InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CUL1

Summary

InnateDB Protein

IDBP-46920.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CUL1

Protein Name

cullin 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000326804

InnateDB Gene

IDBG-46918 (CUL1)

Protein Structure

UniProt Annotation

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. 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(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 cyclin E, 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) direct ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2. {ECO:0000269PubMed:15531760, ECO:0000269PubMed:15640526, ECO:0000269PubMed:18644861, ECO:0000269PubMed:19679664, ECO:0000269PubMed:22113614, ECO:0000269PubMed:23263282, ECO:0000269PubMed:23431138, ECO:0000269PubMed:9663463}.

Subcellular Localization

Disease Associations

Tissue Specificity

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

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 775 experimentally validated interaction(s) in this database.
They are also associated with 23 interaction(s) predicted by orthology.

Experimentally validated
Total	775 [view]
Protein-Protein	774 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	23 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0031625	ubiquitin protein ligase binding

Biological Process

GO:0000082	G1/S transition of mitotic cell cycle
GO:0000086	G2/M transition of mitotic cell cycle
GO:0000278	mitotic cell cycle
GO:0006511	ubiquitin-dependent protein catabolic process
GO:0006513	protein monoubiquitination
GO:0006915	apoptotic process
GO:0007050	cell cycle arrest
GO:0007219	Notch signaling pathway
GO:0008283	cell proliferation
GO:0008285	negative regulation of cell proliferation
GO:0009887	organ morphogenesis
GO:0016032	viral process
GO:0016567	protein ubiquitination
GO:0031145	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
GO:0031146	SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
GO:0051437	positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0051439	regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0097193	intrinsic apoptotic signaling pathway