Biology:SGCG
 Generic protein structure example |
Gamma-sarcoglycan is a protein that in humans is encoded by the SGCG gene.[1][2] The α to δ-sarcoglycans are expressed predominantly (β) or exclusively (α, γ and δ) in striated muscle.[3] A mutation in any of the sarcoglycan genes may lead to a secondary deficiency of the other sarcoglycan proteins, presumably due to destabilisation of the sarcoglycan complex.[4] The disease-causing mutations in the α to δ genes cause disruptions within the dystrophin-associated protein (DAP) complex in the muscle cell membrane.[5] The transmembrane components of the DAP complex link the cytoskeleton to the extracellular matrix in adult muscle fibres,[6] and are essential for the preservation of the integrity of the muscle cell membrane.[7]
Function
Gamma-sarcoglycan is one of several sarcolemmal transmembrane glycoproteins that interact with dystrophin, probably to provide a link between the membrane associated cytoskeleton and the extracellular matrix. Defects in the protein can lead to early onset autosomal recessive muscular dystrophy, in particular limb-girdle muscular dystrophy, type 2C (LGMD2C).[2]
Structure
Gene
Human SGCG gene maps to chromosome 13 at q12, spans over 100 kb of DNA and includes 8 exons.[8]
Protein
Gamma-sarcoglycan is a type II transmembrane protein and consists of 291 amino acids. It has a 35 amino acid intracellular N-terminal region, a 25 amino acid single transmembrane domain, and a 231 amino acid extra-cellular C-terminus.[4]
Clinical significance
Sarcoglycanopathies are autosomal recessive limb girdle muscular dystrophies (LGMDs) caused by mutations in any of the four sarcoglycan genes: α (LGMD2D), β (LGMD2E), γ (LGMD2C) and δ (LGMD2F).[3] Severe childhood autosomal recessive muscular dystrophy (SCARMD) is a progressive muscle-wasting disorder that segregates with microsatellite markers at γ-sarcoglycan gene. Mutations in the γ-sarcoglycan gene were first described in the Maghreb countries of North Africa,[9] where γ-sarcoglycanopathy has a higher than usual incidence. One common mutation, Δ-521T, which causes a severe phenotype, occurs both in the Maghreb population and in other countries.[8] A Cys283Tyr mutation has been identified in the Gypsy population causing a severe phenotype and a Leu193Ser mutation which causes a mild phenotype.[1][10]
Interactions
SGCG has been shown to interact with FLNC.[11][12]
References
- ↑ 1.0 1.1 "A founder mutation in the gamma-sarcoglycan gene of gypsies possibly predating their migration out of India". Human Molecular Genetics 5 (12): 2019–22. Dec 1996. doi:10.1093/hmg/5.12.2019. PMID 8968757.
- ↑ 2.0 2.1 "Entrez Gene: SGCG sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6445.
- ↑ 3.0 3.1 "Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy". Science 270 (5237): 819–22. Nov 1995. doi:10.1126/science.270.5237.819. PMID 7481775. Bibcode: 1995Sci...270..819N.
- ↑ 4.0 4.1 "Severe gamma-sarcoglycanopathy caused by a novel missense mutation and a large deletion". Neuromuscular Disorders 10 (2): 100–7. Feb 2000. doi:10.1016/s0960-8966(99)00063-2. PMID 10714584.
- ↑ "The sarcoglycan complex in the six autosomal recessive limb-girdle muscular dystrophies". Human Molecular Genetics 5 (12): 1963–9. Dec 1996. doi:10.1093/hmg/5.12.1963. PMID 8968750.
- ↑ "epsilon-Sarcoglycan, a broadly expressed homologue of the gene mutated in limb-girdle muscular dystrophy 2D". The Journal of Biological Chemistry 272 (51): 32534–8. Dec 1997. doi:10.1074/jbc.272.51.32534. PMID 9405466.
- ↑ "Assembly of the sarcoglycan complex. Insights for muscular dystrophy". The Journal of Biological Chemistry 273 (52): 34667–70. Dec 1998. doi:10.1074/jbc.273.52.34667. PMID 9856984.
- ↑ 8.0 8.1 "Mutations that disrupt the carboxyl-terminus of gamma-sarcoglycan cause muscular dystrophy". Human Molecular Genetics 5 (11): 1841–7. Nov 1996. doi:10.1093/hmg/5.11.1841. PMID 8923014.
- ↑ "Linkage analysis of families with severe childhood autosomal recessive muscular dystrophy in Morocco indicates genetic homogeneity of the disease in north Africa". Journal of Medical Genetics 31 (4): 342–3. Apr 1994. doi:10.1136/jmg.31.4.342. PMID 8071965.
