Tbio CUL1 Cullin-1

Protein Summary

Description

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.

Uniprot Accession IDs

• Q13616
• D3DWG3
• O60719
• Q08AL6
• Q8IYW1
• CUL-1

Gene Name

• CUL1

Ensembl ID

• ENST00000325222
• ENSP00000326804
• ENSG00000055130
• ENST00000409469
• ENSP00000387160
• ENST00000602748
• ENSP00000473318

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	1
interacting protein	0.99
kinase perturbation	0.99
hub protein	0.85
protein domain	0.85

Protein Classes

PANTHER Classes

Protein / Ligase / Ubiquitin-protein Ligase / Cullin-1

DTO Classes

Protein / Enzyme / Ligase / Ubiquitin-protein Ligase / Cullin-1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 389.94   (req: < 5)

Gene RIFs: 58   (req: <= 3)

Antibodies: 497   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 389.94   (req: >= 5)

Gene RIFs: 58   (req: > 3)

Antibodies: 497   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 24

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (651)

Explore Interacting Targets

1 – 10 of 651

• See Interactions on String-DB

FBXO42

Tbio

Novelty:  0.17658866

p_int:  0.999679246

p_ni:  0.000320754

Score:  0.617

Data Source:  BioPlex,STRINGDB

FBXL15

Tbio

Novelty:  0.18567032

p_int:  0.999656393

p_ni:  0.000343607

Score:  0.975

Data Source:  BioPlex,STRINGDB

FBXO4

Tbio

Novelty:  0.06891705

p_int:  0.999442546

p_ni:  0.000557454

Score:  0.971

Data Source:  BioPlex,STRINGDB

FBXO40

Tbio

Novelty:  0.20308726

p_int:  0.99895066

p_ni:  0.00104934

Score:  0.951

Data Source:  BioPlex,STRINGDB

FBXO6

Tbio

Novelty:  0.02173918

p_int:  0.998923168

p_ni:  0.001076832

Score:  0.972

Data Source:  BioPlex,STRINGDB

FBXO7

Tbio

Novelty:  0.01151907

p_int:  0.998876399

p_ni:  0.001123601

Score:  0.974

Data Source:  BioPlex,STRINGDB

FBXL5

Tbio

Novelty:  0.03103624

p_int:  0.998777197

p_ni:  0.001222803

Score:  0.971

Data Source:  BioPlex,Reactome,STRINGDB

FBXO17

Tbio

Novelty:  0.1320754

p_int:  0.99457516

p_ni:  0.005424834

p_wrong:  6e-9

Score:  0.969

Data Source:  BioPlex,STRINGDB

FBXO44

Tbio

Novelty:  0.06669582

p_int:  0.994169232

p_ni:  0.005830768

Score:  0.967

Data Source:  BioPlex,STRINGDB

CRY1

Tchem

Novelty:  0.00116593

p_int:  0.993853774

p_ni:  0.006146226

Score:  0.583

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (133)

Reactome (96)

KEGG (10)

PathwayCommons (18)

UniProt (1)

WikiPathways (8)

APC/C-mediated degradation of cell cycle proteins (R-HSA-174143)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	APC/C-mediated degradation of cell cycle proteins	87 targets	R-HSA-174143
Reactome	Activation of NF-kappaB in B cells	68 targets	R-HSA-1169091
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
Reactome	C-type lectin receptors (CLRs)	144 targets	R-HSA-5621481

Name	Explore in Pharos	Explore in Source
APC/C-mediated degradation of cell cycle proteins	87 targets	R-HSA-174143
Activation of NF-kappaB in B cells	68 targets	R-HSA-1169091
Adaptive Immune System	894 targets	R-HSA-1280218
Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
C-type lectin receptors (CLRs)	144 targets	R-HSA-5621481

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (29)

Functions (2)

Components (5)

Processes (22)

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1 – 2 of 2

GO Term	Evidence	Assigned by
ubiquitin-protein transferase activity	Inferred from Experiment (EXP)	Reactome
ubiquitin protein ligase binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Disease Associations (null)

No disease associations found

GWAS Traits (6)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 6

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean corpuscular hemoglobin concentration	EFO_0004528	1	1	1		55.5
inflammatory bowel disease	EFO_0003767	1	1	0	1.1	49.7
mean corpuscular volume	EFO_0004526	1	1	1		25.8
mean reticulocyte volume	EFO_0010701	1	1	1		20.5
type 2 diabetes mellitus	MONDO_0005148	1	1	1		11.4

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 6

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean corpuscular hemoglobin concentration	EFO_0004528	1		55.5
inflammatory bowel disease	EFO_0003767	0	1.1	49.7
mean corpuscular volume	EFO_0004526	1		25.8
mean reticulocyte volume	EFO_0010701	1		20.5
type 2 diabetes mellitus	MONDO_0005148	1		11.4

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UniProt Keyword Find Similar Targets

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3D-structure
Complete proteome
Host-virus interaction
Isopeptide bond
Methylation
Reference proteome
Ubl conjugation
Ubl conjugation pathway

GWAS Trait Find Similar Targets

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BMI-adjusted hip circumference
inflammatory bowel disease
mean corpuscular hemoglobin concentration
mean corpuscular volume
mean reticulocyte volume
type 2 diabetes mellitus

MGI Phenotype Find Similar Targets

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cellular phenotype
embryo phenotype
growth/size/body region phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (16)

1 – 5 of 16

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cullin 1	VGNC:4326	463821
Macaque	cullin 1		710581
Mouse	cullin 1	MGI:1349658	26965
Rat	cullin 1	RGD:1308157	362356
Dog	cullin 1	VGNC:39728	475512

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cullin 1
Macaque	cullin 1
Mouse	cullin 1
Rat	cullin 1
Dog	cullin 1

Publication Statistics

PubMed Score 389.94

PubMed score by year

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PubTator Score 196.65

PubTator score by year

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Related Publications

Text Mined References (153)

GeneRif Annotations (58)

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PMID	Year	Title