LEM2_CAEEL
ID LEM2_CAEEL Reviewed; 500 AA.
AC Q9XTB5;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=LEM protein 2;
DE AltName: Full=Ce-MAN1;
DE AltName: Full=MAN1 homolog;
GN Name=lem-2; ORFNames=W01G7.5;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=10982402; DOI=10.1091/mbc.11.9.3089;
RA Lee K.K., Gruenbaum Y., Spann P., Liu J., Wilson K.L.;
RT "C. elegans nuclear envelope proteins emerin, MAN1, lamin, and nucleoporins
RT reveal unique timing of nuclear envelope breakdown during mitosis.";
RL Mol. Biol. Cell 11:3089-3099(2000).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP INTERACTION WITH LMN-1 AND BAF-1, AND DISRUPTION PHENOTYPE.
RX PubMed=12684533; DOI=10.1073/pnas.0730821100;
RA Liu J., Lee K.K., Segura-Totten M., Neufeld E., Wilson K.L., Gruenbaum Y.;
RT "MAN1 and emerin have overlapping function(s) essential for chromosome
RT segregation and cell division in Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:4598-4603(2003).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=16950114; DOI=10.1016/j.cub.2006.06.067;
RA Galy V., Askjaer P., Franz C., Lopez-Iglesias C., Mattaj I.W.;
RT "MEL-28, a novel nuclear-envelope and kinetochore protein essential for
RT zygotic nuclear-envelope assembly in C. elegans.";
RL Curr. Biol. 16:1748-1756(2006).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21176223; DOI=10.1186/gb-2010-11-12-r120;
RA Ikegami K., Egelhofer T.A., Strome S., Lieb J.D.;
RT "Caenorhabditis elegans chromosome arms are anchored to the nuclear
RT membrane via discontinuous association with LEM-2.";
RL Genome Biol. 11:R120.1-R120.2(2010).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22171324; DOI=10.1091/mbc.e11-06-0505;
RA Barkan R., Zahand A.J., Sharabi K., Lamm A.T., Feinstein N., Haithcock E.,
RA Wilson K.L., Liu J., Gruenbaum Y.;
RT "Ce-emerin and LEM-2: essential roles in Caenorhabditis elegans
RT development, muscle function, and mitosis.";
RL Mol. Biol. Cell 23:543-552(2012).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22383942; DOI=10.1371/journal.pone.0024555;
RA Dittrich C.M., Kratz K., Sendoel A., Gruenbaum Y., Jiricny J.,
RA Hengartner M.O.;
RT "LEM-3 - a LEM domain containing nuclease involved in the DNA damage
RT response in C. elegans.";
RL PLoS ONE 7:E24555-E24555(2012).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=25653391; DOI=10.1242/jcs.164202;
RA Morales-Martinez A., Dobrzynska A., Askjaer P.;
RT "Inner nuclear membrane protein LEM-2 is required for correct nuclear
RT separation and morphology in C. elegans.";
RL J. Cell Sci. 128:1090-1096(2015).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=32271860; DOI=10.1083/jcb.201908179;
RA Penfield L., Shankar R., Szentgyoergyi E., Laffitte A., Mauro M.S.,
RA Audhya A., Mueller-Reichert T., Bahmanyar S.;
RT "Regulated lipid synthesis and LEM2/CHMP7 jointly control nuclear envelope
RT closure.";
RL J. Cell Biol. 219:0-0(2020).
