Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

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Skp1 Found 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):	This entry includes SKP1 and SKP1-like protein, elongin-C (also known as TCEB1). SKP1 is part of the E3 ubiquitin ligase complexes. Elongin-C has dual functions, works as a component of RNA polymerase II (Pol II) transcription elongation factor and as the substrate recognition subunit of a Cullin-RING E3 ubiquitin ligase [ (PUBMED:25878247) ]. Mammlian S-phase kinase-associated protein 1 (SKP1) is an essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription [ (PUBMED:20181953) ]. It is also part of the ubiquitin E3 ligase complex (Skp1-Pam-Fbxo45) that controls the core epithelial-to-mesenchymal transition-inducing transcription factors [ (PUBMED:25460509) ]. Budding yeast Skp1 is a kinetochore protein found in several complexes, including the SCF ubiquitin ligase complex, the CBF3 complex that binds centromeric DNA [ (PUBMED:8670864) ], and the RAVE complex that regulates assembly of the V-ATPase [ (PUBMED:11283612) ]. Elongin-C is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites [ (PUBMED:15590694) ]. It forms a complex with SIII regulatory subunits B, which serves as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes [ (PUBMED:15590694) ]. Elongin-C forms a complex with Cul3 that polyubiquitylates monoubiquitylated RNA polymerase II to trigger its proteolysis [ (PUBMED:17296727) ].
GO process:	ubiquitin-dependent protein catabolic process (GO:0006511)
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 4589 Skp1 domains in 4481 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing Skp1 domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with Skp1 domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing Skp1 domain in the selected taxonomic class.

• 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
  2ma9		HIV-1 Vif SOCS-box and Elongin BC solution structure
  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
  3l2o		Structure-Based Mechanism of Dimerization-Dependent Ubiquitination by the SCFFbx4 Ubiquitin Ligase
  3mks		Crystal Structure of yeast Cdc4/Skp1 in complex with an allosteric inhibitor SCF-I2
  3ogk		Structure of COI1-ASK1 in complex with coronatine and an incomplete JAZ1 degron
  3ogl		Structure of COI1-ASK1 in complex with JA-isoleucine and the JAZ1 degron
  3ogm		Structure of COI1-ASK1 in complex with coronatine and the JAZ1 degron
  3v7d		Crystal Structure of ScSkp1-ScCdc4-pSic1 peptide complex
  3wso		3WSO
  3zkj		Crystal Structure of Ankyrin Repeat and Socs Box-Containing Protein 9 (Asb9) in Complex with Elonginb and Elonginc
  3zng		Ankyrin repeat and SOCS-box protein 9 (ASB9) in complex with ElonginB and ElonginC
  3zrc		pVHL54-213-EloB-EloC complex (4R)-4-HYDROXY-1-[(3-METHYLISOXAZOL-5-YL)ACETYL]-N-[4-(1,3-OXAZOL-5-YL)BENZYL]-L-PROLINAMIDE bound
  3zrf		pVHL54-213-EloB-EloC complex_apo
  3ztc		pVHL54-213-EloB-EloC complex _ (2S,4R)-N-((1,1'-biphenyl)-4-ylmethyl)- 4-hydroxy-1-(2-(3-methylisoxazol-5-yl)acetyl)pyrrolidine-2- carboxamide
  3ztd		pVHL54-213-EloB-EloC complex _ methyl 4-(((2S,4R)-4-hydroxy-1-(2-(3- methylisoxazol-5-yl)acetyl)pyrrolidine-2-carboxamido)methyl)benzoate
  3zun		pVHL54-213-EloB-EloC complex_(2S,4R)-4-hydroxy-1-(2-(3-methylisoxazol- 5-yl)acetyl)-N-(4-nitrobenzyl)pyrrolidine-2-carboxamide bound
  4ajy		von Hippel-Lindau protein-ElonginB-ElonginC complex, bound to Hif1- alpha peptide
  4awj		pVHL:EloB:EloC complex, in complex with capped Hydroxyproline
  4b95		pVHL-EloB-EloC complex_(2S,4R)-1-(2-chlorophenyl)carbonyl-N-[(4-chlorophenyl)methyl]-4-oxidanyl-pyrrolidine-2-carboxamide bound
  4b9k		pVHL-ELOB-ELOC complex_(2S,4R)-1-(3-amino-2-methylbenzoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide bound
  4bks		von Hippel Lindau protein:ElonginB:ElonginC complex, in complex with (2S,4R)-1-ethanoyl-N-[[4-(1,3-oxazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide
  4bkt		von Hippel Lindau protein:ElonginB:ElonginC complex, in complex with (2S,4R)-N-methyl-1-[2-(3-methyl-1,2-oxazol-5-yl)ethanoyl]-4-oxidanyl-pyrrolidine-2-carboxamide
  4i6j		A ubiquitin ligase-substrate complex
  4jgh		Structure of the SOCS2-Elongin BC complex bound to an N-terminal fragment of Cullin5
  4n9f		Crystal structure of the Vif-CBFbeta-CUL5-ElOB-ElOC pentameric complex
  4w9c		4W9C
  4w9d		4W9D
  4w9e		4W9E
  4w9f		4W9F
  4w9g		4W9G
  4w9h		4W9H
  4w9i		4W9I
  4w9j		4W9J
  4w9k		4W9K
  4w9l		4W9L
  4wqo		4WQO
  5bo4		5BO4
  5hyw		5HYW
  5hzg		5HZG
  5ibk		5IBK
  5jh5		5JH5
  5lli		5LLI

• Links (links to other resources describing this domain)

• INTERPRO	IPR001232
  PFAM	Skp1

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