This entry includes SKP1 from yeasts, animals and plants. 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 []. It is also part of the ubiquitin E3 ligase complex (Skp1-Pam-Fbxo45) that controls the core epithelial-to-mesenchymal transition-inducing transcription factors [].Budding yeast Skp1 is a kinetochore protein found in several complexes, including the SCF ubiquitin ligase complex, the CBF3 complex that binds centromeric DNA [], and the RAVE complex that regulates assembly of the V-ATPase []. In Dictyostelium discoideum (Slime mold) FP21 was shown to be glycosylated in the cytosol and has homology to SKP1 [].Arabidopsis Skp1 is part of the Skp1/Cullin1/F-box protein COI1 (SCFCOI1) E3 ubiquitin ligase complex required for vegetative and floral organ development as well as for male gametogenesis [, ]. 21 Skp1-related genes, called Arabidopsis-SKP1-like (ASK), have been uncovered in the Arabidopsis genome. They may collectively perform a range of functions and may regulate different developmental and physiological processes [, ].
SKP1 (together with SKP2) was identified as an essential component of the cyclin A-CDK2 S phase kinase complex []. 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 []and is also involved in the ubiquitin pathway []. In Dictyostelium discoideum (Slime mold) FP21 was shown to be glycosylated in the cytosol and has homology to SKP1 [].This entry represents a dimerisation domain found at the C-terminal of SKP1 proteins [], as well as in subunit D of the centromere DNA-binding protein complex Cbf3 []. This domain is multi-helical in structure, and consists of an interlocked herterodimer in F-box proteins.
SKP1 (together with SKP2) was identified as an essential component of the cyclin A-CDK2 S phase kinase complex []. 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 []and is also involved in the ubiquitin pathway []. In Dictyostelium discoideum (Slime mold) FP21 was shown to be glycosylated in the cytosol and has homology to SKP1 [].This entry represents a POZ domain with a core structure consisting of beta(2)/alpha(2)/beta(2)/alpha(2) in two layers, alpha/beta. This domain is found at the N-terminal of SKP1 proteins []as well as in subunit D of the centromere DNA-binding protein complex Cbf3 [].
SKP1 (together with SKP2) was identified as an essential component of the cyclin A-CDK2 S phase kinase complex []. 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 []and is also involved in the ubiquitin pathway []. In Dictyostelium discoideum (Slime mold) FP21 was shown to be glycosylated in the cytosol and has homology to SKP1 [].This entry represents the superfamily of a dimerisation domain found at the C-terminal of SKP1 proteins [], as well as in subunit D of the centromere DNA-binding protein complex Cbf3 []. This domain is multi-helical in structure, and consists of an interlocked herterodimer in F-box proteins.
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 []. 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 []. It is also part of the ubiquitin E3 ligase complex (Skp1-Pam-Fbxo45) that controls the core epithelial-to-mesenchymal transition-inducing transcription factors []. Budding yeast Skp1 is a kinetochore protein found in several complexes, including the SCF ubiquitin ligase complex, the CBF3 complex that binds centromeric DNA [], and the RAVE complex that regulates assembly of the V-ATPase []. Elongin-C is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites []. 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 []. Elongin-C forms a complex with Cul3 that polyubiquitylates monoubiquitylated RNA polymerase II to trigger its proteolysis [].
First identified in cyclin-F as a protein-protein interaction motif, the F-boxis a conserved domain that is present in numerous proteins with a bipartite structure []. Through the F-box, these proteins are linked to the Skp1 protein and the core of SCFs (Skp1-cullin-F-box protein ligase) complexes. SCFs complexes constitute a new class of E3 ligases []. They function in combination with the E2 enzyme Cdc34 to ubiquitinate G1 cyclins, Cdk inhibitors and many other proteins, to mark them for degradation. The binding of the specific substrates by SCFs complexes is mediated by divergent protein-protein interaction motifs present in F-box proteins, like WD40 repeats, leucine rich repeats [, ]or ANK repeats.
