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

Protein Classes

No PANTHER Classes or DTO Classes found

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: 631.46   (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: 631.46   (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

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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GENEVA

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GlyGen

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ARCHS4

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

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

Nearest Tclin Targets

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

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

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (26)

Functions (3)

Components (5)

Processes (18)

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1 – 3 of 3

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

Disease Associations ()

No disease associations found

GWAS Traits (6)

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1 – 5 of 6

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
red blood cell distribution width	EFO_0005192	4	2	4		88.2
mean corpuscular volume	EFO_0004526	1	1	1		64.4
mean reticulocyte volume	EFO_0010701	1	1	1		59.9
mean corpuscular hemoglobin concentration	EFO_0004528	1	1	1		54.4
type II diabetes mellitus	EFO_0001360	3	2	2	1.1	35

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
red blood cell distribution width	EFO_0005192	4		88.2
mean corpuscular volume	EFO_0004526	1		64.4
mean reticulocyte volume	EFO_0010701	1		59.9
mean corpuscular hemoglobin concentration	EFO_0004528	1		54.4
type II diabetes mellitus	EFO_0001360	2	1.1	35

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Antiviral defense
Complete proteome
Cytoplasm
Direct protein sequencing
Host-virus interaction
Immunity
Innate immunity

GWAS Trait Find Similar Targets

No Header	No Header
birth weight
mean corpuscular hemoglobin concentration
mean corpuscular volume
mean reticulocyte volume
red blood cell distribution width
type II diabetes mellitus

MGI Phenotype Find Similar Targets

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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

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	S-phase kinase associated protein 2	VGNC:14453	471570
Macaque	S-phase kinase associated protein 2		700617
Mouse	S-phase kinase-associated protein 2 (p45)	MGI:1351663	27401
Rat	S-phase kinase associated protein 2	RGD:1562456	294790
Dog	S-phase kinase associated protein 2	VGNC:51910	489228

Species	Name	OMA	EggNOG	Inparanoid
Chimp	S-phase kinase associated protein 2
Macaque	S-phase kinase associated protein 2
Mouse	S-phase kinase-associated protein 2 (p45)
Rat	S-phase kinase associated protein 2
Dog	S-phase kinase associated protein 2

Publication Statistics

PubMed Score 631.46

PubMed score by year

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PubTator Score 397.99

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Related Publications

Text Mined References (312)

GeneRif Annotations (265)

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PMID	Year	Title