LEMD2_HUMAN
ID LEMD2_HUMAN Reviewed; 503 AA.
AC Q8NC56; B4DVH5; E7EVT2; Q5T972; Q5T974;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=LEM domain-containing protein 2;
DE Short=hLEM2;
GN Name=LEMD2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH LMNA, TISSUE SPECIFICITY,
RP AND DOMAIN.
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17097643; DOI=10.1016/j.febslet.2006.10.060;
RA Ulbert S., Antonin W., Platani M., Mattaj I.W.;
RT "The inner nuclear membrane protein Lem2 is critical for normal nuclear
RT envelope morphology.";
RL FEBS Lett. 580:6435-6441(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-499, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-499, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-497 AND SER-499, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166; SER-175; SER-499 AND
RP SER-501, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CHMP7.
RX PubMed=28242692; DOI=10.1073/pnas.1613916114;
RA Gu M., LaJoie D., Chen O.S., von Appen A., Ladinsky M.S., Redd M.J.,
RA Nikolova L., Bjorkman P.J., Sundquist W.I., Ullman K.S., Frost A.;
RT "LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure in fission
RT yeast and human cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E2166-E2175(2017).
RN [17]
RP FUNCTION, INTERACTION WITH BANF1 AND TUBULIN, SUBCELLULAR LOCATION, DOMAIN,
RP MUTAGENESIS OF 21-GLU--THR-24; 43-ARG--VAL-202; 145-ALA--LEU-213 AND
RP 415-VAL--GLU-485, AND PHOSPHORYLATION.
RX PubMed=32494070; DOI=10.1038/s41586-020-2232-x;
RA von Appen A., LaJoie D., Johnson I.E., Trnka M.J., Pick S.M.,
RA Burlingame A.L., Ullman K.S., Frost A.;
RT "LEM2 phase separation promotes ESCRT-mediated nuclear envelope
RT reformation.";
RL Nature 582:115-118(2020).
RN [18]
RP INVOLVEMENT IN CTRCT46, AND VARIANT CTRCT46 ARG-13.
RX PubMed=26788539; DOI=10.1002/mgg3.181;
RA Boone P.M., Yuan B., Gu S., Ma Z., Gambin T., Gonzaga-Jauregui C., Jain M.,
RA Murdock T.J., White J.J., Jhangiani S.N., Walker K., Wang Q., Muzny D.M.,
RA Gibbs R.A., Hejtmancik J.F., Lupski J.R., Posey J.E., Lewis R.A.;
RT "Hutterite-type cataract maps to chromosome 6p21.32-p21.31, cosegregates
RT with a homozygous mutation in LEMD2, and is associated with sudden cardiac
RT death.";
RL Mol. Genet. Genomic Med. 4:77-94(2016).
RN [19]
RP INVOLVEMENT IN MARUPS, VARIANT MARUPS PHE-479, AND SUBCELLULAR LOCATION.
RX PubMed=30905398; DOI=10.1016/j.ajhg.2019.02.021;
RA Marbach F., Rustad C.F., Riess A., Dukic D., Hsieh T.C., Jobani I.,
RA Prescott T., Bevot A., Erger F., Houge G., Redfors M., Altmueller J.,
RA Stokowy T., Gilissen C., Kubisch C., Scarano E., Mazzanti L.,
RA Fiskerstrand T., Krawitz P.M., Lessel D., Netzer C.;
RT "The Discovery of a LEMD2-Associated Nuclear Envelopathy with Early
RT Progeroid Appearance Suggests Advanced Applications for AI-Driven Facial
RT Phenotyping.";
RL Am. J. Hum. Genet. 104:749-757(2019).
CC -!- FUNCTION: Nuclear lamina-associated inner nuclear membrane protein that
CC is involved in nuclear structure organization, maintenance of nuclear
CC envelope integrity and nuclear envelope reformation after mitosis
CC (PubMed:16339967, PubMed:17097643, PubMed:28242692, PubMed:32494070).
