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Protein

Prelamin-A/C

Gene

Lmna

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 (By similarity).By similarity
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 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei266Heptad change of phase1
Sitei325StutterBy similarity1
Sitei330Heptad change of phase1

GO - Molecular functioni

  • protein phosphatase 1 binding Source: RGD
  • structural molecule activity Source: InterPro

GO - Biological processi

  • negative regulation of adipose tissue development Source: RGD
  • positive regulation of cell aging Source: UniProtKB
  • positive regulation of osteoblast differentiation Source: RGD
  • protein localization to nucleus Source: UniProtKB
  • response to mechanical stimulus Source: RGD
  • spermatogenesis Source: RGD
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Prelamin-A/C
Cleaved into the following chain:
Gene namesi
Name:Lmna
Synonyms:Lmn1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620456. Lmna.

Subcellular locationi

  • Nucleus By similarity
  • Nucleus envelope By similarity
  • Nucleus lamina By similarity
  • Nucleusnucleoplasm By similarity

  • 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 (By similarity).By similarity

GO - Cellular componenti

  • intermediate filament Source: UniProtKB-KW
  • nuclear envelope Source: UniProtKB
  • nuclear lamina Source: UniProtKB-SubCell
  • nuclear matrix Source: RGD
  • nucleoplasm Source: UniProtKB-SubCell
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Intermediate filament, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003988411 – 662Prelamin-A/CAdd BLAST662
ChainiPRO_00000638131 – 647Lamin-A/CAdd BLAST647
PropeptideiPRO_0000398842648 – 662Removed in Lamin-A/C formBy similarityAdd BLAST15
PropeptideiPRO_0000403445663 – 665Removed in Prelamin-A/C form and in Lamin-A/C formBy similarity3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei3PhosphothreonineBy similarity1
Modified residuei12PhosphoserineBy similarity1
Modified residuei18PhosphoserineBy similarity1
Modified residuei19PhosphothreonineBy similarity1
Modified residuei22PhosphoserineBy similarity1
Modified residuei32N6-acetyllysine; alternateBy similarity1
Modified residuei32N6-succinyllysine; alternateBy similarity1
Modified residuei51PhosphoserineBy similarity1
Modified residuei66PhosphoserineBy similarity1
Modified residuei71PhosphoserineBy similarity1
Cross-linki97Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei107PhosphoserineBy similarity1
Modified residuei108N6-acetyllysineBy similarity1
Modified residuei123N6-acetyllysineBy similarity1
Modified residuei135N6-acetyllysineBy similarity1
Modified residuei155N6-acetyllysineBy similarity1
Modified residuei171N6-acetyllysine; alternateBy similarity1
Modified residuei171N6-succinyllysine; alternateBy similarity1
Modified residuei201N6-acetyllysine; alternateBy similarity1
Cross-linki201Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki208Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei212PhosphoserineBy similarity1
Cross-linki233Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei260N6-acetyllysine; alternateBy similarity1
Cross-linki260Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei270N6-acetyllysine; alternateBy similarity1
Cross-linki270Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei277PhosphoserineBy similarity1
Modified residuei301PhosphoserineBy similarity1
Modified residuei307PhosphoserineBy similarity1
Modified residuei311N6-acetyllysine; alternateBy similarity1
Cross-linki311Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki378Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei390PhosphoserineCombined sources1
Modified residuei392PhosphoserineBy similarity1
Modified residuei395PhosphoserineBy similarity1
Modified residuei398PhosphoserineBy similarity1
Modified residuei403PhosphoserineBy similarity1
Modified residuei404PhosphoserineBy similarity1
Modified residuei407PhosphoserineBy similarity1
Modified residuei409PhosphoserineBy similarity1
Modified residuei414PhosphoserineBy similarity1
Cross-linki417Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki420Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei429PhosphoserineBy similarity1
Modified residuei431PhosphoserineBy similarity1
Modified residuei450N6-acetyllysineBy similarity1
Modified residuei457N6-acetyllysineBy similarity1
Modified residuei458PhosphoserineBy similarity1
Modified residuei463PhosphoserineBy similarity1
Modified residuei496PhosphothreonineCombined sources1
Modified residuei500PhosphoserineCombined sources1
Modified residuei505PhosphothreonineBy similarity1
Modified residuei510PhosphothreonineCombined sources1
Modified residuei546PhosphoserineBy similarity1
Modified residuei548PhosphothreonineBy similarity1
Modified residuei570PhosphoserineBy similarity1
Modified residuei573PhosphoserineBy similarity1
Cross-linki599Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki599Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei613PhosphoserineBy similarity1
Modified residuei614PhosphoserineBy similarity1
Modified residuei617PhosphoserineBy similarity1
Modified residuei620PhosphoserineBy similarity1
Modified residuei629PhosphoserineBy similarity1
Modified residuei633PhosphoserineBy similarity1
Modified residuei637PhosphoserineBy similarity1
Modified residuei653PhosphoserineBy similarity1
Modified residuei662Cysteine methyl esterBy similarity1
Lipidationi662S-farnesyl cysteineBy similarity1

