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

Gene ID: 6502, updated on 27-Dec-2018

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
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

Genomic context

See SKP2 in Genome Data Viewer
Location:
5p13.2
Exon count:
11
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 5 NC_000005.10 (36152043..36184041)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (36152091..36184143)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene UDP glycosyltransferase family 3 member A2 Neighboring gene LMBR1 domain containing 2 Neighboring gene RNA, U6 small nuclear 1305, pseudogene Neighboring gene microRNA 580 Neighboring gene NAD kinase 2, mitochondrial Neighboring gene RAN binding protein 3 like

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

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 Interaction Database

Pathways from BioSystems

  • APC/C-mediated degradation of cell cycle proteins, organism-specific biosystem (from REACTOME)
    APC/C-mediated degradation of cell cycle proteins, organism-specific biosystemThe Anaphase Promoting Complex or Cyclosome (APC/C) functions during mitosis to promote sister chromatid separation and mitotic exit through the degradation of mitotic cyclins and securin. This compl...
  • APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1, organism-specific biosystem (from REACTOME)
    APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1, organism-specific biosystemFrom late mitosis through G1 phase APC/C:Cdh1 insures the continued degradation of the mitotic proteins and during mitotic exit and G1 its substrates include Cdc20, Plk1, Aurora A, Cdc6 and Gemin...
  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Antigen processing: Ubiquitination & Proteasome degradation, organism-specific biosystem (from REACTOME)
    Antigen processing: Ubiquitination & Proteasome degradation, organism-specific biosystemIntracellular foreign or aberrant host proteins are cleaved into peptide fragments of a precise size, such that they can be loaded on to class I MHC molecules and presented externally to cytotoxic T ...
  • C-MYC pathway, organism-specific biosystem (from Pathway Interaction Database)
    C-MYC pathway, organism-specific biosystem
    C-MYC pathway
  • Cell Cycle, organism-specific biosystem (from WikiPathways)
    Cell Cycle, organism-specific biosystemThe cell cycle is the series of events that takes place in a cell leading to its division and duplication (replication). Regulation of the cell cycle involves processes crucial to the survival of a c...
  • Cell Cycle, organism-specific biosystem (from REACTOME)
    Cell Cycle, organism-specific biosystem
    Cell Cycle
  • Cell Cycle, Mitotic, organism-specific biosystem (from REACTOME)
    Cell Cycle, Mitotic, organism-specific biosystemThe replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried o...
  • Cell cycle, organism-specific biosystem (from KEGG)
    Cell cycle, organism-specific biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
  • Cell cycle, conserved biosystem (from KEGG)
    Cell cycle, conserved biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
  • Class I MHC mediated antigen processing & presentation, organism-specific biosystem (from REACTOME)
    Class I MHC mediated antigen processing & presentation, organism-specific biosystemMajor histocompatibility complex (MHC) class I molecules play an important role in cell mediated immunity by reporting on intracellular events such as viral infection, the presence of intracellular b...
  • Cyclin A:Cdk2-associated events at S phase entry, organism-specific biosystem (from REACTOME)
    Cyclin A:Cdk2-associated events at S phase entry, organism-specific biosystemCyclin A:Cdk2 plays a key role in S phase entry by phosphorylation of proteins including Cdh1, Rb, p21 and p27. During G1 phase of the cell cycle, cyclin A is synthesized and associates with Cdk2. Af...
  • Cyclin D associated events in G1, organism-specific biosystem (from REACTOME)
    Cyclin D associated events in G1, organism-specific biosystemThree D-type cyclins are essential for progression from G1 to S-phase. These D cyclins bind to and activate both CDK4 and CDK6. The formation of all possible complexes between the D-type cyclins and...
  • Cyclin E associated events during G1/S transition, organism-specific biosystem (from REACTOME)
    Cyclin E associated events during G1/S transition, organism-specific biosystemThe transition from the G1 to S phase is controlled by the Cyclin E:Cdk2 complexes. As the Cyclin E:Cdk2 complexes are formed, the Cdk2 is phosphorylated by the Wee1 and Myt1 kinases. This phosphoryl...
  • Deubiquitination, organism-specific biosystem (from REACTOME)
    Deubiquitination, organism-specific biosystemUbiquitination, the modification of proteins by the covalent attachment of ubiquitin (Ub), is a key regulatory mechanism for many many cellular processes, including protein degradation by the 26S pro...
  • Epstein-Barr virus infection, organism-specific biosystem (from KEGG)
    Epstein-Barr virus infection, organism-specific biosystemEpstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is associated with oncogenesis. EBV infection to primary human B lymphocytes leads to induction of EBV-specific HLA-restricted cytotoxi...
  • Epstein-Barr virus infection, conserved biosystem (from KEGG)
    Epstein-Barr virus infection, conserved biosystemEpstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is associated with oncogenesis. EBV infection to primary human B lymphocytes leads to induction of EBV-specific HLA-restricted cytotoxi...
  • FOXM1 transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
    FOXM1 transcription factor network, organism-specific biosystem
