Disease relevance of asp

• Two mutations in this domain, Asp 47----Glu, and Asp 64----Asn, present in patients with haemophilia B, reduce calcium binding to the domain greater than 4-fold and greater than 1,000-fold, respectively [1].

High impact information on asp

• The nucleotide sequence codes for two amino acids, Met-Cys, preceding the known N-terminal Asp of the mature protein [2].
• Thus, Asp appears to hold together the microtubule-nucleating gamma-tubulin ring complexes that organize the mitotic centrosome [3].
• Abnormal spindle protein, Asp, and the integrity of mitotic centrosomal microtubule organizing centers [3].
• Removing Asp protein function from Drosophila melanogaster embryo extracts, either by mutation or immunodepletion, resulted in loss of their ability to restore microtubule-organizing center activity to salt-stripped centrosome preparations [3].
• Finally, we show that O-box motifs in two other proteins, Drosophila Abnormal Spindle and Schizosaccharomyces pombe Cut2, contribute to Cdh1-dependent polyubiquitylation in vitro, suggesting that the O-box may mediate degradation of a variety of cell cycle factors [4].

Biological context of asp

• Immunofluorescence studies show that the wild-type Asp protein is localized to the polar regions of the spindle immediately surrounding the centrosome [5].
• This contrasts with meiosis in wild-type males where at late anaphase a dense array of microtubules forms in the central spindle region that has Asp localised at its border [6].
• A requirement for the Abnormal Spindle protein to organise microtubules of the central spindle for cytokinesis in Drosophila [6].
• Drosophila abnormal spindle (asp) mutants exhibit a mitotic metaphase checkpoint arrest with abnormal spindle poles, which reflects a requirement for Asp for the integrity of microtubule organising centres (MTOCs) [6].
• It is required for centrosome maturation on M-phase entry in order to recruit the gamma-tubulin ring complex and activate the abnormal spindle protein, Asp [7].

Anatomical context of asp

• RNAi depletion of the abnormal spindle protein, Asp, which localizes to focused poles of control spindles, produced a severe loss of spindle pole focus, whereas depletion of the pole-associated microtubule depolymerase KLP10A increased spindle microtubule density [8].
• A mutant beta-actin with an amino acid substitution from Gly-245 to Asp has been shown to be related to tumorigenic transformation of a human fibroblast cell line (Leavitt, J. et al. (1987) Mol. Cell. Biol. 7, 2467-2476) [9].
• In contrast, a mutant in which the phosphorylation sites are replaced by phosphate-mimetic Asp residues, as well as a VP16-D-Jun fusion protein, can promote photoreceptor differentiation [10].

Associations of asp with chemical compounds

• After a 4-h labeling period, we detected completed actin polypeptide chains with either an unblocked Asp or an Ac-Asp NH2 terminus [11].
• Nevertheless, the most common variants within F and S are distinguished by only two amino acids (Asn/Asp at 237 and Thr/Ala at 247), and these are the most likely targets for the selection underlying complementary latitudinal clines in F and S frequencies [12].
• Each protein contained a pair of active site motifs (Asp/Thr or Ser/Gly), which is a common characteristic of aspartic proteases including BACE1 [13].

Enzymatic interactions of asp

• Previous studies with Drosophila actin showed that the first detectable intermediate is one with an Ac-Cys NH2 terminus which is subsequently cleaved in a novel reaction to expose the Asp [14].

Other interactions of asp

• Centrosomin (CNN) remains in broad discrete bodies but only at the focused poles of such spindles, whereas Asp (abnormal spindle protein) is always present at the presumptive minus ends of microtubules, whether or not they are focused [15].
• This can be rescued by addition of phosphorylated Asp or active Polo kinase [16].
• abnormal spindle, a gene required for normal spindle structure and function in Drosophila melanogaster, lies immediately adjacent the gene tolloid at 96A/B [5].
• However, when this Ser was changed to Asp or Glu, transformation and transcriptional repression by v-Rel were significantly inhibited and c-Rel showed a diffuse nuclear and cytoplasmic localization in CEF [17].
• These thin central spindles exhibited diffuse localizations of both the Pav and Asp proteins, suggesting that these spindles comprise improperly oriented MTs [18].

Analytical, diagnostic and therapeutic context of asp

• We have used site-directed mutagenesis to change all of the conserved Ser, His, and Asp residues and have found that Ser120, His157, and Asp135 are all required for activity [19].

References