CC -!- FUNCTION: Nuclear lamina-associated inner nuclear membrane protein that
CC is involved in cell division, nuclear structure organization,
CC maintenance of nuclear envelope integrity and nuclear envelope
CC reformation after mitosis (PubMed:12684533, PubMed:21176223,
CC PubMed:22171324, PubMed:25653391, PubMed:32271860). In interphase
CC cells, plays a role in anchoring and spatial arrangement of chromosome
CC arms at the nuclear periphery, forming so-called lem-2 subdomains
CC (PubMed:21176223). Both arms of autosomes but only the left arm of the
CC X chromosome are anchored in lem-2 subdomains; sequences bound by lem-2
CC are mainly repetitive chromosome sequences and inactive genes
CC (PubMed:21176223). Involved in chromosome segregation and cell
CC division, probably via its interaction with the nuclear intermediate
CC filament protein lmn-1, the main component of nuclear lamina
CC (PubMed:12684533). Required to organize the distribution of lmn-1,
CC nuclear pore complexes (NPCs) and chromatin in mitotically active cells
CC (PubMed:22171324). Involved in the nuclear positioning and efficient
CC anchoring of microtubule-organizing centers (MTOCs) to the nuclear
CC envelope during mitosis as well as on maintaining correct nuclear
CC morphology (PubMed:25653391). Contributes to closure of nuclear
CC envelope (NE) holes and prevents excess nuclear membranes after meiosis
CC and mitosis (PubMed:32271860). Together with emr-1, plays a role in
CC baf-1 enrichment at the nuclear envelope in anaphase (PubMed:12684533).
CC Together with emr-1, involved in muscle cell attachment to hypodermal
CC cells, as well as muscle cell location and sarcomere organization
CC (PubMed:22171324). May play a role in radiation-induced DNA damage
CC repair response (PubMed:22383942). {ECO:0000269|PubMed:12684533,
CC ECO:0000269|PubMed:21176223, ECO:0000269|PubMed:22171324,
CC ECO:0000269|PubMed:22383942, ECO:0000269|PubMed:25653391,
CC ECO:0000269|PubMed:32271860}.
CC -!- SUBUNIT: Interacts with lmn-1 (PubMed:12684533). Interacts (via LEM
CC domain and the C-terminal nuclear domain) with baf-1 (PubMed:12684533).
CC {ECO:0000269|PubMed:12684533}.
CC -!- INTERACTION:
CC Q9XTB5; Q03565: baf-1; NbExp=2; IntAct=EBI-2535391, EBI-2535603;
CC Q9XTB5; Q21443: lmn-1; NbExp=3; IntAct=EBI-2535391, EBI-314110;
CC -!- SUBCELLULAR LOCATION: Nucleus inner membrane
CC {ECO:0000269|PubMed:10982402, ECO:0000269|PubMed:12684533}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:10982402,
CC ECO:0000269|PubMed:12684533}; Nucleoplasmic side {ECO:0000305}. Nucleus
CC envelope {ECO:0000269|PubMed:10982402, ECO:0000269|PubMed:16950114,
CC ECO:0000269|PubMed:21176223, ECO:0000269|PubMed:25653391,
CC ECO:0000269|PubMed:32271860}. Chromosome {ECO:0000269|PubMed:16950114,
CC ECO:0000269|PubMed:25653391, ECO:0000269|PubMed:32271860}. Note=Remains
CC in the nuclear envelope until mid-late anaphase and reassociates with
CC the chromatin periphery at telophase (PubMed:10982402). Recruited to
CC the reforming nuclear envelope initially at the apical surfaces of
CC chromatin, from where it spreads to the lateral surfaces facing the
CC spindle microtubules (PubMed:25653391). Requires mel-28 for chromatin
CC reassociation after mitosis and for nuclear envelope localization
CC (PubMed:16950114). In meiosis at anaphase II, appears on the chromatin
CC surface farthest from the extruding polar body (PubMed:32271860). After
CC anaphase II, forms a plaque on the oocyte-derived pronucleus adjacent
CC to the meiotic spindle (PubMed:32271860). Later disperses into a
CC uniform rim around the oocyte-derived pronucleus (PubMed:32271860).
CC {ECO:0000269|PubMed:10982402, ECO:0000269|PubMed:16950114,
CC ECO:0000269|PubMed:25653391, ECO:0000269|PubMed:32271860}.
CC -!- TISSUE SPECIFICITY: Ubiquitous (PubMed:12684533). High expression in
CC germline and intestine (PubMed:25653391). {ECO:0000269|PubMed:12684533,
CC ECO:0000269|PubMed:25653391}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development and in adults.
