SKP2 S-phase kinase-associated protein 2 (p45) [ Homo sapiens ]

Gene ID: 6502, updated on 19-Feb-2012

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Summary

Official Symbol: SKP2provided by HGNC
Official Full Name: S-phase kinase-associated protein 2 (p45)provided by HGNC
Primary source: HGNC:10901
See related: Ensembl:ENSG00000145604; HPRD:03256; MIM:601436; Vega:OTTHUMG00000131106
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FBL1; FLB1; FBXL1
Summary: 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]

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Genomic context

Location :: 5p13

Sequence :: Chromosome: 5; NC_000005.9 (36152189..36184147)

See SKP2 in Epigenomics, MapViewer

Chromosome 5 - NC_000005.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Data indicate that androgens repress Skp2 expression via p107-dependent and -independent pathways in prostate cancer cells.
Title: Androgens repress expression of the F-box protein Skp2 via p107 dependent and independent mechanisms in LNCaP prostate cancer cells.
turnover of p21 was independent of the SCF (skp2) E3 ligase but could be inhibited, at least in part, by reducing hdm2, although this depended on the cell type studied.
Title: Hdm2- and proteasome-dependent turnover limits p21 accumulation during S phase.
High expression of Skp2 was negatively correlated with lower PTEN expression in glottic carcinoma.
Title: [Expression of Skp2 and PTEN and its correlation in glottic carcinoma].
High expression of Skp2 is an independent adverse prognostic factor of extranodal NK/T cell lymphoma.
Title: The role of Skp2 in extranodal NK/T-cell lymphoma.
Androgen suppresses proliferation of 104-R2 cells by inducing G(1) cell cycle arrest through reduction of Skp2. Overexpression of Skp2 in 104-R2 cells blocked the growth inhibition caused by androgens.
Title: Androgen suppresses proliferation of castration-resistant LNCaP 104-R2 prostate cancer cells through androgen receptor, Skp2, and c-Myc.
Studies indicate that SKP2 works in concert with Akt to induce FOXO1 ubiquitination and proteasome degradation.
Title: Regulation of FOXO protein stability via ubiquitination and proteasome degradation.
HBx mutants with changes that correspond to a combination of core promoter mutations up-regulate SKP2, which then down-regulates p21 via ubiquitin-mediated proteasomal degradation, increasing hepatocellular carcinoma risk.
Title: Hepatitis B virus core promoter mutations contribute to hepatocarcinogenesis by deregulating SKP2 and its target, p21.
Data show a link between inhibition of androgen receptor signaling, down-regulation of Skp2, and the appearance of secretory, tumor-promoting senescent cells in prostate tumors.
Title: Androgen depletion induces senescence in prostate cancer cells through down-regulation of Skp2.
Skp2 overexpression is associated with recurrence following radical prostatectomy in prostate cancer.
Title: The impact of Skp2 overexpression on recurrence-free survival following radical prostatectomy.
pVHL destabilizes the F-box protein Skp2
Title: von Hippel-Lindau protein promotes Skp2 destabilization on DNA damage.

