ID SYNE1_HUMAN Reviewed; 8797 AA. AC Q8NF91; B3W695; E7EQI5; H0Y4C0; O94890; Q3ZCV0; Q5JV19; Q5JV22; Q8N9P7; AC Q8TCP1; Q8WWW6; Q8WWW7; Q8WXF6; Q96N17; Q9C0A7; Q9H525; Q9H526; Q9NS36; AC Q9NU50; Q9UJ06; Q9UJ07; Q9ULF8; DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot. DT 28-NOV-2012, sequence version 4. DT 27-MAR-2024, entry version 208. DE RecName: Full=Nesprin-1 {ECO:0000305}; DE AltName: Full=Enaptin; DE AltName: Full=KASH domain-containing protein 1; DE Short=KASH1; DE AltName: Full=Myocyte nuclear envelope protein 1; DE Short=Myne-1; DE AltName: Full=Nuclear envelope spectrin repeat protein 1; DE AltName: Full=Synaptic nuclear envelope protein 1; DE Short=Syne-1; GN Name=SYNE1 {ECO:0000312|HGNC:HGNC:17089}; GN Synonyms=C6orf98, KIAA0796, KIAA1262, KIAA1756, MYNE1; 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 [MRNA] (ISOFORMS 2 AND 3), FUNCTION, SUBCELLULAR RP LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF 8758-LEU--CYS-8763, AND RP VARIANTS VAL-7302 AND ALA-8323. RC TISSUE=Heart, Placenta, Skeletal muscle, Spleen, and Testis; RX PubMed=11792814; DOI=10.1242/jcs.114.24.4485; RA Zhang Q., Skepper J.N., Yang F., Davies J.D., Hegyi L., Roberts R.G., RA Weissberg P.L., Ellis J.A., Shanahan C.M.; RT "Nesprins: a novel family of spectrin-repeat-containing proteins that RT localize to the nuclear membrane in multiple tissues."; RL J. Cell Sci. 114:4485-4498(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND VARIANTS RP THR-4596; MET-5015; VAL-7302 AND ALA-8323. RC TISSUE=Heart, Spleen, and Testis; RX PubMed=12408964; DOI=10.1016/s0888-7543(02)96859-x; RA Zhang Q., Ragnauth C., Greener M.J., Shanahan C.M., Roberts R.G.; RT "The nesprins are giant actin-binding proteins, orthologous to Drosophila RT melanogaster muscle protein MSP-300."; RL Genomics 80:473-481(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 11), SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND VARIANT ALA-8323. RX PubMed=11801724; DOI=10.1242/jcs.115.1.61; RA Mislow J.M.K., Kim M.S., Davis D.B., McNally E.M.; RT "Myne-1, a spectrin repeat transmembrane protein of the myocyte inner RT nuclear membrane, interacts with lamin A/C."; RL J. Cell Sci. 115:61-70(2002). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 10). RC TISSUE=Ovary; RX PubMed=18709643; DOI=10.1002/ijc.23763; RA Marme A., Zimmermann H.P., Moldenhauer G., Schorpp-Kistner M., Muller C., RA Keberlein O., Giersch A., Kretschmer J., Seib B., Spiess E., Hunziker A., RA Merchan F., Moller P., Hahn U., Kurek R., Marme F., Bastert G., RA Wallwiener D., Ponstingl H.; RT "Loss of Drop1 expression already at early tumor stages in a wide range of RT human carcinomas."; RL Int. J. Cancer 123:2048-2056(2008). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND TISSUE SPECIFICITY. RC TISSUE=Cerebellum; RX PubMed=15093733; DOI=10.1016/j.yexcr.2004.01.014; RA Padmakumar V.C., Abraham S., Braune S., Noegel A.A., Tunggal B., RA Karakesisoglou I., Korenbaum E.; RT "Enaptin, a giant actin-binding protein, is an element of the nuclear RT membrane and the actin cytoskeleton."; RL Exp. Cell Res. 295:330-339(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 8 AND 9), AND VARIANTS VAL-7302 AND RP ALA-8323. RA Zhang Q., Shanahan C.M.; RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GSRP-56). RC TISSUE=Testis; 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 [8] 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 [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-856 (ISOFORM 1). RC TISSUE=Kidney; RX PubMed=12808039; DOI=10.1091/mbc.e02-07-0446; RA Gough L.L., Fan J., Chu S., Winnick S., Beck K.A.; RT "Golgi localization of Syne-1."; RL Mol. Biol. Cell 14:2410-2424(2003). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 28-778 AND 2901-3476 (ISOFORM 1). RC TISSUE=Adrenal gland, and Teratocarcinoma; 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 [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 443-8797 (ISOFORM 5). RC TISSUE=Brain; RX PubMed=11214970; DOI=10.1093/dnares/7.6.347; RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIX. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:347-355(2000). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 743-8797 (ISOFORM 6). RC TISSUE=Brain; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4219-8797 (ISOFORM 7), AND RP VARIANTS THR-4596 AND MET-5015. RC TISSUE=Brain; RX PubMed=10574462; DOI=10.1093/dnares/6.5.337; RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XV. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:337-345(1999). RN [14] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6922-8797 (ISOFORM 1), AND RP VARIANTS VAL-7302 AND ALA-8323. RC TISSUE=Brain; RX PubMed=9872452; DOI=10.1093/dnares/5.5.277; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XI. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 5:277-286(1998). RN [15] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] OF 8406-8797 (ISOFORM 1). RA Ma F.-R., Zhu L.-P.; RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases. RN [17] RP SUBUNIT, AND INTERACTION WITH EMD AND LMNA. RX PubMed=12163176; DOI=10.1016/s0014-5793(02)03105-8; RA Mislow J.M., Holaska J.M., Kim M.S., Lee K.K., Segura-Totten M., RA Wilson K.L., McNally E.M.; RT "Nesprin-1alpha self-associates and binds directly to emerin and lamin A in RT vitro."; RL FEBS Lett. 525:135-140(2002). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8223; THR-8274; SER-8277 AND RP SER-8280, AND 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 [19] RP ALTERNATIVE SPLICING (ISOFORM GSRP-56), SUBCELLULAR LOCATION (ISOFORM RP GSRP-56), INTERACTION WITH TRPV2 (ISOFORM GSRP-56), AND TISSUE SPECIFICITY RP (ISOFORM GSRP-56). RX PubMed=16875688; DOI=10.1016/j.yexcr.2006.06.026; RA Kobayashi Y., Katanosaka Y., Iwata Y., Matsuoka M., Shigekawa M., RA Wakabayashi S.; RT "Identification and characterization of GSRP-56, a novel Golgi-localized RT spectrin repeat-containing protein."; RL Exp. Cell Res. 312:3152-3164(2006). RN [20] RP INVOLVEMENT IN SCAR8. RX PubMed=17159980; DOI=10.1038/ng1927; RA Gros-Louis F., Dupre N., Dion P., Fox M.A., Laurent S., Verreault S., RA Sanes J.R., Bouchard J.-P., Rouleau G.A.; RT "Mutations in SYNE1 lead to a newly discovered form of autosomal recessive RT cerebellar ataxia."; RL Nat. Genet. 