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P02545

- LMNA_HUMAN

UniProt

P02545 - LMNA_HUMAN

Protein

Prelamin-A/C

Gene

LMNA

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 199 (01 Oct 2014)
      Sequence version 1 (20 Mar 1987)
      Previous versions | rss
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    Functioni

    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.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei266 – 2661Heptad change of phase
    Sitei325 – 3251StutterBy similarity
    Sitei330 – 3301Heptad change of phase
    Sitei646 – 6472Cleavage; by endoprotease

    GO - Molecular functioni

    1. protein binding Source: IntAct
    2. structural molecule activity Source: InterPro

    GO - Biological processi

    1. activation of signaling protein activity involved in unfolded protein response Source: Reactome
    2. apoptotic process Source: Reactome
    3. cellular component disassembly involved in execution phase of apoptosis Source: Reactome
    4. cellular protein metabolic process Source: Reactome
    5. cellular response to hypoxia Source: UniProtKB
    6. endoplasmic reticulum unfolded protein response Source: Reactome
    7. establishment or maintenance of microtubule cytoskeleton polarity Source: BHF-UCL
    8. mitotic cell cycle Source: Reactome
    9. mitotic nuclear envelope disassembly Source: Reactome
    10. mitotic nuclear envelope reassembly Source: Reactome
    11. muscle organ development Source: UniProtKB
    12. negative regulation of extrinsic apoptotic signaling pathway Source: Ensembl
    13. negative regulation of release of cytochrome c from mitochondria Source: Ensembl
    14. positive regulation of cell aging Source: UniProtKB
    15. protein localization to nucleus Source: UniProtKB
    16. regulation of cell migration Source: BHF-UCL
    17. sterol regulatory element binding protein import into nucleus Source: Ensembl
    18. ventricular cardiac muscle cell development Source: Ensembl

    Enzyme and pathway databases

    ReactomeiREACT_13472. Breakdown of the nuclear lamina.
    REACT_160242. Initiation of Nuclear Envelope Reformation.
    REACT_160251. Clearance of Nuclear Envelope Membranes from Chromatin.
    REACT_18273. XBP1(S) activates chaperone genes.
    REACT_200828. Depolymerisation of the Nuclear Lamina.
    REACT_75792. Meiotic synapsis.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Prelamin-A/C
    Cleaved into the following chain:
    Alternative name(s):
    70 kDa lamin
    Renal carcinoma antigen NY-REN-32
    Gene namesi
    Name:LMNA
    Synonyms:LMN1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:6636. LMNA.

    Subcellular locationi

    Nucleus. Nucleus envelope. Nucleus lamina. Nucleusnucleoplasm
    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 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. cytosol Source: Reactome
    3. intermediate filament Source: UniProtKB
    4. lamin filament Source: Ensembl
    5. nuclear envelope Source: UniProtKB
    6. nuclear lamina Source: UniProtKB
    7. nuclear speck Source: UniProtKB-SubCell
    8. nucleoplasm Source: Reactome
    9. nucleus Source: UniProtKB
    10. perinuclear region of cytoplasm Source: UniProtKB

