Mouse Anti-LMNA Antibody (4C10) (CBMAB-1393CQ)

Mouse

Human

4C10

IgG1

WB

Human

IgG1

Monoclonal

The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Supernatant

>95% as determined by analysis by SDS-PAGE

Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.

Prelamin-A/C

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. Diseases associated with LMNA include Hutchinson-Gilford Progeria and Mandibuloacral Dysplasia. Among its related pathways are DNA Damage and Oncogenic MAPK signaling.

FPL; IDC; LFP; CDDC; EMD2; FPLD; HGPS; LDP1; LMN1; LMNC; MADA; PRO1; CDCD1; CMD1A; FPLD2; LMNL1; CMT2B1; LGMD1B

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.

Cellular protein localization Source: CAFA
Cellular response to hypoxia Source: UniProtKB
DNA double-strand break attachment to nuclear envelope Source: UniProtKB
Establishment or maintenance of microtubule cytoskeleton polarity Source: BHF-UCL
IRE1-mediated unfolded protein response Source: Reactome
Mitotic nuclear envelope reassembly Source: Reactome
Muscle organ development Source: UniProtKB
Negative regulation of cardiac muscle hypertrophy in response to stress Source: UniProtKB
Negative regulation of cell population proliferation Source: CAFA
Nuclear envelope organization Source: CAFA
Positive regulation of cell aging Source: UniProtKB
Protein localization to nucleus Source: UniProtKB
Regulation of cell migration Source: BHF-UCL
Regulation of telomere maintenance Source: BHF-UCL

Nucleus; Nucleus envelope; Nucleus lamina; Nucleoplasm; Nucleus matrix. Farnesylation of prelamin-A/C facilitates nuclear envelope targeting and subsequent cleavage 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

Emery-Dreifuss muscular dystrophy 2, autosomal dominant (EDMD2):
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.
Emery-Dreifuss muscular dystrophy 3, autosomal recessive (EDMD3):
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.
Cardiomyopathy, dilated 1A (CMD1A):
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Lipodystrophy, familial partial, 2 (FPLD2):
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.
Charcot-Marie-Tooth disease 2B1 (CMT2B1):
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.
Hutchinson-Gilford progeria syndrome (HGPS):
The disease is caused by variants 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). Rare genetic disorder characterized by features reminiscent of marked premature aging.
Cardiomyopathy, dilated, with hypergonadotropic hypogonadism (CMDHH):
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.
Mandibuloacral dysplasia with type A lipodystrophy (MADA):
A form of mandibuloacral dysplasia, a rare progeroid disorder with clinical and genetic heterogeneity, characterized by growth retardation, craniofacial dysmorphic features due to distal bone resorption, musculoskeletal and skin abnormalities associated with lipodystrophy. MADA is an autosomal recessive disease 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.
Lethal tight skin contracture syndrome (LTSCS):
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.
Heart-hand syndrome Slovenian type (HHS-Slovenian):
Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co-occurrence of a congenital cardiac disease and limb malformations.
Muscular dystrophy congenital LMNA-related (MDCL):
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.
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.

Increased phosphorylation of the lamins occurs before envelope disintegration and probably plays a role in regulating lamin associations. Phosphorylation status of S-22 determines its localization between double-strand break (DSB) sites and the nuclear matrix (PubMed:31548606).
Proteolytic cleavage of the C-terminal of 18 residues of prelamin-A/C results in the production of lamin-A/C. The prelamin-A/C maturation pathway includes farnesylation of CAAX motif, ZMPSTE24/FACE1 mediated cleavage of the last three amino acids, methylation of the C-terminal cysteine and endoproteolytic removal of the last 15 C-terminal amino acids. Proteolytic cleavage requires prior farnesylation and methylation, and absence of these blocks cleavage.
Sumoylation is necessary for the localization to the nuclear envelope.
Farnesylation of prelamin-A/C facilitates nuclear envelope targeting.