39:80-85(2007). RN [21] RP FUNCTION, DOMAIN, AND INTERACTION WITH SUN1 AND SUN2. RX PubMed=18396275; DOI=10.1016/j.yexcr.2008.02.022; RA Stewart-Hutchinson P.J., Hale C.M., Wirtz D., Hodzic D.; RT "Structural requirements for the assembly of LINC complexes and their RT function in cellular mechanical stiffness."; RL Exp. Cell Res. 314:1892-1905(2008). RN [22] RP INVOLVEMENT IN AMC3. RX PubMed=19542096; DOI=10.1093/hmg/ddp290; RA Attali R., Warwar N., Israel A., Gurt I., McNally E., Puckelwartz M., RA Glick B., Nevo Y., Ben-Neriah Z., Melki J.; RT "Mutation of SYNE-1, encoding an essential component of the nuclear lamina, RT is responsible for autosomal recessive arthrogryposis."; RL Hum. Mol. Genet. 18:3462-3469(2009). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [24] RP TISSUE SPECIFICITY, AND INTERACTION WITH SYNE3. RX PubMed=22518138; DOI=10.1155/2012/736524; RA Taranum S., Sur I., Muller R., Lu W., Rashmi R.N., Munck M., Neumann S., RA Karakesisoglou I., Noegel A.A.; RT "Cytoskeletal interactions at the nuclear envelope mediated by nesprins."; RL Int. J. Cell Biol. 2012:736524-736524(2012). RN [25] RP SPECTRIN REPEATS. RX PubMed=23671687; DOI=10.1371/journal.pone.0063633; RA Autore F., Pfuhl M., Quan X., Williams A., Roberts R.G., Shanahan C.M., RA Fraternali F.; RT "Large-scale modelling of the divergent spectrin repeats in nesprins: giant RT modular proteins."; RL PLoS ONE 8:E63633-E63633(2013). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8223 AND THR-8360, AND 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 [27] RP INTERACTION WITH TMEM258. RX PubMed=28716842; DOI=10.1083/jcb.201606043; RA Ding Z.Y., Wang Y.H., Huang Y.C., Lee M.C., Tseng M.J., Chi Y.H., RA Huang M.L.; RT "Outer nuclear membrane protein Kuduk modulates the LINC complex and RT nuclear envelope architecture."; RL J. Cell Biol. 216:2827-2841(2017). RN [28] RP X-RAY CRYSTALLOGRAPHY (2.32 ANGSTROMS) OF 8769-8797 IN COMPLEX WITH SUN2, RP AND SUBUNIT. RX PubMed=22632968; DOI=10.1016/j.cell.2012.03.046; RA Sosa B.A., Rothballer A., Kutay U., Schwartz T.U.; RT "LINC complexes form by binding of three KASH peptides to domain interfaces RT of trimeric SUN proteins."; RL Cell 149:1035-1047(2012). RN [29] RP VARIANTS COLORECTAL CANCER [LARGE SCALE ANALYSIS] MET-3671; ASP-4210; RP HIS-4223; ARG-5507 AND HIS-8468. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [30] RP VARIANTS EDMD4 HIS-8095; LEU-8387 AND LYS-8461. RX PubMed=17761684; DOI=10.1093/hmg/ddm238; RA Zhang Q., Bethmann C., Worth N.F., Davies J.D., Wasner C., Feuer A., RA Ragnauth C.D., Yi Q., Mellad J.A., Warren D.T., Wheeler M.A., Ellis J.A., RA Skepper J.N., Vorgerd M., Schlotter-Weigel B., Weissberg P.L., RA Roberts R.G., Wehnert M., Shanahan C.M.; RT "Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss RT muscular dystrophy and are critical for nuclear envelope integrity."; RL Hum. Mol. Genet. 16:2816-2833(2007). RN [31] RP VARIANTS ARG-655; THR-3088 AND SER-3892. RX PubMed=24123876; DOI=10.1136/jmedgenet-2013-101644; RA Schuurs-Hoeijmakers J.H., Vulto-van Silfhout A.T., Vissers L.E., RA van de Vondervoort I.I., van Bon B.W., de Ligt J., Gilissen C., RA Hehir-Kwa J.Y., Neveling K., del Rosario M., Hira G., Reitano S., RA Vitello A., Failla P., Greco D., Fichera M., Galesi O., Kleefstra T., RA Greally M.T., Ockeloen C.W., Willemsen M.H., Bongers E.M., Janssen I.M., RA Pfundt R., Veltman J.A., Romano C., Willemsen M.A., van Bokhoven H., RA Brunner H.G., de Vries B.B., de Brouwer A.P.; RT "Identification of pathogenic gene variants in small families with RT intellectually disabled siblings by exome sequencing."; RL J. Med. Genet. 50:802-811(2013). RN [32] RP VARIANT SER-1062. RX PubMed=25787250; DOI=10.1073/pnas.1503696112; RA Cromer M.K., Choi M., Nelson-Williams C., Fonseca A.L., Kunstman J.W., RA Korah R.M., Overton J.D., Mane S., Kenney B., Malchoff C.D., Stalberg P., RA Akerstroem G., Westin G., Hellman P., Carling T., Bjoerklund P., RA Lifton R.P.; RT "Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in RT insulin-producing adenomas."; RL Proc. Natl. Acad. Sci. U.S.A. 112:4062-4067(2015). RN [33] RP VARIANT AMC3 8193-ARG--LEU-8797 DEL, AND INVOLVEMENT IN AMC3. RX PubMed=24319099; DOI=10.1093/hmg/ddt618; RA Laquerriere A., Maluenda J., Camus A., Fontenas L., Dieterich K., RA Nolent F., Zhou J., Monnier N., Latour P., Gentil D., Heron D., RA Desguerres I., Landrieu P., Beneteau C., Delaporte B., Bellesme C., RA Baumann C., Capri Y., Goldenberg A., Lyonnet S., Bonneau D., Estournet B., RA Quijano-Roy S., Francannet C., Odent S., Saint-Frison M.H., Sigaudy S., RA Figarella-Branger D., Gelot A., Mussini J.M., Lacroix C., RA Drouin-Garraud V., Malinge M.C., Attie-Bitach T., Bessieres B., RA Bonniere M., Encha-Razavi F., Beaufrere A.M., Khung-Savatovsky S., RA Perez M.J., Vasiljevic A., Mercier S., Roume J., Trestard L., RA Saugier-Veber P., Cordier M.P., Layet V., Legendre M., RA Vigouroux-Castera A., Lunardi J., Bayes M., Jouk P.S., Rigonnot L., RA Granier M., Sternberg D., Warszawski J., Gut I., Gonzales M., Tawk M., RA Melki J.; RT "Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis RT multiplex congenita with axoglial defects."; RL Hum. Mol. Genet. 23:2279-2289(2014). RN [34] RP VARIANT AMC3 8746-ARG--LEU-8797 DEL, AND INVOLVEMENT IN AMC3. RX PubMed=27782104; DOI=10.1038/ejhg.2016.144; RA Baumann M., Steichen-Gersdorf E., Krabichler B., Petersen B.S., Weber U., RA Schmidt W.M., Zschocke J., Mueller T., Bittner R.E., Janecke A.R.; RT "Homozygous SYNE1 mutation causes congenital onset of muscular weakness RT with distal arthrogryposis: a genotype-phenotype correlation."; RL Eur. J. Hum. Genet. 25:262-266(2017). CC -!- FUNCTION: Multi-isomeric modular protein which forms a linking network CC between organelles and the actin cytoskeleton to maintain the CC subcellular spatial organization. As a component of the LINC (LInker of CC Nucleoskeleton and Cytoskeleton) complex involved in the connection CC between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic CC interactions established by the LINC complex play an important role in CC the transmission of mechanical forces across the nuclear envelope and CC in nuclear movement and positioning. May be involved in nucleus- CC centrosome attachment and nuclear migration in neural progenitors CC implicating LINC complex association with SUN1/2 and probably CC association with cytoplasmic dynein-dynactin motor complexes; SYNE1 and CC SYNE2 may act redundantly. Required for centrosome migration to the CC apical cell surface during early ciliogenesis. May be involved in CC nuclear remodeling during sperm head formation in spermatogenesis; a CC probable SUN3:SYNE1/KASH1 LINC complex may tether spermatid nuclei to CC posterior cytoskeletal structures such as the manchette. CC {ECO:0000250|UniProtKB:Q6ZWR6, ECO:0000269|PubMed:11792814, CC ECO:0000269|PubMed:18396275}. CC -!