    Keywords - Cellular componenti

    Intermediate filament, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    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.11 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti25 – 251R → G in EDMD2. 1 Publication
    Corresponds to variant rs58327533 [ dbSNP | Ensembl ].
    VAR_039746
    Natural varianti25 – 251R → P in EDMD2; mis-localized in the nucleus; causes nuclear deformations and LMNB1 redistribution. 1 Publication
    Corresponds to variant rs61578124 [ dbSNP | Ensembl ].
    VAR_039747
    Natural varianti32 – 321Missing in EDMD2. 1 Publication
    VAR_039749
    Natural varianti33 – 331E → G in EDMD2. 1 Publication
    VAR_039751
    Natural varianti35 – 351L → V in EDMD2. 1 Publication
    Corresponds to variant rs56694480 [ dbSNP | Ensembl ].
    VAR_039752
    Natural varianti39 – 391N → S in MDCL and EDMD2. 2 Publications
    VAR_063588
    Natural varianti43 – 431A → T in EDMD2. 1 Publication
    Corresponds to variant rs60446065 [ dbSNP | Ensembl ].
    VAR_039753
    Natural varianti45 – 451Y → C in EDMD2. 2 Publications
    Corresponds to variant rs58436778 [ dbSNP | Ensembl ].
    VAR_009971
    Natural varianti50 – 501R → P in EDMD2 and MDCL. 2 Publications
    Corresponds to variant rs60695352 [ dbSNP | Ensembl ].
    VAR_009972
    Natural varianti50 – 501R → S in EDMD2. 1 Publication
    Corresponds to variant rs59931416 [ dbSNP | Ensembl ].
    VAR_039754
    Natural varianti63 – 631I → N in EDMD2. 2 Publications
    VAR_039756
    Natural varianti63 – 631I → S in EDMD2. 1 Publication
    Corresponds to variant rs57793737 [ dbSNP | Ensembl ].
    VAR_009974
    Natural varianti65 – 651E → G in EDMD2. 1 Publication
    VAR_039757
    Natural varianti112 – 1121Missing in EDMD2. 2 Publications
    VAR_009976
    Natural varianti133 – 1331R → P in EDMD2. 1 Publication
    Corresponds to variant rs60864230 [ dbSNP | Ensembl ].
    VAR_017657
    Natural varianti140 – 1401L → P in EDMD2. 2 Publications
    VAR_039760
    Natural varianti150 – 1501T → P in EDMD2. 2 Publications
    Corresponds to variant rs58917027 [ dbSNP | Ensembl ].
    VAR_039762
    Natural varianti189 – 1891R → P in EDMD2; found also in a patient with limb-girdle muscular dystrophy; sporadic. 1 Publication
    VAR_064962
    Natural varianti190 – 1901R → Q in EDMD2 and CMD1A; aberrant localization with decreased nuclear rim staining and increased formation of intranuclear foci. 2 Publications
    VAR_039763
    Natural varianti190 – 1901R → RR in EDMD2. 1 Publication
    VAR_064963
    Natural varianti196 – 1994RLQT → S in EDMD2.
    VAR_039766
    Natural varianti206 – 2061F → L in EDMD2. 1 Publication
    VAR_064964
    Natural varianti222 – 2221H → P in EDMD2. 1 Publication
    VAR_039769
    Natural varianti222 – 2221H → Y in EDMD2. 1 Publication
    Corresponds to variant rs28928901 [ dbSNP | Ensembl ].
    VAR_009979
    Natural varianti232 – 2321G → E in EDMD2. 1 Publication
    VAR_039771
    Natural varianti248 – 2481L → P in EDMD2. 1 Publication
    VAR_039772
    Natural varianti249 – 2491R → Q in EDMD2. 8 Publications
    VAR_009980
    Natural varianti249 – 2491R → W in MDCL and EDMD2; mislocalized in the nucleus; causes nuclear deformations and LMNB1 redistribution. 2 Publications
    VAR_063589
    Natural varianti261 – 2611Missing in EDMD2. 3 Publications
    VAR_009981
    Natural varianti267 – 2671Y → C in EDMD2. 1 Publication
    VAR_039774
    Natural varianti268 – 2681S → P in EDMD2. 1 Publication
    VAR_064965
    Natural varianti271 – 2711L → P in EDMD2. 1 Publication
    VAR_064966
    Natural varianti294 – 2941Q → P in EDMD2. 2 Publications
    VAR_009982
    Natural varianti295 – 2951S → P in EDMD2. 1 Publication
    VAR_064967
    Natural varianti303 – 3031S → P in EDMD2. 1 Publication
    VAR_064968
    Natural varianti336 – 3361R → Q in EDMD2. 1 Publication
    VAR_009983
    Natural varianti343 – 3431R → Q in EDMD2.
    VAR_009984
    Natural varianti355 – 3551Missing in EDMD2. 1 Publication
    VAR_064969
    Natural varianti358 – 3581E → K in EDMD2 and MDCL; 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; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 4 Publications
    VAR_009985
    Natural varianti361 – 3611E → K in EDMD2. 1 Publication
    VAR_064970
    Natural varianti371 – 3711M → K in EDMD2; 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. 1 Publication
