Skp1Found in Skp1 protein family
|SMART accession number:||SM00512|
|Description:||Family of Skp1 (kinetochore protein required for cell cycle progression) and elongin C (subunit of RNA polymerase II transcription factor SIII) homologues.|
|Interpro abstract (IPR001232):|
SKP1 (together with SKP2) was identified as an essential component of the cyclin A-CDK2 S phase kinase complex [(PUBMED:10205047)]. It was found to bind several F-box containing proteins (e.g., Cdc4, Skp2, cyclin F) and to be involved in the ubiquitin protein degradation pathway. A yeast homologue of SKP1 (P52286) was identified in the centromere bound kinetochore complex [(PUBMED:8670864)] and is also involved in the ubiquitin pathway [(PUBMED:9390558)]. In Dictyostelium discoideum (Slime mold) FP21 was shown to be glycosylated in the cytosol and has homology to SKP1 [(PUBMED:7852383)].
|GO process:||ubiquitin-dependent protein catabolic process (GO:0006511)|
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- Evolution (species in which this domain is found)
Click on to expand nodes. To display all proteins with a Skp1 domain in a specific node, click on it.
This tree shows only several representative species. The complete taxonomic breakdown of all proteins with Skp1 domain is also avaliable.
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Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Stebbins CE, KaelinWGJ r, Pavletich NP
- Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function.
- Science. 1999; 284: 455-61
- Display abstract
Mutation of the VHL tumor suppressor is associated with the inherited von Hippel-Lindau (VHL) cancer syndrome and the majority of kidney cancers. VHL binds the ElonginC-ElonginB complex and regulates levels of hypoxia-inducible proteins. The structure of the ternary complex at 2.7 angstrom resolution shows two interfaces, one between VHL and ElonginC and another between ElonginC and ElonginB. Tumorigenic mutations frequently occur in a 35-residue domain of VHL responsible for ElonginC binding. A mutational patch on a separate domain of VHL indicates a second macromolecular binding site. The structure extends the similarities to the SCF (Skp1-Cul1-F-box protein) complex that targets proteins for degradation, supporting the hypothesis that VHL may function in an analogous pathway.
- Krek W
- Proteolysis and the G1-S transition: the SCF connection.
- Curr Opin Genet Dev. 1998; 8: 36-42
- Display abstract
Temporal control of ubiquitin-proteasome mediated protein degradation is critical for normal G1 and S phase progression. Recent work has shown that central to the temporal control mechanism is a relationship between newly identified E3 ubiquitin protein ligases, designated SCFs (Skp1-cullin-F-box protein ligase complexes), which confer substrate specificity on ubiquitination reactions and the activities of protein kinases that phosphorylate substrates destined for destruction at specific sites, thereby converting them into preferred targets for ubiquitin modification catalyzed by SCFs. The constituents of SCFs are members of evolutionary conserved protein families. SCF-based ubiquitination pathways may play a key role in diverse biological processes, such as cell proliferation, differentiation and development.
- Lonergan KM et al.
- Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2.
- Mol Cell Biol. 1998; 18: 732-41
- Display abstract
The von Hippel-Lindau tumor suppressor protein (pVHL) binds to elongins B and C and posttranscriptionally regulates the accumulation of hypoxia-inducible mRNAs under normoxic (21% O2) conditions. Here we report that pVHL binds, via elongin C, to the human homolog of the Caenorhabditis elegans Cul2 protein. Coimmunoprecipitation and chromatographic copurification data suggest that pVHL-Cul2 complexes exist in native cells. pVHL mutants that were unable to bind to complexes containing elongin C and Cul2 were likewise unable to inhibit the accumulation of hypoxia-inducible mRNAs. A model for the regulation of hypoxia-inducible mRNAs by pVHL is presented based on the apparent similarity of elongin C and Cul2 to Skp1 and Cdc53, respectively. These latter proteins form complexes that target specific proteins for ubiquitin-dependent proteolysis.
- Connelly C, Hieter P
- Budding yeast SKP1 encodes an evolutionarily conserved kinetochore protein required for cell cycle progression.
