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Symbol: skr-2 Name: SKp1 Related (ubiquitin ligase complex component) Entrez gene ID: 172773 Ensembl gene ID: F46A9.4 Species: Worm (Taxid: 6239) Functional description: Protein SKR-2; SKp1 Related (ubiquitin ligase complex component) family member (skr-2) [Source:RefSeq peptide;Acc:NP_492512] [Ensembl]; skr-2 encodes a homolog of Skp1 in S. cerevisiae, a core component of the SCF (Skp1p, Cullin, F-box) ubiquitin-ligase complex that facilitates ubiquitin-mediated protein degradation; SKR-2 is required for the restraint of cell proliferation, progression through the pachytene stage of meiosis, and the formation of bivalent chromosomes at diakinesis; SKR-2::GFP is detected exclusively in the intestine. SKR-2 can interact in vivo and in vitro with CUL-1, a C. elegans cullin homolog, and also with a number of F-box proteins, including LIN-23, that serve as the substrate-recognition subunits of the SCF complex. As Saccharomyces cerevisiae Skp1p can associate with F-box and non-F-box proteins to regulate a diverse number of cellular processes, it is possible that SKR-2 has functions distinct from ubiquitin-mediated protein degradation. skr-2(RNAi) animals show several defects, including hyperplasia (both in arrested embryos, and in the somatic gonad and hypodermis of adult escapers), mispositioning of the mitotic spindle in early embryos, ectopic blebbing, and abnormal polar bodies. More generally, animals injected with skr-2(RNAi) show reduced brood sizes, with embryonic lethality in F1 animals; the development of F1 embryos appeared to be arrested between gastrulation and the 2-fold phase, in a manner similar to that of cul-1(RNAi) embryos. Zygotic-specific RNAi directed against skr-2 allows survival to adulthood, but adult hermaphrodites are sterile due to an arrest of germ cells in the pachytene stage of meiosis; they also show an expanded transistion zone in the gonad and gaps in the gonad arm, with univalent diakinetic chromosomes in those germ cells escaping past pachytene stage. Expression of a SKR-2::GFP reporter gene is restricted to the intestine, despite the close sequence similarity of skr-2 to the (ubiquitously expressed) skr-1. SKR-2 may, like Skp1p, function within a particular SCF ubiquitin-ligase (E3) complex by binding both a cullin (a homolog of S. cerevisiae Cdc53) and an F box protein (through direct interaction with an F box motif). However, Skp1p also can associate with other proteins besides SCF components, so the function of SKR-2 is not necessarily confined to, or even partially involved with, C. elegans ubiquitin-ligase complexes. SKR-2, in two-hybrid assays, binds to CUL-1, but not to CUL-2 through CUL-6; SKR-2 also binds to the F-box protein LIN-23, which, like SKR-2, results in hyperplasia when genetically inactivated. When expressed in mammalian cells, SKR-2 is coimmunoprecipitated with CUL-1, but not with CUL-2, CUL-3, or CUL-4. SKR-2 also binds to at least 10 different F-box proteins: C14B1.3, F14D2.8, T10E9.1, T05H4.2, T07E3.4, Y37H2A.5, Y47F10C.3, Y113G7B.3, Y113G7B.4, and C31C9.3; however, SKR-2 fails to bind the 5 F-box proteins SEL-10, T01E8.4, F48E8.7A, C02F5.7A, or C26E6.5. skr-2's most closely related paralog in the C. elegans genome is skr-1, with which it shares a statistically significant evolutionary grouping. skr-2 resides next to skr-1 in a 2.7 kb region on chromosome I, and the two genes are highly similar (83% nucleotide identity), implying that they arose from a recent, local genomic duplication. Because of the high similarity of these two genes, RNAi directed against either skr-2 or skr-1 is expected to inactivate both genes simultaneously, and it is thus not clear whether these genes comprise a functionally redundant set. [WormBase] Observation: RNA interference in adulthood of skr-1 and skr-2 shortened the extended lifespan of daf-2(mu150) mutants by up to 44%. No effect in the lifespan of wild-type worms or in the extended lifespans of glp-1(e2141ts) or eat-2(ad1116) mutants was observed. Assays: Classification: Aging Relevance Analysis/Source:  GenAge GenDRHomologs Edit \ Update (Admin) | Delete |
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