    FOXM1 transcription factor network
  • FoxO family signaling, organism-specific biosystem (from Pathway Interaction Database)
    FoxO family signaling, organism-specific biosystem
    FoxO family signaling
  • FoxO signaling pathway, organism-specific biosystem (from KEGG)
    FoxO signaling pathway, organism-specific biosystemThe forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative str...
  • G1 Phase, organism-specific biosystem (from REACTOME)
    G1 Phase, organism-specific biosystemEarly cell cycle progression in G1 is under the control of the D-type cyclins together with Cdk4 and Cdk6. An important target for these CDKs is the Retinoblastoma (Rb) protein, which when phosphoryl...
  • G1/S Transition, organism-specific biosystem (from REACTOME)
    G1/S Transition, organism-specific biosystemCyclin E - Cdk2 complexes control the transition from G1 into S-phase. In this case, the binding of p21Cip1/Waf1 or p27kip1 is inhibitory. Important substrates for Cyclin E - Cdk2 complexes include p...
  • Herpes simplex infection, organism-specific biosystem (from KEGG)
    Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Herpes simplex infection, conserved biosystem (from KEGG)
    Herpes simplex infection, conserved biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Metabolism of proteins, organism-specific biosystem (from REACTOME)
    Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
  • Mitotic G1-G1/S phases, organism-specific biosystem (from REACTOME)
    Mitotic G1-G1/S phases, organism-specific biosystem
    Mitotic G1-G1/S phases
  • Notch signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    Notch signaling pathway, organism-specific biosystem
    Notch signaling pathway
  • Pathways in cancer, organism-specific biosystem (from KEGG)
    Pathways in cancer, organism-specific biosystem
    Pathways in cancer
  • Post-translational protein modification, organism-specific biosystem (from REACTOME)
    Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
  • Regulation of mitotic cell cycle, organism-specific biosystem (from REACTOME)
    Regulation of mitotic cell cycle, organism-specific biosystem
    Regulation of mitotic cell cycle
  • Regulation of retinoblastoma protein, organism-specific biosystem (from Pathway Interaction Database)
    Regulation of retinoblastoma protein, organism-specific biosystem
    Regulation of retinoblastoma protein
  • Retinoblastoma (RB) in Cancer, organism-specific biosystem (from WikiPathways)
    Retinoblastoma (RB) in Cancer, organism-specific biosystemDescribes the role of retinoblastoma (RB) gene in cancer.
  • S Phase, organism-specific biosystem (from REACTOME)
    S Phase, organism-specific biosystemDNA synthesis occurs in the S phase, or the synthesis phase, of the cell cycle. The cell duplicates its hereditary material, and two copies of the chromosome are formed. As DNA replication continues,...
  • SCF(Skp2)-mediated degradation of p27/p21, organism-specific biosystem (from REACTOME)
    SCF(Skp2)-mediated degradation of p27/p21, organism-specific biosystemDuring G1, the activity of cyclin-dependent kinases (CDKs) is kept in check by the CDK inhibitors (CKIs) p27 and p21, thereby preventing premature entry into S phase (see Guardavaccaro and Pagano, 20...
  • SCF-SKP2 complex, organism-specific biosystem (from KEGG)
    SCF-SKP2 complex, organism-specific biosystemStructural complex; Genetic information processing; Ubiquitin system
  • SCF-SKP2 complex, conserved biosystem (from KEGG)
    SCF-SKP2 complex, conserved biosystemStructural complex; Genetic information processing; Ubiquitin system
  • Small cell lung cancer, organism-specific biosystem (from KEGG)
    Small cell lung cancer, organism-specific biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% ...
  • Small cell lung cancer, conserved biosystem (from KEGG)
    Small cell lung cancer, conserved biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% ...
  • Ub-specific processing proteases, organism-specific biosystem (from REACTOME)
    Ub-specific processing proteases, organism-specific biosystemUb-specific processing proteases (USPs) are the largest of the DUB families with more than 50 members in humans. The USP catalytic domain varies considerably in size and consists of six conserved mo...
  • Ubiquitin mediated proteolysis, organism-specific biosystem (from KEGG)
    Ubiquitin mediated proteolysis, organism-specific biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
  • Ubiquitin mediated proteolysis, conserved biosystem (from KEGG)
    Ubiquitin mediated proteolysis, conserved biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
  • Viral carcinogenesis, organism-specific biosystem (from KEGG)
    Viral carcinogenesis, organism-specific biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
  • Viral carcinogenesis, conserved biosystem (from KEGG)
    Viral carcinogenesis, conserved biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
  • mTOR signaling pathway, organism-specific biosystem (from KEGG)
    mTOR signaling pathway, organism-specific biosystemThe mammalian (mechanistic) target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase, which exists in two complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2). mTORC1 conta...
  • mTOR signaling pathway, conserved biosystem (from KEGG)
    mTOR signaling pathway, conserved biosystemThe mammalian (mechanistic) target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase, which exists in two complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2). mTORC1 conta...
  • p53 pathway, organism-specific biosystem (from Pathway Interaction Database)
    p53 pathway, organism-specific biosystem
    p53 pathway

