SYNE1_HUMAN
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 03-AUG-2022, entry version 199.
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=10.1006/geno.2002.6859;
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; Q9UH99: SUN2; NbExp=3; 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";
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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; CCDS5235.1; -. [Q8NF91-4]
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; 83.
DR CORUM; Q8NF91; -.
DR IntAct; Q8NF91; 39.
DR MINT; Q8NF91; -.
DR STRING; 9606.ENSP00000356224; -.
DR CarbonylDB; Q8NF91; -.
DR GlyGen; Q8NF91; 2 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; Q8NF91; -.
DR PhosphoSitePlus; Q8NF91; -.
DR BioMuta; SYNE1; -.
DR DMDM; 425906075; -.
DR EPD; Q8NF91; -.
DR jPOST; Q8NF91; -.
DR MassIVE; Q8NF91; -.
DR MaxQB; Q8NF91; -.
DR PaxDb; Q8NF91; -.
DR PeptideAtlas; Q8NF91; -.
DR PRIDE; 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 Antibodypedia; 19931; 164 antibodies from 25 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 CTD; 23345; -.
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; NMIREST; -.
DR OrthoDB; 47at2759; -.
DR TreeFam; TF329280; -.
DR PathwayCommons; Q8NF91; -.
DR Reactome; R-HSA-1221632; Meiotic synapsis.
DR SignaLink; Q8NF91; -.
DR SIGNOR; Q8NF91; -.
DR BioGRID-ORCS; 23345; 9 hits in 1072 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 189 other tissues.
DR ExpressionAtlas; Q8NF91; baseline and differential.
DR Genevisible; Q8NF91; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0034993; C:meiotic nuclear membrane microtubule tethering complex; IDA:UniProtKB.
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: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:0007030; P:Golgi organization; IDA:UniProtKB.
DR GO; GO:0042692; P:muscle cell differentiation; IDA:UniProtKB.
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:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR CDD; cd00014; CH; 2.
DR CDD; cd00176; SPEC; 14.
DR Gene3D; 1.10.418.10; -; 2.
DR InterPro; IPR001589; Actinin_actin-bd_CS.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR036872; CH_dom_sf.
DR InterPro; IPR012315; KASH.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR002017; Spectrin_repeat.
DR Pfam; PF00307; CH; 2.
DR Pfam; PF10541; KASH; 1.
DR Pfam; PF00435; Spectrin; 10.
DR SMART; SM00033; CH; 2.
DR SMART; SM01249; KASH; 1.
DR SMART; SM00150; SPEC; 45.
DR SUPFAM; SSF47576; SSF47576; 1.
DR PROSITE; PS00019; ACTININ_1; 1.
DR PROSITE; PS00020; ACTININ_2; 1.
DR PROSITE; PS50021; CH; 2.
DR PROSITE; PS51049; KASH; 1.
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; unknown pathological 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; unknown pathological 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; unknown pathological 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; unknown pathological 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
