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Lamin A/C
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| PDB rendering based on 1ifr. | ||||||||||||||
| Available structures: 1ifr, 1ivt, 1ufg, 1x8y | ||||||||||||||
| Identifiers | ||||||||||||||
| Symbols | LMNA; CDCD1; CDDC; CMD1A; CMT2B1; EMD2; FPL; FPLD; HGPS; IDC; LDP1; LFP; LGMD1B; LMN1; LMNC; PRO1 | |||||||||||||
| External IDs | OMIM: 150330 MGI: 96794 HomoloGene: 41321 | |||||||||||||
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| RNA expression pattern | ||||||||||||||
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| Orthologs | ||||||||||||||
| Human | Mouse | |||||||||||||
| Entrez | 4000 | 16905 | ||||||||||||
| Ensembl | ENSG00000160789 | ENSMUSG00000028063 | ||||||||||||
| Uniprot | P02545 | Q3U7I5 | ||||||||||||
| Refseq | NM_005572 (mRNA) NP_005563 (protein) |
NM_001002011 (mRNA) NP_001002011 (protein) |
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| Location | Chr 1: 154.32 - 154.38 Mb | Chr 3: 88.57 - 88.59 Mb | ||||||||||||
| Pubmed search | [1] | [2] | ||||||||||||
Lamin A/C also known as LMNA is a protein which in humans is encoded by the LMNA gene.[1][2] Lamin A/C belongs to the lamin family of proteins.
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Function
The nuclear lamina consists of a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Through alternate splicing, this gene encodes three type A lamin isoforms.[3]
Early in mitosis, MPF phospohrylates specific serine residues in all three nuclear lamins, causing depolymerization of the lamin intermediate filaments. The phosphorylated lamin B dimers remain associated with the nuclear membrane via their isoprenyl anchor. Lamin A is targeted to the nuclear membrane by an isoprenyl group but it is cleaved shortly after arriving at the membrane. It stays associated with the membrane through protein-protein interactions of itself and other membrane associated proteins, such as LAP1. Depolymerization of the nuclear lamins leads to disintegration of the nuclear envelope. Transfection experiments demonstrate that phosphorylation of human lamin A is required for lamin depolymerization, and thus for disassembly of the nuclear envelope, which normally occurs early in mitosis.
Clinical significance
Mutations in the LMNA gene associated with several diseases, including Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. A truncated version of lamin A, commonly known as progerin, causes Hutchinson-Gilford progeria syndrome.[4][5]
Interactions
LMNA has been shown to interact with ALOX12,[6] Thymopoietin,[7][8] ZNF239,[9] NARF,[10] Emerin[11][12][13][14] and SREBF1.[15]
References
- ^ Kamat AK, Rocchi M, Smith DI, Miller OJ (March 1993). "Lamin A/C gene and a related sequence map to human chromosomes 1q12.1-q23 and 10". Somat. Cell Mol. Genet. 19 (2): 203–8. doi:. PMID 8511676.
- ^ Wydner KL, McNeil JA, Lin F, Worman HJ, Lawrence JB (March 1996). "Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization". Genomics 32 (3): 474–8. doi:. PMID 8838815.
- ^ "Entrez Gene: LMNA lamin A/C". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4000.
- ^ Capell BC, Collins FS (December 2006). "Human laminopathies: nuclei gone genetically awry". Nat. Rev. Genet. 7 (12): 940–52. doi:. PMID 17139325.
- ^ Rankin J, Ellard S (October 2006). "The laminopathies: a clinical review". Clin. Genet. 70 (4): 261–74. doi:. PMID 16965317.
- ^ Tang, K; Finley R L, Nie D, Honn K V (Mar. 2000). "Identification of 12-lipoxygenase interaction with cellular proteins by yeast two-hybrid screening". Biochemistry (UNITED STATES) 39 (12): 3185-91. ISSN 0006-2960. PMID 10727209.
- ^ Markiewicz, Ewa; Dechat Thomas, Foisner Roland, Quinlan Roy A, Hutchison Christopher J (Dec. 2002). "Lamin A/C binding protein LAP2alpha is required for nuclear anchorage of retinoblastoma protein". Mol. Biol. Cell (United States) 13 (12): 4401-13. doi:. ISSN 1059-1524. PMID 12475961.
- ^ Dechat, T; Korbei B, Vaughan O A, Vlcek S, Hutchison C J, Foisner R (Oct. 2000). "Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins". J. Cell. Sci. (ENGLAND) 113 Pt 19: 3473-84. ISSN 0021-9533. PMID 10984438.
- ^ Dreuillet, Caroline; Tillit Jeanne, Kress Michel, Ernoult-Lange Michèle (Nov. 2002). "In vivo and in vitro interaction between human transcription factor MOK2 and nuclear lamin A/C". Nucleic Acids Res. (England) 30 (21): 4634-42. PMID 12409453.
- ^ Barton, R M; Worman H J (Oct. 1999). "Prenylated prelamin A interacts with Narf, a novel nuclear protein". J. Biol. Chem. (UNITED STATES) 274 (42): 30008-18. ISSN 0021-9258. PMID 10514485.
- ^ Wilkinson, Fiona L; Holaska James M, Zhang Zhayi, Sharma Aarti, Manilal Sushila, Holt Ian, Stamm Stefan, Wilson Katherine L, Morris Glenn E (Jun. 2003). "Emerin interacts in vitro with the splicing-associated factor, YT521-B". Eur. J. Biochem. (Germany) 270 (11): 2459-66. ISSN 0014-2956. PMID 12755701.
