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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)LengthDescriptionGraphical viewFeature identifierActions
Sitei266 – 2661Heptad change of phase
Sitei325 – 3251StutterBy similarity
Sitei330 – 3301Heptad change of phase

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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 662662Prelamin-A/CPRO_0000398841Add
BLAST
Chaini1 – 647647Lamin-A/CPRO_0000063813Add
BLAST
Propeptidei648 – 66215Removed in Lamin-A/C formBy similarityPRO_0000398842Add
BLAST
Propeptidei663 – 6653Removed in Prelamin-A/C form and in Lamin-A/C formBy similarityPRO_0000403445

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei3 – 31PhosphothreonineBy similarity
Modified residuei12 – 121PhosphoserineBy similarity
Modified residuei18 – 181PhosphoserineBy similarity
Modified residuei19 – 191PhosphothreonineBy similarity
Modified residuei22 – 221PhosphoserineBy similarity
Modified residuei32 – 321N6-acetyllysine; alternateBy similarity
Modified residuei32 – 321N6-succinyllysine; alternateBy similarity
Modified residuei51 – 511PhosphoserineBy similarity
Modified residuei66 – 661PhosphoserineBy similarity
Modified residuei71 – 711PhosphoserineBy similarity
Cross-linki97 – 97Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei107 – 1071PhosphoserineBy similarity
Modified residuei108 – 1081N6-acetyllysineBy similarity
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); alternateBy similarity
Cross-linki208 – 208Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei212 – 2121PhosphoserineBy similarity
Cross-linki233 – 233Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei260 – 2601N6-acetyllysine; alternateBy similarity
Cross-linki260 – 260Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei270 – 2701N6-acetyllysine; alternateBy similarity
Cross-linki270 – 270Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei277 – 2771PhosphoserineBy similarity
Modified residuei301 – 3011PhosphoserineBy similarity
Modified residuei307 – 3071PhosphoserineBy similarity
Modified residuei311 – 3111N6-acetyllysine; alternateBy similarity
Cross-linki311 – 311Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki378 – 378Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei390 – 3901PhosphoserineCombined sources
Modified residuei392 – 3921PhosphoserineBy similarity
Modified residuei395 – 3951PhosphoserineBy similarity
Modified residuei398 – 3981PhosphoserineBy similarity
Modified residuei403 – 4031PhosphoserineBy similarity
Modified residuei404 – 4041PhosphoserineBy similarity
Modified residuei407 – 4071PhosphoserineBy similarity
Modified residuei409 – 4091PhosphoserineBy similarity
Modified residuei414 – 4141PhosphoserineBy similarity
Cross-linki417 – 417Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki420 – 420Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei429 – 4291PhosphoserineBy similarity
Modified residuei431 – 4311PhosphoserineBy similarity
Modified residuei450 – 4501N6-acetyllysineBy similarity
Modified residuei457 – 4571N6-acetyllysineBy similarity
Modified residuei458 – 4581PhosphoserineBy similarity
Modified residuei463 – 4631PhosphoserineBy similarity
Modified residuei496 – 4961PhosphothreonineCombined sources
Modified residuei500 – 5001PhosphoserineCombined sources
Modified residuei505 – 5051PhosphothreonineBy similarity
Modified residuei510 – 5101PhosphothreonineCombined sources
Modified residuei546 – 5461PhosphoserineBy similarity
Modified residuei548 – 5481PhosphothreonineBy similarity
Modified residuei570 – 5701PhosphoserineBy similarity
Modified residuei573 – 5731PhosphoserineBy similarity
Cross-linki599 – 599Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki599 – 599Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei613 – 6131PhosphoserineBy similarity
Modified residuei614 – 6141PhosphoserineBy similarity
Modified residuei617 – 6171PhosphoserineBy similarity
Modified residuei620 – 6201PhosphoserineBy similarity
Modified residuei629 – 6291PhosphoserineBy similarity
Modified residuei633 – 6331PhosphoserineBy similarity
Modified residuei637 – 6371PhosphoserineBy similarity
Modified residuei653 – 6531PhosphoserineBy similarity
Modified residuei662 – 6621Cysteine methyl esterBy similarity
Lipidationi662 – 6621S-farnesyl cysteineBy similarity

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)LengthDescriptionGraphical viewFeature identifierActions
Sitei647 – 6482Cleavage; by endoproteaseBy similarity

Keywords - PTMi

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

Proteomic databases

PaxDbiP48679.
PRIDEiP48679.

PTM databases

iPTMnetiP48679.
PhosphoSiteiP48679.

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 interactions.
STRINGi10116.ENSRNOP00000026705.

Structurei

3D structure databases

ProteinModelPortaliP48679.
SMRiP48679. Positions 29-65, 313-386, 428-549.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini432 – 544113LTDAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 130130Interaction with MLIPBy similarityAdd
BLAST
Regioni1 – 3333HeadAdd
BLAST
Regioni34 – 383350RodAdd
BLAST
Regioni34 – 7037Coil 1AAdd
BLAST
Regioni71 – 8010Linker 1
Regioni81 – 218138Coil 1BAdd
BLAST
Regioni219 – 24224Linker 2Add
BLAST
Regioni243 – 383141Coil 2Add
BLAST
Regioni384 – 665282TailAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi417 – 4226Nuclear localization signalSequence analysis

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti470 – 4701K → R in CAA47342 (PubMed:1426247).Curated
Sequence conflicti524 – 5241T → S in CAA47342 (PubMed:1426247).Curated
Sequence conflicti584 – 5841R → P in CAA47342 (PubMed:1426247).Curated
Sequence conflicti606 – 6061A → P in CAA47342 (PubMed:1426247).Curated

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.
SMRiP48679. Positions 29-65, 313-386, 428-549.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP48679. 2 interactions.
STRINGi10116.ENSRNOP00000026705.

PTM databases

iPTMnetiP48679.
PhosphoSiteiP48679.

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: July 6, 2016
This is version 134 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.