Post-translational modificationi

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 (By similarity).By similarity
Sumoylation is necessary for the localization to the nuclear envelope.By similarity
Farnesylation of prelamin-A/C facilitates nuclear envelope targeting.By similarity
Increased phosphorylation of the lamins occurs before envelope disintegration and probably plays a role in regulating lamin associations.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei647 – 648Cleavage; by endoproteaseBy similarity2

Keywords - PTMi

Acetylation, Isopeptide bond, Lipoprotein, Methylation, Phosphoprotein, Prenylation, Ubl conjugation

Proteomic databases

PaxDbiP48679.
PRIDEiP48679.

PTM databases

iPTMnetiP48679.
PhosphoSitePlusiP48679.

Interactioni

Subunit structurei

Homodimer of lamin A and lamin C. Interacts with lamin-associated polypeptides IA, IB and TMPO-alpha, RB1 and with emerin. Interacts with SREBF1, SREBF2, SUN1, SUN2 and TMEM43. Proteolytically processed isoform A interacts with NARF. Prelamin-A/C interacts with EMD. Interacts with MLIP; may regulate MLIP localization to the nucleus envelope. Interacts with DMPK; may regulate nuclear envelope stability Interacts with SUV39H1; the interaction increases stability of SUV39H1 (By similarity).By similarity

GO - Molecular functioni

  • protein phosphatase 1 binding Source: RGD

Protein-protein interaction databases

IntActiP48679. 2 interactors.
STRINGi10116.ENSRNOP00000026705.

Structurei

3D structure databases

ProteinModelPortaliP48679.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini432 – 544LTDAdd BLAST113

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 130Interaction with MLIPBy similarityAdd BLAST130
Regioni1 – 33HeadAdd BLAST33
Regioni34 – 383RodAdd BLAST350
Regioni34 – 70Coil 1AAdd BLAST37
Regioni71 – 80Linker 110
Regioni81 – 218Coil 1BAdd BLAST138
Regioni219 – 242Linker 2Add BLAST24
Regioni243 – 383Coil 2Add BLAST141
Regioni384 – 665TailAdd BLAST282

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi417 – 422Nuclear localization signalSequence analysis6

Sequence similaritiesi

Belongs to the intermediate filament family.Curated
Contains 1 LTD domain.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0977. Eukaryota.
ENOG410Y2H6. LUCA.
HOGENOMiHOG000007711.
HOVERGENiHBG013015.
InParanoidiP48679.
PhylomeDBiP48679.

