Reviewed, UniProtKB/Swiss-Prot P02545 (LMNA_HUMAN)

Names and origin

Protein names

Recommended name:
    Lamin-A/C
Alternative name(s):
    70 kDa lamin
    Renal carcinoma antigen NY-REN-32

Gene names

Name:	LMNA
Synonyms:	LMN1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	664 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

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.
Subunit structure	Homodimer of lamin A and lamin C. Interacts with lamin-associated polypeptides IA, IB and TMPO-alpha, RB1 and with emerin. Interacts with SREBF1 and SREBF2. Proteolytically processed isoform A interacts with NARF.
Subcellular location	Nucleus.
Post-translational modification	Increased phosphorylation of the lamins occurs before envelope disintegration and probably plays a role in regulating lamin associations. The C-terminal 18 residues are removed by proteolytic cleavage in isoform A. Proteolytic cleavage requires prior farnesylation and absence of farnesylation blocks cleavage By similarity.
Involvement in disease	Defects in LMNA are a cause of Emery-Dreifuss muscular dystrophy type 2 (EDMD2) [MIM:181350]. EDMD2 is an autosomal dominant disorder characterized by slowly progressive muscle wasting and weakness, early contractures of the elbows Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. Defects in LMNA are a cause of Emery-Dreifuss muscular dystrophy type 3 (EDMD3) [MIM:604929]. EDMD3 is an autosomal recessive disorder characterized by early contractures, muscle wasting and weakness and cardiomyopathy. Defects in LMNA are the cause of cardiomyopathy dilated type 1A (CMD1A) [MIM:115200]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. Defects in LMNA are the cause of cardiomyopathy dilated with quadriceps myopathy (CMDQM) [MIM:607920]. CMDQM is a severe dilated cardiomyopathy with conduction defects or atrial/ventricular arrhythmias, associated with quadriceps muscle myopathy. Cardiac involvement precedes neuromuscular disease. Defects in LMNA are a cause of generalized lipoatrophy associated with diabetes, hepatic steatosis, hypertrophic cardiomyopathy and leukomelanodermic papules (LDHCP) [MIM:608056]. LDHCP is a disorder characterized by acquired generalized lipoatrophy with metabolic alterations, massive liver steatosis, distinctive cutaneous manifestations, and cardiac abnormalities involving both endocardium and myocardium. Defects in LMNA are a cause of familial partial lipodystrophy type 2 (FPLD2) [MIM:151660]; also known as familial partial lipodystrophy Dunnigan type. FPLD2 is an autosomal dominant disorder characterized by marked loss of subcutaneous adipose tissue from the extremities and trunk but by excess fat deposition in the head and neck. Frequently associated with profound insulin resistance, dyslipidemia, and diabetes. Defects in LMNA are the cause of limb-girdle muscular dystrophy type 1B (LGMD1B) [MIM:159001].LGMD1B is an autosomal dominant degenerative myopathy with age-related atrioventricular cardiac conduction disturbances and the absence of early contractures. LGMD1B is characterized by slowly progressive skeletal muscle weakness of the hip and shoulder girdles. Muscle biopsy shows mild dystrophic changes. Defects in LMNA are the cause of Charcot-Marie-Tooth disease type 2B1 (CMT2B1) [MIM:605588]. CMT2B1 is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2B1 inheritance is autosomal recessive. Defects in LMNA are the cause of Hutchinson-Gilford progeria syndrome (HGPS) [MIM:176670]. HGPS is a rare genetic disorder characterized by features reminiscent of marked premature aging. Defects in LMNA are a cause of familial atrial fibrillation (ATFB) [MIM:607554]. Atrial fibrillation is a cardiac arrhythmia characterized by rapid and irregular activation of the atrium. It causes thromboembolism, tachycardia-mediated cardiomyopathy and heart failure. Defects in LMNA are a cause of Werner syndrome (WRN) [MIM:277700]. WRN is an autosomal, recessively inherited, segmental progeroid syndrome, in which multiple aspects (or segments) of aging phenotypes seem to be entailed. The features of Werner syndrome are scleroderma-like skin changes, especially in the extremities, cataract, subcutaneous calcification, premature arteriosclerosis, diabetes mellitus, and a wizened and prematurely aged facies. Defects in LMNA are the cause of mandibuloacral dysplasia with type A lipodystrophy (MADA) [MIM:248370]. Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, joint contractures, and types A or B patterns of lipodystrophy. Type A lipodystrophy observed in MADA, is characterized by fat loss restricted to the extremities. Defects in LMNA are a cause of lethal tight skin contracture syndrome [MIM:275210]; also called restrictive dermopathy (RD). Lethal tight skin contracture syndrome is a 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. Defects in LMNA are a cause of tendinous calcinosis arthropathy and progeroid features (TCAPF) [MIM:611618]. This disorder consists of an autosomal recessive arthropathy syndrome affecting predominantly the distal femora and proximal tibia in the knees with tendinous calcifications, associated with progeroide appearance, such as pinched nose and micrognathia, cataract, alopecia, generalized lipodystrophy and sclerodermatous skin.
Miscellaneous	There are three types of lamins in human cells: A, B, and C. The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively.
Sequence similarities	Belongs to the intermediate filament family.
Sequence caution	The sequence CAA27173.1 differs from that shown. Reason: Frameshift at position 582.

Ontologies

Keywords
Cellular component	Intermediate filament Nucleus
Coding sequence diversity	Alternative splicing
Disease	Cardiomyopathy Charcot-Marie-Tooth disease Disease mutation Limb-girdle muscular dystrophy
Domain	Coiled coil
PTM	Acetylation Lipoprotein Phosphoprotein Prenylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Molecular function	protein binding Ref.6 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ALOX12	P18054	3	EBI-351935,EBI-1633210

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: P02545-1)

Also known as: Lamin A;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform C (identifier: P02545-2)

Also known as: Lamin C;

The sequence of this isoform differs from the canonical sequence as follows:
     567-572: GSHCSS → VSGSRR
     573-664: Missing.

Isoform ADelta10 (identifier: P02545-3)

Also known as: Lamin ADelta10;

The sequence of this isoform differs from the canonical sequence as follows:
     537-566: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 664	664	Lamin-A/C
Regions
	Region	1 – 33	33	Head
	Region	34 – 383	350	Rod
	Region	34 – 70	37	Coil 1A
	Region	71 – 80	10	Linker 1
	Region	81 – 218	138	Coil 1B
	Region	219 – 242	24	Linker 2
	Region	243 – 383	141	Coil 2
	Region	384 – 664	281	Tail
	Motif	417 – 422	6	Nuclear localization signal Potential
Sites
	Site	266	1	Heptad change of phase
	Site	325	1	Stutter By similarity
	Site	330	1	Heptad change of phase
Amino acid modifications
	Modified residue	1	1	Blocked amino end (Met)
	Modified residue	10	1	Phosphothreonine
	Modified residue	12	1	Phosphoserine By similarity
	Modified residue	19	1	Phosphothreonine
	Modified residue	22	1	Phosphoserine
	Modified residue	277	1	Phosphoserine
	Modified residue	390	1	Phosphoserine
	Modified residue	392	1	Phosphoserine
	Modified residue	395	1	Phosphoserine
	Modified residue	403	1	Phosphoserine
	Modified residue	404	1	Phosphoserine
	Modified residue	406	1	Phosphoserine
	Modified residue	407	1	Phosphoserine
	Modified residue	409	1	Phosphothreonine
	Modified residue	414	1	Phosphoserine
	Modified residue	416	1	Phosphothreonine
	Modified residue	417	1	N6-acetyllysine
	Modified residue	423	1	Phosphoserine
	Modified residue	424	1	Phosphothreonine
	Modified residue	496	1	Phosphothreonine By similarity
	Modified residue	505	1	Phosphothreonine By similarity
	Modified residue	507	1	Phosphoserine By similarity
	Modified residue	510	1	Phosphothreonine By similarity
	Modified residue	628	1	Phosphoserine
	Modified residue	632	1	Phosphoserine
	Modified residue	636	1	Phosphoserine
	Modified residue	652	1	Phosphoserine
	Lipidation	661	1	S-farnesyl cysteine By similarity
Natural variations
	Alternative sequence	537 – 566	30	Missing in isoform ADelta10.
	Alternative sequence	567 – 572	6	GSHCSS → VSGSRR in isoform C.
