SYNE2_HUMAN
ID SYNE2_HUMAN Reviewed; 6885 AA.
AC Q8WXH0; B4DND7; B4DPR6; I6XXQ5; Q540G1; Q86YP9; Q8N1S3; Q8NF49; Q8TER7;
AC Q8WWW3; Q8WWW4; Q8WWW5; Q8WXH1; Q9NU50; Q9UFQ4; Q9Y2L4; Q9Y4R1;
DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Nesprin-2 {ECO:0000305};
DE AltName: Full=KASH domain-containing protein 2;
DE Short=KASH2;
DE AltName: Full=Nuclear envelope spectrin repeat protein 2;
DE AltName: Full=Nucleus and actin connecting element protein;
DE Short=Protein NUANCE;
DE AltName: Full=Synaptic nuclear envelope protein 2;
DE Short=Syne-2;
GN Name=SYNE2 {ECO:0000312|HGNC:HGNC:17084}; Synonyms=KIAA1011, NUA;
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 1 AND 9), FUNCTION, CHARACTERIZATION,
RP INTERACTION WITH F-ACTIN, AND VARIANTS THR-1969; VAL-2284; ASN-2359;
RP THR-2395; GLY-2802; VAL-2942; HIS-3253; ARG-3309 AND MET-5186.
RX PubMed=12118075; DOI=10.1242/jcs.115.15.3207;
RA Zhen Y.-Y., Libotte T., Munck M., Noegel A.A., Korenbaum E.;
RT "NUANCE, a giant protein connecting the nucleus and actin cytoskeleton.";
RL J. Cell Sci. 115:3207-3222(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5; 6; 7 AND 10).
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8), ALTERNATIVE SPLICING, AND
RP SUBCELLULAR LOCATION (ISOFORM 8).
RX PubMed=22768332; DOI=10.1371/journal.pone.0040098;
RA Rajgor D., Mellad J.A., Autore F., Zhang Q., Shanahan C.M.;
RT "Multiple novel nesprin-1 and nesprin-2 variants act as versatile tissue-
RT specific intracellular scaffolds.";
RL PLoS ONE 7:E40098-E40098(2012).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
RC TISSUE=Testis;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 11 AND 12), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-956 AND 5133-6885 (ISOFORM 1), AND VARIANT
RP MET-5186.
RC TISSUE=Heart, Spleen, and Tongue;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 8), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-88 (ISOFORM 3), AND NUCLEOTIDE SEQUENCE [LARGE
RP SCALE MRNA] OF 1-196 (ISOFORM 13).
RC TISSUE=Brain, and Ovary;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3367-6885 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [10]
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 [11]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5754-6885.
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=12958361; DOI=10.1126/science.1088176;
RA Schirmer E.C., Florens L., Guan T., Yates J.R. III, Gerace L.;
RT "Nuclear membrane proteins with potential disease links found by
RT subtractive proteomics.";
RL Science 301:1380-1382(2003).
RN [14]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH EMD AND
RP LMNA.
RX PubMed=15671068; DOI=10.1242/jcs.01642;
RA Zhang Q., Ragnauth C.D., Skepper J.N., Worth N.F., Warren D.T.,
RA Roberts R.G., Weissberg P.L., Ellis J.A., Shanahan C.M.;
RT "Nesprin-2 is a multi-isomeric protein that binds lamin and emerin at the
RT nuclear envelope and forms a subcellular network in skeletal muscle.";
RL J. Cell Sci. 118:673-687(2005).
RN [15]
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4108, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP SUBCELLULAR LOCATION, INTERACTION WITH MKS3, AND FUNCTION.
RX PubMed=19596800; DOI=10.1242/jcs.043794;
RA Dawe H.R., Adams M., Wheway G., Szymanska K., Logan C.V., Noegel A.A.,
RA Gull K., Johnson C.A.;
RT "Nesprin-2 interacts with meckelin and mediates ciliogenesis via
RT remodelling of the actin cytoskeleton.";
RL J. Cell Sci. 122:2716-2726(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4108, AND IDENTIFICATION BY
RP 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 [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-955, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [20]
RP INTERACTION WITH SUN1 AND SUN2.
RX PubMed=19933576; DOI=10.1074/jbc.m109.071910;
RA Haque F., Mazzeo D., Patel J.T., Smallwood D.T., Ellis J.A., Shanahan C.M.,
RA Shackleton S.;
RT "Mammalian SUN protein interaction networks at the inner nuclear membrane
RT and their role in laminopathy disease processes.";
RL J. Biol. Chem. 285:3487-3498(2010).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2781 AND SER-6361, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
RP FUNCTION.
RX PubMed=20724637; DOI=10.1126/science.1189072;
RA Luxton G.W., Gomes E.R., Folker E.S., Vintinner E., Gundersen G.G.;
RT "Linear arrays of nuclear envelope proteins harness retrograde actin flow
RT for nuclear movement.";
RL Science 329:956-959(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2781, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [26]
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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-841; SER-5785; SER-6361 AND
RP SER-6459, AND 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 [28]
RP ALTERNATIVE SPLICING (ISOFORMS 3 AND 13).