- SUBUNIT: Core component of LINC complexes which are composed of inner CC nuclear membrane SUN domain-containing proteins coupled to outer CC nuclear membrane KASH domain-containing nesprins. SUN and KASH domain- CC containing proteins seem to bind each other promiscuously; however, CC differentially expression of LINC complex constituents can give rise to CC specific assemblies. At least SUN1/2-containing core LINC complexes are CC proposed to be hexameric composed of three protomers of each KASH and CC SUN domain-containing protein. The SUN2:SYNE1/KASH1 LINC complex is a CC heterohexamer; the homotrimeric cloverleave-like conformation of the CC SUN domain is a prerequisite for LINC complex formation in which three CC separate SYNE1/KASH1 peptides bind at the interface of adjacent SUN CC domains. Self-associates. Interacts with SYNE3. Interacts with CC SPAG4/SUN4. May interact with MUSK. Interacts with F-actin via its N- CC terminal domain. Interacts with EMD and LMNA in vitro. Interacts (via CC KASH domain) with TMEM258 (PubMed:28716842). CC {ECO:0000250|UniProtKB:Q6ZWR6, ECO:0000269|PubMed:12163176, CC ECO:0000269|PubMed:18396275, ECO:0000269|PubMed:22518138, CC ECO:0000269|PubMed:28716842}. CC -!- INTERACTION: CC Q8NF91; Q9NRI5: DISC1; NbExp=7; IntAct=EBI-928867, EBI-529989; CC Q8NF91; O94901: SUN1; NbExp=6; IntAct=EBI-928867, EBI-2796904; CC Q8NF91; Q9UH99: SUN2; NbExp=7; IntAct=EBI-928867, EBI-1044964; CC Q8NF91-1; O94901: SUN1; NbExp=2; IntAct=EBI-6170938, EBI-2796904; CC Q8NF91-1; Q9UH99: SUN2; NbExp=2; IntAct=EBI-6170938, EBI-1044964; CC Q8NF91-3; P50402: EMD; NbExp=5; IntAct=EBI-10760352, EBI-489887; CC Q8NF91-11; P50402: EMD; NbExp=3; IntAct=EBI-10758913, EBI-489887; CC Q8NF91-11; Q8NF91-11: SYNE1; NbExp=3; IntAct=EBI-10758913, EBI-10758913; CC -!- SUBCELLULAR LOCATION: Nucleus outer membrane {ECO:0000305}; Single-pass CC type IV membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. CC Nucleus. Nucleus envelope. Cytoplasm, cytoskeleton. Cytoplasm, CC myofibril, sarcomere. Note=The largest part of the protein is CC cytoplasmic, while its C-terminal part is associated with the nuclear CC envelope, most probably the outer nuclear membrane. In skeletal and CC smooth muscles, a significant amount is found in the sarcomeres. In CC myoblasts, relocalized from the nuclear envelope to the nucleus and CC cytoplasm during cell differentiation. CC -!- SUBCELLULAR LOCATION: [Isoform GSRP-56]: Golgi apparatus CC {ECO:0000269|PubMed:16875688}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=12; CC Name=1; Synonyms=Nesprin-1 Giant, Enaptin; CC IsoId=Q8NF91-1; Sequence=Displayed; CC Name=2; Synonyms=Beta; CC IsoId=Q8NF91-2; Sequence=VSP_007130; CC Name=3; Synonyms=Alpha; CC IsoId=Q8NF91-3; Sequence=VSP_007132, VSP_007144; CC Name=4; CC IsoId=Q8NF91-4; Sequence=VSP_007134, VSP_007139, VSP_007140, CC VSP_007144; CC Name=5; CC IsoId=Q8NF91-5; Sequence=VSP_007135, VSP_007136; CC Name=6; CC IsoId=Q8NF91-6; Sequence=VSP_007137, VSP_007138; CC Name=7; CC IsoId=Q8NF91-7; Sequence=VSP_007141, VSP_007142; CC Name=8; Synonyms=Beta 2; CC IsoId=Q8NF91-8; Sequence=VSP_007131; CC Name=9; Synonyms=Alpha 2; CC IsoId=Q8NF91-9; Sequence=VSP_007133, VSP_007143, VSP_007144; CC Name=10; Synonyms=drop1; CC IsoId=Q8NF91-10; Sequence=VSP_057478, VSP_057479, VSP_057480; CC Name=11; Synonyms=myne-1, 131kDa; CC IsoId=Q8NF91-11; Sequence=VSP_057476; CC Name=GSRP-56; Synonyms=56kDa; CC IsoId=Q8NF91-12; Sequence=VSP_057477, VSP_057481, VSP_057482; CC -!- TISSUE SPECIFICITY: Expressed in HeLa, A431, A172 and HaCaT cells (at CC protein level). Widely expressed. Highly expressed in skeletal and CC smooth muscles, heart, spleen, peripheral blood leukocytes, pancreas, CC cerebellum, stomach, kidney and placenta. Isoform GSRP-56 is CC predominantly expressed in heart and skeletal muscle (at protein CC level). {ECO:0000269|PubMed:11792814, ECO:0000269|PubMed:11801724, CC ECO:0000269|PubMed:15093733, ECO:0000269|PubMed:16875688, CC ECO:0000269|PubMed:22518138}. CC -!- DOMAIN: The KASH domain, which contains a transmembrane domain, CC mediates the nuclear envelope targeting and is involved in the binding CC to SUN1 and SUN2 through recognition of their SUN domains. CC {ECO:0000269|PubMed:18396275}. CC -!- PTM: The disulfid bond with SUN1 or SUN2 is required for stability of CC the respective LINC complex under tensile forces. CC {ECO:0000250|UniProtKB:Q8WXH0}. CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 8 (SCAR8) CC [MIM:610743]: A form of spinocerebellar ataxia, a clinically and CC genetically heterogeneous group of cerebellar disorders. Patients show CC progressive incoordination of gait and often poor coordination of CC hands, speech and eye movements, due to degeneration of the cerebellum CC with variable involvement of the brainstem and spinal cord. SCAR8 is an CC autosomal recessive form. {ECO:0000269|PubMed:17159980}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Emery-Dreifuss muscular dystrophy 4, autosomal dominant CC (EDMD4) [MIM:612998]: A form of Emery-Dreifuss muscular dystrophy, a CC degenerative myopathy characterized by weakness and atrophy of muscle CC without involvement of the nervous system, early contractures of the CC elbows, Achilles tendons and spine, and cardiomyopathy associated with CC cardiac conduction defects. {ECO:0000269|PubMed:17761684}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Arthrogryposis multiplex congenita 3, myogenic type (AMC3) CC [MIM:618484]: A form of arthrogryposis multiplex congenita, a CC heterogeneous group of disorders characterized by multiple joint CC contractures resulting, in some cases, from reduced or absent fetal CC movements. AMC3 is an autosomal recessive form characterized by CC decreased fetal movements, muscular hypotonia, delayed motor CC development, loss of ambulation, variable skeletal defects, and CC persistent contractures of interphalangeal joints. CC {ECO:0000269|PubMed:19542096, ECO:0000269|PubMed:24319099, CC ECO:0000269|PubMed:27782104}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 10]: Lost in uterus, cervix, kidney, lung, CC thyroid and pancreas carcinomas, already at early tumor stages. CC {ECO:0000269|PubMed:18709643}. CC -!- MISCELLANEOUS: [Isoform 11]: Muscle-specific. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform GSRP-56]: Interacts with TRPV2. CC {ECO:0000269|PubMed:16875688}. CC -!- SIMILARITY: Belongs to the nesprin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC02992.