    VAR_009986
    Natural varianti377 – 3771R → L in EDMD2 and LGMD1B. 2 Publications
    VAR_039777
    Natural varianti386 – 3861R → K in EDMD2; 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. 3 Publications
    VAR_009987
    Natural varianti446 – 4461D → V in EDMD2. 1 Publication
    VAR_039780
    Natural varianti449 – 4491G → D in EDMD2. 1 Publication
    VAR_064971
    Natural varianti453 – 4531R → W in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 6 Publications
    VAR_009988
    Natural varianti454 – 4541L → P in EDMD2. 1 Publication
    VAR_064972
    Natural varianti456 – 4561N → I in EDMD2; mislocalized in the nucleus; does not alter nuclear size or shape. 1 Publication
    VAR_039781
    Natural varianti456 – 4561N → K in EDMD2. 1 Publication
    VAR_039782
    Natural varianti461 – 4611D → Y in EDMD2. 1 Publication
    VAR_064973
    Natural varianti467 – 4671W → R in EDMD2. 1 Publication
    VAR_064974
    Natural varianti469 – 4691I → T in EDMD2. 1 Publication
    VAR_009990
    Natural varianti520 – 5201W → S in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 1 Publication
    VAR_039784
    Natural varianti527 – 5271R → P in EDMD2 and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; reduced binding to SUN1; no decrease in the stability compared with wild-type. 8 Publications
    VAR_009995
    Natural varianti528 – 5281T → K in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 3 Publications
    VAR_009996
    Natural varianti528 – 5281T → R in EDMD2. 2 Publications
    VAR_039785
    Natural varianti530 – 5301L → P in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; reduced binding to SUN1; no decrease in the stability compared with wild-type. 1 Publication
    VAR_009997
    Natural varianti541 – 5411R → H in EDMD2. 1 Publication
    VAR_039787
    Natural varianti541 – 5411R → P in EDMD2; mis-localized in the nucleus; does not alter nuclear size or shape. 1 Publication
    VAR_064975
    Natural varianti541 – 5411R → S in EDMD2 and CMD1A; modest and non-specific nuclear membrane alterations; the phenotype is entirely reversed by coexpression of the S-541 mutation and wild-type lamin-C. 2 Publications
    VAR_039788
    Natural varianti602 – 6021G → S in EDMD2. 1 Publication
    Corresponds to variant rs60662302 [ dbSNP | Ensembl ].
    VAR_064976
    Natural varianti624 – 6241R → H in EDMD2. 1 Publication
    VAR_039791
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti225 – 2251R → Q in EDMD3. 1 Publication
    VAR_067697
    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.12 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti60 – 601R → G in CMD1A and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 2 Publications
    Corresponds to variant rs28928900 [ dbSNP | Ensembl ].
    VAR_034706
    Natural varianti85 – 851L → R in CMD1A; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 1 Publication
    Corresponds to variant rs28933090 [ dbSNP | Ensembl ].
    VAR_009975
    Natural varianti89 – 891R → L in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci. 2 Publications
    Corresponds to variant rs59040894 [ dbSNP | Ensembl ].
    VAR_039758
    Natural varianti92 – 921L → F in CMD1A. 1 Publication
    VAR_067257
    Natural varianti97 – 971K → E in CMD1A. 1 Publication
    Corresponds to variant rs59065411 [ dbSNP | Ensembl ].
    VAR_039759
    Natural varianti101 – 1011R → P in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci. 1 Publication
    VAR_070174
    Natural varianti143 – 1431S → P in CMD1A. 1 Publication
    Corresponds to variant rs61661343 [ dbSNP | Ensembl ].
    VAR_039761
    Natural varianti161 – 1611E → K in CMD1A. 2 Publications
    Corresponds to variant rs28933093 [ dbSNP | Ensembl ].
    VAR_017660
    Natural varianti166 – 1661R → P in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci. 1 Publication
    VAR_070176
    Natural varianti190 – 1901R → Q in EDMD2 and CMD1A; aberrant localization with decreased nuclear rim staining and increased formation of intranuclear foci. 2 Publications
    VAR_039763
    Natural varianti190 – 1901R → W in CMD1A. 3 Publications
    Corresponds to variant rs59026483 [ dbSNP | Ensembl ].
    VAR_039764
    Natural varianti192 – 1921D → G in CMD1A; dramatically increases the size of intranuclear speckles and reduces 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. 1 Publication