First identified in cyclin-F as a protein-protein interaction motif, the F-boxis a conserved domain that is present in numerous proteins with a bipartite structure []. Through the F-box, these proteins are linked to the Skp1 protein and the core of SCFs (Skp1-cullin-F-box protein ligase) complexes. SCFs complexes constitute a new class of E3 ligases []. They function in combination with the E2 enzyme Cdc34 to ubiquitinate G1 cyclins, Cdk inhibitors and many other proteins, to mark them for degradation. The binding of the specific substrates by SCFs complexes is mediated by divergent protein-protein interaction motifs present in F-box proteins, like WD40 repeats, leucine rich repeats [, ]or ANK repeats.
A number of genes are expressed exclusively in the retina, where they appear to control the specialised functions of various different cell types []. One of these retinal genes (termed FAM138A/B/C/F) is found within a region of subtelomeric DNA and exhibits polymorphic distribution among multiple chromosomes []. This gene encodes a putative 85-amino acid polypeptide (also known as retina-specific protein F379) that shares a high level of similarity with the retinal protein FAM138D; both also include a well-conserved N-terminal domain that is shared by a wide range of proteins, including podocalyxin-like protein 1, proto-oncogene c-Rel, suppressor of G2 allele of SKP1 homologue, and ubiquitin carboxyl-terminal hydrolase 19.
The BTB (for BR-C, ttk and bab) []or POZ (for Pox virus and Zinc finger) [, ]domain is a versatile protein-protein interaction motif involved in many cellular functions, including transcriptional regulation, cytoskeleton dynamics, ion channel assembly and gating, and targeting proteins for ubiquitination []. The BTB domain can occur alongside other domains: BTB-zinc finger (BTB-ZF), BTB-BACK-Kelch (BBK), voltage-gated potassium channel T1 (T1-Kv) [], MATH-BTB, BTB-NPH3 and BTB-BACK-PHR (BBP). Other proteins, such as Skp1 and ElonginC, consist almost exclusively of the core BTB fold. In all of these protein families, the BTB core fold is structurally conserved, consisting of a 2-layer alpha/beta topology where a cluster of alpha helices is flanked by short β-sheets []. POZ domains from several zinc finger proteins have been shown to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes including N-CoR and SMRT [, , ]. The POZ or BTB domain is also known as BR-C/Ttk or ZiN.This entry includes the BTB/POZ domain, as well as Skp1 N-terminal region which has an α/β structure similar to that of the BTB/POZ domain fold [, ].
Proteins in this entry contain an N-terminal F-box and a C-terminal F-box associated (FBA) domain. The F-box is a conserved domain that is present in numerous proteins with a bipartite structure []. Through the F-box, these proteins are linked to the Skp1 protein and the core of SCFs (Skp1-cullin-F-box protein ligase) complexes. SCFs complexes constitute a new class of E3 ligases []. They function in combination with the E2 enzyme Cdc34 to ubiquitinate G1 cyclins, Cdk inhibitors and many other proteins, to mark them for degradation. The binding of the specific substrates by SCFs complexes is mediated by divergent protein-protein interaction motifs present in F-box proteins, like WD40 repeats, leucine rich repeats [, ]or ANK repeats.
This entry includes cullin-associated NEDD8-dissociated proteins 1 (CAND1 also known as TIP120A) and 2 (CAND2); these proteins have a C-terminal TATA-binding protein interacting (TIP20) domain. CAND1 is required for the assembly of the SCF E3 ubiquitin ligase complex. The SCF ubiquitin E3 ligase consists of SKP1, CUL1 and F-box protein, and it regulates ubiquitin-dependent proteolysis. CAND1 binds to CUL1, preventing it from associating with the other components that form the ligase. Neddylation of CUL1 (or the presence of SKP1 and ATP) dissociates it from CAND1, allowing the ligase complex to form [, , ]. CAND1 also interacts with CUL3, a component of the Cul3-dependent E3 ubiquitin ligase complex []. CAND1 has been proposed to be an F-box protein exchange factor, and as substrates of the ligase complex are degraded by the proteasome and depleted, the ligase complex enters an intermediate, deneddylated state when CAND1 can bind, promoting dissociation of the substrate-recognition subunit and recruitment of a new substrate-recognition subunit []. CAND2 is uncharacterized but is assumed to have similar roles to CAND1.