- Cell. 1996; 86: 275-85
- Display abstract
The budding yeast SKP1 gene, identified as a dosage suppressor of a known kinetochore protein mutant, encodes an intrinsic 22.3 kDa subunit of CBF3, a multiprotein complex that binds centromere DNA in vitro. Temperature-sensitive mutations in SKP1 define two distinct phenotypic classes. skp1-4 mutants arrest predominantly as large budded cells with a G2 DNA content and short mitotic spindle, consistent with a role in kinetochore function. skp1-3 mutants, however, arrest predominantly as multiply budded cells with a G1 DNA content, suggesting an additional role during the G1/S phase. Identification of Skp1p homologs from C. elegans, A. thaliana, and H. sapiens indicates that SKP1 is evolutionarily highly conserved. Skp1p therefore represents an intrinsic kinetochore protein conserved throughout eukaryotic evolution and may be directly involved in linking kinetochore function with the cell cycle-regulatory machinery.
- Garrett KP, Haque D, Conaway RC, Conaway JW
- A human cDNA encoding the small subunit of RNA polymerase II transcription factor SIII.
- Gene. 1994; 150: 413-4
- Display abstract
A full-length cDNA encoding a human homolog of the 15-kDa subunit (p15) of RNA polymerase II elongation factor SIII was isolated and sequenced. Comparison of the open reading frames of the human p15 cDNA and the previously characterized rat p15 cDNA [Garrett et al., Proc. Natl. Acad. Sci. USA 91 (1994) 5237-5241] indicates that they encode identical proteins and are 93% conserved in nucleotide sequence.
- Metabolism (metabolic pathways involving proteins which contain this domain)
% proteins involved KEGG pathway ID Description 26.67 map04120 Ubiquitin mediated proteolysis 23.33 map04111 Cell cycle - yeast 23.33 map04310 Wnt signaling pathway 23.33 map04110 Cell cycle 3.33 map05211 Renal cell carcinoma
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with Skp1 domain which could be assigned to a KEGG orthologous group, and not all proteins containing Skp1 domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of Skp1 domains in PDB
PDB code Main view Title 1fqv Insights into scf ubiquitin ligases from the structure of the skp1-skp2 complex 1fs1 Insights into scf ubiquitin ligases from the structure of the skp1-skp2 complex 1fs2 Insights into scf ubiquitin ligases from the structure of the skp1-skp2 complex 1hv2 Solution structure of yeast elongin c in complex with a von hippel-lindau peptide 1ldk Structure of the cul1-rbx1-skp1-f boxskp2 scf ubiquitin ligase complex 1lm8 Structure of a hif-1a-pvhl-elonginb-elonginc complex 1lqb Crystal structure of a hydroxylated hif-1 alpha peptide bound to the pvhl/elongin-c/elongin-b complex 1nex Crystal structure of scskp1-sccdc4-cpd peptide complex 1p22 Structure of a beta-trcp1-skp1-beta-catenin complex: destruction motif binding and lysine specificity on the scfbeta-trcp1 ubiquitin ligase 1vcb The vhl-elonginc-elonginb structure 2ass Crystal structure of the skp1-skp2-cks1 complex 2ast Crystal structure of skp1-skp2-cks1 in complex with a p27 peptide 2c9w Crystal structure of socs-2 in complex with elongin-b and elongin-c at 1.9a resolution 2e31 Structural basis for selection of glycosylated substrate by scffbs1 ubiquitin ligase 2e32 Structural basis for selection of glycosylated substrate by scffbs1 ubiquitin ligase 2fnj Crystal structure of a b30.2/spry domain-containing protein gustavus in complex with elongin b and elongin c 2izv Crystal structure of socs-4 in complex with elongin-b and elongin-c at 2.55a resolution 2jz3 Socs box elonginbc ternary complex 2ovp Structure of the skp1-fbw7 complex 2ovq Structure of the skp1-fbw7-cyclinedegc complex 2ovr Structure of the skp1-fbw7-cyclinedegn complex 2p1m Tir1-ask1 complex structure 2p1n Mechanism of auxin perception by the tir1 ubiqutin ligase 2p1o Mechanism of auxin perception by the tir1 ubiquitin ligase 2p1p Mechanism of auxin perception by the tir1 ubiquitin ligase 2p1q Mechanism of auxin perception by the tir1 ubiquitin ligase 3c6n Small molecule agonists and antagonists of f-box protein- substrate interactions in auxin perception and signaling 3c6o Small molecule agonists and antagonists of f-box protein- substrate interactions in auxin perception and signaling 3c6p Small molecule agonists and antagonists of f-box protein- substrate interactions in auxin perception and signaling 3dcg Crystal structure of the hiv vif bc-box in complex with human elonginb and elonginc
- Links (links to other resources describing this domain)
PFAM Skp1 INTERPRO IPR001232