    Corresponds to variant rs57045855 [ dbSNP | Ensembl ].
    VAR_039765
    Natural varianti195 – 1951N → K in CMD1A; 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. 1 Publication
    Corresponds to variant rs28933091 [ dbSNP | Ensembl ].
    VAR_009977
    Natural varianti203 – 2031E → G in CMD1A; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death. 1 Publication
    Corresponds to variant rs28933092 [ dbSNP | Ensembl ].
    VAR_009978
    Natural varianti203 – 2031E → K in CMD1A; decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death. 2 Publications
    Corresponds to variant rs61195471 [ dbSNP | Ensembl ].
    VAR_039767
    Natural varianti210 – 2101I → S in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and increased formation of intranuclear foci. 1 Publication
    VAR_070177
    Natural varianti215 – 2151L → P in CMD1A; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci. 2 Publications
    VAR_039768
    Natural varianti317 – 3171E → K in CMD1A. 2 Publications
    VAR_039775
    Natural varianti318 – 3181A → T in CMD1A; no effect on nuclear morphology and lamin A localization. 1 Publication
    VAR_070179
    Natural varianti349 – 3491R → L in CMD1A. 1 Publication
    VAR_039776
    Natural varianti388 – 3881R → H in CMD1A; no effect on nuclear morphology but restricts lamin A to the cytoplasm. 1 Publication
    VAR_070180
    Natural varianti399 – 3991R → C in FPLD2 and CMD1A; no effect on nuclear morphology and lamin A localization. 2 Publications
    VAR_039778
    Natural varianti435 – 4351R → C in CMD1A. 1 Publication
    VAR_039779
    Natural varianti471 – 4711R → H in CMD1A; no effect on nuclear morphology and lamin A localization. 1 Publication
    VAR_070182
    Natural varianti523 – 5231G → R in CMD1A. 1 Publication
    VAR_067258
    Natural varianti541 – 5411R → S in EDMD2 and CMD1A; modest and non-specific nuclear membrane alterations; the phenotype is entirely reversed by coexpression of the S-541 mutation and wild-type lamin-C. 2 Publications
    VAR_039788
    Natural varianti573 – 5731S → L in CMD1A, FPLD2 and MADA. 3 Publications
    VAR_039789
    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.7 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti28 – 281R → W in FPLD2. 1 Publication
    Corresponds to variant rs59914820 [ dbSNP | Ensembl ].
    VAR_039748
    Natural varianti60 – 601R → G in CMD1A and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 2 Publications
    Corresponds to variant rs28928900 [ dbSNP | Ensembl ].
    VAR_034706
    Natural varianti62 – 621R → G in FPLD2. 1 Publication
    Corresponds to variant rs56793579 [ dbSNP | Ensembl ].
    VAR_039755
    Natural varianti133 – 1331R → L in FPLD2. 1 Publication
    VAR_016913
    Natural varianti230 – 2301D → N in FPLD2. 1 Publication
    VAR_039770
    Natural varianti399 – 3991R → C in FPLD2 and CMD1A; no effect on nuclear morphology and lamin A localization. 2 Publications
    VAR_039778
    Natural varianti439 – 4391R → C in FPLD2; increase in nuclear blebbing and formation of honeycomb-like structures in the nuclei with no accumulation of prelamin A in skin fibroblasts; causes oligomerization of the C-terminal globular domain of lamins A and C under no-reducing conditions and increases binding affinity for DNA; increases sensitivity to oxidative stress; no significant differences in stability and structure compared with the wild-type.
    VAR_070181
    Natural varianti465 – 4651G → D in FPLD2. 1 Publication
    VAR_009989
    Natural varianti482 – 4821R → L in FPLD2. 1 Publication
    VAR_009991
    Natural varianti482 – 4821R → Q in FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 2 Publications
    Corresponds to variant rs11575937 [ dbSNP | Ensembl ].
    VAR_009992
    Natural varianti482 – 4821R → W in FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; decreases binding affinity for DNA; increases sensitivity to oxidative stress. 2 Publications
    VAR_009993
    Natural varianti486 – 4861K → N in FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type.
    VAR_009994
    Natural varianti527 – 5271R → P in EDMD2 and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; reduced binding to SUN1; no decrease in the stability compared with wild-type. 8 Publications
    VAR_009995
    Natural varianti573 – 5731S → L in CMD1A, FPLD2 and MADA. 3 Publications
    VAR_039789
