LEMD2_MOUSE
ID LEMD2_MOUSE Reviewed; 511 AA.
AC Q6DVA0; Q8C4H8; Q8R0N2;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=LEM domain-containing protein 2;
DE AltName: Full=Nuclear envelope transmembrane protein 25;
DE Short=NET25;
GN Name=Lemd2; Synonyms=Lem2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, FUNCTION, TISSUE
RP SPECIFICITY, INTERACTION WITH LAMIN, AND DEVELOPMENTAL STAGE.
RC STRAIN=FVB/N;
RX PubMed=16339967; DOI=10.1242/jcs.02701;
RA Brachner A., Reipert S., Foisner R., Gotzmann J.;
RT "LEM2 is a novel MAN1-related inner nuclear membrane protein associated
RT with A-type lamins.";
RL J. Cell Sci. 118:5797-5810(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, and Eye;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 225-511.
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17062158; DOI=10.1186/1471-2121-7-38;
RA Chen I.-H., Huber M., Guan T., Bubeck A., Gerace L.;
RT "Nuclear envelope transmembrane proteins (NETs) that are up-regulated
RT during myogenesis.";
RL BMC Cell Biol. 7:38-38(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-507 AND SER-509, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP FUNCTION.
RX PubMed=19720741; DOI=10.1128/mcb.00270-09;
RA Huber M.D., Guan T., Gerace L.;
RT "Overlapping functions of nuclear envelope proteins NET25 (Lem2) and emerin
RT in regulation of extracellular signal-regulated kinase signaling in
RT myoblast differentiation.";
RL Mol. Cell. Biol. 29:5718-5728(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-507, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25790465; DOI=10.1371/journal.pone.0116196;
RA Tapia O., Fong L.G., Huber M.D., Young S.G., Gerace L.;
RT "Nuclear envelope protein Lem2 is required for mouse development and
RT regulates MAP and AKT kinases.";
RL PLoS ONE 10:E0116196-E0116196(2015).
CC -!- FUNCTION: Nuclear lamina-associated inner nuclear membrane protein that
CC is involved in nuclear structure organization and maintenance of
CC nuclear structure integrity and nuclear envelope reformation after
CC mitosis (PubMed:16339967). Plays a role as transmembrane adapter for
CC the endosomal sorting complexes required for transport (ESCRT), and is
CC thereby involved in ESCRT-mediated nuclear envelope reformation (By
CC similarity). Promotes ESCRT-mediated nuclear envelope closure by
CC recruiting CHMP7 and downstream ESCRT-III proteins IST1/CHMP8 and
CC CHMP2A to the reforming NE during anaphase (By similarity). During
CC nuclear reassembly, condenses into a liquid-like coating around
CC microtubule spindles and coassembles with CHMP7 to form a
CC macromolecular O-ring seal at the confluence between membranes,
CC chromatin, and the spindle to facilitate early nuclear sealing (By
CC similarity). Required for embryonic development and is involved in
CC regulation of several signaling pathways such as MAPK and AKT
CC (PubMed:25790465). Required for myoblast differentiation involving
CC regulation of ERK signaling (PubMed:17062158, PubMed:19720741).
CC {ECO:0000250|UniProtKB:Q8NC56, ECO:0000269|PubMed:16339967,
CC ECO:0000269|PubMed:17062158, ECO:0000269|PubMed:19720741,
CC ECO:0000269|PubMed:25790465}.
CC -!- SUBUNIT: Interacts (via N-terminus) with LMNA isoform C (via C-
CC terminus) (in vitro) (PubMed:16339967). Interacts (via LEM domain) with
CC BANF1 (By similarity). Interacts (via C-terminus) with CHMP7 (By
CC similarity). Interacts (via N-terminus) with tubulin; the interaction
CC causes microtubule bundling and stabilization (in vitro) (By
CC similarity). {ECO:0000250|UniProtKB:Q8NC56,
CC ECO:0000269|PubMed:16339967}.