- ^ Lattanzi, Giovanna; Cenni Vittoria, Marmiroli Sandra, Capanni Cristina, Mattioli Elisabetta, Merlini Luciano, Squarzoni Stefano, Maraldi Nadir Mario (Apr. 2003). "Association of emerin with nuclear and cytoplasmic actin is regulated in differentiating myoblasts". Biochem. Biophys. Res. Commun. (United States) 303 (3): 764-70. ISSN 0006-291X. PMID 12670476.
- ^ Sakaki, M; Koike H, Takahashi N, Sasagawa N, Tomioka S, Arahata K, Ishiura S (Feb. 2001). "Interaction between emerin and nuclear lamins". J. Biochem. (Japan) 129 (2): 321-7. ISSN 0021-924X. PMID 11173535.
- ^ Clements, L; Manilal S, Love D R, Morris G E (Jan. 2000). "Direct interaction between emerin and lamin A". Biochem. Biophys. Res. Commun. (UNITED STATES) 267 (3): 709-14. doi:. ISSN 0006-291X. PMID 10673356.
- ^ Lloyd, David J; Trembath Richard C, Shackleton Sue (Apr. 2002). "A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies". Hum. Mol. Genet. (England) 11 (7): 769-77. ISSN 0964-6906. PMID 11929849.
Further reading
- Gruenbaum Y, Wilson KL, Harel A, et al. (2000). "Review: nuclear lamins--structural proteins with fundamental functions.". J. Struct. Biol. 129 (2-3): 313–23. doi:. PMID 10806082.
- Worman HJ, Courvalin JC (2000). "The inner nuclear membrane.". J. Membr. Biol. 177 (1): 1–11. doi:. PMID 10960149.
- Burke B, Mounkes LC, Stewart CL (2002). "The nuclear envelope in muscular dystrophy and cardiovascular diseases.". Traffic 2 (10): 675–83. doi:. PMID 11576443.
- Mounkes LC, Burke B, Stewart CL (2001). "The A-type lamins: nuclear structural proteins as a focus for muscular dystrophy and cardiovascular diseases.". Trends Cardiovasc. Med. 11 (7): 280–5. doi:. PMID 11709282.
- Vigouroux C, Magré J, Desbois-Mouthon C, et al. (2002). "[Major insulin resistance syndromes: clinical and physiopathological aspects]". J. Soc. Biol. 195 (3): 249–57. PMID 11833462.
- Helbling-Leclerc A, Bonne G, Schwartz K (2002). "Emery-Dreifuss muscular dystrophy.". Eur. J. Hum. Genet. 10 (3): 157–61. doi:. PMID 11973618.
- Burke B, Stewart CL (2002). "Life at the edge: the nuclear envelope and human disease.". Nat. Rev. Mol. Cell Biol. 3 (8): 575–85. doi:. PMID 12154369.
- Novelli G, D'Apice MR (2004). "The strange case of the "lumper" lamin A/C gene and human premature ageing.". Trends in molecular medicine 9 (9): 370–5. doi:. PMID 13129702.
- Pasotti M, Repetto A, Pisani A, Arbustini E (2004). "[Diseases associated with lamin A/C gene defects: what the clinical cardiologist ought to know]". Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology 5 (2): 98–111. PMID 15080529.
- Al-Shali KZ, Hegele RA (2005). "Laminopathies and atherosclerosis.". Arterioscler. Thromb. Vasc. Biol. 24 (9): 1591–5. doi:. PMID 15205220.
- Garg A, Cogulu O, Ozkinay F, et al. (2005). "A novel homozygous Ala529Val LMNA mutation in Turkish patients with mandibuloacral dysplasia.". J. Clin. Endocrinol. Metab. 90 (9): 5259–64. doi:. PMID 15998779.
- Lees-Miller SP (2006). "Dysfunction of lamin A triggers a DNA damage response and cellular senescence.". DNA Repair (Amst.) 5 (2): 286–9. doi:. PMID 16344005.
- Donadille B, Lascols O, Capeau J, Vigouroux C (2006). "Etiological investigations in apparent type 2 diabetes: when to search for lamin A/C mutations?". Diabetes Metab. 31 (6): 527–32. doi:. PMID 16357800.
- Young SG, Meta M, Yang SH, Fong LG (2007). "Prelamin A farnesylation and progeroid syndromes.". J. Biol. Chem. 281 (52): 39741–5. doi:. PMID 17090536.
- Halaschek-Wiener J, Brooks-Wilson A (2007). "Progeria of stem cells: stem cell exhaustion in Hutchinson-Gilford progeria syndrome.". J. Gerontol. A Biol. Sci. Med. Sci. 62 (1): 3–8. PMID 17301031.
- Mazereeuw-Hautier J, Wilson LC, Mohammed S, et al. (2007). "Hutchinson-Gilford progeria syndrome: clinical findings in three patients carrying the G608G mutation in LMNA and review of the literature.". Br. J. Dermatol. 156 (6): 1308–14. doi:. PMID 17459035.
- Sliwińska MA (2007). "[The role of lamins and mutations of LMNA gene in physiological and premature aging]". Postepy Biochem. 53 (1): 46–52. PMID 17718387.
- Genschel J, Schmidt HH (December 2000). "Mutations in the LMNA gene encoding lamin A/C". Hum. Mutat. 16 (6): 451–9. doi:. PMID 11102973.
- Scaffidi P, Misteli T. (April 2005). "Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome.". Nat Med. 11 (4): 440–5. doi:. PMID 15750600. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1351119&blobtype=pdf.
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