Family and domain databases

Gene3Di2.60.40.1260. 1 hit.
InterProiIPR001664. IF.
IPR018039. Intermediate_filament_CS.
IPR001322. Lamin_tail_dom.
[Graphical view]
PANTHERiPTHR23239. PTHR23239. 1 hit.
PfamiPF00038. Filament. 1 hit.
PF00932. LTD. 1 hit.
[Graphical view]
SMARTiSM01391. Filament. 1 hit.
[Graphical view]
SUPFAMiSSF74853. SSF74853. 1 hit.
PROSITEiPS00226. IF. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Isoform A and isoform C are present in equal amounts in the lamina of mammals.
Isoform Lamin A (identifier: P48679-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
METPSQRRPT RSGAQASSTP LSPTRITRLQ EKEDLQELND RLAVYIDRVR
60 70 80 90 100
SLETENAGLR LRITESEEVV SREVSGIKAA YEAELGDARK TLDSVAKERA
110 120 130 140 150
RLQLELSKVR EEFKELKARN TKKEGDLLAA QARLKDLEAL LNSKEAALST
160 170 180 190 200
ALSEKRTLEG ELHDLRGQVA KLEAALGEAK KQLQDEMLRR VDAENRLQTL
210 220 230 240 250
KEELDFQKNI YSEELRETKR RHETRLVEID NGKQREFESR LADALQELRA
260 270 280 290 300
QHEDQVEQYK KELEKTYSAK LDNARQSAER NSNLVGAAHE ELQQSRIRID
310 320 330 340 350
SLSAQLSQLQ KQLAAKEAKL RDLEDSLARE RDTSRRLLAE KEREMAEMRA
360 370 380 390 400
RMQQQLDEYQ ELLDIKLALD MEIHAYRKLL EGEEERLRLS PSPTSQRSRG
410 420 430 440 450
RASSHSSQSQ GGGSVTKKRK LESSESRSSF SQHARTSGRV AVEEVDEEGK
460 470 480 490 500
FVRLRNKSNE DQSMGNWQIK RQNGDDPLMT YRFPPKFTLK AGQVVTIWAS
510 520 530 540 550
GAGATHSPPT DLVWKAQNTW GCGTSLRTAL INATGEEVAM RKLVRSLTMV
560 570 580 590 600
EDNDDEEEDG DELLHHHRGS HCSSSGDPAE YNLRSRTVLC GTCGQPADKA
610 620 630 640 650
ASGSGAQVGG SISSGSSASS VTVTRSFRSV GGSGGGSFGD NLVTRSYLLG
660
NSSPRTQSSQ NCSIM
Length:665
Mass (Da):74,324
Last modified:February 1, 1996 - v1
Checksum:i9CC553005C8534E4
GO
Isoform Lamin C (identifier: P48679-2)
Sequence is not available
Length:
Mass (Da):

Sequence cautioni

The sequence CAA47342 differs from that shown. Reason: Frameshift at positions 21, 83 and 584.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti470K → R in CAA47342 (PubMed:1426247).Curated1
Sequence conflicti524T → S in CAA47342 (PubMed:1426247).Curated1
Sequence conflicti584R → P in CAA47342 (PubMed:1426247).Curated1
Sequence conflicti606A → P in CAA47342 (PubMed:1426247).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66870 mRNA. Translation: CAA47342.1. Frameshift.
X76297 mRNA. Translation: CAA53945.1.
PIRiS27267.
UniGeneiRn.44161.

Genome annotation databases

UCSCiRGD:620456. rat. [P48679-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66870 mRNA. Translation: CAA47342.1. Frameshift.
X76297 mRNA. Translation: CAA53945.1.
PIRiS27267.
UniGeneiRn.44161.

3D structure databases

ProteinModelPortaliP48679.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP48679. 2 interactors.
STRINGi10116.ENSRNOP00000026705.

PTM databases

iPTMnetiP48679.
PhosphoSitePlusiP48679.

Proteomic databases

PaxDbiP48679.
PRIDEiP48679.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:620456. rat. [P48679-1]

Organism-specific databases

RGDi620456. Lmna.

Phylogenomic databases

eggNOGiKOG0977. Eukaryota.
ENOG410Y2H6. LUCA.
HOGENOMiHOG000007711.
HOVERGENiHBG013015.
InParanoidiP48679.
PhylomeDBiP48679.

Miscellaneous databases

PROiP48679.

Family and domain databases

Gene3Di2.60.40.1260. 1 hit.
InterProiIPR001664. IF.
IPR018039. Intermediate_filament_CS.
IPR001322. Lamin_tail_dom.
[Graphical view]
PANTHERiPTHR23239. PTHR23239. 1 hit.
PfamiPF00038. Filament. 1 hit.
PF00932. LTD. 1 hit.
[Graphical view]
SMARTiSM01391. Filament. 1 hit.
[Graphical view]
SUPFAMiSSF74853. SSF74853. 1 hit.
PROSITEiPS00226. IF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLMNA_RAT
AccessioniPrimary (citable) accession number: P48679
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 2, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.