SGCG

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a
Wikidata
View/Edit Human

Gamma-sarcoglycan is a protein that in humans is encoded by the SGCG gene. The α to δ-sarcoglycans are expressed predominantly (β) or exclusively (α, γ and δ) in striated muscle. 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. The disease-causing mutations in the α to δ genes cause disruptions within the dystrophin-associated protein (DAP) complex in the muscle cell membrane. The transmembrane components of the DAP complex link the cytoskeleton to the extracellular matrix in adult muscle fibres, and are essential for the preservation of the integrity of the muscle cell membrane.

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).

Structure

Gene

Human SGCG gene maps to chromosome 13 at q12, spans over 100 kb of DNA and includes 8 exons.

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.

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). 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, 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. A Cys283Tyr mutation has been identified in the Gypsy population causing a severe phenotype and a Leu193Ser mutation which causes a mild phenotype.

Interactions

SGCG has been shown to interact with FLNC.

Further reading

• Noguchi S, McNally EM, Ben Othmane K, Hagiwara Y, Mizuno Y, Yoshida M, Yamamoto H, Bönnemann CG, Gussoni E, Denton PH, Kyriakides T, Middleton L, Hentati F, Ben Hamida M, Nonaka I, Vance JM, Kunkel LM, Ozawa E (1995). "Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy". Science. 270 (5237): 819–22. doi:10.1126/science.270.5237.819. PMID 7481775.
• Ben Othmane K, Speer MC, Stauffer J, Blel S, Middleton L, Ben Hamida C, Etribi A, Loeb D, Hentati F, Roses AD (1995). "Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy (LGMD2C)". Am. J. Hum. Genet. 57 (3): 732–4. PMC 1801260. PMID 7668303.
• Jorde LB, Watkins WS, Viskochil D, O'Connell P, Ward K (1993). "Linkage disequilibrium in the neurofibromatosis 1 (NF1) region: implications for gene mapping". Am. J. Hum. Genet. 53 (5): 1038–50. PMC 1682302. PMID 8105688.
• Jung D, Leturcq F, Sunada Y, Duclos F, Tomé FM, Moomaw C, Merlini L, Azibi K, Chaouch M, Slaughter C, Fardeau M, Kaplan JC, Campbell KP (1996). "Absence of gamma-sarcoglycan (35 DAG) in autosomal recessive muscular dystrophy linked to chromosome 13q12". FEBS Lett. 381 (1–2): 15–20. doi:10.1016/0014-5793(96)00056-7. PMID 8641426.
• McNally EM, Passos-Bueno MR, Bönnemann CG, Vainzof M, de Sá Moreira E, Lidov HG, Othmane KB, Denton PH, Vance JM, Zatz M, Kunkel LM (1996). "Mild and severe muscular dystrophy caused by a single gamma-sarcoglycan mutation". Am. J. Hum. Genet. 59 (5): 1040–7. PMC 1914841. PMID 8900232.
• McNally EM, Duggan D, Gorospe JR, Bönnemann CG, Fanin M, Pegoraro E, Lidov HG, Noguchi S, Ozawa E, Finkel RS, Cruse RP, Angelini C, Kunkel LM, Hoffman EP (1997). "Mutations that disrupt the carboxyl-terminus of gamma-sarcoglycan cause muscular dystrophy". Hum. Mol. Genet. 5 (11): 1841–7. doi:10.1093/hmg/5.11.1841. PMID 8923014.
• Chan YM, Bönnemann CG, Lidov HG, Kunkel LM (1999). "Molecular organization of sarcoglycan complex in mouse myotubes in culture". J. Cell Biol. 143 (7): 2033–44. doi:10.1083/jcb.143.7.2033. PMC 2175228. PMID 9864373.
• Thompson TG, Chan YM, Hack AA, Brosius M, Rajala M, Lidov HG, McNally EM, Watkins S, Kunkel LM (2000). "Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein". J. Cell Biol. 148 (1): 115–26. doi:10.1083/jcb.148.1.115. PMC 3207142. PMID 10629222.
• Nowak KJ, Walsh P, Jacob RL, Johnsen RD, Peverall J, McNally EM, Wilton SD, Kakulas BA, Laing NG (2000). "Severe gamma-sarcoglycanopathy caused by a novel missense mutation and a large deletion". Neuromuscul. Disord. 10 (2): 100–7. doi:10.1016/S0960-8966(99)00063-2. PMID 10714584.
• Yoshida M, Hama H, Ishikawa-Sakurai M, Imamura M, Mizuno Y, Araishi K, Wakabayashi-Takai E, Noguchi S, Sasaoka T, Ozawa E (2000). "Biochemical evidence for association of dystrobrevin with the sarcoglycan-sarcospan complex as a basis for understanding sarcoglycanopathy". Hum. Mol. Genet. 9 (7): 1033–40. doi:10.1093/hmg/9.7.1033. PMID 10767327.
• Crosbie RH, Lim LE, Moore SA, Hirano M, Hays AP, Maybaum SW, Collin H, Dovico SA, Stolle CA, Fardeau M, Tomé FM, Campbell KP (2000). "Molecular and genetic characterization of sarcospan: insights into sarcoglycan-sarcospan interactions". Hum. Mol. Genet. 9 (13): 2019–27. doi:10.1093/hmg/9.13.2019. PMID 10942431.
• Barresi R, Moore SA, Stolle CA, Mendell JR, Campbell KP (2001). "Expression of gamma -sarcoglycan in smooth muscle and its interaction with the smooth muscle sarcoglycan-sarcospan complex". J. Biol. Chem. 275 (49): 38554–60. doi:10.1074/jbc.M007799200. PMID 10993904.
• Wheeler MT, Zarnegar S, McNally EM (2003). "Zeta-sarcoglycan, a novel component of the sarcoglycan complex, is reduced in muscular dystrophy". Hum. Mol. Genet. 11 (18): 2147–54. doi:10.1093/hmg/11.18.2147. PMID 12189167.
• Vermeer S, Verrips A, Willemsen MA, ter Laak HJ, Ginjaar IB, Hamel BC (2004). "Novel mutations in three patients with LGMD2C with phenotypic differences". Pediatr. Neurol. 30 (4): 291–4. doi:10.1016/j.pediatrneurol.2003.11.006. PMID 15087111.
• White SJ, Uitte de Willige S, Verbove D, Politano L, Ginjaar I, Breuning MH, den Dunnen JT (2006). "Sarcoglycanopathies and the risk of undetected deletion alleles in diagnosis". Hum. Mutat. 26 (1): 59. doi:10.1002/humu.9347. PMID 15954112.
• Duncan DR, Kang PB, Rabbat JC, Briggs CE, Lidov HG, Darras BT, Kunkel LM (2006). "A novel mutation in two families with limb-girdle muscular dystrophy type 2C". Neurology. 67 (1): 167–9. doi:10.1212/01.wnl.0000223600.78363.dd. PMID 16832103.
• Rafii MS, Hagiwara H, Mercado ML, Seo NS, Xu T, Dugan T, Owens RT, Hook M, McQuillan DJ, Young MF, Fallon JR (2006). "Biglycan binds to alpha- and gamma-sarcoglycan and regulates their expression during development". J. Cell. Physiol. 209 (2): 439–47. doi:10.1002/jcp.20740. PMC 2929672. PMID 16883602.

External links

• LOVD mutation database: SGCG