A new member of the troponin C superfamily: Comparison of the primary structures of rat oncomodulin and rat parvalbumin

1983 ◽  
Vol 3 (11) ◽  
pp. 1071-1075 ◽  
Author(s):  
J. P. Mac Manus ◽  
D. C. Watson ◽  
M. Yaguchi
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Isoelectric Point ◽  
Base Pair ◽  
Calcium Binding ◽  
Troponin C ◽  
Calcium Binding Protein ◽  
Single Base ◽  
Binding Domains ◽  
Single Base Pair

When the amino-acid sequence of the 108-residue, rat tumour calcium-binding protein, oncomodulin, was aligned with that of rat muscle parvalbumin, 55 homologous positions were found, with an additional 33 single base-pair substitutions. This extensive homology, with virtual identity of the calcium-binding domains, signalled oncomodulin to be a member of the troponin C superfamily. The presence of Cys-18 and Phe-66 in oncomodulin, plus its isoelectric point of 3.9) suggest that this tumour protein is a 8-parva Jbumin, rather than a muscle α-parvalbumin.

The amino acid sequence of porcine intestinal calcium-binding protein

1979 ◽  
Vol 57 (6) ◽  
pp. 737-748 ◽  
Author(s):  
Theo Hofmann ◽  
Michiko Kawakami ◽  
Anthony J. W. Hitchman ◽  
Joan E. Harrison ◽  
Keith J. Dorrington
Keyword(s):  
Mass Spectrometry ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Intestinal Mucosa ◽  
Calcium Binding ◽  
Binding Protein ◽  
Troponin C ◽  
Calcium Binding Protein ◽  
Mass Spectrometry Analysis ◽  
Spectrometry Analysis

The complete amino acid sequence of the calcium-binding protein (CaBP) from pig intestinal mucosa has been determined: Ac-Ser-Ala-Gln-Lys-Ser-Pro-Ala-Glu-Leu-Lys-Ser-Ile-Phe-Glu-Lys-Tyr-Ala-Ala-Lys-Glu-Gly-Asp-Pro-Asn-Gln-Leu-Ser-Lys-Glu-Glu-Leu-Lys-Gln-Leu-Ile-Gln-Ala-Glu-Phe-Pro-Ser-Leu-Leu-Lys-Gly-Pro-Arg-Thr-Leu-Asp-Asp-Leu-Phe-Gln-Glu-Leu-Asp-Lys-Asn-Gly-Asn-Gly-Glu-Val-Ser-Phe-Glu-Glu-Phe-Gln-Val-Leu-Val-Lys-Lys-Ile-Ser-Gln-OH. The N-terminal octapeptide sequence was determined by mass spectrometry analysis by Morris and Dell. The first 45 residues of bovine CaBP differ only in six positions from the corresponding sequence of the porcine protein, except that the sequence starts in position two of the porcine sequence. The mammalian intestinal CaBP's belong to the troponin-C superfamily on the basis of an analysis by Barker and Dayhoff.

A single-base-pair substitution abolishes d-amino-acid oxidase activity in the mouse

1992 ◽  
Vol 1139 (4) ◽  
pp. 315-318 ◽  
Author(s):  
Masato Sasaki ◽  
Ryuichi Konno ◽  
Masahiro Nihio ◽  
Akira Niwa ◽  
Yosihiro Yasumura ◽  
...  
Keyword(s):  
Amino Acid ◽  
Base Pair ◽  
Oxidase Activity ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Single Base ◽  
Single Base Pair Substitution ◽  
Single Base Pair ◽  
Base Pair Substitution

scholarly journals Spontaneous mutation at the mtr locus of Neurospora: the spectrum of mutant types.

Genetics ◽  
1991 ◽  
Vol 129 (1) ◽  
pp. 39-45
Author(s):  
D Stadler ◽  
H Macleod ◽  
D Dillon
Keyword(s):  
Amino Acid ◽  
Base Pair ◽  
High Frequency ◽  
Tandem Duplication ◽  
Spontaneous Mutation ◽  
Amino Acid Permease ◽  
Single Base ◽  
Single Base Pair ◽  
Tandem Duplications ◽  
Repeat Induced Point Mutation

Abstract We have isolated 135 strains of Neurospora which have mutations at the mtr locus resulting from independent spontaneous events. mtr is the structural gene for the neutral amino acid permease. The mutants have been characterized by their reversion behavior (both spontaneous and induced) and by hybridization studies of restriction digests of their DNA. About half of the mutants (54%) appear to result from single base-pair substitutions. Thirty-four percent have deletions, including some which extend into neighboring genes. Most of the remaining mutants have insertions. Several of the insertions are tandem duplications of 400-1000 bp and these mutants are unstable, reverting to mtr+ with a high frequency. When tandem-duplication mutants go through a cross, they are modified: the mutant progeny are fully stable. This modification is probably due to RIP (repeat-induced point mutation). This process has an important bearing on the comparison of germinal to somatic mutation.

