Lmna
entrez
16905
canonical
uniprot
P48678
canonical
ensembl
ENSMUSG00000028063
resolver
ensp
ENSMUSP00000029699
resolver
ensp
ENSMUSP00000040265
resolver
ensp
ENSMUSP00000113093
resolver
ensp
ENSMUSP00000235825
resolver
genesymbol
Lmna
resolver
genesymbol_syn
Lmn1
resolver
uniprot
B3RH23
resolver
uniprot
B3RH24
resolver
uniprot
P11516
resolver
uniprot
P97859
resolver
uniprot
Q3TIH0
resolver
uniprot
Q3TTS8
resolver
uniprot
Q3U733
resolver
uniprot
Q3U7I5
resolver
uniprot
Q3UCA0
resolver
uniprot
Q3UCJ8
resolver
uniprot
Q3UCU3
resolver
uniprot
Q91WF2
resolver
uniprot
Q9DC21
resolver
uniprot_entry
LMNA_MOUSE
resolver
uniprot_sec
B3RH23
resolver
uniprot_sec
B3RH24
resolver
uniprot_sec
P11516
resolver
uniprot_sec
P97859
resolver
uniprot_sec
Q3TIH0
resolver
uniprot_sec
Q3TTS8
resolver
uniprot_sec
Q3U733
resolver
uniprot_sec
Q3U7I5
resolver
uniprot_sec
Q3UCA0
resolver
uniprot_sec
Q3UCJ8
resolver
uniprot_sec
Q3UCU3
resolver
uniprot_sec
Q91WF2
resolver
uniprot_sec
Q9DC21
resolver
amino_acid_sequence
METPSQRRATRSGAQASSTPLSPTRITRLQEKEDLQELNDRLAVYIDRVRSLETENAGLRLRITESEEVVSREVSGIKAAYEAELGDARKTLDSVAKERARLQLELSKVREEFKELKARNTKKEGDLLAAQARLKDLEALLNSKEAALSTALSEKRTLEGELHDLRGQVAKLEAALGEAKKQLQDEMLRRVDAENRLQTLKEELDFQKNIYSEELRETKRRHETRLVEIDNGKQREFESRLADALQELRAQHEDQVEQYKKELEKTYSAKLDNARQSAERNSNLVGAAHEELQQSRIRIDSLSAQLSQLQKQLAAKEAKLRDLEDSLARERDTSRRLLAEKEREMAEMRARMQQQLDEYQELLDIKLALDMEIHAYRKLLEGEEERLRLSPSPTSQRSRGRASSHSSQSQGGGSVTKKRKLESSESRSSFSQHARTSGRVAVEEVDEEGKFVRLRNKSNEDQSMGNWQIRRQNGDDPLMTYRFPPKFTLKAGQVVTIWASGAGATHSPPTDLVWKAQNTWGCGSSLRTALINSTGEEVAMRKLVRSLTMVEDNEDDDEDGEELLHHHRGSHCSGSGDPAEYNLRSRTVLCGTCGQPADKAAGGAGAQVGGSISSGSSASSVTVTRSFRSVGGSGGGSFGDNLVTRSYLLGNSSPRSQSSQNCSIM
uniprot
proteins
function
FUNCTION: [Lamin-A/C]: Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:10579712, PubMed:28241138, PubMed:31576060). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:10579712, PubMed:28241138). Lamin A and C also regulate matrix stiffness by conferring nuclear mechanical properties (By similarity). 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 (PubMed:10579712, PubMed:28241138). Lamin A and C are present in equal amounts in the lamina of mammals (By similarity). Also involved in DNA repair: recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (By similarity). Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:11799477, PubMed:19124654, PubMed:23535822). Required for osteoblastogenesis and bone formation (By similarity). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:21547077, PubMed:21982926). Required for cardiac homeostasis (PubMed:26436652). {ECO:0000250|UniProtKB:P02545, ECO:0000269|PubMed:10579712, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:19124654, ECO:0000269|PubMed:21547077, ECO:0000269|PubMed:21982926, ECO:0000269|PubMed:23535822, ECO:0000269|PubMed:26436652, ECO:0000269|PubMed:28241138, ECO:0000269|PubMed:31576060}.; FUNCTION: [Prelamin-A/C]: 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. {ECO:0000250|UniProtKB:P02545}.; FUNCTION: [Isoform C2]: Isoform C2 may have a role in determining the organization of nuclear and chromosomal structures during spermatogenesis. {ECO:0000269|PubMed:8187835}.
