Homo sapiens Protein: LMNA | |||||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||||
InnateDB Protein | IDBP-103386.7 | ||||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||
Gene Symbol | LMNA | ||||||||||||||||||||||||||||
Protein Name | lamin A/C | ||||||||||||||||||||||||||||
Synonyms | CDCD1; CDDC; CMD1A; CMT2B1; EMD2; FPL; FPLD; FPLD2; HGPS; IDC; LDP1; LFP; LGMD1B; LMN1; LMNC; LMNL1; PRO1; | ||||||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||||||
Ensembl Protein | ENSP00000292304 | ||||||||||||||||||||||||||||
InnateDB Gene | IDBG-103380 (LMNA) | ||||||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||||||
Function | Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics. Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation. Required for osteoblastogenesis and bone formation. Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone.Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence. | ||||||||||||||||||||||||||||
Subcellular Localization | Nucleus. Nucleus envelope. Nucleus lamina. Nucleus, nucleoplasm. Note=Farnesylation of prelamin-A/C facilitates nuclear envelope targeting and subsequent cleaveage by ZMPSTE24/FACE1 to remove the farnesyl group produces mature lamin- A/C, which can then be inserted into the nuclear lamina. EMD is required for proper localization of non-farnesylated prelamin-A/C.Isoform C: Nucleus speckle {ECO:0000269PubMed:16061563}. | ||||||||||||||||||||||||||||
Disease Associations | Emery-Dreifuss muscular dystrophy 2, autosomal dominant (EDMD2) [MIM:181350]: A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. {ECO:0000269PubMed:10080180, ECO:0000269PubMed:10739764, ECO:0000269PubMed:10908904, ECO:0000269PubMed:10939567, ECO:0000269PubMed:11503164, ECO:0000269PubMed:12032588, ECO:0000269PubMed:12649505, ECO:0000269PubMed:14684700, ECO:0000269PubMed:14985400, ECO:0000269PubMed:15744034, ECO:0000269PubMed:20848652}. Note=The disease is caused by mutations affecting the gene represented in this entry.Emery-Dreifuss muscular dystrophy 3, autosomal recessive (EDMD3) [MIM:181350]: A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. {ECO:0000269PubMed:22431096}. Note=The disease is caused by mutations affecting the gene represented in this entry.Cardiomyopathy, dilated 1A (CMD1A) [MIM:115200]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269PubMed:10580070, ECO:0000269PubMed:11561226, ECO:0000269PubMed:11897440, ECO:0000269PubMed:12486434, ECO:0000269PubMed:12628721, ECO:0000269PubMed:12920062, ECO:0000269PubMed:14684700, ECO:0000269PubMed:15140538, ECO:0000269PubMed:15219508, ECO:0000269PubMed:16061563, ECO:0000269PubMed:20160190, ECO:0000269PubMed:21846512}. Note=The disease is caused by mutations affecting the gene represented in this entry.Lipodystrophy, familial partial, 2 (FPLD2) [MIM:151660]: A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol. {ECO:0000269PubMed:10587585, ECO:0000269PubMed:10655060, ECO:0000269PubMed:10739751, ECO:0000269PubMed:12015247, ECO:0000269PubMed:12196663, ECO:0000269PubMed:12629077, ECO:0000269PubMed:17250669}. Note=The disease is caused by mutations affecting the gene represented in this entry.Limb-girdle muscular dystrophy 1B (LGMD1B) [MIM:159001]: An autosomal dominant degenerative myopathy with age-related atrioventricular cardiac conduction disturbances, dilated cardiomyopathy, and the absence of early contractures. Characterized by slowly progressive skeletal muscle weakness of the hip and shoulder girdles. Muscle biopsy shows mild dystrophic changes. {ECO:0000269PubMed:10814726, ECO:0000269PubMed:11525883, ECO:0000269PubMed:12032588, ECO:0000269PubMed:12673789, ECO:0000269PubMed:15744034, ECO:0000269PubMed:17136397}. Note=The disease is caused by mutations affecting the gene represented in this entry.Charcot-Marie-Tooth disease 2B1 (CMT2B1) [MIM:605588]: A recessive axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced. {ECO:0000269PubMed:11799477}. Note=The disease is caused by mutations affecting the gene represented in this entry.Hutchinson-Gilford progeria syndrome (HGPS) [MIM:176670]: Rare genetic disorder characterized by features reminiscent of marked premature aging. {ECO:0000269PubMed:12714972, ECO:0000269PubMed:12768443, ECO:0000269PubMed:12927431, ECO:0000269PubMed:15286156, ECO:0000269PubMed:15622532, ECO:0000269PubMed:21791255}. Note=The disease is caused by mutations affecting the gene represented in this entry. HGPS is caused by the toxic accumulation of a truncated form of lamin-A/C. This mutant protein, called progerin (isoform 6), acts to deregulate mitosis and DNA damage signaling, leading to premature cell death and senescence. The mutant form is mainly generated by a silent or missense mutation at codon 608 of prelamin A that causes activation of a cryptic splice donor site, resulting in production