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC1366

Gene Ontology Provided by GOA

Function Evidence Code Pubs
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
contributes_to ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin-protein transferase activity EXP
Inferred from Experiment
more info
PubMed 
ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
 
Process Evidence Code Pubs
G1/S transition of mitotic cell cycle IEA
Inferred from Electronic Annotation
more info
 
G2/M transition of mitotic cell cycle IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cell proliferation TAS
Traceable Author Statement
more info
PubMed 
cellular response to cell-matrix adhesion IEA
Inferred from Electronic Annotation
more info
 
defense response to virus IMP
Inferred from Mutant Phenotype
more info
PubMed 
innate immune response IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of intracellular estrogen receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
positive regulation of protein polyubiquitination IEA
Inferred from Electronic Annotation
more info
 
positive regulation of smooth muscle cell proliferation IEA
Inferred from Electronic Annotation
more info
 
post-translational protein modification TAS
Traceable Author Statement
more info
 
proteasome-mediated ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein K48-linked ubiquitination IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein deubiquitination TAS
Traceable Author Statement
more info
 
protein polyubiquitination TAS
Traceable Author Statement
more info
 
regulation of apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
regulation of cell cycle IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
SCF ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
SCF ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
nucleolus IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
 

General protein information

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)

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

  1. NG_029643.2 RefSeqGene

    Range
    5001..36999
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001243120.1NP_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
    Consensus CDS
    CCDS58944.1
    UniProtKB/Swiss-Prot
    Q13309
    Related
    ENSP00000478031.1, ENST00000620197.4
    Conserved Domains (2) summary
    sd00034
    Location:1843
    LRR_AMN1; leucine-rich repeat [structural motif]
    cl28166
    Location:17131
    AMN1; Antagonist of mitotic exit network protein 1
  2. NM_005983.3NP_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
    Q13309
    UniProtKB/TrEMBL
    A0A024R069
    Related
    ENSP00000274255.6, ENST00000274255.10
    Conserved Domains (3) summary
    sd00034
    Location:183207
    LRR_AMN1; leucine-rich repeat [structural motif]
    pfam12937
    Location:97141
    F-box-like; F-box-like
    cl28166
    Location:193345
    AMN1; Antagonist of mitotic exit network protein 1
  3. NM_032637.3NP_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, CA415778, DA223617
    Consensus CDS
    CCDS3915.1
    UniProtKB/Swiss-Prot
    Q13309
    Related
    ENSP00000274254.5, ENST00000274254.9
    Conserved Domains (3) summary
    sd00034
    Location:183207
    LRR_AMN1; leucine-rich repeat [structural motif]
    pfam12937
    Location:97141
    F-box-like; F-box-like
    cl28166
    Location:193345
    AMN1; Antagonist of mitotic exit network protein 1

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p12 Primary Assembly

    Range
    36152043..36184041
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011514082.3XP_011512384.1  S-phase kinase-associated protein 2 isoform X1

    See identical proteins and their annotated locations for XP_011512384.1

    Conserved Domains (3) summary
    cd09293
    Location:193345
    AMN1; Antagonist of mitotic exit network protein 1
    sd00034
    Location:183207
    LRR_AMN1; leucine-rich repeat [structural motif]
    pfam12937
    Location:97143
    F-box-like; F-box-like
  2. XM_011514083.3XP_011512385.1  S-phase kinase-associated protein 2 isoform X2

    See identical proteins and their annotated locations for XP_011512385.1

    Conserved Domains (2) summary
    cd09293
    Location:24176
    AMN1; Antagonist of mitotic exit network protein 1
    sd00034
    Location:1438
    LRR_AMN1; leucine-rich repeat [structural motif]
  3. XM_017009753.1XP_016865242.1  S-phase kinase-associated protein 2 isoform X3

RNA

  1. XR_001742203.2 RNA Sequence

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