    Natural varianti582 – 5821R → H in FPLD2. 1 Publication
    Corresponds to variant rs57830985 [ dbSNP | Ensembl ].
    VAR_009998
    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.6 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti208 – 2081Missing in LGMD1B. 1 Publication
    VAR_034708
    Natural varianti377 – 3771R → H in LGMD1B. 5 Publications
    VAR_016205
    Natural varianti377 – 3771R → L in EDMD2 and LGMD1B. 2 Publications
    VAR_039777
    Natural varianti481 – 4811Y → H in LGMD1B. 1 Publication
    VAR_039783
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti298 – 2981R → C in CMT2B1. 1 Publication
    VAR_017661
    Hutchinson-Gilford progeria syndrome (HGPS) [MIM:176670]: Rare genetic disorder characterized by features reminiscent of marked premature aging.6 Publications
    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).1 Publication
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti138 – 1381E → K in HGPS; might be associated with early and severe strokes. 1 Publication
    VAR_070175
    Natural varianti140 – 1401L → R in HGPS; phenotype originally designated as atypical Werner syndrome. 1 Publication
    Corresponds to variant rs60652225 [ dbSNP | Ensembl ].
    VAR_017658
    Natural varianti143 – 1431S → F in HGPS. 1 Publication
    Corresponds to variant rs58912633 [ dbSNP | Ensembl ].
    VAR_034707
    Natural varianti145 – 1451E → K in HGPS; atypical. 1 Publication
    Corresponds to variant rs60310264 [ dbSNP | Ensembl ].
    VAR_017659
    Natural varianti471 – 4711R → C in HGPS. 1 Publication
    Corresponds to variant rs28928902 [ dbSNP | Ensembl ].
    VAR_017662
    Natural varianti527 – 5271R → C in HGPS. 1 Publication
    VAR_017663
    Natural varianti542 – 5421K → N in HGPS. 1 Publication
    VAR_034710
    Natural varianti608 – 6081G → S in HGPS; reduced binding to SUN1; may affect splicing by activating a cryptic splice donor site. 2 Publications
    VAR_017664
    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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti57 – 571A → P in CMDHH; phenotype originally designated as atypical Werner syndrome. 1 Publication
    Corresponds to variant rs28928903 [ dbSNP | Ensembl ].
    VAR_017656
    Natural varianti59 – 591L → R in CMDHH. 2 Publications
    VAR_064055
    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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti527 – 5271R → H in MADA. 1 Publication
    VAR_018727
    Natural varianti529 – 5291A → V in MADA. 1 Publication
    VAR_034709
    Natural varianti573 – 5731S → L in CMD1A, FPLD2 and MADA. 3 Publications
    VAR_039789
    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.1 Publication
    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.1 Publication
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti39 – 391N → S in MDCL and EDMD2. 2 Publications
    VAR_063588
    Natural varianti50 – 501R → P in EDMD2 and MDCL. 2 Publications
    Corresponds to variant rs60695352 [ dbSNP | Ensembl ].
    VAR_009972
    Natural varianti249 – 2491R → W in MDCL and EDMD2; mislocalized in the nucleus; causes nuclear deformations and LMNB1 redistribution. 2 Publications
    VAR_063589
    Natural varianti302 – 3021L → P in MDCL. 1 Publication
    VAR_063590
    Natural varianti358 – 3581E → K in EDMD2 and MDCL; 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; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 4 Publications
    VAR_009985
    Natural varianti380 – 3801L → S in MDCL. 1 Publication
    VAR_063591
    Natural varianti453 – 4531R → P in MDCL. 1 Publication
    VAR_063592
    Natural varianti455 – 4551R → P in MDCL. 1 Publication
    VAR_063593
    Natural varianti456 – 4561N → D in MDCL. 1 Publication
    VAR_063594
    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.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi201 – 2011K → L: Decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death. 1 Publication
    Mutagenesisi644 – 6441R → A: Does not affect tail cleavage. 1 Publication
    Mutagenesisi647 – 6471L → R: Completely inhibits tail cleavage. 1 Publication
    Mutagenesisi648 – 6481L → A: Completely inhibits tail cleavage. 1 Publication
    Mutagenesisi650 – 6501N → A: Partially inhibits tail cleavage. 1 Publication
    Mutagenesisi661 – 6611C → S: Loss of interaction with NARF. Abolishes farnesylation. 2 Publications