of isoform 6 with a deletion of 50 amino acids near the C terminus. Progerin lacks the conserved ZMPSTE24/FACE1 cleavage site and therefore remains permanently farnesylated. Thus, although it can enter the nucleus and associate with the nuclear envelope, it cannot incorporate normally into the nuclear lamina (PubMed:12714972). {ECO:0000269PubMed:12714972}.Cardiomyopathy, dilated, with hypergonadotropic hypogonadism (CMDHH) [MIM:212112]: A disorder characterized by the association of genital anomalies, hypergonadotropic hypogonadism and dilated cardiomyopathy. Patients can present other variable clinical manifestations including mental retardation, skeletal anomalies, scleroderma-like skin, graying and thinning of hair, osteoporosis. Dilated cardiomyopathy is characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. {ECO:0000269PubMed:12927431, ECO:0000269PubMed:17150192, ECO:0000269PubMed:19283854}. Note=The disease is caused by mutations affecting the gene represented in this entry.Mandibuloacral dysplasia with type A lipodystrophy (MADA) [MIM:248370]: A disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroid appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased. {ECO:0000269PubMed:12075506, ECO:0000269PubMed:15998779, ECO:0000269PubMed:16278265}. Note=The disease is caused by mutations affecting the gene represented in this entry.Lethal tight skin contracture syndrome (LTSCS) [MIM:275210]: Rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance. {ECO:0000269PubMed:15317753}. Note=The disease is caused by mutations affecting the gene represented in this entry.Heart-hand syndrome Slovenian type (HHS-Slovenian) [MIM:610140]: Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co- occurrence of a congenital cardiac disease and limb malformations. {ECO:0000269PubMed:18611980}. Note=The disease is caused by mutations affecting the gene represented in this entry.Muscular dystrophy congenital LMNA-related (MDCL) [MIM:613205]: A form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint contractures. {ECO:0000269PubMed:18551513}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=Defects in LMNA may cause a late-onset cardiocutaneous progeria syndrome characterized by cutaneous manifestations of aging appearing in the third decade of life, cardiac valve calcification and dysfunction, prominent atherosclerosis, and cardiomyopathy, leading to death on average in the fourth decade. {ECO:0000269PubMed:23666920}. | ||||||||||||||||||||||||||||
Tissue Specificity | In the arteries, prelamin-A/C accumulation is not observed in young healthy vessels but is prevalent in medial vascular smooth muscle cells (VSMCs) from aged individuals and in atherosclerotic lesions, where it often colocalizes with senescent and degenerate VSMCs. Prelamin-A/C expression increases with age and disease. In normal aging, the accumulation of prelamin-A/C is caused in part by the down-regulation of ZMPSTE24/FACE1 in response to oxidative stress. {ECO:0000269PubMed:20458013}. | ||||||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 247 experimentally validated interaction(s) in this database.
They are also associated with 55 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||||||
InterPro |
IPR001322
Lamin Tail Domain IPR001664 Intermediate filament protein IPR009053 Prefoldin |
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PFAM |
PF00932
PF00038 |
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PRINTS | |||||||||||||||||||||||||||||
PIRSF | |||||||||||||||||||||||||||||
SMART | |||||||||||||||||||||||||||||
TIGRFAMs | |||||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||||
SwissProt | P02545 | ||||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-P02545 | ||||||||||||||||||||||||||||
TrEMBL | W5X314 | ||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||
Entrez Gene | 4000 | ||||||||||||||||||||||||||||
UniGene | Hs.707716 | ||||||||||||||||||||||||||||
RefSeq | NP_733822 | ||||||||||||||||||||||||||||
HUGO | HGNC:6636 | ||||||||||||||||||||||||||||
OMIM | 150330 | ||||||||||||||||||||||||||||
CCDS | |||||||||||||||||||||||||||||
HPRD | 01035 | ||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||
EMBL | AF381029 AK295390 AL135927 AL355388 AL356734 AY357727 AY847595 AY847596 AY847597 BC000511 BC003162 BC014507 CH471121 KF791131 KF791132 KF791133 KF791134 KF791135 KF791136 KF791137 KF791138 KF791139 KF791140 KF791141 KF791142 KF791143 KF791144 M13451 M13452 X03444 X03445 | ||||||||||||||||||||||||||||
GenPept | AAA36160 AAA36164 AAH00511 AAH03162 AAH14507 AAK59326 AAR29466 AAW32538 AAW32539 AAW32540 AHI07399 AHI07400 AHI07401 AHI07402 AHI07403 AHI07404 AHI07405 AHI07406 AHI07407 AHI07408 AHI07409 AHI07410 AHI07411 AHI07412 BAG58344 CAA27173 CAA27174 CAI15521 CAI15522 EAW52997 EAW52999 | ||||||||||||||||||||||||||||