UniProt functional annotation for Q13616



	UniProt functional annotation for Q13616

UniProt code: Q13616.

Organism: Homo sapiens (Human).

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

Function: Core component of multiple cullin-RING-based SCF (SKP1-CUL1- F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). In the SCF complex, serves as a rigid scaffold that organizes the SKP1- F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and exchange of the substrate recognition component is mediated by TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC) and/or SCF(FBXW11) direct ubiquitination of CEP68 (PubMed:25704143, PubMed:25503564). SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of CCNE1, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO1) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys- 22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2. {ECO:0000269|PubMed:15531760, ECO:0000269|PubMed:15640526, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:19679664, ECO:0000269|PubMed:22113614, ECO:0000269|PubMed:22405651, ECO:0000269|PubMed:23263282, ECO:0000269|PubMed:23431138, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:9663463}.

Pathway: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:22405651}.

Subunit: Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin- protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable F- box domain-containing protein as substrate-specific subunit (PubMed:10230406, PubMed:15145941, PubMed:15531760, PubMed:16714087, PubMed:16797541, PubMed:17098746, PubMed:18203720, PubMed:20596027, PubMed:22405651, PubMed:22113614, PubMed:23263282, PubMed:23431138, PubMed:25503564, PubMed:11961546, PubMed:22748924). Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXW2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO10) complex containing FBXO10. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC. This complex binds phosphorylated NFKBIA. Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1, CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF. Component of the SCF(FBXL3) complex composed of CUL1, SKP1, RBX1 and FBXL3. Component of the SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21. Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1 and FBXW7 (PubMed:22405651). Interacts with CHEK2; mediates CHEK2 ubiquitination and regulates its function. Part of a complex with TIP120A/CAND1 and RBX1. The unneddylated form interacts with TIP120A/CAND1 and the interaction mediates the exchange of the F-box substrate-specific subunit. Can self-associate. Interacts with FBXW8. Interacts with RNF7. Interacts with CUL7; the interaction seems to be mediated by FBXW8. Interacts with TRIM21. Interacts with COPS2. Interacts with UBE2M (PubMed:21940857). Identified in a complex with RBX1 and GLMN (PubMed:22405651, PubMed:22748924). Interacts with CEP68 as part of the SCF(FBXW11) complex; the interaction is probably mediated by FBXW11 and the complex also contains CDK5RAP2 and PCNT (PubMed:25503564). Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346). Interacts with COPS9 isoform 2 (PubMed:23776465). Interacts with UBXN1 (PubMed:28152074). Interacts with KAT7, probably as part of an SCF complex; the interaction mediates KAT7 ubiquitination (By similarity). Interacts with NOTCH2 (PubMed:29149593). Part of a complex that contains DCUN1D5, CUL1 and RBX1; this complex is bridged by CUL1 (PubMed:24192928). Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (PubMed:24192928, PubMed:26906416, PubMed:23201271, PubMed:21940857, PubMed:25349211, PubMed:28581483). {ECO:0000250|UniProtKB:Q9WTX6, ECO:0000269|PubMed:10230406, ECO:0000269|PubMed:10230407, ECO:0000269|PubMed:10851089, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:11961546, ECO:0000269|PubMed:12504026, ECO:0000269|PubMed:12609982, ECO:0000269|PubMed:15145941, ECO:0000269|PubMed:15531760, ECO:0000269|PubMed:15537541, ECO:0000269|PubMed:15640526, ECO:0000269|PubMed:16714087, ECO:0000269|PubMed:16797541, ECO:0000269|PubMed:16880511, ECO:0000269|PubMed:17098746, ECO:0000269|PubMed:18203720, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:20190741, ECO:0000269|PubMed:20596027, ECO:0000269|PubMed:21940857, ECO:0000269|PubMed:22113614, ECO:0000269|PubMed:22405651, ECO:0000269|PubMed:22748924, ECO:0000269|PubMed:23201271, ECO:0000269|PubMed:23263282, ECO:0000269|PubMed:23431138, ECO:0000269|PubMed:23776465, ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:24192928, ECO:0000269|PubMed:25349211, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:26906416, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:28152074, ECO:0000269|PubMed:28581483, ECO:0000269|PubMed:29149593}.