CC Plays a role as transmembrane adapter for the endosomal sorting
CC complexes required for transport (ESCRT), and is thereby involved in
CC ESCRT-mediated nuclear envelope reformation (PubMed:28242692,
CC PubMed:32494070). 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 (PubMed:28242692). 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
CC (PubMed:32494070). Required for embryonic development and involved in
CC regulation of several signaling pathways such as MAPK and AKT (By
CC similarity). Required for myoblast differentiation involving regulation
CC of ERK signaling (By similarity). {ECO:0000250|UniProtKB:Q6DVA0,
CC ECO:0000269|PubMed:16339967, ECO:0000269|PubMed:17097643,
CC ECO:0000269|PubMed:28242692, ECO:0000269|PubMed:32494070}.
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 (PubMed:32494070). Interacts (via C-terminus) with CHMP7
CC (PubMed:28242692). Interacts (via N-terminus) with tubulin; the
CC interaction causes microtubule bundling and stabilization (in vitro)
CC (PubMed:32494070). {ECO:0000269|PubMed:16339967,
CC ECO:0000269|PubMed:28242692, ECO:0000269|PubMed:32494070}.
CC -!- SUBCELLULAR LOCATION: Nucleus inner membrane
CC {ECO:0000269|PubMed:16339967, ECO:0000269|PubMed:17097643,
CC ECO:0000269|PubMed:28242692, ECO:0000269|PubMed:30905398,
CC ECO:0000269|PubMed:32494070}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16339967}. Nucleus envelope
CC {ECO:0000269|PubMed:28242692}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:32494070}. 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
CC (PubMed:16339967). Evenly distributed around the NE during interphase
CC (PubMed:16339967). During metaphase, found in a reticular network
CC (PubMed:28242692). Recruited to the reforming NE on chromatin disks in
CC early anaphase (PubMed:28242692). In late anaphase, concentrates at the
CC NE core proximal to spindle microtubules, and then broadening to a
CC distributed nuclear rim pattern (PubMed:28242692, PubMed:32494070).
CC {ECO:0000269|PubMed:16339967, ECO:0000269|PubMed:28242692,
CC ECO:0000269|PubMed:32494070}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NC56-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NC56-2; Sequence=VSP_044847;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, including bone marrow,
CC brain, kidney, colon, skeletal muscle, thymus, testis and uterus.
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 (PubMed:16339967, PubMed:32494070). In late
CC anaphase, as the reforming nuclear envelope (NE) surrounds the
CC chromatin disk, both the LEM domain and the disordered regions are
CC necessary for localization to the NE core (PubMed:32494070).
CC {ECO:0000269|PubMed:16339967, ECO:0000269|PubMed:32494070}.
CC -!- DOMAIN: The disordered regions, also named low complexity domain,
CC confer the ability to phase separate (PubMed:32494070). In late
CC anaphase, as the reforming nuclear envelope (NE) surrounds the
CC chromatin disk, both the LEM domain and the disordered regions are
CC necessary for localization to the NE core (PubMed:32494070). During NE
CC reformation, the proline-arginine-rich sequence within the disordered
CC region binds microtubules, targeting LEM2 condensation to spindle
CC microtubules traversing the nascent NE (PubMed:32494070).
CC {ECO:0000269|PubMed:32494070}.
CC -!- DOMAIN: The winged-helix (WH) region (residues 395-503) 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:0000269|PubMed:32494070}.
CC -!- PTM: Phosphorylated; strongly phosphorylated in mitosis compared to
CC G1/S. {ECO:0000269|PubMed:32494070}.
CC -!- DISEASE: Cataract 46, juvenile-onset, with or without arrhythmic
CC cardiomyopathy (CTRCT46) [MIM:212500]: A form of cataract, an
CC opacification of the crystalline lens of the eye that frequently
CC results in visual impairment or blindness. Opacities vary in
CC morphology, are often confined to a portion of the lens, and may be
CC static or progressive. In general, the more posteriorly located and
CC dense an opacity, the greater the impact on visual function. CTRCT46
CC can be associated with variable onset of a severe form of arrhythmic
CC cardiomyopathy resulting in sudden cardiac death.
CC {ECO:0000269|PubMed:26788539}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Marbach-Rustad progeroid syndrome (MARUPS) [MIM:619322]: An
CC autosomal dominant syndrome characterized by progeria-like appearance
CC with little subcutaneous fat and triangular facies, growth retardation,
CC short stature, hypoplastic mandible crowded with unerupted
CC supernumerary teeth, and cerebellar intention tremor.