    Keywords - Diseasei

    Cardiomyopathy, Charcot-Marie-Tooth disease, Congenital muscular dystrophy, Disease mutation, Emery-Dreifuss muscular dystrophy, Limb-girdle muscular dystrophy, Neurodegeneration, Neuropathy

    Organism-specific databases

    MIMi115200. phenotype.
    151660. phenotype.
    159001. phenotype.
    176670. phenotype.
    181350. phenotype.
    212112. phenotype.
    248370. phenotype.
    275210. phenotype.
    605588. phenotype.
    610140. phenotype.
    613205. phenotype.
    Orphaneti79474. Atypical Werner syndrome.
    280365. Autosomal codominant severe lipodystrophic laminopathy.
    98853. Autosomal dominant Emery-Dreifuss muscular dystrophy.
    264. Autosomal dominant limb-girdle muscular dystrophy type 1B.
    98855. Autosomal recessive Emery-Dreifuss muscular dystrophy.
    98856. Charcot-Marie-Tooth disease type 2B1.
    157973. Congenital muscular dystrophy due to LMNA mutation.
    2229. Dilated cardiomyopathy - hypergonadotropic hypogonadism.
    300751. Familial dilated cardiomyopathy with conduction defect due to LMNA mutation.
    293899. Familial isolated arrhythmogenic ventricular dysplasia, biventricular form.
    293888. Familial isolated arrhythmogenic ventricular dysplasia, left dominant form.
    293910. Familial isolated arrhythmogenic ventricular dysplasia, right dominant form.
    2348. Familial partial lipodystrophy, Dunnigan type.
    79084. Familial partial lipodystrophy, Kobberling type.
    168796. Heart-hand syndrome, Slovenian type.
    740. Hutchinson-Gilford progeria syndrome.
    137871. Laminopathy type Decaudain-Vigouroux.
    54260. Left ventricular noncompaction.
    1662. Lethal restrictive dermopathy.
    363618. LMNA-related cardiocutaneous progeria syndrome.
    90153. Mandibuloacral dysplasia with type A lipodystrophy.
    99706. Progeria-associated arthropathy.
    PharmGKBiPA231.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 661661Prelamin-A/CPRO_0000398835Add
    BLAST
    Chaini1 – 646646Lamin-A/CPRO_0000063810Add
    BLAST
    Propeptidei647 – 66115Removed in Lamin-A/C formPRO_0000398836Add
    BLAST
    Propeptidei662 – 6643Removed in Prelamin-A/C form and in Lamin-A/C formPRO_0000403442

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication
    Modified residuei3 – 31Phosphothreonine1 Publication
    Modified residuei12 – 121Phosphoserine2 Publications
    Modified residuei18 – 181Phosphoserine1 Publication
    Modified residuei19 – 191Phosphothreonine3 Publications
    Modified residuei22 – 221Phosphoserine4 Publications
    Modified residuei32 – 321N6-acetyllysine; alternateBy similarity
    Modified residuei32 – 321N6-succinyllysine; alternateBy similarity
    Modified residuei108 – 1081N6-acetyllysine1 Publication
    Modified residuei123 – 1231N6-acetyllysineBy similarity
    Modified residuei135 – 1351N6-acetyllysineBy similarity
    Modified residuei155 – 1551N6-acetyllysineBy similarity
    Modified residuei171 – 1711N6-acetyllysine; alternateBy similarity
    Modified residuei171 – 1711N6-succinyllysine; alternateBy similarity
    Modified residuei201 – 2011N6-acetyllysine; alternateBy similarity
    Cross-linki201 – 201Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
    Modified residuei212 – 2121Phosphoserine1 Publication
    Modified residuei260 – 2601N6-acetyllysineBy similarity
    Modified residuei270 – 2701N6-acetyllysine1 Publication
    Modified residuei277 – 2771Phosphoserine2 Publications
    Modified residuei301 – 3011Phosphoserine2 Publications
    Modified residuei311 – 3111N6-acetyllysine1 Publication
    Modified residuei390 – 3901Phosphoserine4 Publications
    Modified residuei392 – 3921Phosphoserine4 Publications
    Modified residuei395 – 3951Phosphoserine3 Publications
    Modified residuei404 – 4041Phosphoserine2 Publications
    Modified residuei407 – 4071PhosphoserineBy similarity
    Modified residuei414 – 4141Phosphoserine2 Publications
    Modified residuei431 – 4311Phosphoserine1 Publication
    Modified residuei450 – 4501N6-acetyllysine1 Publication
    Modified residuei457 – 4571N6-acetyllysineBy similarity
    Modified residuei458 – 4581Phosphoserine3 Publications
    Modified residuei463 – 4631Phosphoserine1 Publication
    Modified residuei496 – 4961PhosphothreonineBy similarity
    Modified residuei505 – 5051Phosphothreonine1 Publication
    Modified residuei510 – 5101PhosphothreonineBy similarity
    Modified residuei546 – 5461PhosphoserineBy similarity
    Modified residuei628 – 6281Phosphoserine5 Publications