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH39121.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAM95335.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin.; Evidence={ECO:0000305}; CC Sequence=BAB71097.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305}; CC Sequence=BAC04284.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAD28486.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Enaptin entry; CC URL="https://en.wikipedia.org/wiki/Enaptin"; 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; AY061755; AAL33798.1; -; mRNA. DR EMBL; AY061756; AAL33799.1; -; mRNA. DR EMBL; AY184203; AAO27771.1; -; mRNA. DR EMBL; AY184206; AAO27774.1; -; mRNA. DR EMBL; AF535142; AAN03486.1; -; mRNA. DR EMBL; AF444779; AAL38031.1; -; mRNA. DR EMBL; FM162565; CAQ57272.1; -; mRNA. DR EMBL; AF495910; AAN60442.1; -; mRNA. DR EMBL; AL049548; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL136079; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL589963; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL591507; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL078582; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL138832; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL357081; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL450401; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; KF458330; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC039121; AAH39121.1; ALT_INIT; mRNA. DR EMBL; AY135172; AAM95335.1; ALT_SEQ; mRNA. DR EMBL; AY183142; AAO23669.1; -; mRNA. DR EMBL; AK056122; BAB71097.1; ALT_SEQ; mRNA. DR EMBL; AK094094; BAC04284.1; ALT_INIT; mRNA. DR EMBL; AB051543; BAB21847.1; -; mRNA. DR EMBL; AL713682; CAD28486.2; ALT_INIT; mRNA. DR EMBL; AB033088; BAA86576.1; -; mRNA. DR EMBL; AB018339; BAA34516.2; -; mRNA. DR EMBL; AF043290; AAC02992.2; ALT_INIT; mRNA. DR CCDS; CCDS5236.2; -. [Q8NF91-1] DR RefSeq; NP_001334631.1; NM_001347702.1. DR RefSeq; NP_149062.1; NM_033071.3. [Q8NF91-4] DR RefSeq; NP_892006.3; NM_182961.3. [Q8NF91-1] DR PDB; 4DXR; X-ray; 2.32 A; B=8769-8797. DR PDB; 6R15; X-ray; 1.82 A; B=8769-8797. DR PDB; 6XF2; X-ray; 7.11 A; A/C=2070-2200. DR PDBsum; 4DXR; -. DR PDBsum; 6R15; -. DR PDBsum; 6XF2; -. DR SASBDB; Q8NF91; -. DR SMR; Q8NF91; -. DR BioGRID; 116928; 92. DR ComplexPortal; CPX-7667; LINC complex, SUN2-SYNE1 variant. DR ComplexPortal; CPX-7668; LINC complex, SUN1-SYNE1 variant. DR CORUM; Q8NF91; -. DR IntAct; Q8NF91; 49. DR MINT; Q8NF91; -. DR STRING; 9606.ENSP00000356224; -. DR CarbonylDB; Q8NF91; -. DR GlyCosmos; Q8NF91; 2 sites, 2 glycans. DR GlyGen; Q8NF91; 9 sites, 2 O-linked glycans (9 sites). DR iPTMnet; Q8NF91; -. DR PhosphoSitePlus; Q8NF91; -. DR SwissPalm; Q8NF91; -. DR BioMuta; SYNE1; -. DR DMDM; 425906075; -. DR EPD; Q8NF91; -. DR jPOST; Q8NF91; -. DR MassIVE; Q8NF91; -. DR MaxQB; Q8NF91; -. DR PaxDb; 9606-ENSP00000356224; -. DR PeptideAtlas; Q8NF91; -. DR ProteomicsDB; 17580; -. DR ProteomicsDB; 34724; -. DR ProteomicsDB; 73268; -. [Q8NF91-1] DR ProteomicsDB; 73269; -. [Q8NF91-2] DR ProteomicsDB; 73270; -. [Q8NF91-3] DR ProteomicsDB; 73271; -. [Q8NF91-4] DR ProteomicsDB; 73272; -. [Q8NF91-5] DR ProteomicsDB; 73273; -. [Q8NF91-6] DR ProteomicsDB; 73274; -. [Q8NF91-7] DR ProteomicsDB; 73275; -. [Q8NF91-8] DR ProteomicsDB; 73276; -. [Q8NF91-9] DR Pumba; Q8NF91; -. DR Antibodypedia; 19931; 203 antibodies from 26 providers. DR Ensembl; ENST00000367253.8; ENSP00000356222.4; ENSG00000131018.25. [Q8NF91-6] DR Ensembl; ENST00000367255.10; ENSP00000356224.5; ENSG00000131018.25. [Q8NF91-1] DR Ensembl; ENST00000413186.6; ENSP00000414510.2; ENSG00000131018.25. [Q8NF91-5] DR GeneID; 23345; -. DR KEGG; hsa:23345; -. DR MANE-Select; ENST00000367255.10; ENSP00000356224.5; NM_182961.4; NP_892006.3. DR UCSC; uc003qot.5; human. [Q8NF91-1] DR UCSC; uc003qov.4; human. DR AGR; HGNC:17089; -. DR DisGeNET; 23345; -. DR GeneCards; SYNE1; -. DR GeneReviews; SYNE1; -. DR HGNC; HGNC:17089; SYNE1. DR HPA; ENSG00000131018; Tissue enhanced (brain, choroid plexus). DR MalaCards; SYNE1; -. DR MIM; 608441; gene. DR MIM; 610743; phenotype. DR MIM; 612998; phenotype. DR MIM; 618484; phenotype. DR neXtProt; NX_Q8NF91; -. DR OpenTargets; ENSG00000131018; -. DR Orphanet; 98853; Autosomal dominant Emery-Dreifuss muscular dystrophy. DR Orphanet; 88644; Autosomal recessive ataxia, Beauce type. DR Orphanet; 319332; Autosomal recessive myogenic arthrogryposis multiplex congenita. DR PharmGKB; PA134975331; -. DR VEuPathDB; HostDB:ENSG00000131018; -. DR eggNOG; KOG0516; Eukaryota. DR GeneTree; ENSGT00940000154481; -. DR HOGENOM; CLU_000025_1_0_1; -. DR InParanoid; Q8NF91; -. DR OMA; QASSRKC; -. DR OrthoDB; 5478539at2759; -. DR TreeFam; TF329280; -. DR PathwayCommons; Q8NF91; -. DR Reactome; R-HSA-1221632; Meiotic synapsis. DR SignaLink; Q8NF91; -. DR SIGNOR; Q8NF91; -. DR BioGRID-ORCS; 23345; 10 hits in 1150 CRISPR screens. DR ChiTaRS; SYNE1; human. DR GeneWiki; Enaptin; -. DR GenomeRNAi; 23345; -. DR Pharos; Q8NF91; Tbio. DR PRO; PR:Q8NF91; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q8NF91; Protein. DR Bgee; ENSG00000131018; Expressed in cerebellar hemisphere and 191 other cell types or tissues. DR ExpressionAtlas; Q8NF91; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0044327; C:dendritic spine head; IEA:Ensembl. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0034993; C:meiotic nuclear membrane microtubule tethering complex; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0030496; C:midbody; IEA:Ensembl. DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IDA:HPA. DR GO; GO:0005640; C:nuclear outer membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005730; C:nucleolus; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; HDA:UniProtKB. DR GO; GO:0000932; C:P-body; IDA:BHF-UCL. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0045211; C:postsynaptic membrane; IDA:UniProtKB. DR GO; GO:0030017; C:sarcomere; IDA:MGI. DR GO; GO:0003779; F:actin binding; IDA:UniProtKB. DR GO; GO:0051015; F:actin filament binding; ISS:UniProtKB. DR GO; GO:0140444; F:cytoskeleton-nuclear membrane anchor activity; IDA:GO_Central. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005521; F:lamin binding; IPI:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl. DR GO; GO:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl. DR GO; GO:0007030; P:Golgi organization; IDA:UniProtKB. DR GO; GO:0042692; P:muscle cell differentiation; IDA:UniProtKB. DR GO; GO:2001054; P:negative regulation of mesenchymal cell apoptotic process; IEA:Ensembl. DR GO; GO:0061886; P:negative regulation of mini excitatory postsynaptic potential; IEA:Ensembl. DR GO; GO:0090292; P:nuclear matrix anchoring at nuclear membrane; IDA:UniProtKB. DR GO; GO:0006997; P:nucleus organization; NAS:UniProtKB. DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl. DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IEA:Ensembl. DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IEA:Ensembl. DR GO; GO:1903353; P:regulation of nucleus organization; IEA:Ensembl. DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IEA:Ensembl. DR GO; GO:0009416; P:response to light stimulus; IEA:Ensembl. DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW. DR CDD; cd21241; CH_SYNE1_rpt1; 1. DR CDD; cd21243; CH_SYNE1_rpt2; 1. DR CDD; cd00176; SPEC; 14. DR Gene3D; 1.20.58.60; -; 33. DR Gene3D; 1.10.418.10; Calponin-like domain; 2. DR InterPro; IPR001589; Actinin_actin-bd_CS. DR InterPro; IPR039906; Anc-1/SYNE1/2-like. DR InterPro; IPR001715; CH_dom. DR InterPro; IPR036872; CH_dom_sf. DR InterPro; IPR047290; CH_SYNE1_rpt1. DR InterPro; IPR047291; CH_SYNE1_rpt2. DR InterPro; IPR012315; KASH. DR InterPro; IPR018159; Spectrin/alpha-actinin. DR InterPro; IPR002017; Spectrin_repeat. DR PANTHER; PTHR21524:SF5; KLARSICHT PROTEIN; 1. DR PANTHER; PTHR21524; SPECTRIN REPEAT CONTAINING NUCLEAR ENVELOPE PROTEIN 2; 1. DR Pfam; PF00307; CH; 2. DR Pfam; PF10541; KASH; 1. DR Pfam; PF00435; Spectrin; 11. DR SMART; SM00033; CH; 2. DR SMART; SM01249; KASH; 1. DR SMART; SM00150; SPEC; 45. DR SUPFAM; SSF47576; Calponin-homology domain, CH-domain; 1. DR SUPFAM; SSF46966; Spectrin repeat; 48. DR PROSITE; PS00019; ACTININ_1; 1. DR PROSITE; PS00020; ACTININ_2; 1. DR PROSITE; PS50021; CH; 2. DR PROSITE; PS51049; KASH; 1. DR Genevisible; Q8NF91; HS. PE 1: Evidence at protein level; KW 3D-structure; Actin-binding; Alternative splicing; Coiled coil; Cytoplasm; KW Cytoskeleton; Differentiation; Disease variant; Disulfide bond; KW Emery-Dreifuss muscular dystrophy; Golgi apparatus; Membrane; KW Neurodegeneration; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Spermatogenesis; Transmembrane; Transmembrane helix. FT CHAIN 1..8797 FT /note="Nesprin-1" FT /id="PRO_0000163591" FT TOPO_DOM 1..8746 FT /note="Cytoplasmic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385" FT TRANSMEM 8747..8767 FT /note="Helical; Anchor for type IV membrane protein" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385" FT TOPO_DOM 8768..8797 FT /note="Perinuclear space" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385" FT DOMAIN 27..134 FT /note="Calponin-homology (CH) 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044" FT DOMAIN 178..283 FT /note="Calponin-homology (CH) 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044" FT REPEAT 314..397 FT /note="Spectrin 1" FT REPEAT 398..502 FT /note="Spectrin 2" FT REPEAT 503..609 FT /note="Spectrin 3" FT REPEAT 610..703 FT /note="Spectrin 4" FT REPEAT 704..815 FT /note="Spectrin 5" FT REPEAT 816..923 FT /note="Spectrin 6" FT REPEAT 924..1024 FT /note="Spectrin 7" FT REPEAT 1025..1122 FT /note="Spectrin 8" FT REPEAT 1123..1246 FT /note="Spectrin 9" FT REPEAT 1247..1335 FT /note="Spectrin 10" FT REPEAT 1336..1444 FT /note="Spectrin 11" FT REPEAT 1445..1550 FT /note="Spectrin 12" FT REPEAT 1551..1653 FT /note="Spectrin 13" FT REPEAT 1654..1763 FT /note="Spectrin 14" FT REPEAT 1764..1879 FT /note="Spectrin 15" FT REPEAT 1880..1976 FT /note="Spectrin 16" FT REPEAT 1977..2081 FT /note="Spectrin 17" FT REPEAT 2082..2195 FT /note="Spectrin 18" FT REPEAT 2196..2303 FT /note="Spectrin 19" FT REPEAT 2304..2401 FT /note="Spectrin 20" FT REPEAT 2402..2513 FT /note="Spectrin 21" FT REPEAT 2514..2619 FT /note="Spectrin 22" FT REPEAT 2620..2731 FT /note="Spectrin 23" FT REPEAT 2732..2838 FT /note="Spectrin 24" FT REPEAT 2839..2962 FT /note="Spectrin 25" FT REPEAT 2963..3062 FT /note="Spectrin 26" FT REPEAT 3063..3171 FT /note="Spectrin 27" FT REPEAT 3172..3275 FT /note="Spectrin 28" FT REPEAT 3276..3387 FT /note="Spectrin 29" FT REPEAT 3388..3490 FT /note="Spectrin 30" FT REPEAT 3491..3593 FT /note="Spectrin 31" FT REPEAT 3594..3720 FT /note="Spectrin 32" FT REPEAT 3721..3814 FT /note="Spectrin 33" FT REPEAT 3815..3920 FT /note="Spectrin 34" FT REPEAT 3921..4028 FT /note="Spectrin 35" FT REPEAT 4029..4139 FT /note="Spectrin 36" FT REPEAT 4140..4235 FT /note="Spectrin 37" FT REPEAT 4236..4339 FT /note="Spectrin 38" FT REPEAT 4340..4451 FT /note="Spectrin 39" FT REPEAT 4452..4560 FT /note="Spectrin 40" FT REPEAT 4561..4669 FT /note="Spectrin 41" FT REPEAT 4670..4776 FT /note="Spectrin 42" FT REPEAT 4777..4882 FT /note="Spectrin 43" FT REPEAT 4883..4991 FT /note="Spectrin 44" FT REPEAT 4992..5099 FT /note="Spectrin 45" FT REPEAT 5100..5209 FT /note="Spectrin 46" FT REPEAT 5210..5318 FT /note="Spectrin 47" FT REPEAT 5319..5424 FT /note="Spectrin 48" FT REPEAT 5425..5522 FT /note="Spectrin 49" FT REPEAT 5523..5630 FT /note="Spectrin 50" FT REPEAT 5631..5736 FT /note="Spectrin 51" FT REPEAT 5737..5842 FT /note="Spectrin 52" FT REPEAT 5962..6071 FT /note="Spectrin 53" FT REPEAT 6072..6178 FT /note="Spectrin 54" FT REPEAT 6374..6485 FT /note="Spectrin 55" FT REPEAT 6486..6581 FT /note="Spectrin 56" FT REPEAT 6582..6691 FT /note="Spectrin 57" FT REPEAT 6692..6795 FT /note="Spectrin 58" FT REPEAT 6796..6902 FT /note="Spectrin 59" FT REPEAT 6903..7020 FT /note="Spectrin 60" FT REPEAT 7021..7128 FT /note="Spectrin 61" FT REPEAT 7129..7237 FT /note="Spectrin 62" FT REPEAT 7238..7350 FT /note="Spectrin 63" FT REPEAT 7351..7454 FT /note="Spectrin 64" FT REPEAT 7455..7558 FT /note="Spectrin 65" FT REPEAT 7559..7671 FT /note="Spectrin 66" FT REPEAT 7672..7783 FT /note="Spectrin 67" FT REPEAT 7784..7883 FT /note="Spectrin 68" FT REPEAT 7884..7997 FT /note="Spectrin 69" FT REPEAT 7998..8106 FT /note="Spectrin 70" FT REPEAT 8107..8216 FT /note="Spectrin 71" FT REPEAT 8329..8438 FT /note="Spectrin 72" FT REPEAT 8439..8548 FT /note="Spectrin 73" FT REPEAT 8549..8666 FT /note="Spectrin 74" FT DOMAIN 8738..8797 FT /note="KASH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385" FT REGION 1..289 FT /note="Actin-binding" FT REGION 5859..5886 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 8246..8279 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 8671..8734 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 314..8666 FT /evidence="ECO:0000255" FT COMPBIAS 5862..5886 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 8247..8267 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 8671..8731 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 732 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6ZWR6" FT MOD_RES 