Tbio SKP1 S-phase kinase-associated protein 1

Protein Summary

Description

Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. 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, CEP68 and probably NFKB2 (PubMed:25704143). 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(FBXO11) 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. This gene encodes a component of SCF complexes, which are composed of this protein, cullin 1, a ring-box protein, and one member of the F-box family of proteins. This protein binds directly to the F-box motif found in F-box proteins. SCF complexes are involved in the regulated ubiquitination of specific protein substrates, which targets them for degradation by the proteosome. Specific F-box proteins recognize different target protein(s), and many specific SCF substrates have been identified including regulators of cell cycle progression and development. Studies have also characterized the protein as an RNA polymerase II elongation factor. Alternative splicing of this gene results in two transcript variants. A related pseudogene has been identified on chromosome 7. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P63208
• D3DQ97
• D3DQ98
• P34991
• Q8TAY2

Gene Name

• SKP1

Ensembl ID

• ENST00000353411
• ENSP00000231487
• ENSG00000113558
• ENST00000517625
• ENSP00000429961
• ENST00000522552
• ENSP00000429472
• ENST00000522855
• ENSP00000429686

Symbol

• EMC19
• OCP2
• SKP1A
• TCEB1L
• OCP2
• p19A
• EMC19
• SKP1A
• OCP-II
• TCEB1L

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	1
virus perturbation	1
transcription factor perturbation	0.99
kinase perturbation	0.98
co-expressed gene	0.94

Protein Classes

PANTHER Classes

Protein / Ligase / Ubiquitin-protein Ligase / S-phase Kinase-associated Protein 1

DTO Classes

Protein / Enzyme / Ligase / Ubiquitin-protein Ligase / S-phase Kinase-associated Protein 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: 628.36   (req: < 5)

Gene RIFs: 32   (req: <= 3)

Antibodies: 495   (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: 628.36   (req: >= 5)

Gene RIFs: 32   (req: > 3)

Antibodies: 495   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

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 (641)

Explore Interacting Targets

1 – 10 of 641

• See Interactions on String-DB

FBXL8

Tdark

Novelty:  0.84091737

p_int:  0.999999997

p_ni:  2e-9

p_wrong:  1e-9

Score:  0.963

Data Source:  BioPlex,STRINGDB

PCGF1

Tbio

Novelty:  0.06481661

p_int:  0.999999995

p_ni:  5e-9

Score:  0.972

Data Source:  BioPlex,STRINGDB

FBXW9

Tdark

Novelty:  1.16615529

p_int:  0.999999993

p_ni:  7e-9

Score:  0.979

Data Source:  BioPlex,STRINGDB

FBXO33

Tdark

Novelty:  0.23409767

p_int:  0.999999993

p_ni:  7e-9

Score:  0.681

Data Source:  BioPlex,STRINGDB

FBXO9

Tbio

Novelty:  0.2145394

p_int:  0.999999992

p_ni:  8e-9

Score:  0.988

Data Source:  BioPlex,STRINGDB

FBXO5

Tbio

Novelty:  0.01571484

p_int:  0.999999992

p_ni:  6e-9

p_wrong:  2e-9

Score:  0.973

Data Source:  BioPlex,Reactome,STRINGDB

KDM2A

Tchem

Family:  Epigenetic

Novelty:  0.01990727

p_int:  0.999999986

p_ni:  1.3e-8

Score:  0.987

Data Source:  BioPlex,STRINGDB

FBXL4

Tbio

Novelty:  0.04286856

p_int:  0.999999986

p_ni:  1.2e-8

p_wrong:  2e-9

Score:  0.976

Data Source:  BioPlex,STRINGDB

FBXW2

Tbio

Novelty:  0.01492058

p_int:  0.999999985

p_ni:  1.3e-8

p_wrong:  2e-9

Score:  0.982

Data Source:  BioPlex,STRINGDB

MTUS1

Tbio

Novelty:  0.01066081

p_int:  0.99999998

p_ni:  2e-8

Data Source:  BioPlex

Nearest Tclin Targets

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

Pathways (192)

Reactome (100)

KEGG (9)

PathwayCommons (16)

UniProt (1)

WikiPathways (66)

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 (27)

Functions (4)

Components (7)

Processes (16)

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1 – 4 of 4

GO Term	Evidence	Assigned by
beta-catenin binding	Inferred from Direct Assay (IDA)	ParkinsonsUK-UCL
ubiquitin-protein transferase activity	Inferred from Direct Assay (IDA)	UniProtKB
cullin family protein binding	Inferred from Physical Interaction (IPI)	ParkinsonsUK-UCL
protein domain specific binding	Inferred from Physical Interaction (IPI)	CAFA

Disease Associations (null)

No disease associations found

GWAS Traits (15)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 15

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
systemic lupus erythematosus	EFO_0002690	3	2	0	1.4	83.4
multiple sclerosis	MONDO_0005301	2	2	0	1.1	80.1
eosinophil count	EFO_0004842	2	2	3		61.9
eosinophil percentage of leukocytes	EFO_0007991	1	2	2		57.4
serum non-albumin protein measurement	EFO_0004568	1	2	2		50.2

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 15

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
systemic lupus erythematosus	EFO_0002690	0	1.4	83.4
multiple sclerosis	MONDO_0005301	0	1.1	80.1
eosinophil count	EFO_0004842	3		61.9
eosinophil percentage of leukocytes	EFO_0007991	2		57.4
serum non-albumin protein measurement	EFO_0004568	2		50.2

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Complete proteome
Direct protein sequencing
Host-virus interaction
Isopeptide bond
Phosphoprotein
Reference proteome
Ubl conjugation
Ubl conjugation pathway

GWAS Trait Find Similar Targets

No Header	No Header
allergic rhinitis
asthma
autoimmune thyroid disease
cup-to-disc ratio measurement
Eczema
eosinophil count
eosinophil percentage of leukocytes
hypothyroidism
mean platelet volume
multiple sclerosis

IDG Resources

No IDG generated resources found

Orthologs (15)

1 – 5 of 15

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	protein phosphatase 2 catalytic subunit alpha [Source:HGNC Symbol;Acc:HGNC:9299]
Mouse	S-phase kinase-associated protein 1A	MGI:103575	21402
Rat	S-phase kinase-associated protein 1	RGD:1359648	287280
Dog	S-phase kinase associated protein 1		474682
Horse	S-phase kinase associated protein 1		100062946

Species	Name	OMA	EggNOG	Inparanoid
Macaque	protein phosphatase 2 catalytic subunit alpha [Source:HGNC Symbol;Acc:HGNC:9299]
Mouse	S-phase kinase-associated protein 1A
Rat	S-phase kinase-associated protein 1
Dog	S-phase kinase associated protein 1
Horse	S-phase kinase associated protein 1

Publication Statistics

PubMed Score 628.36

PubMed score by year

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PubTator Score 217.14

PubTator score by year

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Related Publications

Text Mined References (130)

GeneRif Annotations (32)

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PMID	Year	Title