	Alternative sequence	573 – 664	92	Missing in isoform C.
	Natural variant	10	1	T → I in an atypical progeroid patient; diagnosed as Seip syndrome.
	Natural variant	25	1	R → G in EDMD2.
	Natural variant	25	1	R → P in EDMD2.
	Natural variant	28	1	R → W in FPLD2.
	Natural variant	32	1	Missing in EDMD2.
	Natural variant	33	1	E → D in CMT2; autosomal dominant form.
	Natural variant	33	1	E → G in EDMD.
	Natural variant	35	1	L → V in EDMD2.
	Natural variant	43	1	A → T in EDMD2.
	Natural variant	45	1	Y → C in EDMD.
	Natural variant	50	1	R → P in EDMD.
	Natural variant	50	1	R → S in EDMD2.
	Natural variant	57	1	A → P in WRN; atypical. dbSNP rs28928903.
	Natural variant	60	1	R → G in CMD1A and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. dbSNP rs28928900.
	Natural variant	62	1	R → G in FPLD2.
	Natural variant	63	1	I → N in EDMD.
	Natural variant	63	1	I → S in EDMD.
	Natural variant	65	1	E → G in EDMD; unclassified muscular dystrophy.
	Natural variant	85	1	L → R in CMD1A; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. dbSNP rs28933090.
	Natural variant	89	1	R → L in CMD1A.
	Natural variant	97	1	K → E in CMD1A.
	Natural variant	112	1	Missing in EDMD.
	Natural variant	133	1	R → L in LDHCP.
	Natural variant	133	1	R → P in EDMD2.
	Natural variant	140	1	L → P in EDMD.
	Natural variant	140	1	L → R in WRN.
	Natural variant	143	1	S → F in HGPS.
	Natural variant	143	1	S → P in CMD1A.
	Natural variant	145	1	E → K in HGPS; atypical.
	Natural variant	150	1	T → P in EDMD; autosomal dominant form.
	Natural variant	161	1	E → K in ATFB.
	Natural variant	190	1	R → Q in EDMD2.
	Natural variant	190	1	R → W in CMD1A.
	Natural variant	192	1	D → G in CMD1A; dramatically increases the size of intranuclear speckles and reduced their number; this phenotype is only partially reversed by coexpression of the G-192 mutation and wild-type lamin-C; precludes insertion of lamin-C into the nuclear envelope when co-transfected with the G-192 LMNA; G-192 lamin-C expression totally disrupts the SUMO1 pattern.
	Natural variant	195	1	N → K in CMD1A; has a dramatically aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; causes an increased loss of endogenous EMD from the nuclear envelope; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type.
	Natural variant	196 – 199	4	RLQT → S in EDMD2.
	Natural variant	203	1	E → G in CMD1A; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. dbSNP rs28933092.
	Natural variant	203	1	E → K in CMD1A.
	Natural variant	208	1	Missing in LGMD1B.
	Natural variant	215	1	L → P in CMD1A.
	Natural variant	222	1	H → P in EDMD.
	Natural variant	222	1	H → Y in EDMD. dbSNP rs28928901.
	Natural variant	230	1	D → N in FPLD2.
	Natural variant	232	1	G → E in EDMD.
	Natural variant	248	1	L → P in EDMD2.