Clinical Outcomes for Patients with Severe Chronic Neutropenia Due to Mutations in the Gene for Neutrophil Elastase, ELANE

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3275-3275 ◽  
Author(s):  
Vahagn Makaryan ◽  
Cornelia Zeidler ◽  
Audrey Anna Bolyard ◽  
Julia Skokowa ◽  
Merideth L. Kelley ◽  
...  
Keyword(s):  
Amino Acid ◽  
Base Pair ◽  
Mrna Splicing ◽  
Amino Acid Substitutions ◽  
Median Dose ◽  
Congenital Neutropenia ◽  
Single Base ◽  
Single Base Pair ◽  
Apparent Association ◽  
Chronic Neutropenia

Abstract Abstract 3275 Background: Mutations in the gene for neutrophil elastase, ELANE, are the most common cause of both cyclic (CyN) and congenital neutropenia (CN). Hypothesis: The risk of transformation to AML and effectiveness of G-CSF therapy for CyN and CN are consequences of the specific mutations and types of mutations in ELANE. Methods: We analyzed the treatment responses to G-CSF and occurrence of MDS/AML in 307 patients (CyN 118 and CN 189) with ELANE mutations observed prospectively for 0.4 to 24.9 years through the Severe Chronic Neutropenia International Registry (SCNIR). Most, but not all, patients have received long-term treatment with G-CSF. The median dose in CyN patients was 2.2 μg/kg/day (median duration 14.5 years; mean duration 13.9 years; range: 0.6 – 24.9 years) and the median dose in CN patients was 6.8 μg/kg/day (median duration 10.8 years; mean duration 11 years, range: 0.4 – 24.1 years). Findings: In this population, there are 110 different ELANE mutations: 68 single base pair/amino acid substitutions; 16 frameshifts; 10 terminations; 8 intronic mutations predicted to alter mRNA splicing; and 7 in-frame deletions or insertions. There is also one single-base mutation in the 5' UTR near the start codon. Single base pair/amino acid substitutions are the most common in both CyN and CN populations. Several mutations, particularly in exons 4 and 5 and intron 4, have been observed in both CyN and CN patients. This overlap confounds the use of genetic testing for differential diagnosis of these conditions. Twenty-nine of 189 (15%) CN patients developed MDS/AML, associated with 26 different ELANE mutations. Clusters of MDS/AML cases were observed at two loci: 3 of 4 patients with mutations at C151Y and 3 of 9 patients with mutations at G214R developed MDS/AML. There are 85 mutations which have thus far not been associated with MDS/AML. There is no apparent association of AML with mutations in particular regions of the gene, i.e., specific exons or introns. However, there is an apparent association between type of mutation and risk of leukemia. MDS/AML occurred in decreasing frequency with frameshifts 6/19 (32%); terminations 3/12 (25%); intronic predicted to alter mRNA splicing 3/15 (20%); in-frame deletions or insertions 1/7 (14%); and single base pair/amino acid substitutions 16/136 (12%). The apparent high risk associated with the substitution mutations C151Y and G214R may be attributable to major changes in the protein structure due to the size and charge/polarity differences of the exchanged amino acids. Significantly, there are no cases of CyN associated with MDS/AML and no cases of CyN associated with frameshift mutations. Because of the association of higher G-CSF doses with greater risk of AML, we examined the relationship between G-CSF dose and ELANE genotype. Of 233 patients with available dosing data, 74 received G-CSF doses greater than 8 μg/kg/day; a dose level previously associated with increased risk of MDS/AML (Rosenberg et al, Blood 2008). The ELANE mutations in this sub-population were: frameshifts 9/19 (47%); terminations 6/14 (43%); intronic 4/41 (10%); in-frame deletions or insertions 1/8 (12%); single base pair/amino acid substitutions 53/149 (36%); and 5'UTR 1/1 (100% at 16 μg/kg/day). The median G-CSF doses for these 233 patients were: frameshifts 7.0 μg/kg/day; terminations 5.1 μg/kg/day; single base pair/amino acid substitutions 5.1 μg/kg/day; intronic 2.4 μg/kg/day; in-frame deletions or insertions 5.4 μg/kg/day; 5'UTR 16 μg/kg/day. Conclusions: The association of certain mutations, i.e., C151Y and G214R, and frameshift and termination mutations with higher risk of MDS/AML and higher requirements for G-CSF therapy are important findings that should prove helpful to clinicians and guide further basic research. Registries and repositories are extremely valuable for understanding the consequences of rare hematological diseases such as cyclic and congenital neutropenia. Disclosures: Boxer: Amgen: Equity Ownership. Dale:AMGEN: Consultancy.

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