Tbio SKP2 S-phase kinase-associated protein 2

Protein Summary

Description

Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration. Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus. This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class; in addition to an F-box, this protein contains 10 tandem leucine-rich repeats. This protein is an essential element of the cyclin A-CDK2 S-phase kinase. It specifically recognizes phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S phase and interacts with S-phase kinase-associated protein 1 (SKP1 or p19). In addition, this gene is established as a protooncogene causally involved in the pathogenesis of lymphomas. Alternative splicing of this gene generates three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2011]

Uniprot Accession IDs

• Q13309
• A8K5E0
• B4DJT4
• Q8TDZ0
• Q8TDZ1
• Q9BV69

Gene Name

• SKP2

Ensembl ID

• ENST00000274254
• ENSP00000274254
• ENSG00000145604
• ENST00000274255
• ENSP00000274255
• ENST00000620197
• ENSP00000478031

Symbol

• FBXL1
• p45
• FBL1
• FLB1
• FBXL1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor perturbation	0.99
ligand (protein) perturbation	0.83
small molecule perturbation	0.82
transcription factor binding site profile	0.81
cellular component	0.79

IDG Partner Tools

GlyGen

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: 616.92   (req: < 5)

Gene RIFs: 265   (req: <= 3)

Antibodies: 391   (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: 616.92   (req: >= 5)

Gene RIFs: 265   (req: > 3)

Antibodies: 391   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 21

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

GWAS Traits (5)

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
red blood cell distribution width	EFO_0005192	3	1	3		78.2
mean corpuscular hemoglobin concentration	EFO_0004528	1	1	1		56.9
mean corpuscular volume	EFO_0004526	1	1	1		34.5
mean reticulocyte volume	EFO_0010701	1	1	1		30.8
birth weight	EFO_0004344	1	1	1		18.3

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
red blood cell distribution width	EFO_0005192	3		78.2
mean corpuscular hemoglobin concentration	EFO_0004528	1		56.9
mean corpuscular volume	EFO_0004526	1		34.5
mean reticulocyte volume	EFO_0010701	1		30.8
birth weight	EFO_0004344	1		18.3

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Protein Data Bank (6)

1 – 5 of 6

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (102)

Reactome (31)

KEGG (8)

PathwayCommons (7)

UniProt (1)

WikiPathways (55)

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	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	73 targets	R-HSA-174178
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
Reactome	Cell Cycle	597 targets	R-HSA-1640170

Name	Explore in Pharos	Explore in Source
APC/C-mediated degradation of cell cycle proteins	87 targets	R-HSA-174143
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	73 targets	R-HSA-174178
Adaptive Immune System	894 targets	R-HSA-1280218
Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
Cell Cycle	597 targets	R-HSA-1640170

Gene Ontology Terms (26)

Functions (3)

Components (5)

Processes (18)

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GO Term	Evidence	Assigned by
ubiquitin-protein transferase activity	Inferred from Experiment (EXP)	Reactome
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
ubiquitin protein ligase activity	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (598)

Explore Interacting Targets

1 – 10 of 598

• See Interactions on String-DB

CKS1B

Tbio

Family: Enzyme

Novelty: 0.00766779

p_int: 0.999999598

p_ni: 4.02e-7

Score: 0.998

Data Source: BioPlex,Reactome,STRINGDB

CDK2

Tchem

Family: Kinase

Novelty: 0.00032118

p_int: 0.999998736

p_ni: 0.000001264

Score: 0.992

Data Source: BioPlex,Reactome,STRINGDB

SKP1

Tbio

Family: Enzyme

Novelty: 0.00149739

p_int: 0.999997093

p_ni: 0.000002907

Score: 0.999

Data Source: BioPlex,Reactome,STRINGDB

SMTNL2

Tdark

Novelty: 0.33805653

p_int: 0.999985392

p_ni: 0.000014608

Score: 0.218

Data Source: BioPlex,STRINGDB

CCNA2

Tchem

Novelty: 0.00049887

p_int: 0.99996406

p_ni: 0.00003594

Score: 0.991

Data Source: BioPlex,STRINGDB

REC8

Tbio

Novelty: 0.00732742

p_int: 0.999952424

p_ni: 0.000047576

Data Source: BioPlex

RICTOR

Tbio

Novelty: 0.00250734

p_int: 0.99956488

p_ni: 0.00043512

p_wrong: 1e-9

Score: 0.311

Data Source: BioPlex,STRINGDB

CDK1

Tchem

Family: Kinase

Novelty: 0.00040776

p_int: 0.999430446

p_ni: 0.000569554

Score: 0.935

Data Source: BioPlex,STRINGDB

CDK3

Tchem

Family: Kinase

Novelty: 0.03380289

p_int: 0.999428911

p_ni: 0.000571058

p_wrong: 3.1e-8

Score: 0.649

Data Source: BioPlex,STRINGDB

TRIM49

Tdark

Novelty: 0.51794727

p_int: 0.998563566

p_ni: 0.001436429

p_wrong: 5e-9

Score: 0.546

Data Source: BioPlex,STRINGDB

Publication Statistics

PubMed Score  616.92

PubMed score by year

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PubTator Score  397.99

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Acetylation
Alternative splicing
Antiviral defense
Complete proteome
Cytoplasm
Direct protein sequencing
Host-virus interaction
Immunity
Innate immunity

GWAS Trait Find Similar Targets

birth weight
mean corpuscular hemoglobin concentration
mean corpuscular volume
mean reticulocyte volume
red blood cell distribution width

MGI Phenotype Find Similar Targets

cellular phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
liver/biliary system phenotype
renal/urinary system phenotype
reproductive system phenotype