Submit: New GeneRIF Correction See all (155)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Cdk9, the catalytic subunit of P-TEFb, is ubiquitinated by Skp1/Cul1/F-box protein E3 ubiquitin ligase Skp2, which facilitates the formation of the RNA-protein complex between P-TEFb, Tat, and TAR, thereby enhancing Tat transactivation	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
BAB87202.1	NP_003583.2	CUL1	BIND	PubMed	Skp2-Fbox interacts with Cul1 [15-410] to form part of the Cul1-Rbx1-Skp1-F Boxskp2 Scf Ubiquitin Ligase complex.
BAB87202.1	NP_733779.1	SKP1	BIND	PubMed	Skp2-Fbox interacts with SKP1A to form part of the Cul1-Rbx1-Skp1-F Boxskp2 Scf Ubiquitin Ligase complex.
NP_005974.2	Q9UM11	FZR1	BIND	PubMed	Cdh1 interacts with Skp2.
NP_005974.2	NP_004173.1	UXT	BIND	PubMed	STAP1 interacts with SKP2.
Q13309	P20248	CCNA2	HPRD	PubMed
Q13309	P24864	CCNE1	HPRD	PubMed
Q13309	O60563	CCNT1	HPRD	PubMed
Q13309	P49427	CDC34	HPRD	PubMed
Q13309	P24941	CDK2	HPRD	PubMed
Q13309	P50750	CDK9	HPRD	PubMed
Q13309	P46527	CDKN1B	HPRD	PubMed
Q13309	P49918	CDKN1C	HPRD	PubMed
Q13309	Q9H211	CDT1	HPRD	PubMed
Q13309	P61024	CKS1B	HPRD	PubMed
Q13309	Q13616	CUL1	HPRD	PubMed
Q13309	Q13619	CUL4A	HPRD	PubMed
Q13309	Q16531	DDB1	HPRD	PubMed
Q13309	Q01094	E2F1	HPRD	PubMed
Q13309	Q99607	ELF4	HPRD	PubMed
Q13309	Q9UM11	FZR1	HPRD	PubMed
Q13309	Q13098	GPS1	HPRD	PubMed
Q13309	P10244	MYBL2	HPRD	PubMed
Q13309	P01106	MYC	HPRD	PubMed
Q13309	Q13415	ORC1	HPRD	PubMed
Q13309	O60925	PFDN1	HPRD	PubMed
Q13309	P06400	RB1	HPRD	PubMed
Q13309	P63208	SKP1	HPRD	PubMed
Q13309	P15923	TCF3	HPRD	PubMed
Q13309	Ubiquitin B	UBB	HPRD	PubMed
Q13309	P30291	WEE1	HPRD	PubMed
BioGRID:112393	BioGRID:106710	AKT1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Co-localization; Reconstituted Complex
BioGRID:112393	BioGRID:119674	ASB2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:107142	BRCA2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:113593	BTG2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:114417	CCNA1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:112393	BioGRID:107331	CCNA2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112393	BioGRID:107338	CCNE1	BioGRID	PubMed	Reconstituted Complex
BioGRID:112393	BioGRID:114125	CDC14B	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:107427	CDC20	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:107432	CDC34	BioGRID	PubMed	Reconstituted Complex
BioGRID:112393	BioGRID:107434	CDH1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:107452	CDK2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112393	BioGRID:107459	CDK9	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:107460	CDKN1A	BioGRID	PubMed	Affinity Capture-Western
	NP_004055.1	CDKN1B	BIND	PubMed	Skp2 interacts with p27.
	NP_004055.1	CDKN1B	BIND	PubMed	CDKN1B (p27Kip1) interacts with SKP2 (p45Skp2).
BioGRID:112393	BioGRID:107461	CDKN1B	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:112393	BioGRID:107462	CDKN1C	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:123555	CDT1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:112393	BioGRID:107582	CKS1B	BioGRID	PubMed	Affinity Capture-Western; FRET; Reconstituted Complex
BioGRID:112393	BioGRID:126480	CKS1BP7	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112393	BioGRID:116183	COPS5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112393	BioGRID:116176	COPS6	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112393	BioGRID:114032	CUL1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Co-crystal Structure; Co-fractionation; Reconstituted Complex
BioGRID:112393	BioGRID:114029	CUL4A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:113743	CUL5	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:198624	Cdk1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112393	BioGRID:108009	DDB1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:108176	DUSP1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:108201	E2F1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112393	BioGRID:108315	ELF4	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:117645	FBXW8	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:108597	FOXO1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112393	BioGRID:108598	FOXO3	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:112393	BioGRID:119489	FZR1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:109655	IFI27	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:120041	ING3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:109920	JAK2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:200858	Jak3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:110443	MLL	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:110690	MYBL2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:110694	MYC	BioGRID	PubMed	Affinity Capture-Western; PCA; Reconstituted Complex
BioGRID:112393	BioGRID:119685	NLK	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:111040	ORC1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112393	BioGRID:111264	PHB	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:111310	PIM1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:112393	BioGRID:111687	PSMD9	BioGRID	PubMed	FRET
BioGRID:112393	BioGRID:111833	RAG2	BioGRID	PubMed	Protein-peptide
BioGRID:112393	BioGRID:116356	RASSF1	BioGRID	PubMed	Affinity Capture-Western
	NP_000312.1	RB1	BIND	PubMed	Skp2 interacts with Rb.
BioGRID:112393	BioGRID:111860	RB1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:111869	RBL2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:115301	RBX1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112393	BioGRID:112391	SKP1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Co-crystal Structure; Reconstituted Complex; Two-hybrid
BioGRID:112393	BioGRID:110264	SMAD4	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112393	BioGRID:112550	SP1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:112749	TAL1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:112791	TCF3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:115443	TOB1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:112615	TRIM21	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Co-fractionation; Reconstituted Complex
BioGRID:112393	BioGRID:113100	TSC2	BioGRID	PubMed	Phenotypic Suppression
BioGRID:112393	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:112393	BioGRID:113200	UFD1L	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:114465	USP13	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:116430	USP18	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:112393	BioGRID:113269	VHL	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
	NP_003381.1	WEE1	BIND	PubMed	Wee1A interacts with an unspecified isoform of SKP2.
BioGRID:112393	BioGRID:113303	WEE1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112393	BioGRID:113361	YWHAB	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex

