CUL1
CUL1 (Cullin 1) is a Protein Coding gene. Diseases associated with CUL1 include Xeroderma Pigmentosum Group E and Parkinson Disease 15, Autosomal Recessive Early-Onset. Among its related pathways are Signaling by NOTCH1 and IL-1 signaling pathway. Gene Ontology (GO) annotations related to this gene include ubiquitin protein ligase binding. An important paralog of this gene is CUL2.
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.
Biological Process
Animal organ morphogenesis Source: Ensembl
Cell population proliferation Source: Ensembl
Cellular iron ion homeostasis Source: Reactome
Fc-epsilon receptor signaling pathway Source: Reactome
G1/S transition of mitotic cell cycle Source: ProtInc
G2/M transition of mitotic cell cycle Source: Reactome
Interleukin-1-mediated signaling pathway Source: Reactome
Intrinsic apoptotic signaling pathway Source: ProtInc
Negative regulation of G2/M transition of mitotic cell cycle Source: Reactome
NIK/NF-kappaB signaling Source: Reactome
Post-translational protein modification Source: Reactome
Protein K48-linked ubiquitination Source: Ensembl
Protein monoubiquitination Source: Ensembl
Protein polyubiquitination Source: Reactome
Protein ubiquitination Source: UniProtKB
Regulation of mitotic cell cycle phase transition Source: Reactome
SCF complex assembly Source: Reactome
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
Stimulatory C-type lectin receptor signaling pathway Source: Reactome
Stress-activated MAPK cascade Source: Reactome
T cell receptor signaling pathway Source: Reactome
Viral process Source: UniProtKB-KW
Wnt signaling pathway Source: Reactome
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).
(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).
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Datasheet