2270 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q6ZWR6" FT MOD_RES 5657 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6ZWR6" FT MOD_RES 8223 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:24275569" FT MOD_RES 8274 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES 8277 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES 8280 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES 8305 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6ZWR6" FT MOD_RES 8360 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT DISULFID 8774 FT /note="Interchain (C-563 in SUN2); alternate" FT /evidence="ECO:0000250|UniProtKB:Q8WXH0" FT DISULFID 8774 FT /note="Interchain (with C-657 in SUN1); alternate" FT /evidence="ECO:0000250|UniProtKB:Q8WXH0" FT VAR_SEQ 1..7843 FT /note="Missing (in isoform 9)" FT /evidence="ECO:0000303|Ref.6" FT /id="VSP_007133" FT VAR_SEQ 1..7838 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11792814" FT /id="VSP_007132" FT VAR_SEQ 1..7658 FT /note="Missing (in isoform 11)" FT /evidence="ECO:0000303|PubMed:11801724" FT /id="VSP_057476" FT VAR_SEQ 1..5585 FT /note="Missing (in isoform 8)" FT /evidence="ECO:0000303|Ref.6" FT /id="VSP_007131" FT VAR_SEQ 1..5476 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11792814" FT /id="VSP_007130" FT VAR_SEQ 1..2918 FT /note="Missing (in isoform GSRP-56)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_057477" FT VAR_SEQ 103 FT /note="K -> KSMHRGSP (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15093733" FT /id="VSP_007134" FT VAR_SEQ 297..313 FT /note="Missing (in isoform 10)" FT /evidence="ECO:0000303|PubMed:18709643" FT /id="VSP_057478" FT VAR_SEQ 1437..1443 FT /note="DIKTMEM -> EYVIDKS (in isoform 5)" FT /evidence="ECO:0000303|PubMed:11214970" FT /id="VSP_007135" FT VAR_SEQ 1444..8797 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:11214970" FT /id="VSP_007136" FT VAR_SEQ 1702..1725 FT /note="LQNEVVSQASFYSKLLQLKESLFS -> SSRKCEEGKNKMLFVTVTLFKIIK FT (in isoform 6)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_007137" FT VAR_SEQ 1726..8797 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_007138" FT VAR_SEQ 3049 FT /note="C -> W (in isoform 10)" FT /evidence="ECO:0000303|PubMed:18709643" FT /id="VSP_057479" FT VAR_SEQ 3050..8797 FT /note="Missing (in isoform 10)" FT /evidence="ECO:0000303|PubMed:18709643" FT /id="VSP_057480" FT VAR_SEQ 3325..3394 FT /note="ALLSVKQEKEIQMKMIVTRGESVLQNTSPEGIPTIQQQLQSVKDMWASLLSA FT GIRCKSQLEGALSKWTSY -> VCIFTQKYLQPTEFVFLKISRLHPPGVMMSHSLHDKS FT QMLCECNAVCLGCTCQRIPESSDPGCFPKNKIK (in isoform GSRP-56)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_057481" FT VAR_SEQ 3395..8797 FT /note="Missing (in isoform GSRP-56)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_057482" FT VAR_SEQ 3620..3641 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15093733" FT /id="VSP_007139" FT VAR_SEQ 3912..3967 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15093733" FT /id="VSP_007140" FT VAR_SEQ 5571..5580 FT /note="TLLEESKEID -> VTLGKIIFKK (in isoform 7)" FT /evidence="ECO:0000303|PubMed:10574462" FT /id="VSP_007141" FT VAR_SEQ 5581..8797 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:10574462" FT /id="VSP_007142" FT VAR_SEQ 7844..7874 FT /note="AKASHESKASEIEYKLGKVNDRWQHLLDLIA -> MVVAEDLSALRMAEDGC FT VDADLPDCNCDVTR (in isoform 9)" FT /evidence="ECO:0000303|Ref.6" FT /id="VSP_007143" FT VAR_SEQ 8325 FT /note="S -> SDVMIPESPEAYVKLTENAIKNTS (in isoform 3, isoform FT 4 and isoform 9)" FT /evidence="ECO:0000303|PubMed:11792814, FT ECO:0000303|PubMed:15093733, ECO:0000303|Ref.6" FT /id="VSP_007144" FT VARIANT 655 FT /note="Q -> R (found in a patient with mild intellectual FT disability, spastic paraplegia, axon neuropathy and FT leukoencephalopathy; uncertain significance; FT dbSNP:rs9397509)" FT /evidence="ECO:0000269|PubMed:24123876" FT /id="VAR_056211" FT VARIANT 885 FT /note="L -> V (in dbSNP:rs17082709)" FT /id="VAR_056212" FT VARIANT 1035 FT /note="V -> A (in dbSNP:rs214976)" FT /id="VAR_056213" FT VARIANT 1062 FT /note="R -> S" FT /evidence="ECO:0000269|PubMed:25787250" FT /id="VAR_074190" FT VARIANT 2030 FT /note="S -> G (in dbSNP:rs35763277)" FT /id="VAR_056214" FT VARIANT 2795 FT /note="A -> V (in dbSNP:rs214950)" FT /id="VAR_056215" FT VARIANT 3088 FT /note="A -> T (found in a patient with mild intellectual FT disability, spastic paraplegia, axon neuropathy and FT leukoencephalopathy; uncertain significance; FT dbSNP:rs398123005)" FT /evidence="ECO:0000269|PubMed:24123876" FT /id="VAR_070561" FT VARIANT 3671 FT /note="V -> M (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs567753957)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036250" FT VARIANT 3874 FT /note="K -> T (in dbSNP:rs13210127)" FT /id="VAR_056216" FT VARIANT 3892 FT /note="L -> S (found in a patient with mild intellectual FT disability, spastic paraplegia, axon neuropathy and FT leukoencephalopathy; uncertain significance; FT dbSNP:rs180727534)" FT /evidence="ECO:0000269|PubMed:24123876" FT /id="VAR_070562" FT VARIANT 3954 FT /note="S -> T (in dbSNP:rs7775119)" FT /id="VAR_056217" FT VARIANT 4060 FT /note="E -> D (in dbSNP:rs4645434)" FT /id="VAR_056218" FT VARIANT 4121 FT /note="K -> N (in dbSNP:rs28385621)" FT /id="VAR_056219" FT VARIANT 4121 FT /note="K -> R (in dbSNP:rs9479297)" FT /id="VAR_056220" FT VARIANT 4203 FT /note="E -> K (in dbSNP:rs2130262)" FT /id="VAR_056221" FT VARIANT 4210 FT /note="E -> D (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036251" FT VARIANT 4223 FT /note="R -> H (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs140492158)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036252" FT VARIANT 4546 FT /note="V -> I (in dbSNP:rs4870093)" FT /id="VAR_056222" FT VARIANT 4596 FT /note="S -> T (in dbSNP:rs6911096)" FT /evidence="ECO:0000269|PubMed:10574462, FT ECO:0000269|PubMed:12408964" FT /id="VAR_056223" FT VARIANT 4944 FT /note="L -> M (in dbSNP:rs2306916)" FT /id="VAR_056224" FT VARIANT 5015 FT /note="L -> M (in dbSNP:rs2306916)" FT /evidence="ECO:0000269|PubMed:10574462, FT ECO:0000269|PubMed:12408964" FT /id="VAR_056225" FT VARIANT 5377 FT /note="M -> L (in dbSNP:rs35987150)" FT /id="VAR_056226" FT VARIANT 5426 FT /note="T -> M (in dbSNP:rs2306914)" FT /id="VAR_056227" FT VARIANT 5507 FT /note="L -> R (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036253" FT VARIANT 6566 FT /note="M -> I (in dbSNP:rs35654757)" FT /id="VAR_056228" FT VARIANT 6664 FT /note="T -> I (in dbSNP:rs35079654)" FT /id="VAR_056229" FT VARIANT 6951 FT /note="Q -> H (in dbSNP:rs3945783)" FT /id="VAR_056230" FT VARIANT 7302 FT /note="F -> V (in dbSNP:rs2147377)" FT /evidence="ECO:0000269|PubMed:11792814, FT ECO:0000269|PubMed:12408964, ECO:0000269|PubMed:9872452, FT ECO:0000269|Ref.6" FT /id="VAR_056231" FT VARIANT 7506 FT /note="S -> G (in dbSNP:rs35763277)" FT /id="VAR_056232" FT VARIANT 8095 FT /note="R -> H (in EDMD4; dbSNP:rs119103246)" FT /evidence="ECO:0000269|PubMed:17761684" FT /id="VAR_062974" FT VARIANT 8161 FT /note="N -> H (in dbSNP:rs36215251)" FT /id="VAR_056233" FT VARIANT 8168 FT /note="A -> S (in dbSNP:rs17082236)" FT /id="VAR_056234" FT VARIANT 8193..8797 FT /note="Missing (in AMC3)" FT /evidence="ECO:0000269|PubMed:24319099" FT /id="VAR_082986" FT VARIANT 8323 FT /note="G -> A (in dbSNP:rs2252755)" FT /evidence="ECO:0000269|PubMed:11792814, FT ECO:0000269|PubMed:11801724, ECO:0000269|PubMed:12408964, FT ECO:0000269|PubMed:9872452, ECO:0000269|Ref.6" FT /id="VAR_015548" FT VARIANT 8387 FT /note="V -> L (in EDMD4; uncertain significance; FT dbSNP:rs119103247)" FT /evidence="ECO:0000269|PubMed:17761684" FT /id="VAR_062975" FT VARIANT 8461 FT /note="E -> K (in EDMD4; dbSNP:rs119103248)" FT /evidence="ECO:0000269|PubMed:17761684" FT /id="VAR_062976" FT VARIANT 8468 FT /note="R -> H (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs143049227)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036254" FT VARIANT 8687 FT /note="T -> I (in dbSNP:rs35591210)" FT /id="VAR_056235" FT VARIANT 8741 FT /note="L -> M (in dbSNP:rs2295190)" FT /id="VAR_056236" FT VARIANT 8746..8797 FT /note="Missing (in AMC3)" FT /evidence="ECO:0000269|PubMed:27782104" FT /id="VAR_082987" FT MUTAGEN 8758..8763 FT /note="Missing: Abolishes the nuclear envelope targeting, FT induces a cytoplasmic localization." FT /evidence="ECO:0000269|PubMed:11792814" FT CONFLICT 98 FT /note="F -> L (in Ref. 2; AAN60442)" FT /evidence="ECO:0000305" FT CONFLICT 494 FT /note="S -> P (in Ref. 9; AAM95335)" FT /evidence="ECO:0000305" FT CONFLICT 1440 FT /note="T -> P (in Ref. 12; CAD28486)" FT /evidence="ECO:0000305" FT CONFLICT 3096 FT /note="N -> D (in Ref. 10; BAB71097)" FT /evidence="ECO:0000305" FT CONFLICT 5526 FT /note="A -> T (in Ref. 1; AAL33798)" FT /evidence="ECO:0000305" FT CONFLICT 5564 FT /note="E -> K (in Ref. 1; AAL33798)" FT /evidence="ECO:0000305" FT CONFLICT 5735 FT /note="E -> A (in Ref. 5; AAN03486)" FT /evidence="ECO:0000305" FT CONFLICT 6549 FT /note="K -> E (in Ref. 1; AAL33798, 2; AAN60442 and 6; FT AAO27774)" FT /evidence="ECO:0000305" FT CONFLICT 6626 FT /note="L -> P (in Ref. 1; AAL33798, 2; AAN60442 and 6; FT AAO27774)" FT /evidence="ECO:0000305" FT CONFLICT 6645 FT /note="E -> V (in Ref. 1; AAL33798, 2; AAN60442 and 6; FT AAO27774)" FT /evidence="ECO:0000305" FT CONFLICT 6923 FT /note="I -> T (in Ref. 1; AAL33798, 2; AAN60442 and 6; FT AAO27774)" FT /evidence="ECO:0000305" FT CONFLICT 6929 FT /note="V -> A (in Ref. 1; AAL33798, 2; AAN60442 and 6; FT AAO27774)" FT /evidence="ECO:0000305" FT CONFLICT 7075 FT /note="E -> D (in Ref. 1; AAL33798, 2; AAN60442 and 6; FT AAO27774)" FT /evidence="ECO:0000305" FT CONFLICT 7091 FT /note="N -> T (in Ref. 1; AAL33798, 2; AAN60442 and 6; FT AAO27774)" FT /evidence="ECO:0000305" FT HELIX 8770..8776 FT /evidence="ECO:0007829|PDB:6R15" FT HELIX 8779..8782 FT /evidence="ECO:0007829|PDB:6R15" FT STRAND 8783..8785 FT /evidence="ECO:0007829|PDB:6R15" FT STRAND 8787..8793 FT /evidence="ECO:0007829|PDB:4DXR" SQ SEQUENCE 8797 AA; 1011086 MW; 02A53B8AFBF34A17 CRC64; MATSRGASRC PRDIANVMQR LQDEQEIVQK RTFTKWINSH LAKRKPPMVV DDLFEDMKDG VKLLALLEVL SGQKLPCEQG RRMKRIHAVA NIGTALKFLE GRKIKLVNIN STDIADGRPS IVLGLMWTII LYFQIEELTS NLPQLQSLSS SASSVDSIVS SETPSPPSKR KVTTKIQGNA KKALLKWVQY TAGKQTGIEV KDFGKSWRSG VAFHSVIHAI RPELVDLETV KGRSNRENLE DAFTIAETEL GIPRLLDPED VDVDKPDEKS IMTYVAQFLK HYPDIHNAST DGQEDDEILP GFPSFANSVQ NFKREDRVIF KEMKVWIEQF ERDLTRAQMV ESNLQDKYQS FKHFRVQYEM KRKQIEHLIQ PLHRDGKLSL DQALVKQSWD RVTSRLFDWH IQLDKSLPAP LGTIGAWLYR AEVALREEIT VQQVHEETAN TIQRKLEQHK DLLQNTDAHK RAFHEIYRTR SVNGIPVPPD QLEDMAERFH FVSSTSELHL MKMEFLELKY RLLSLLVLAE SKLKSWIIKY GRRESVEQLL QNYVSFIENS KFFEQYEVTY QILKQTAEMY VKADGSVEEA ENVMKFMNET TAQWRNLSVE VRSVRSMLEE VISNWDRYGN TVASLQAWLE DAEKMLNQSE NAKKDFFRNL PHWIQQHTAM NDAGNFLIET CDEMVSRDLK QQLLLLNGRW RELFMEVKQY AQADEMDRMK KEYTDCVVTL SAFATEAHKK LSEPLEVSFM NVKLLIQDLE DIEQRVPVMD AQYKIITKTA HLITKESPQE EGKEMFATMS KLKEQLTKVK ECYSPLLYES QQLLIPLEEL EKQMTSFYDS LGKINEIITV LEREAQSSAL FKQKHQELLA CQENCKKTLT LIEKGSQSVQ KFVTLSNVLK HFDQTRLQRQ IADIHVAFQS MVKKTGDWKK HVETNSRLMK KFEESRAELE KVLRIAQEGL EEKGDPEELL RRHTEFFSQL DQRVLNAFLK ACDELTDILP EQEQQGLQEA VRKLHKQWKD LQGEAPYHLL HLKIDVEKNR FLASVEECRT ELDRETKLMP QEGSEKIIKE HRVFFSDKGP HHLCEKRLQL IEELCVKLPV RDPVRDTPGT CHVTLKELRA AIDSTYRKLM EDPDKWKDYT SRFSEFSSWI STNETQLKGI KGEAIDTANH GEVKRAVEEI RNGVTKRGET LSWLKSRLKV LTEVSSENEA QKQGDELAKL SSSFKALVTL LSEVEKMLSN FGDCVQYKEI VKNSLEELIS GSKEVQEQAE KILDTENLFE AQQLLLHHQQ KTKRISAKKR DVQQQIAQAQ QGEGGLPDRG HEELRKLEST LDGLERSRER QERRIQVTLR KWERFETNKE TVVRYLFQTG SSHERFLSFS SLESLSSELE QTKEFSKRTE SIAVQAENLV KEASEIPLGP QNKQLLQQQA KSIKEQVKKL EDTLEEDIKT MEMVKTKWDH FGSNFETLSV WITEKEKELN ALETSSSAMD MQISQIKVTI QEIESKLSSI VGLEEEAQSF AQFVTTGESA RIKAKLTQIR RYGEELREHA QCLEGTILGH LSQQQKFEEN LRKIQQSVSE FEDKLAVPIK ICSSATETYK VLQEHMDLCQ ALESLSSAIT AFSASARKVV NRDSCVQEAA ALQQQYEDIL RRAKERQTAL ENLLAHWQRL EKELSSFLTW LERGEAKASS PEMDISADRV KVEGELQLIQ ALQNEVVSQA SFYSKLLQLK ESLFSVASKD DVKMMKLHLE QLDERWRDLP QIINKRINFL QSVVAEHQQF DELLLSFSVW IKLFLSELQT TSEISIMDHQ VALTRHKDHA AEVESKKGEL QSLQGHLAKL GSLGRAEDLH LLQGKAEDCF QLFEEASQVV ERRQLALSHL AEFLQSHASL SGILRQLRQT VEATNSMNKN ESDLIEKDLN DALQNAKALE SAAVSLDGIL SKAQYHLKIG SSEQRTSCRA TADQLCGEVE RIQNLLGTKQ SEADALAVLK KAFQDQKEEL LKSIEDIEER TDKERLKEPT RQALQQRLRV FNQLEDELNS HEHELCWLKD KAKQIAQKDV AFAPEVDREI NRLEVTWDDT KRLIHENQGQ CCGLIDLMRE YQNLKSAVSK VLENASSVIV TRTTIKDQED LKWAFSKHET AKNKMNYKQK DLDNFTSKGK HLLSELKKIH SSDFSLVKTD MESTVDKWLD VSEKLEENMD RLRVSLSIWD DVLSTRDEIE GWSNNCVPQM AENISNLDNH LRAEELLKEF ESEVKNKALR LEELHSKVND LKELTKNLET PPDLQFIEAD LMQKLEHAKE ITEVAKGTLK DFTAQSTQVE KFINDITTWF TKVEESLMNC AQNETCEALK KVKDIQKELQ SQQSNISSTQ ENLNSLCRKY HSAELESLGR AMTGLIKKHE AVSQLCSKTQ ASLQESLEKH FSESMQEFQE WFLGAKAAAK ESSDRTGDSK VLEAKLHDLQ NILDSVSDGQ SKLDAVTQEG QTLYAHLSKQ IVSSIQEQIT KANEEFQAFL KQCLKDKQAL QDCASELGSF EDQHRKLNLW IHEMEERFNT ENLGESKQHI PEKKNEVHKV EMFLGELLAA RESLDKLSQR GQLLSEEGHG AGQEGRLCSQ LLTSHQNLLR MTKEKLRSCQ VALQEHEALE EALQSMWFWV KAIQDRLACA ESTLGSKDTL EKRLSQIQDI LLMKGEGEVK LNMAIGKGEQ ALRSSNKEGQ RVIQTQLETL KEVWADIMSS SVHAQSTLES VISQWNDYVE RKNQLEQWME SVDQKIEHPL QPQPGLKEKF VLLDHLQSIL SEAEDHTRAL HRLIAKSREL YEKTEDESFK DTAQEELKTQ FNDIMTVAKE KMRKVEEIVK DHLMYLDAVH EFTDWLHSAK EELHRWSDMS GDSSATQKKL SKIKELIDSR EIGASRLSRV ESLAPEVKQN TTASGCELMH TEMQALRADW KQWEDSVFQT QSCLENLVSQ MALSEQEFSG QVAQLEQALE QFSALLKTWA QQLTLLEGKN TDEEIVECWH KGQEILDALQ KAEPRTEDLK SQLNELCRFS RDLSTYSGKV SGLIKEYNCL CLQASKGCQN KEQILQQRFR KAFRDFQQWL VNAKITTAKC FDIPQNISEV STSLQKIQEF LSESENGQHK LNMMLSKGEL LSTLLTKEKA KGIQAKVTAA KEDWKNFHSN LHQKESALEN LKIQMKDFEV SAEPIQDWLS KTEKMVHESS NRLYDLPAKR REQQKLQSVL EEIHCYEPQL NRLKEKAQQL WEGQAASKSF RHRVSQLSSQ YLALSNLTKE KVSRLDRIVA EHNQFSLGIK ELQDWMTDAI HMLDSYCHPT SDKSVLDSRT LKLEALLSVK QEKEIQMKMI VTRGESVLQN TSPEGIPTIQ QQLQSVKDMW ASLLSAGIRC KSQLEGALSK WTSYQDGVRQ FSGWMDSMEA NLNESERQHA ELRDKTTMLG KAKLLNEEVL SYSSLLETIE VKGAGMTEHY VTQLELQDLQ ERYRAIQERA KEAVTKSEKL VRLHQEYQRD LKAFEVWLGQ EQEKLDQYSV LEGDAHTHET TLRDLQELQV HCAEGQALLN SVLHTREDVI PSGIPQAEDR ALESLRQDWQ AYQHRLSETR TQFNNVVNKL RLMEQKFQQV DEWLKTAEEK VSPRTRRQSN RATKEIQLHQ MKKWHEEVTA YRDEVEEVGA RAQEILDESH VNSRMGCQAT QLTSRYQALL LQVLEQIKFL EEEIQSLEES ESSLSSYSDW YGSTHKNFKN VATKIDKVDT VMMGKKLKTL EVLLKDMEKG HSLLKSAREK GERAVKYLEE GEAERLRKEI HDHMEQLKEL TSTVRKEHMT LEKGLHLAKE FSDKCKALTQ WIAEYQEILH VPEEPKMELY EKKAQLSKYK SLQQTVLSHE PSVKSVREKG EALLELVQDV TLKDKIDQLQ SDYQDLCSIG KEHVFSLEAK VKDHEDYNSE LQEVEKWLLQ MSGRLVAPDL LETSSLETIT QQLAHHKAMM EEIAGFEDRL NNLQMKGDTL IGQCADHLQA KLKQNVHAHL QGTKDSYSAI CSTAQRMYQS LEHELQKHVS RQDTLQQCQA WLSAVQPDLE PSPQPPLSRA EAIKQVKHFR ALQEQARTYL DLLCSMCDLS NASVKTTAKD IQQTEQTIEQ KLVQAQNLTQ GWEEIKHLKS ELWIYLQDAD QQLQNMKRRH SELELNIAQN MVSQVKDFVK KLQSKQASVN TIIEKVNKLT KKEESPEHKE INHLNDQWLD LCRQSNNLCL QREEDLQRTR DYHDCMNVVE VFLEKFTTEW DNLARSDAES TAVHLEALKK LALALQERKY AIEDLKDQKQ KMIEHLNLDD KELVKEQTSH LEQRWFQLED LIKRKIQVSV TNLEELNVVQ SRFQELMEWA EEQQPNIAEA LKQSPPPDMA QNLLMDHLAI CSELEAKQML LKSLIKDADR VMADLGLNER QVIQKALSDA QSHVNCLSDL VGQRRKYLNK ALSEKTQFLM AVFQATSQIQ QHERKIMFRE HICLLPDDVS KQVKTCKSAQ ASLKTYQNEV TGLWAQGREL MKEVTEQEKS EVLGKLQELQ SVYDSVLQKC SHRLQELEKN LVSRKHFKED FDKACHWLKQ ADIVTFPEIN LMNESSELHT QLAKYQNILE QSPEYENLLL TLQRTGQTIL PSLNEVDHSY LSEKLNALPR QFNVIVALAK DKFYKVQEAI LARKEYASLI ELTTQSLSEL EAQFLRMSKV PTDLAVEEAL SLQDGCRAIL DEVAGLGEAV DELNQKKEGF RSTGQPWQPD KMLHLVTLYH RLKRQTEQRV SLLEDTTSAY QEHEKMCQQL ERQLKSVKEE QSKVNEETLP AEEKLKMYHS LAGSLQDSGI VLKRVTIHLE DLAPHLDPLA YEKARHQIQS WQGELKLLTS AIGETVTECE SRMVQSIDFQ TEMSRSLDWL RRVKAELSGP VYLDLNLQDI QEEIRKIQIH QEEVQSSLRI MNALSHKEKE KFTKAKELIS ADLEHSLAEL SELDGDIQEA LRTRQATLTE IYSQCQRYYQ VFQAANDWLE DAQELLQLAG NGLDVESAEE NLKSHMEFFS TEDQFHSNLE ELHSLVATLD PLIKPTGKED LEQKVASLEL RSQRMSRDSG AQVDLLQRCT AQWHDYQKAR EEVIELMNDT EKKLSEFSLL KTSSSHEAEE KLSEHKALVS VVNSFHEKIV ALEEKASQLE KTGNDASKAT LSRSMTTVWQ RWTRLRAVAQ DQEKILEDAV DEWTGFNNKV KKATEMIDQL QDKLPGSSAE KASKAELLTL LEYHDTFVLE LEQQQSALGM LRQQTLSMLQ DGAAPTPGEE PPLMQEITAM QDRCLNMQEK VKTNGKLVKQ ELKDREMVET QINSVKCWVQ ETKEYLGNPT IEIDAQLEEL QILLTEATNH RQNIEKMAEE QKEKYLGLYT ILPSELSLQL AEVALDLKIR DQIQDKIKEV EQSKATSQEL SRQIQKLAKD LTTILTKLKA KTDNVVQAKT DQKVLGEELD GCNSKLMELD AAVQKFLEQN GQLGKPLAKK IGKLTELHQQ TIRQAENRLS KLNQAASHLE EYNEMLELIL KWIEKAKVLA HGTIAWNSAS QLREQYILHQ TLLEESKEID SELEAMTEKL QYLTSVYCTE KMSQQVAELG RETEELRQMI KIRLQNLQDA AKDMKKFEAE LKKLQAALEQ AQATLTSPEV GRLSLKEQLS HRQHLLSEME SLKPKVQAVQ LCQSALRIPE DVVASLPLCH AALRLQEEAS RLQHTAIQQC NIMQEAVVQY EQYEQEMKHL QQLIEGAHRE IEDKPVATSN IQELQAQISR HEELAQKIKG YQEQIASLNS KCKMLTMKAK HATMLLTVTE VEGLAEGTED LDGELLPTPS AHPSVVMMTA GRCHTLLSPV TEESGEEGTN SEISSPPACR SPSPVANTDA SVNQDIAYYQ ALSAERLQTD AAKIHPSTSA SQEFYEPGLE PSATAKLGDL QRSWETLKNV ISEKQRTLYE ALERQQKYQD SLQSISTKME AIELKLSESP EPGRSPESQM AEHQALMDEI LMLQDEINEL QSSLAEELVS ESCEADPAEQ LALQSTLTVL AERMSTIRMK ASGKRQLLEE KLNDQLEEQR QEQALQRYRC EADELDSWLL STKATLDTAL SPPKEPMDME AQLMDCQNML VEIEQKVVAL SELSVHNENL LLEGKAHTKD EAEQLAGKLR RLKGSLLELQ RALHDKQLNM QGTAQEKEES DVDLTATQSP GVQEWLAQAR TTWTQQRQSS LQQQKELEQE LAEQKSLLRS VASRGEEILI QHSAAETSGD AGEKPDVLSQ ELGMEGEKSS AEDQMRMKWE SLHQEFSTKQ KLLQNVLEQE QEQVLYSRPN RLLSGVPLYK GDVPTQDKSA VTSLLDGLNQ AFEEVSSQSG GAKRQSIHLE QKLYDGVSAT STWLDDVEER LFVATALLPE ETETCLFNQE ILAKDIKEMS EEMDKNKNLF SQAFPENGDN RDVIEDTLGC LLGRLSLLDS VVNQRCHQMK ERLQQILNFQ NDLKVLFTSL ADNKYIILQK LANVFEQPVA EQIEAIQQAE DGLKEFDAGI IELKRRGDKL QVEQPSMQEL SKLQDMYDEL MMIIGSRRSG LNQNLTLKSQ YERALQDLAD LLETGQEKMA GDQKIIVSSK EEIQQLLDKH KEYFQGLESH MILTETLFRK IISFAVQKET QFHTELMAQA SAVLKRAHKR GVELEYILET WSHLDEDQQE LSRQLEVVES SIPSVGLVEE NEDRLIDRIT LYQHLKSSLN EYQPKLYQVL DDGKRLLISI SCSDLESQLN QLGECWLSNT NKMSKELHRL ETILKHWTRY QSESADLIHW LQSAKDRLEF WTQQSVTVPQ ELEMVRDHLN AFLEFSKEVD AQSSLKSSVL STGNQLLRLK KVDTATLRSE LSRIDSQWTD LLTNIPAVQE KLHQLQMDKL PSRHAISEVM SWISLMENVI QKDEDNIKNS IGYKAIHEYL QKYKGFKIDI NCKQLTVDFV NQSVLQISSQ DVESKRSDKT DFAEQLGAMN KSWQILQGLV TEKIQLLEGL LESWSEYENN VQCLKTWFET QEKRLKQQHR IGDQASVQNA LKDCQDLEDL IKAKEKEVEK IEQNGLALIQ NKKEDVSSIV MSTLRELGQT WANLDHMVGQ LKILLKSVLD QWSSHKVAFD KINSYLMEAR YSLSRFRLLT GSLEAVQVQV DNLQNLQDDL EKQERSLQKF GSITNQLLKE CHPPVTETLT NTLKEVNMRW NNLLEEIAEQ LQSSKALLQL WQRYKDYSKQ CASTVQQQED RTNELLKAAT NKDIADDEVA TWIQDCNDLL KGLGTVKDSL FFLHELGEQL KQQVDASAAS AIQSDQLSLS QHLCALEQAL CKQQTSLQAG VLDYETFAKS LEALEAWIVE AEEILQGQDP SHSSDLSTIQ ERMEELKGQM LKFSSMAPDL DRLNELGYRL PLNDKEIKRM QNLNRHWSLI SSQTTERFSK LQSFLLQHQT FLEKCETWME FLVQTEQKLA VEISGNYQHL LEQQRAHELF QAEMFSRQQI LHSIIIDGQR LLEQGQVDDR DEFNLKLTLL SNQWQGVIRR AQQRRGIIDS QIRQWQRYRE MAEKLRKWLV EVSYLPMSGL GSVPIPLQQA RTLFDEVQFK EKVFLRQQGS YILTVEAGKQ LLLSADSGAE AALQAELAEI QEKWKSASMR LEEQKKKLAF LLKDWEKCEK GIADSLEKLR TFKKKLSQSL PDHHEELHAE QMRCKELENA VGSWTDDLTQ LSLLKDTLSA YISADDISIL NERVELLQRQ WEELCHQLSL RRQQIGERLN EWAVFSEKNK ELCEWLTQME SKVSQNGDIL IEEMIEKLKK DYQEEIAIAQ ENKIQLQQMG ERLAKASHES KASEIEYKLG KVNDRWQHLL DLIAARVKKL KETLVAVQQL DKNMSSLRTW LAHIESELAK PIVYDSCNSE EIQRKLNEQQ ELQRDIEKHS TGVASVLNLC EVLLHDCDAC ATDAECDSIQ QATRNLDRRW RNICAMSMER RLKIEETWRL WQKFLDDYSR FEDWLKSSER TAAFPSSSGV IYTVAKEELK KFEAFQRQVH ECLTQLELIN KQYRRLAREN RTDSACSLKQ MVHEGNQRWD NLQKRVTSIL RRLKHFIGQR EEFETARDSI LVWLTEMDLQ LTNIEHFSEC DVQAKIKQLK AFQQEISLNH NKIEQIIAQG EQLIEKSEPL DAAIIEEELD ELRRYCQEVF GRVERYHKKL IRLPLPDDEH DLSDRELELE DSAALSDLHW HDRSADSLLS PQPSSNLSLS LAQPLRSERS GRDTPASVDS IPLEWDHDYD LSRDLESAMS RALPSEDEEG QDDKDFYLRG AVGLSGDHSA LESQIRQLGK ALDDSRFQIQ QTENIIRSKT PTGPELDTSY KGYMKLLGEC SSSIDSVKRL EHKLKEEEES LPGFVNLHST ETQTAGVIDR WELLQAQALS KELRMKQNLQ KWQQFNSDLN SIWAWLGDTE EELEQLQRLE LSTDIQTIEL QIKKLKELQK AVDHRKAIIL SINLCSPEFT QADSKESRDL QDRLSQMNGR WDRVCSLLEE WRGLLQDALM QCQGFHEMSH GLLLMLENID RRKNEIVPID SNLDAEILQD HHKQLMQIKH ELLESQLRVA SLQDMSCQLL VNAEGTDCLE AKEKVHVIGN RLKLLLKEVS RHIKELEKLL DVSSSQQDLS SWSSADELDT SGSVSPTSGR STPNRQKTPR GKCSLSQPGP SVSSPHSRST KGGSDSSLSE PGPGRSGRGF LFRVLRAALP LQLLLLLLIG LACLVPMSEE DYSCALSNNF ARSFHPMLRY TNGPPPL //