uniprot
proteins
mass_dalton
74238
uniprot
proteins
mutagenesis
MUTAGEN 97; /note="K->R: Decreased acetylation by KAT8, leading to impaired nuclear architecture; when associated with R-108 and R-311."; /evidence="ECO:0000269|PubMed:31576060"; MUTAGEN 108; /note="K->R: Decreased acetylation by KAT8, leading to impaired nuclear architecture; when associated with R-97 and R-311."; /evidence="ECO:0000269|PubMed:31576060"; MUTAGEN 201; /note="K->L: Decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death."; /evidence="ECO:0000269|PubMed:18606848"; MUTAGEN 203; /note="E->G,K: Decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death."; /evidence="ECO:0000269|PubMed:18606848"; MUTAGEN 311..319; /note="KQLAAKEAK->QQLAAKEAQ: Mimics acetylation, promoting nuclear architecture."; /evidence="ECO:0000269|PubMed:31576060"; MUTAGEN 311; /note="K->R: Decreased acetylation by KAT8, leading to impaired nuclear architecture; when associated with R-97 and R-108."; /evidence="ECO:0000269|PubMed:31576060
uniprot
proteins
post_translational_modification
PTM: Proteolytic cleavage of the C-terminal of 18 residues of prelamin-A/C results in the production of lamin-A/C (PubMed:17652517). The prelamin-A/C maturation pathway includes farnesylation of CAAX motif by protein farnesyltransferase (FNTA and FNTB), removal of the last three amino acids (-AAX) by RCE1/FACE2 and/or ZMPSTE24, methylation of the C-terminal cysteine by ICMT and endoproteolytic removal of the last 15 C-terminal amino acids by ZMPSTE24 (PubMed:17652517). Proteolytic cleavage requires prior farnesylation and methylation, and absence of these blocks cleavage (PubMed:17652517). {ECO:0000269|PubMed:17652517}.; PTM: Farnesylation of prelamin-A/C facilitates nuclear envelope targeting. {ECO:0000250|UniProtKB:P02545}.; PTM: Phosphorylation plays a key role in lamin organization, subcellular localization and nuclear envelope disintegration. Phosphorylation by CDK1 at Ser-22 and Ser-392 at the onset of mitosis drives lamin disassembly and nuclear envelope breakdown. Phosphorylation at Ser-22 and Ser-392 during interphase promotes localization to the nucleoplasm and regulates lamina assembly. Phosphorylation at Ser-22, Ser-392 and Ser-629 during interphase causes redistribution between the nucleus and the cytoplasm. Phosphorylation at Ser-22 by CDK1 regulates matrix stiffness. Phosphorylation status of Ser-22 determines its localization between double-strand break (DSB) sites and the nuclear matrix. Phosphorylated by ATR at Ser-282 in response to DNA damage, leading to lamin disassembly and nuclear envelope rupture. Phosphorylation also regulates stability in micronuclei arising from genome instability: phosphorylation at Ser-395 by ATR in response to genome instability and double-stranded DNA breaks primes LMNA for subsequent phosphorylation at Ser-392 by CDK1 and micronuclei envelope rupture. The rupture of micronuclear envelope triggers the cGAS-STING pathway thereby activating the type I interferon response and innate immunity. {ECO:0000250|UniProtKB:P02545}.; PTM: [Isoform C]: Isoform C is phosphorylated on Ser-392, Ser-407 and Ser-409 at interphase. {ECO:0000269|PubMed:1959608}.; PTM: Acetylation by KAT8 is required for nuclear architecture. {ECO:0000269|PubMed:31576060}.; PTM: Sumoylation is necessary for the localization to the nuclear envelope. {ECO:0000250|UniProtKB:P02545}.; PTM: The N-terminus is blocked.
uniprot
proteins
protein_family
Intermediate filament family
uniprot
proteins
pubmed
10579712
uniprot
proteins
pubmed
11799477
uniprot
proteins
pubmed
11929849
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16380439
uniprot
proteins
pubmed
16452087
uniprot
proteins
pubmed
16648470
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
17652517
uniprot
proteins
pubmed
18230648
uniprot
proteins
pubmed
18606848
uniprot
proteins
pubmed
19124654
uniprot
proteins
pubmed
19131326
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
1959608
uniprot
proteins
pubmed
19843581
uniprot
proteins
pubmed
19933576
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21498514
uniprot
proteins
pubmed
21547077
uniprot
proteins
pubmed
21982926
uniprot
proteins
pubmed
22349700
uniprot
proteins
pubmed
23535822
uniprot
proteins
pubmed
23695662
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
2583287
uniprot
proteins
pubmed
26436652
uniprot
proteins
pubmed
2719959
uniprot
proteins
pubmed
28241138
uniprot
proteins
pubmed
31576060
uniprot
proteins
pubmed
7781761
uniprot
proteins
pubmed
7916626
uniprot
proteins
pubmed
8187835
uniprot
proteins
sequence_length
665
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus lamina {ECO:0000269|PubMed:28241138}. Nucleus envelope {ECO:0000250|UniProtKB:P02545}. Nucleus, nucleoplasm {ECO:0000269|PubMed:26436652}. Nucleus matrix {ECO:0000250|UniProtKB:P02545}. Note=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. Also localizes to the micronuclear envelope in response to response to genome instability. {ECO:0000250|UniProtKB:P02545}.
uniprot
proteins