Subunit: (Microbial infection) Interacts with Epstein-Barr virus BPLF1. {ECO:0000269|PubMed:20190741}.

Subunit: (Microbial infection) Interacts with Human adenovirus early E1A protein; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBXW7) complex. {ECO:0000269|PubMed:19679664}.

Subunit: (Microbial infection) Interacts with vaccinia virus protein C9L. {ECO:0000269|PubMed:29444943}.

Tissue specificity: Expressed in lung fibroblasts. {ECO:0000269|PubMed:9663463}.

Ptm: Neddylated; which enhances the ubiquitination activity of SCF and prevents binding of the inhibitor CAND1. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (PubMed:10597293, PubMed:10713156, PubMed:15537541, PubMed:18805092). {ECO:0000269|PubMed:10597293, ECO:0000269|PubMed:10713156, ECO:0000269|PubMed:15537541, ECO:0000269|PubMed:18805092, ECO:0000269|PubMed:20190741, ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:27565346}.

Ptm: (Microbial infection) Deneddylated by Epstein-Barr virus BPLF1 leading to a S-phase-like environment that is required for efficient replication of the viral genome (PubMed:20190741). {ECO:0000269|PubMed:20190741}.

Similarity: Belongs to the cullin family. {ECO:0000255|PROSITE- ProRule:PRU00330}.

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:		Core component of multiple cullin-RING-based SCF (SKP1-CUL1- F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). In the SCF complex, serves as a rigid scaffold that organizes the SKP1- F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and exchange of the substrate recognition component is mediated by TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC) and/or SCF(FBXW11) direct ubiquitination of CEP68 (PubMed:25704143, PubMed:25503564). SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of CCNE1, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO1) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys- 22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2. {ECO:0000269\|PubMed:15531760, ECO:0000269\|PubMed:15640526, ECO:0000269\|PubMed:18644861, ECO:0000269\|PubMed:19679664, ECO:0000269\|PubMed:22113614, ECO:0000269\|PubMed:22405651, ECO:0000269\|PubMed:23263282, ECO:0000269\|PubMed:23431138, ECO:0000269\|PubMed:25503564, ECO:0000269\|PubMed:25704143, ECO:0000269\|PubMed:27565346, ECO:0000269\|PubMed:9663463}.


