Prelamin-A/C (LMNA)
The protein contains 664 amino acids for an estimated molecular weight of 74139 Da.
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. Recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (PubMed:31548606). 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 (PubMed:10080180, PubMed:22431096, PubMed:10814726, PubMed:11799477, PubMed:18551513). Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920).', '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. (updated: Feb. 10, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Apoptotic process
Cellular component disassembly involved in execution phase of apoptosis
Cellular protein localization
Cellular protein metabolic process
Cellular response to hypoxia
DNA double-strand break attachment to nuclear envelope
Endoplasmic reticulum unfolded protein response
Establishment or maintenance of microtubule cytoskeleton polarity
IRE1-mediated unfolded protein response
Mitotic cell cycle
Mitotic nuclear membrane disassembly
Mitotic nuclear membrane reassembly
Muscle organ development
Negative regulation of cardiac muscle hypertrophy in response to stress
Negative regulation of cell population proliferation
Negative regulation of extrinsic apoptotic signaling pathway
Negative regulation of mesenchymal cell proliferation
Negative regulation of release of cytochrome c from mitochondria
Nuclear envelope organization
Obsolete activation of signaling protein activity involved in unfolded protein response
Obsolete sterol regulatory element binding protein import into nucleus
Positive regulation of cell aging
Positive regulation of gene expression
Positive regulation of histone H3-K9 trimethylation
Protein import into nucleus
Protein localization to nucleus
Regulation of cell migration
Regulation of protein localization to nucleus
Regulation of protein stability
Regulation of telomere maintenance
Ventricular cardiac muscle cell development
The reference OMIM entry for this protein is 115200
Cardiomyopathy, dilated, 1a; cmd1a
Cardiomyopathy, dilated, with conduction defect 1; cdcd1
Cardiomyopathy, idiopathic dilated
Cardiomyopathy, familial idiopathic
Cardiomyopathy, congestive
A number sign (#) is used with this entry because dilated cardiomyopathy-1A (CMD1A) is caused by heterozygous mutation in the lamin A/C gene (LMNA; 150330) on chromosome 1q21. Allelic disorders include the autosomal dominant form of Emery-Dreifuss muscular dystrophy (181350) and Hutchinson-Gilford progeria syndrome (176670), among others.
DESCRIPTION
Dilated cardiomyopathy (CMD) is characterized by cardiac dilatation and reduced systolic function. CMD is the most frequent form of cardiomyopathy and accounts for more than half of all cardiac transplantations performed in patients between 1 and 10 years of age. A heritable pattern is present in 20 to 30% of cases. Most familial CMD pedigrees show an autosomal dominant pattern of inheritance, usually presenting in the second or third decade of life (summary by Levitas et al., 2010). - Genetic Heterogeneity of Dilated Cardiomyopathy Mutations in many other genes have been found to cause different forms of dilated cardiomyopathy. These include CMD1C (601493), with or without left ventricular noncompaction, caused by mutation in the LDB3 gene (605906) on 10q22-q23; CMD1D (601494), caused by mutation in the TNNT2 gene (191045) on 1q32; CMD1E (601154), caused by mutation in the SCN5A gene (600163) on 3p; CMD1G (604145), caused by mutation in the TTN gene (188840) on 2q31; CMD1I (604765), caused by mutation in the DES gene (125660) on 2q35; CMD1J (605362), caused by mutation in the EYA4 gene (603550) on 6q23-q24; CMD1L (606685), caused by mutation in the SGCD gene (601411) on 5q33; CMD1M (607482), caused by mutation in the CSRP3 gene (600824) on 11p15.1; CMD1O (608569), caused by mutation in the ABCC9 gene (601439) on 12p12.1; CMD1P (609909), caused by mutation in the PLN gene (172405) on 6q22.1; CMD1R (613424), caused by mutation in the ACTC gene (102540) on 15q14; CMD1S (613426), caused by mutation in the MYH7 gene (160760) on 14q12; CMD1T (613740), caused by mutation in the TMPO gene (188380) on chromosome 12q22; CMD1U (613694), caused by mutation in the PSEN1 gene (104311) on 14q24.3; CMD1V (613697), caused by mutation in the PSEN2 gene (600759) on 1q31-q42; CMD1W (611407), caused by mutation in the gene encoding metavinculin (VCL; 193065) on 10q22-q23; CMD1X (611615), caused by mutation in the gene encoding fukutin (FKTN; 607440) on 9q31; CMD1Y (611878), caused by mutation in the TPM1 gene (191010) on 15q22.1; CMD1Z (611879), caused by mutation in the TNNC1 gene (191040) on 3p21.3-p14.3; CMD1AA (612158), caused by mutation in the ACTN2 gene (102573) on 1q42-q43; CMD1BB (612877), caused by mutation in the DSG2 gene (125671) on 18q12.1-q12.2; CMD1CC (613122), caused by mutation in the NEXN gene (613121) on 1p31.1; CMD1DD (613172), caused by mutation in the RBM20 gene (613171) on chromosome 10q25.2; CMD1EE (613252), caused by mutation in the MYH6 gene (160710) on chromosome 14q12; CMD1FF (613286), caused by mutation in the TNNI3 gene (191044) on chromosome 19q13.4; CMD1GG (613642), caused by mutation in the SDHA gene (600857) on chromosome 5p15; and CMD1HH (613881), caused by mutation in the BAG3 gene (603883) on chromosome 10q26.11; CMD1II (615184), caused by mutation in the CRYAB gene (123590) on chromosome 6q21; CMD1JJ (615235), caused by mutation in the LAMA4 gene (600133) on chromosome 6q21; CMD1KK (615248), caused by mutation in the MYPN gene (608517) on chromosome 10q21; CMD1LL (615373), caused by mutation in the PRDM16 gene (605557) on chromosome 1p36; and CMD1MM (see 615396 ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Dec. 10, 2018: Protein entry updated
Automatic update: model status changed
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 115200 was added.