Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1: Absence of structural mutations in five patients with brody disease

Alex Odermatt, Peter E M Taschner, Stephen W. Scherer, Barbara Beatty, Vijay K. Khanna, David Cornblath, Vinay Chaudhry, Won Chee Yee, Bertold Schrank, George Karpati, Martijn H. Breuning, Nine Knoers, David H. MacLennan

Research output: Contribution to journalArticle

Abstract

Sarcolipin (SLN) is a low-molecular-weight protein that copurifies with the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase (SERCA1). Genomic DNA and cDNA encoding human sarcolipin (SLN) were isolated and characterized and the SLN gene was mapped to chromosome 11q22-q23. Human, rabbit, and mouse cDNAs encode a protein of 31 amino acids. Homology of SLN with phospholamban (PLN) suggests that the first 7 hydrophilic amino acids are cytoplasmic, the next 19 hydrophobic amino acids form a single transmembrane helix, and the last 5 hydrophilic amino acids are lumenal. The cytoplasmic and transmembrane sequences are not well conserved among the three species, but the lumenal sequence is highly conserved. Like SERCA1, SLN is highly expressed in rabbit fast-twitch skeletal muscle, but it is expressed to a lower extent in slow-twitch muscle and to an even lower extent in cardiac muscle, where SERCA2a and PLN are highly expressed. It is expressed in only trace amounts in pancreas and prostate. SLN and PLN genes resemble each other in having two small exons, with their entire coding sequences lying in exon 2 and a large intron separating the two segments. Brody disease is an inherited disorder of skeletal muscle function, characterized by exercise-induced impairment of muscle relaxation. Mutations in the ATP2A1 gene encoding SERCA1 have been associated with the autosomal recessive inheritance of Brody disease in three families, but not with autosomal dominant inheritance of the disease. A search for mutations in the SLN gene in five Brody families, four of which were not linked to ATP2A1, did not reveal any alterations in coding, splice junction or promoter sequences. The homozygous deletion of C438 in the coding sequence of ATP2A1 in Brody disease family 3, leading to a frameshift and truncation following Pro147 in SERCA1, is the fourth ATP2A1 mutation to be associated with autosomal recessive Brody disease.

Original languageEnglish (US)
Pages (from-to)541-553
Number of pages13
JournalGenomics
Volume45
Issue number3
DOIs
StatePublished - Nov 1 1997

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Proteolipids
Mutation
Genes
Amino Acids
Skeletal Muscle
Exons
Complementary DNA
Rabbits
Muscle Relaxation
Calcium-Transporting ATPases
Sarcoplasmic Reticulum
Brody myopathy
sarcolipin
Introns
Prostate
Pancreas
Myocardium
Proteins
Chromosomes
Molecular Weight

ASJC Scopus subject areas

  • Genetics

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Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1 : Absence of structural mutations in five patients with brody disease. / Odermatt, Alex; Taschner, Peter E M; Scherer, Stephen W.; Beatty, Barbara; Khanna, Vijay K.; Cornblath, David; Chaudhry, Vinay; Yee, Won Chee; Schrank, Bertold; Karpati, George; Breuning, Martijn H.; Knoers, Nine; MacLennan, David H.

In: Genomics, Vol. 45, No. 3, 01.11.1997, p. 541-553.

Research output: Contribution to journalArticle

Odermatt, A, Taschner, PEM, Scherer, SW, Beatty, B, Khanna, VK, Cornblath, D, Chaudhry, V, Yee, WC, Schrank, B, Karpati, G, Breuning, MH, Knoers, N & MacLennan, DH 1997, 'Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1: Absence of structural mutations in five patients with brody disease', Genomics, vol. 45, no. 3, pp. 541-553. https://doi.org/10.1006/geno.1997.4967
Odermatt, Alex ; Taschner, Peter E M ; Scherer, Stephen W. ; Beatty, Barbara ; Khanna, Vijay K. ; Cornblath, David ; Chaudhry, Vinay ; Yee, Won Chee ; Schrank, Bertold ; Karpati, George ; Breuning, Martijn H. ; Knoers, Nine ; MacLennan, David H. / Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1 : Absence of structural mutations in five patients with brody disease. In: Genomics. 1997 ; Vol. 45, No. 3. pp. 541-553.
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abstract = "Sarcolipin (SLN) is a low-molecular-weight protein that copurifies with the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase (SERCA1). Genomic DNA and cDNA encoding human sarcolipin (SLN) were isolated and characterized and the SLN gene was mapped to chromosome 11q22-q23. Human, rabbit, and mouse cDNAs encode a protein of 31 amino acids. Homology of SLN with phospholamban (PLN) suggests that the first 7 hydrophilic amino acids are cytoplasmic, the next 19 hydrophobic amino acids form a single transmembrane helix, and the last 5 hydrophilic amino acids are lumenal. The cytoplasmic and transmembrane sequences are not well conserved among the three species, but the lumenal sequence is highly conserved. Like SERCA1, SLN is highly expressed in rabbit fast-twitch skeletal muscle, but it is expressed to a lower extent in slow-twitch muscle and to an even lower extent in cardiac muscle, where SERCA2a and PLN are highly expressed. It is expressed in only trace amounts in pancreas and prostate. SLN and PLN genes resemble each other in having two small exons, with their entire coding sequences lying in exon 2 and a large intron separating the two segments. Brody disease is an inherited disorder of skeletal muscle function, characterized by exercise-induced impairment of muscle relaxation. Mutations in the ATP2A1 gene encoding SERCA1 have been associated with the autosomal recessive inheritance of Brody disease in three families, but not with autosomal dominant inheritance of the disease. A search for mutations in the SLN gene in five Brody families, four of which were not linked to ATP2A1, did not reveal any alterations in coding, splice junction or promoter sequences. The homozygous deletion of C438 in the coding sequence of ATP2A1 in Brody disease family 3, leading to a frameshift and truncation following Pro147 in SERCA1, is the fourth ATP2A1 mutation to be associated with autosomal recessive Brody disease.",
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