CC {ECO:0000269|PubMed:12684533, ECO:0000269|PubMed:25653391}.
CC -!- DISRUPTION PHENOTYPE: Moderate increase in embryonic lethality of
CC progeny of X-ray-irradiated adults (PubMed:22383942). Reduced lifespan
CC to 18.6 days compared to 22 days for wild type animals
CC (PubMed:22171324). Decreased contour ration of interphase nuclei,
CC nuclear envelope invaginations and faster turnover of emr-1 at nuclear
CC envelope (PubMed:25653391). Delay of daughter nuclei separation
CC (PubMed:25653391). Two microtubule-organizing centers (MTOCs) found in
CC close association with nuclei during nuclear separation instead of only
CC one as in wild type animals (PubMed:25653391). RNAi-mediated knockdown
CC leads to embryonic lethality and chromosome segregation defects in the
CC F1 progeny (PubMed:12684533). Simultaneous knockout of lem-2 and emr-1
CC leads to embryonic lethality, 8.5% shorter animals in larval stage L2,
CC abnormal gonads and a developmental stop at late L2/early L3
CC (PubMed:22171324). Missing cell divisions in the postembryonic
CC mesodermal lineage and failure to produce any of the differentiated M
CC lineage cells (PubMed:22171324). Defects in the organization of
CC chromatin, nuclear intermediate filaments, and nuclear pore complexes
CC (NPCs), and defects in mitosis in cells that continue to divide after
CC embryogenesis (PubMed:22171324). In the mitotic zone of the gonad, lmn-
CC 1 and NPCs are mislocalized and nuclei are misshaped (PubMed:22171324).
CC Misshaped nuclei with large lmn-1 aggregates, clustered NPCs and
CC condensed chromatin in somatic hypodermal cells (PubMed:22171324).
CC Defects in motility, sarcomere organization, and muscle attachment to
CC hypodermis (PubMed:22171324). Decreased motility and near paralysis at
CC day 6 (PubMed:22171324). Disorganized thin and thick filaments of
CC sarcomeres and abnormally positioned muscles at day 3 and 6
CC (PubMed:22171324). Decreased pumping rate of the pharynx
CC (PubMed:22171324). Simultaneous RNAi-mediated knockdown of lem-2 and
CC emr-1 causes anaphase chromatin bridges and redistribution of baf-1
CC from the nuclear periphery to the segregating chromatin during anaphase
CC (PubMed:12684533). RNAi-mediated knockdown in a cnep-1 mutant
CC background leads to severe nuclear sealing defects (PubMed:32271860).
CC {ECO:0000269|PubMed:12684533, ECO:0000269|PubMed:22171324,
CC ECO:0000269|PubMed:22383942, ECO:0000269|PubMed:25653391,
CC ECO:0000269|PubMed:32271860}.
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DR EMBL; BX284602; CAB03457.1; -; Genomic_DNA.
DR EMBL; AL032634; CAB03457.1; JOINED; Genomic_DNA.
DR PIR; T26067; T26067.
DR RefSeq; NP_496944.1; NM_064543.1.
DR AlphaFoldDB; Q9XTB5; -.
DR SMR; Q9XTB5; -.
DR BioGRID; 40342; 3.
DR IntAct; Q9XTB5; 3.
DR STRING; 6239.W01G7.5; -.
DR iPTMnet; Q9XTB5; -.
DR EPD; Q9XTB5; -.
DR PaxDb; Q9XTB5; -.
DR PeptideAtlas; Q9XTB5; -.
DR EnsemblMetazoa; W01G7.5.1; W01G7.5.1; WBGene00002275.
DR GeneID; 175058; -.
DR KEGG; cel:CELE_W01G7.5; -.
DR UCSC; W01G7.5; c. elegans.
DR CTD; 175058; -.
DR WormBase; W01G7.5; CE20129; WBGene00002275; lem-2.
