasomal degradation of NS5A (PubMed:27194766). {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:27194766, ECO:0000269\|PubMed:7553852}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:22770219}. Nucleus {ECO:0000269\|PubMed:22770219}.
Ptm:		Ubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Deubiquitinated by USP13. {ECO:0000269\|PubMed:21571647}.
Ptm:		Acetylation 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}.
Sequence caution:		Sequence=AAC50242.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB87202.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};