CC {ECO:0000269|PubMed:30905398}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AK301083; BAG62687.1; -; mRNA.
DR EMBL; AK074959; BAC11316.1; -; mRNA.
DR EMBL; AL158049; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC051803; AAH51803.1; -; mRNA.
DR CCDS; CCDS47411.1; -. [Q8NC56-2]
DR CCDS; CCDS4785.1; -. [Q8NC56-1]
DR RefSeq; NP_001137416.1; NM_001143944.1. [Q8NC56-2]
DR RefSeq; NP_001335638.1; NM_001348709.1. [Q8NC56-2]
DR RefSeq; NP_851853.1; NM_181336.3. [Q8NC56-1]
DR AlphaFoldDB; Q8NC56; -.
DR SMR; Q8NC56; -.
DR BioGRID; 128735; 98.
DR IntAct; Q8NC56; 39.
DR STRING; 9606.ENSP00000293760; -.
DR GlyGen; Q8NC56; 1 site.
DR iPTMnet; Q8NC56; -.
DR PhosphoSitePlus; Q8NC56; -.
DR SwissPalm; Q8NC56; -.
DR BioMuta; LEMD2; -.
DR DMDM; 74751184; -.
DR EPD; Q8NC56; -.
DR jPOST; Q8NC56; -.
DR MassIVE; Q8NC56; -.
DR MaxQB; Q8NC56; -.
DR PaxDb; Q8NC56; -.
DR PeptideAtlas; Q8NC56; -.
DR PRIDE; Q8NC56; -.
DR ProteomicsDB; 18702; -.
DR ProteomicsDB; 72855; -. [Q8NC56-1]
DR Antibodypedia; 1891; 142 antibodies from 24 providers.
DR DNASU; 221496; -.
DR Ensembl; ENST00000293760.10; ENSP00000293760.5; ENSG00000161904.12. [Q8NC56-1]
DR Ensembl; ENST00000508327.5; ENSP00000421704.1; ENSG00000161904.12. [Q8NC56-2]
DR Ensembl; ENST00000614475.4; ENSP00000478539.1; ENSG00000161904.12. [Q8NC56-1]
DR GeneID; 221496; -.
DR KEGG; hsa:221496; -.
DR MANE-Select; ENST00000293760.10; ENSP00000293760.5; NM_181336.4; NP_851853.1.
DR UCSC; uc011drl.3; human. [Q8NC56-1]
DR CTD; 221496; -.
DR DisGeNET; 221496; -.
DR GeneCards; LEMD2; -.
DR HGNC; HGNC:21244; LEMD2.
DR HPA; ENSG00000161904; Low tissue specificity.
DR MalaCards; LEMD2; -.
DR MIM; 212500; phenotype.
DR MIM; 616312; gene.
DR MIM; 619322; phenotype.
DR neXtProt; NX_Q8NC56; -.
DR OpenTargets; ENSG00000161904; -.
DR Orphanet; 441447; Early-onset posterior subcapsular cataract.
DR Orphanet; 98994; Total early-onset cataract.
DR PharmGKB; PA134952135; -.
DR VEuPathDB; HostDB:ENSG00000161904; -.
DR eggNOG; ENOG502QRKK; Eukaryota.
DR GeneTree; ENSGT00940000160955; -.
DR HOGENOM; CLU_045257_0_0_1; -.
DR InParanoid; Q8NC56; -.
DR OMA; EDNSTSW; -.
DR PhylomeDB; Q8NC56; -.
DR TreeFam; TF315385; -.
DR PathwayCommons; Q8NC56; -.
DR Reactome; R-HSA-2980766; Nuclear Envelope Breakdown.
DR Reactome; R-HSA-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR Reactome; R-HSA-4419969; Depolymerisation of the Nuclear Lamina.
DR Reactome; R-HSA-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III.
DR SignaLink; Q8NC56; -.
DR BioGRID-ORCS; 221496; 146 hits in 1080 CRISPR screens.
DR ChiTaRS; LEMD2; human.
DR GenomeRNAi; 221496; -.