DR eggNOG; KOG0147; Eukaryota.
DR GeneTree; ENSGT00940000171142; -.
DR HOGENOM; CLU_530214_0_0_1; -.
DR InParanoid; Q9XTB5; -.
DR OMA; GNECAVW; -.
DR OrthoDB; 1134186at2759; -.
DR Reactome; R-CEL-9013405; RHOD GTPase cycle.
DR Reactome; R-CEL-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III.
DR PRO; PR:Q9XTB5; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00002275; Expressed in embryo and 3 other tissues.
DR GO; GO:0005694; C:chromosome; IDA:UniProtKB.
DR GO; GO:0005639; C:integral component of nuclear inner membrane; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:WormBase.
DR GO; GO:0005521; F:lamin binding; IDA:WormBase.
DR GO; GO:0051276; P:chromosome organization; IDA:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IGI:WormBase.
DR GO; GO:0031023; P:microtubule organizing center organization; IMP:UniProtKB.
DR GO; GO:0000281; P:mitotic cytokinesis; IGI:WormBase.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0006998; P:nuclear envelope organization; IMP:UniProtKB.
DR GO; GO:0031468; P:nuclear membrane reassembly; IMP:UniProtKB.
DR GO; GO:1902531; P:regulation of intracellular signal transduction; IEA:InterPro.
DR GO; GO:0010165; P:response to X-ray; IMP:WormBase.
DR Gene3D; 1.10.10.1180; -; 1.
DR Gene3D; 1.10.720.40; -; 1.
DR InterPro; IPR011015; LEM/LEM-like_dom_sf.
DR InterPro; IPR003887; LEM_dom.
DR InterPro; IPR034997; Man1.
DR InterPro; IPR041885; MAN1_winged_helix_dom.
DR PANTHER; PTHR13428:SF12; PTHR13428:SF12; 1.
DR Pfam; PF03020; LEM; 1.
DR SMART; SM00540; LEM; 1.
DR SUPFAM; SSF63451; SSF63451; 1.
DR PROSITE; PS50954; LEM; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Chromosome; Membrane; Nucleus; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..500
FT /note="LEM protein 2"
FT /id="PRO_0000206144"
FT TOPO_DOM 1..325
FT /note="Nuclear"
FT /evidence="ECO:0000255"
FT TRANSMEM 326..346
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 347..378
FT /note="Perinuclear space"
FT /evidence="ECO:0000255"
FT TRANSMEM 379..399
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 400..500
FT /note="Nuclear"
FT /evidence="ECO:0000255"
FT DOMAIN 1..45
FT /note="LEM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00313"
FT REGION 39..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 54..76
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 85..101
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 104..121
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..157
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 166..202
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 500 AA; 55158 MW; E5B25805D4A422BE CRC64;
MVDVEKMSDA ELRAELNVRG ANVGPVTGTT RSLYEKKLKK LLSGGAKTPA RPTVAKPAPK
PTPKSAPAPK SPKSPPARRS IPRAAATAAN STINSTFNRS EIEEMSDSDD DMRDDDDDDE
EILSPKSKQS SFRSANSTAS SVGRGRPVSS TPNKRLSPVY KPSPVPKNTP RTTSSSSKTT
INTTTTRIPS TPRRITSVPG LITDFTPSFS TFGSDRPGAT PPRKSIYTSK VSKVLHDLGN
TTGEEDDDDE FEGQETSRII YKTEEPSRRG IVKNAWNKVL GYGFDASKNP GDSYDLRAGA
SRIRVQKNPR TGKVTVKQTN IFNEAIYFAL YVILILFVVL GIAYALTTTH RPKTADFSGY
WGVLKAAGRD SLNFFYNYAI LPVVSLGIFV VLGAGIYFGH RKYKEAKEQE EAKLYELIER
ITELIRESSI DGDPYVSQPH VRDVLFPPAK RRSAELARWE QAVKFIDTNE SRVATDVLVL
PSGNECAVWK WIGNQSQKRW