Function	Evidence Code	Pubs
protein binding	IPI Inferred from Physical Interaction more info	PubMed
ubiquitin-protein ligase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
G1 phase of mitotic cell cycle	TAS Traceable Author Statement more info
G1/S transition of mitotic cell cycle	TAS Traceable Author Statement more info
G2/M transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
S phase of mitotic cell cycle	TAS Traceable Author Statement more info
anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process	TAS Traceable Author Statement more info
cell proliferation	TAS Traceable Author Statement more info	PubMed
mitotic cell cycle	TAS Traceable Author Statement more info
negative regulation of survival gene product expression	IEA Inferred from Electronic Annotation more info
positive regulation of intracellular estrogen receptor signaling pathway	IEA Inferred from Electronic Annotation more info
protein polyubiquitination	IEA Inferred from Electronic Annotation more info
regulation of cell cycle	IEA Inferred from Electronic Annotation more info
ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
SCF ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
nucleoplasm	TAS Traceable Author Statement more info

General protein information

Preferred Names: S-phase kinase-associated protein 2

Names: S-phase kinase-associated protein 2; p45skp2; F-box/LRR-repeat protein 1; CDK2/cyclin A-associated protein p45

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029643.1 RefSeqGene

Range

5001..36999

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001243120.1 → NP_001230049.1 S-phase kinase-associated protein 2 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two alternate coding exons compared to variant 1. The first causes the translation start site to move downstream while the second is in-frame. The resulting isoform (3) is shorter at the N-terminus and lacks an alternate internal segment compared to isoform 1.

Source sequence(s)

AC008942, AK296223, CA415778, DA223617

UniProtKB/TrEMBL

B4DJT4

Conserved Domains (1) summary

cl15308
Location:17 – 131
Blast Score: 80

AMN1; Antagonist of mitotic exit network protein 1
NM_005983.3 → NP_005974.2 S-phase kinase-associated protein 2 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AB050979, AC008942, AK296223, CA415778, DA223617

Consensus CDS

CCDS3916.1

UniProtKB/TrEMBL

B4DJT4

UniProtKB/Swiss-Prot

Q13309

Related

ENSP00000274255, OTTHUMP00000161734, ENST00000274255, OTTHUMT00000253769

Conserved Domains (2) summary

cl15308
Location:193 – 345
Blast Score: 96

AMN1; Antagonist of mitotic exit network protein 1

cl02535
Location:97 – 143
Blast Score: 160

F-box; F-box domain
NM_032637.3 → NP_116026.1 S-phase kinase-associated protein 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice junction at the 5' end of a coding exon compared to variant 1, that causes a frameshift. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

BC007441, CA415778, DA223617

Consensus CDS

CCDS3915.1

UniProtKB/Swiss-Prot

Q13309

Related

ENSP00000274254, OTTHUMP00000161733, ENST00000274254, OTTHUMT00000253768

Conserved Domains (2) summary

cl15308
Location:193 – 345
Blast Score: 96

AMN1; Antagonist of mitotic exit network protein 1

cl02535
Location:97 – 143
Blast Score: 158

F-box; F-box domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000005.9 Reference GRCh37.p5 Primary Assembly

Range

36152189..36184147

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000137.1 Alternate HuRef

Range

36103338..36135150

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC008942.6 (47467..79425)	None
genomic	CH471119.1	EAW55934.1
		EAW55935.1
		EAW55936.1
		EAW55937.1
		EAW55938.1
mRNA	AB050979.1	BAB87200.1
mRNA	AB050980.1	BAB87201.1
mRNA	AB050981.1	BAB87202.1
mRNA	AK291255.1	BAF83944.1
mRNA	AK295152.1	BAG58168.1
mRNA	AK296223.1	BAG58946.1
mRNA	AY029177.1	AAK31593.1
mRNA	BC001441.2	AAH01441.1
mRNA	BC007441.2	AAH07441.1
mRNA	CA415778.1	None
mRNA	DA223617.1	None
mRNA	U33761.1	AAC50242.1