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

Summary

Official Symbol: SKP2provided by HGNC
Official Full Name: S-phase kinase associated protein 2provided by HGNC
Primary source: HGNC:HGNC:10901
See related: Ensembl:ENSG00000145604 MIM:601436; AllianceGenome:HGNC:10901
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: p45; 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]
Expression: Broad expression in placenta (RPKM 19.8), lymph node (RPKM 3.9) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5p13.2

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (36152111..36193530)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (36400405..36441818)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (36152213..36184421)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Clinical potential of SKP2 as diagnostic marker and therapeutic target in small cell lung cancer.
Title: Clinical potential of SKP2 as diagnostic marker and therapeutic target in small cell lung cancer.
Fatty Acid Synthase Promotes Hepatocellular Carcinoma Growth via S-Phase Kinase-Associated Protein 2/p27[KIP1] Regulation.
Title: Fatty Acid Synthase Promotes Hepatocellular Carcinoma Growth via S-Phase Kinase-Associated Protein 2/p27(KIP1) Regulation.
Promoter methylation and enhanced SKP2 are associated with the downregulation of CDKN1C in cervical squamous cell carcinoma.
Title: Promoter methylation and enhanced SKP2 are associated with the downregulation of CDKN1C in cervical squamous cell carcinoma.
O-GlcNAcylation of E3 ubiquitin ligase SKP2 promotes hepatocellular carcinoma proliferation.
Title: O-GlcNAcylation of E3 ubiquitin ligase SKP2 promotes hepatocellular carcinoma proliferation.
Targeting RCC1 to block the human soft-tissue sarcoma by disrupting nucleo-cytoplasmic trafficking of Skp2.
Title: Targeting RCC1 to block the human soft-tissue sarcoma by disrupting nucleo-cytoplasmic trafficking of Skp2.
Targeted inhibition of SCF[SKP2] confers anti-tumor activities resulting in a survival benefit in osteosarcoma.
Title: Targeted inhibition of SCF(SKP2) confers anti-tumor activities resulting in a survival benefit in osteosarcoma.
Skp2: A critical molecule for ubiquitination and its role in cancer.
Title: Skp2: A critical molecule for ubiquitination and its role in cancer.
SKP2 Knockout in Rb1/p53-Deficient Mouse Models of Osteosarcoma Induces Immune Infiltration and Drives a Transcriptional Program with a Favorable Prognosis.
Title: SKP2 Knockout in Rb1/p53-Deficient Mouse Models of Osteosarcoma Induces Immune Infiltration and Drives a Transcriptional Program with a Favorable Prognosis.
MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57[Kip2] targeting.
Title: MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57(Kip2) targeting.
A critical role of the endothelial S-phase kinase-associated protein 2/phosphatase and tensin homologue axis in angiogenesis and psoriasis.
Title: A critical role of the endothelial S-phase kinase-associated protein 2/phosphatase and tensin homologue axis in angiogenesis and psoriasis.

Submit: New GeneRIF Correction See all GeneRIFs (343)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH64840 (e-PCR)
- UniSTS:84225

D8S2279 (e-PCR)
- UniSTS:473907

L28202 (e-PCR)
- UniSTS:59957

L18426 (e-PCR)
- UniSTS:34648

D11S3114 (e-PCR)
- UniSTS:152207

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin-like ligase-substrate adaptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in G1/S transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in G2/M transition of mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to virus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in innate immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of double-strand break repair via homologous recombination	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of intracellular estrogen receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein polyubiquitination	IEA Inferred from Electronic Annotation more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein K48-linked ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein K63-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell cycle	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of SCF ubiquitin ligase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of SCF ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleolus	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: S-phase kinase-associated protein 2

Names: CDK2/cyclin A-associated protein p45; F-box/LRR-repeat protein 1; S-phase kinase-associated protein 2, E3 ubiquitin protein ligase; p45skp2

NCBI Reference Sequences (RefSeq)

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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_029643.3 RefSeqGene

Range

5002..37210

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

See identical proteins and their annotated locations for NP_001230049.1

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/Swiss-Prot

Q13309

Conserved Domains (2) summary

sd00034
Location:18 → 43

LRR_AMN1; leucine-rich repeat [structural motif]

cl28166
Location:17 → 131

AMN1; Antagonist of mitotic exit network protein 1
NM_005983.4 → NP_005974.2 S-phase kinase-associated protein 2 isoform 1

See identical proteins and their annotated locations for NP_005974.2

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/Swiss-Prot

A8K5E0, B4DJT4, Q13309, Q8TDZ0, Q8TDZ1, Q9BV69

UniProtKB/TrEMBL

A0A0A0MTL5

Related

ENSP00000274255.6, ENST00000274255.11

Conserved Domains (3) summary

cd09293
Location:193 → 345

AMN1; Antagonist of mitotic exit network protein 1

sd00034
Location:183 → 207

LRR_AMN1; leucine-rich repeat [structural motif]

pfam12937
Location:97 → 141

F-box-like
NM_032637.4 → NP_116026.1 S-phase kinase-associated protein 2 isoform 2

See identical proteins and their annotated locations for NP_116026.1

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, DA223617

Consensus CDS

CCDS3915.1

UniProtKB/TrEMBL

A0A7I2V5B8

Related

ENSP00000274254.5, ENST00000274254.9

Conserved Domains (3) summary

cd09293
Location:193 → 345

AMN1; Antagonist of mitotic exit network protein 1

sd00034
Location:183 → 207

LRR_AMN1; leucine-rich repeat [structural motif]

pfam12937
Location:97 → 141

F-box-like

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

36152111..36193530

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047417536.1 → XP_047273492.1 S-phase kinase-associated protein 2 isoform X1

UniProtKB/TrEMBL

A0A7I2V2J7

Related

ENSP00000503340.1, ENST00000677984.1

RNA

XR_001742203.3 RNA Sequence

Related

ENST00000513151.6

Alternate T2T-CHM13v2.0

Genomic

NC_060929.1 Alternate T2T-CHM13v2.0

Range

36400405..36441818

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054353187.1 → XP_054209162.1 S-phase kinase-associated protein 2 isoform X1

UniProtKB/TrEMBL

A0A7I2V2J7
XM_054353188.1 → XP_054209163.1 S-phase kinase-associated protein 2 isoform X2