CC -!- SUBCELLULAR LOCATION: Nucleus inner membrane
CC {ECO:0000269|PubMed:16339967, ECO:0000269|PubMed:17062158}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:16339967}. Nucleus envelope
CC {ECO:0000250|UniProtKB:Q8NC56}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:Q8NC56}. Note=Lamina-associated protein residing
CC in the inner nuclear membrane (INM) of the nuclear envelope (NE)
CC (PubMed:16339967). The localization to the INM is dependent on LMNA (By
CC similarity). Evenly distributed around the NE during interphase
CC (PubMed:16339967). During metaphase, found in a reticular network (By
CC similarity). Recruited to the reforming NE on chromatin disks in early
CC anaphase (By similarity). In late anaphase, concentrates at the NE core
CC proximal to spindle microtubules, and then broadening to a distributed
CC nuclear rim pattern (By similarity). {ECO:0000250|UniProtKB:Q8NC56,
CC ECO:0000269|PubMed:16339967}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, including liver, brain,
CC heart, testis, lung and spleen. {ECO:0000269|PubMed:16339967}.
CC -!- DEVELOPMENTAL STAGE: Expressed at detectable levels throughout later
CC stages of mouse development such as 12 dpc, 14 dpc, 16 dpc and 18 dpc.
CC {ECO:0000269|PubMed:16339967}.
CC -!- DOMAIN: The LEM domain is required for inner nuclear membrane (INM)
CC localization and contains a BANF1 conserved binding motif which allows
CC localization to chromatin (By similarity). In late anaphase, as the
CC reforming nuclear envelope (NE) surrounds the chromatin disk, both the
CC LEM domain and the disordered regions are necessary for localization to
CC the NE core (By similarity). {ECO:0000250|UniProtKB:Q8NC56}.
CC -!- DOMAIN: The disordered regions, also named low complexity domain,
CC confer the ability to phase separate (By similarity). In late anaphase,
CC as the reforming nuclear envelope (NE) surrounds the chromatin disks,
CC both the LEM domain and the disordered regions are necessary for
CC localization to the NE core (By similarity). During NE reformation, the
CC proline-arginine-rich sequence within the disordered region binds
CC microtubules, targeting LEM2 condensation to spindle microtubules
CC traversing the nascent NE (By similarity).
CC {ECO:0000250|UniProtKB:Q8NC56}.
CC -!- DOMAIN: The winged-helix (WH) region (residues 403-511) activates the
CC ESCRT-II/ESCRT-III hybrid protein, CHMP7, to form co-oligomeric rings
CC around spindle microtubules to facilitate early nuclear sealing.
CC {ECO:0000250|UniProtKB:Q8NC56}.
CC -!- PTM: Phosphorylated; strongly phosphorylated in mitosis compared to
CC G1/S. {ECO:0000250|UniProtKB:Q8NC56}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal by 11.5 dpc. At 10.5 dpc most
CC tissues are substantially reduced in size, specifically neural and
CC heart structures are developmentally less advanced and/or abnormal. At
CC 10.5 dpc hyperactive MAPK and AKT signaling has been observed.
CC {ECO:0000269|PubMed:25790465}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH26588.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC38419.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY640307; AAT71319.1; -; mRNA.
DR EMBL; AK082131; BAC38419.1; ALT_SEQ; mRNA.
DR EMBL; AK143224; BAE25316.1; -; mRNA.
DR EMBL; BC026588; AAH26588.1; ALT_INIT; mRNA.
DR CCDS; CCDS50043.1; -.
DR RefSeq; NP_666187.2; NM_146075.2.
DR AlphaFoldDB; Q6DVA0; -.
DR SMR; Q6DVA0; -.
DR BioGRID; 230294; 1.
DR IntAct; Q6DVA0; 1.
DR MINT; Q6DVA0; -.
DR STRING; 10090.ENSMUSP00000058221; -.
DR iPTMnet; Q6DVA0; -.
DR PhosphoSitePlus; Q6DVA0; -.
DR EPD; Q6DVA0; -.
DR jPOST; Q6DVA0; -.
DR MaxQB; Q6DVA0; -.
DR PaxDb; Q6DVA0; -.
DR PeptideAtlas; Q6DVA0; -.
DR PRIDE; Q6DVA0; -.
DR ProteomicsDB; 265059; -.
DR Antibodypedia; 1891; 142 antibodies from 24 providers.
DR DNASU; 224640; -.
DR Ensembl; ENSMUST00000055117; ENSMUSP00000058221; ENSMUSG00000044857.
DR GeneID; 224640; -.
DR KEGG; mmu:224640; -.
DR UCSC; uc008bfm.2; mouse.
DR CTD; 221496; -.
DR MGI; MGI:2385045; Lemd2.
DR VEuPathDB; HostDB:ENSMUSG00000044857; -.
