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 09-APR-2025, entry version 181. 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 (NE) integrity and NE 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 NE reformation (PubMed:28242692, PubMed:32494070). CC Promotes ESCRT-mediated NE closure by recruiting CHMP7 and downstream CC ESCRT-III proteins IST1/CHMP8 and CHMP2A to the reforming NE during CC anaphase (PubMed:28242692). During nuclear reassembly, condenses into a CC liquid-like coating around microtubule spindles and coassembles with CC CHMP7 to form a macromolecular O-ring seal at the confluence between CC membranes, chromatin, and the spindle to facilitate early nuclear CC sealing (PubMed:32494070). Plays a role in the organization of CC heterochromatin associated with the NE and in the maintenance of NE CC organization under mechanical stress (By similarity). Required for CC embryonic development and involved in regulation of several signaling CC pathways such as MAPK and AKT (By similarity). Required for myoblast CC differentiation involving regulation of ERK signaling (By similarity). CC Essential for cardiac homeostasis and proper heart function (By CC 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 -!- INTERACTION: CC Q8NC56; Q96HU1: SGSM3; NbExp=2; IntAct=EBI-6149955, EBI-7362971; 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. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_001348709.2. [Q8NC56-2] DR RefSeq; NP_851853.1; NM_181336.4. [Q8NC56-1] DR AlphaFoldDB; Q8NC56; -. DR SMR; Q8NC56; -. DR BioGRID; 128735; 115. DR IntAct; Q8NC56; 68. DR MINT; Q8NC56; -. DR STRING; 9606.ENSP00000293760; -. DR GlyGen; Q8NC56; 3 sites, 9 N-linked glycans (2 sites), 1 O-linked glycan (1 site). DR iPTMnet; Q8NC56; -. DR PhosphoSitePlus; Q8NC56; -. DR SwissPalm; Q8NC56; -. DR BioMuta; LEMD2; -. DR DMDM; 74751184; -. DR jPOST; Q8NC56; -. DR MassIVE; Q8NC56; -. DR PaxDb; 9606-ENSP00000293760; -. DR PeptideAtlas; Q8NC56; -. DR ProteomicsDB; 18702; -. DR ProteomicsDB; 72855; -. [Q8NC56-1] DR Pumba; Q8NC56; -. DR Antibodypedia; 1891; 152 antibodies from 25 providers. DR DNASU; 221496; -. DR Ensembl; ENST00000293760.10; ENSP00000293760.5; ENSG00000161904.13. [Q8NC56-1] DR Ensembl; ENST00000508327.5; ENSP00000421704.1; ENSG00000161904.13. [Q8NC56-2] 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 AGR; HGNC:21244; -. 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 Orphanet; 659873; Wormian bones-micrognathia-abnormal dentition-progeroid syndrome. 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; STSWFCQ; -. DR OrthoDB; 118234at2759; -. 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; Depolymerization 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; 162 hits in 1162 CRISPR screens. DR CD-CODE; 38BEFE36; Synthetic Condensate 000277. 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 114 other cell types or tissues. DR ExpressionAtlas; Q8NC56; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:ARUK-UCL. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW. 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; IDA:MGI. DR GO; GO:0031965; C:nuclear membrane; IDA:HPA. DR GO; GO:0034399; C:nuclear periphery; IBA:GO_Central. DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell. DR GO; GO:0060914; P:heart formation; IEA:Ensembl. DR GO; GO:0043409; P:negative regulation of MAPK cascade; IEA:Ensembl. DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl. DR GO; GO:0022008; P:neurogenesis; IEA:Ensembl. DR GO; GO:0006998; P:nuclear envelope organization; IMP:UniProtKB. DR GO; GO:0071763; P:nuclear membrane organization; IBA:GO_Central. DR GO; GO:0071168; P:protein localization to chromatin; IMP:ARUK-UCL. DR GO; GO:0035914; P:skeletal muscle cell differentiation; IGI:MGI. DR FunFam; 1.10.720.40:FF:000001; LEM domain containing 2, isoform CRA_a; 1. DR FunFam; 1.10.10.1180:FF:000002; LEM domain-containing protein 2; 1. DR Gene3D; 1.10.720.40; -; 1. DR Gene3D; 1.10.10.1180; MAN1, winged-helix domain; 1. DR InterPro; IPR052277; INM_ESCRT-Associated. DR InterPro; IPR011015; LEM/LEM-like_dom_sf. DR InterPro; IPR003887; LEM_dom. DR InterPro; IPR018996; Man1/Src1-like_C. DR InterPro; IPR041885; MAN1_winged_helix_dom. DR PANTHER; PTHR13428; INNER NUCLEAR MEMBRANE PROTEIN MAN1 LEM DOMAIN CONTAINING PROTEIN; 1. DR PANTHER; PTHR13428:SF8; LEM DOMAIN-CONTAINING PROTEIN 2; 1. DR Pfam; PF03020; LEM; 1. DR Pfam; PF09402; MSC; 1. DR SMART; SM00540; LEM; 1. DR SUPFAM; SSF63451; LEM domain; 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; KW Proteomics identification; Reference proteome; Transmembrane; KW 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 75..87 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 184..197 FT /note="Low complexity" 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; dbSNP:rs1767330976)" 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 microtubule-containing FT 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 //