DR Pharos; Q8NC56; Tbio.
DR PRO; PR:Q8NC56; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8NC56; protein.
DR Bgee; ENSG00000161904; Expressed in right hemisphere of cerebellum and 112 other tissues.
DR ExpressionAtlas; Q8NC56; baseline and differential.
DR Genevisible; Q8NC56; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; TAS:ARUK-UCL.
DR GO; GO:0005639; C:integral component of nuclear inner membrane; IDA:MGI.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; TAS:Reactome.
DR GO; GO:0005637; C:nuclear inner membrane; TAS:ARUK-UCL.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
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; IEA:Ensembl.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0022008; P:neurogenesis; IEA:Ensembl.
DR GO; GO:0006998; P:nuclear envelope organization; IMP:UniProtKB.
DR GO; GO:0071168; P:protein localization to chromatin; IMP:ARUK-UCL.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IGI: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; Alternative splicing; Cataract; Cytoplasm; Cytoskeleton;
KW Disease variant; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..503
FT /note="LEM domain-containing protein 2"
FT /id="PRO_0000285249"
FT TRANSMEM 213..233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 377..397
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 2..42
FT /note="LEM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00313"
FT REGION 42..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 74..130
FT /note="Required for nuclear retention and interaction with
FT LMNA isoform C"
FT /evidence="ECO:0000269|PubMed:16339967"
FT REGION 127..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 172..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 395..503
FT /note="Winged-Helix (WH)"
FT /evidence="ECO:0000303|PubMed:32494070"
FT COMPBIAS 42..74
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 134..149
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 175
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 497
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..302
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044847"
FT VARIANT 13
FT /note="L -> R (in CTRCT46; dbSNP:rs878852983)"
FT /evidence="ECO:0000269|PubMed:26788539"
FT /id="VAR_076992"
FT VARIANT 479
FT /note="S -> F (in MARUPS)"
FT /evidence="ECO:0000269|PubMed:30905398"
FT /id="VAR_085694"
FT MUTAGEN 21..24
FT /note="GPIT->AAAA: Disrupts LEMD2 accumulation within the
FT nuclear envelope (NE) and subsequent NE core enrichment in
FT anaphase cells."
FT /evidence="ECO:0000269|PubMed:32494070"
FT MUTAGEN 43..202
FT /note="Missing: Compromises nuclear envelope enrichment."
FT /evidence="ECO:0000269|PubMed:32494070"
FT MUTAGEN 145..213
FT /note="Missing: Failure to enrich at mictrotubule-
FT containing nuclear envelope core during anaphase."
FT /evidence="ECO:0000269|PubMed:32494070"
FT MUTAGEN 415..485
FT /note="Missing: Does not affect nuclear envelope
FT enrichment."
FT /evidence="ECO:0000269|PubMed:32494070"
FT CONFLICT 316
FT /note="S -> F (in Ref. 1; BAG62687)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 503 AA; 56975 MW; 5C24BF18B0423952 CRC64;
MAGLSDLELR RELQALGFQP GPITDTTRDV YRNKLRRLRG EARLRDEERL REEARPRGEE
RLREEARLRE DAPLRARPAA ASPRAEPWLS QPASGSAYAT PGAYGDIRPS AASWVGSRGL
AYPARPAQLR RRASVRGSSE EDEDARTPDR ATQGPGLAAR RWWAASPAPA RLPSSLLGPD
PRPGLRATRA GPAGAARARP EVGRRLERWL SRLLLWASLG LLLVFLGILW VKMGKPSAPQ
EAEDNMKLLP VDCERKTDEF CQAKQKAALL ELLHELYNFL AIQAGNFECG NPENLKSKCI
PVMEAQEYIA NVTSSSSAKF EAALTWILSS NKDVGIWLKG EDQSELVTTV DKVVCLESAH
PRMGVGCRLS RALLTAVTNV LIFFWCLAFL WGLLILLKYR WRKLEEEEQA MYEMVKKIID
VVQDHYVDWE QDMERYPYVG ILHVRDSLIP PQSRRRMKRV WDRAVEFLAS NESRIQTESH
RVAGEDMLVW RWTKPSSFSD SER