DR eggNOG; ENOG502QRKK; Eukaryota.
DR GeneTree; ENSGT00940000160955; -.
DR HOGENOM; CLU_045257_0_0_1; -.
DR InParanoid; Q6DVA0; -.
DR OMA; EDNSTSW; -.
DR OrthoDB; 873705at2759; -.
DR PhylomeDB; Q6DVA0; -.
DR TreeFam; TF315385; -.
DR Reactome; R-MMU-4419969; Depolymerisation of the Nuclear Lamina.
DR Reactome; R-MMU-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III.
DR BioGRID-ORCS; 224640; 13 hits in 74 CRISPR screens.
DR ChiTaRS; Lemd2; mouse.
DR PRO; PR:Q6DVA0; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q6DVA0; protein.
DR Bgee; ENSMUSG00000044857; Expressed in granulocyte and 224 other tissues.
DR ExpressionAtlas; Q6DVA0; baseline and differential.
DR Genevisible; Q6DVA0; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005639; C:integral component of nuclear inner membrane; ISO:MGI.
DR GO; GO:0005635; C:nuclear envelope; ISO:MGI.
DR GO; GO:0031965; C:nuclear membrane; IDA:MGI.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0031490; F:chromatin DNA binding; IBA:GO_Central.
DR GO; GO:0060914; P:heart formation; IMP:UniProtKB.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:MGI.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0022008; P:neurogenesis; IMP:UniProtKB.
DR GO; GO:0006998; P:nuclear envelope organization; ISO:MGI.
DR GO; GO:0071168; P:protein localization to chromatin; ISO:MGI.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IMP:MGI.
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; IPR034994; LEMD2.
DR InterPro; IPR041885; MAN1_winged_helix_dom.
DR InterPro; IPR018996; MSC.
DR PANTHER; PTHR13428:SF8; PTHR13428:SF8; 1.
DR Pfam; PF03020; LEM; 1.
DR Pfam; PF09402; MSC; 1.
DR SMART; SM00540; LEM; 1.
DR SUPFAM; SSF63451; SSF63451; 1.
DR PROSITE; PS50954; LEM; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Cytoskeleton; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8NC56"
FT CHAIN 2..511
FT /note="LEM domain-containing protein 2"
FT /id="PRO_0000285250"
FT TRANSMEM 221..241
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 385..405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 2..42
FT /note="LEM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00313"
FT REGION 18..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 80..141
FT /note="Required for nuclear retention and interaction with
FT LMNA isoform C"
FT /evidence="ECO:0000250|UniProtKB:Q8NC56"
FT REGION 80..112
FT /note="Interaction with lamin A/C complexes"
FT /evidence="ECO:0000250"
FT REGION 128..206
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 403..511
FT /note="Winged-Helix (WH)"
FT /evidence="ECO:0000250|UniProtKB:Q8NC56"
FT COMPBIAS 30..80
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 145..167
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q8NC56"
FT MOD_RES 505
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NC56"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 509
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT CONFLICT 357
FT /note="T -> A (in Ref. 2; BAC38419)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 511 AA; 57507 MW; 190BEA7724BF7EDB CRC64;
MAGLSDLELR RELQALGFQP GPITDTTRNV YRNKLRRLRG EARLRDDERL REDAGPREDA
GPRGPERQRE EARLREEAPL RARPAASVLR SEPWPLSPSP PAPSAASDAS GPYGNFGASA
SPWAASRGLS YPPHAGPGPL RRRASVRGSS EDDEDTRTPD RHAPGRGRHW WAPPSASARP
HSALLGADAR PGLKGSRTGS AGAGRTRPEV GRWLERCLSR LLLWASLGLL LGFLAILWVK
MGKPSAPQEA EDNMKLLPVD CERKTDEFCQ AKQKAALLEL LHELYNFLAI QAGNFECGNP
EKLKSKCIPV LEAQEYIANV TSSPSSRFKA ALTWILSSNK DVGIWLKGED PSELATTVDK
VVCLESARPR MGIGCRLSRA LLTAVTHVLI FFWCLAFLWG LLILLKYRWR KLEEEEQAMY
EMVKKIIDVV QDHYVDWEQD MERYPYVGIL HVRDSLIPPQ SRRRMKRVWD RAVEFLASNE
SRIQTESHRV AGEDMLVWRW TKPSSFSDSE R