Pathway:		Protein modification; protein ubiquitination. {ECO:0000269\|PubMed:22405651}.
Subunit:		Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin- protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable F- box domain-containing protein as substrate-specific subunit (PubMed:10230406, PubMed:15145941, PubMed:15531760, PubMed:16714087, PubMed:16797541, PubMed:17098746, PubMed:18203720, PubMed:20596027, PubMed:22405651, PubMed:22113614, PubMed:23263282, PubMed:23431138, PubMed:25503564, PubMed:11961546, PubMed:22748924). Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXW2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO10) complex containing FBXO10. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC. This complex binds phosphorylated NFKBIA. Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1, CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF. Component of the SCF(FBXL3) complex composed of CUL1, SKP1, RBX1 and FBXL3. Component of the SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21. Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1 and FBXW7 (PubMed:22405651). Interacts with CHEK2; mediates CHEK2 ubiquitination and regulates its function. Part of a complex with TIP120A/CAND1 and RBX1. The unneddylated form interacts with TIP120A/CAND1 and the interaction mediates the exchange of the F-box substrate-specific subunit. Can self-associate. Interacts with FBXW8. Interacts with RNF7. Interacts with CUL7; the interaction seems to be mediated by FBXW8. Interacts with TRIM21. Interacts with COPS2. Interacts with UBE2M (PubMed:21940857). Identified in a complex with RBX1 and GLMN (PubMed:22405651, PubMed:22748924). Interacts with CEP68 as part of the SCF(FBXW11) complex; the interaction is probably mediated by FBXW11 and the complex also contains CDK5RAP2 and PCNT (PubMed:25503564). Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346). Interacts with COPS9 isoform 2 (PubMed:23776465). Interacts with UBXN1 (PubMed:28152074). Interacts with KAT7, probably as part of an SCF complex; the interaction mediates KAT7 ubiquitination (By similarity). Interacts with NOTCH2 (PubMed:29149593). Part of a complex that contains DCUN1D5, CUL1 and RBX1; this complex is bridged by CUL1 (PubMed:24192928). Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (PubMed:24192928, PubMed:26906416, PubMed:23201271, PubMed:21940857, PubMed:25349211, PubMed:28581483). {ECO:0000250\|UniProtKB:Q9WTX6, ECO:0000269\|PubMed:10230406, ECO:0000269\|PubMed:10230407, ECO:0000269\|PubMed:10851089, ECO:0000269\|PubMed:11337588, ECO:0000269\|PubMed:11961546, ECO:0000269\|PubMed:12504026, ECO:0000269\|PubMed:12609982, ECO:0000269\|PubMed:15145941, ECO:0000269\|PubMed:15531760, ECO:0000269\|PubMed:15537541, ECO:0000269\|PubMed:15640526, ECO:0000269\|PubMed:16714087, ECO:0000269\|PubMed:16797541, ECO:0000269\|PubMed:16880511, ECO:0000269\|PubMed:17098746, ECO:0000269\|PubMed:18203720, ECO:0000269\|PubMed:18644861, ECO:0000269\|PubMed:20190741, ECO:0000269\|PubMed:20596027, ECO:0000269\|PubMed:21940857, ECO:0000269\|PubMed:22113614, ECO:0000269\|PubMed:22405651, ECO:0000269\|PubMed:22748924, ECO:0000269\|PubMed:23201271, ECO:0000269\|PubMed:23263282, ECO:0000269\|PubMed:23431138, ECO:0000269\|PubMed:23776465, ECO:0000269\|PubMed:24076655, ECO:0000269\|PubMed:24192928, ECO:0000269\|PubMed:25349211, ECO:0000269\|PubMed:25503564, ECO:0000269\|PubMed:26906416, ECO:0000269\|PubMed:27565346, ECO:0000269\|PubMed:28152074, ECO:0000269\|PubMed:28581483, ECO:0000269\|PubMed:29149593}.
Subunit:		(Microbial infection) Interacts with Epstein-Barr virus BPLF1. {ECO:0000269\|PubMed:20190741}.
Subunit:		(Microbial infection) Interacts with Human adenovirus early E1A protein; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBXW7) complex. {ECO:0000269\|PubMed:19679664}.
Subunit:		(Microbial infection) Interacts with vaccinia virus protein C9L. {ECO:0000269\|PubMed:29444943}.
Tissue specificity:		Expressed in lung fibroblasts. {ECO:0000269\|PubMed:9663463}.
Ptm:		Neddylated; which enhances the ubiquitination activity of SCF and prevents binding of the inhibitor CAND1. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (PubMed:10597293, PubMed:10713156, PubMed:15537541, PubMed:18805092). {ECO:0000269\|PubMed:10597293, ECO:0000269\|PubMed:10713156, ECO:0000269\|PubMed:15537541, ECO:0000269\|PubMed:18805092, ECO:0000269\|PubMed:20190741, ECO:0000269\|PubMed:24076655, ECO:0000269\|PubMed:27565346}.
Ptm:		(Microbial infection) Deneddylated by Epstein-Barr virus BPLF1 leading to a S-phase-like environment that is required for efficient replication of the viral genome (PubMed:20190741). {ECO:0000269\|PubMed:20190741}.
Similarity:		Belongs to the cullin family. {ECO:0000255\|PROSITE- ProRule:PRU00330}.