- ↑ "A novel gamma-sarcoglycan mutation causing childhood onset, slowly progressive limb girdle muscular dystrophy". Neuromuscular Disorders 8 (5): 305–8. Jun 1998. doi:10.1016/s0960-8966(98)00040-6. PMID 9673983.
- ↑ "Calpain 3 cleaves filamin C and regulates its ability to interact with gamma- and delta-sarcoglycans". Muscle Nerve 28 (4): 472–83. October 2003. doi:10.1002/mus.10465. PMID 14506720.
- ↑ "Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein". J. Cell Biol. 148 (1): 115–26. January 2000. doi:10.1083/jcb.148.1.115. PMID 10629222.
Further reading
- "Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy.". Science 270 (5237): 819–22. 1995. doi:10.1126/science.270.5237.819. PMID 7481775. Bibcode: 1995Sci...270..819N.
- "Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy (LGMD2C)". Am. J. Hum. Genet. 57 (3): 732–4. 1995. PMID 7668303.
- "Linkage disequilibrium in the neurofibromatosis 1 (NF1) region: implications for gene mapping.". Am. J. Hum. Genet. 53 (5): 1038–50. 1993. PMID 8105688.
- "Absence of gamma-sarcoglycan (35 DAG) in autosomal recessive muscular dystrophy linked to chromosome 13q12.". FEBS Lett. 381 (1–2): 15–20. 1996. doi:10.1016/0014-5793(96)00056-7. PMID 8641426.
- "Mild and severe muscular dystrophy caused by a single gamma-sarcoglycan mutation.". Am. J. Hum. Genet. 59 (5): 1040–7. 1996. PMID 8900232.
- "Mutations that disrupt the carboxyl-terminus of gamma-sarcoglycan cause muscular dystrophy.". Hum. Mol. Genet. 5 (11): 1841–7. 1997. doi:10.1093/hmg/5.11.1841. PMID 8923014.
- "Molecular organization of sarcoglycan complex in mouse myotubes in culture.". J. Cell Biol. 143 (7): 2033–44. 1999. doi:10.1083/jcb.143.7.2033. PMID 9864373.
- "Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein.". J. Cell Biol. 148 (1): 115–26. 2000. doi:10.1083/jcb.148.1.115. PMID 10629222.
- "Severe gamma-sarcoglycanopathy caused by a novel missense mutation and a large deletion.". Neuromuscul. Disord. 10 (2): 100–7. 2000. doi:10.1016/S0960-8966(99)00063-2. PMID 10714584.
- "Biochemical evidence for association of dystrobrevin with the sarcoglycan-sarcospan complex as a basis for understanding sarcoglycanopathy.". Hum. Mol. Genet. 9 (7): 1033–40. 2000. doi:10.1093/hmg/9.7.1033. PMID 10767327.
- "Molecular and genetic characterization of sarcospan: insights into sarcoglycan-sarcospan interactions.". Hum. Mol. Genet. 9 (13): 2019–27. 2000. doi:10.1093/hmg/9.13.2019. PMID 10942431.
- "Expression of gamma -sarcoglycan in smooth muscle and its interaction with the smooth muscle sarcoglycan-sarcospan complex.". J. Biol. Chem. 275 (49): 38554–60. 2001. doi:10.1074/jbc.M007799200. PMID 10993904.
- "Zeta-sarcoglycan, a novel component of the sarcoglycan complex, is reduced in muscular dystrophy.". Hum. Mol. Genet. 11 (18): 2147–54. 2003. doi:10.1093/hmg/11.18.2147. PMID 12189167.
- "Novel mutations in three patients with LGMD2C with phenotypic differences.". Pediatr. Neurol. 30 (4): 291–4. 2004. doi:10.1016/j.pediatrneurol.2003.11.006. PMID 15087111.
- "Sarcoglycanopathies and the risk of undetected deletion alleles in diagnosis.". Hum. Mutat. 26 (1): 59. 2006. doi:10.1002/humu.9347. PMID 15954112.
- "A novel mutation in two families with limb-girdle muscular dystrophy type 2C.". Neurology 67 (1): 167–9. 2006. doi:10.1212/01.wnl.0000223600.78363.dd. PMID 16832103.
- "Biglycan binds to alpha- and gamma-sarcoglycan and regulates their expression during development.". J. Cell. Physiol. 209 (2): 439–47. 2006. doi:10.1002/jcp.20740. PMID 16883602.
External links
- LOVD mutation database: SGCG
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