RX PubMed=24718612; DOI=10.1371/journal.pone.0094380;
RA Duong N.T., Morris G.E., Lam le T., Zhang Q., Sewry C.A., Shanahan C.M.,
RA Holt I.;
RT "Nesprins: tissue-specific expression of epsilon and other short
RT isoforms.";
RL PLoS ONE 9:E94380-E94380(2014).
RN [29]
RP SUBUNIT, AND DISULFIDE BOND.
RX PubMed=26244732; DOI=10.1016/j.bpj.2015.06.057;
RA Jahed Z., Shams H., Mofrad M.R.;
RT "A disulfide bond is required for the transmission of forces through SUN-
RT KASH complexes.";
RL Biophys. J. 109:501-509(2015).
RN [30]
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 [31]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 6857-6885 IN COMPLEX WITH SUN2,
RP SUBUNIT, AND MUTAGENESIS OF LEU-6876; TYR-6878 AND PRO-6883.
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 [32]
RP X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 6872-6885 IN COMPLEX WITH SUN2,
RP AND FUNCTION.
RX PubMed=22945352; DOI=10.1038/cr.2012.126;
RA Wang W., Shi Z., Jiao S., Chen C., Wang H., Liu G., Wang Q., Zhao Y.,
RA Greene M.I., Zhou Z.;
RT "Structural insights into SUN-KASH complexes across the nuclear envelope.";
RL Cell Res. 22:1440-1452(2012).
RN [33]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-5940 AND CYS-6200.
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 [34]
RP VARIANT EDMD5 MET-6211.
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).
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. Specifically, SYNE2 and SUN2
CC assemble in arrays of transmembrane actin-associated nuclear (TAN)
CC lines which are bound to F-actin cables and couple the nucleus to
CC retrograde actin flow during actin-dependent nuclear movement. May be
CC involved in nucleus-centrosome attachment. During interkinetic nuclear
CC migration (INM) at G2 phase and nuclear migration in neural progenitors
CC its LINC complex association with SUN1/2 and probable association with
CC cytoplasmic dynein-dynactin motor complexes functions to pull the
CC nucleus toward the centrosome; SYNE1 and SYNE2 may act redundantly.
CC During INM at G1 phase mediates respective LINC complex association
CC with kinesin to push the nucleus away from the centrosome. Involved in
CC nuclear migration in retinal photoreceptor progenitors. Required for
CC centrosome migration to the apical cell surface during early
CC ciliogenesis. {ECO:0000250|UniProtKB:Q6ZWQ0,
CC ECO:0000269|PubMed:12118075, ECO:0000269|PubMed:18396275,
CC ECO:0000269|PubMed:19596800, ECO:0000269|PubMed:20724637,
CC ECO:0000269|PubMed:22945352}.
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 some LINC complex constituents are tissue- or cell type-specific. At
CC least SUN1/2-containing core LINC complexes are proposed to be
CC hexameric composed of three protomers of each KASH and SUN domain-
CC containing protein. The SUN2:SYNE2/KASH2 complex is a heterohexamer;
CC the homotrimeric cloverleave-like conformation of the SUN domain is a
CC prerequisite for LINC complex formation in which three separate
CC SYNE2/KASH2 peptides bind at the interface of adjacent SUN domains.
CC Interacts with EMD, LMNA, MKS3 and F-actin via its N-terminal domain.
CC Interacts with DCTN1 and DYNC1I1/2; suggesting the association with the
CC dynein-dynactin motor complex. Associates with kinesin motor complexes.
CC Interacts with TMEM67. Interacts (via KASH domain) with TMEM258
CC (PubMed:28716842). {ECO:0000250|UniProtKB:Q6ZWQ0,
CC ECO:0000269|PubMed:12118075, ECO:0000269|PubMed:15671068,
CC ECO:0000269|PubMed:18396275, ECO:0000269|PubMed:19596800,
CC ECO:0000269|PubMed:19933576, ECO:0000269|PubMed:22632968,
CC ECO:0000269|PubMed:22945352, ECO:0000269|PubMed:28716842}.
CC -!- INTERACTION:
CC Q8WXH0; Q9UKG1: APPL1; NbExp=3; IntAct=EBI-2372294, EBI-741243;
CC Q8WXH0; Q9Y613: FHOD1; NbExp=4; IntAct=EBI-2372294, EBI-348433;
CC Q8WXH0; Q9UH99: SUN2; NbExp=8; IntAct=EBI-2372294, EBI-1044964;
CC Q8WXH0-1; P02545: LMNA; NbExp=3; IntAct=EBI-6170976, EBI-351935;
CC Q8WXH0-1; O94901: SUN1; NbExp=2; IntAct=EBI-6170976, EBI-2796904;
CC Q8WXH0-1; Q9UH99: SUN2; NbExp=2; IntAct=EBI-6170976, EBI-1044964;
CC Q8WXH0-3; P50402: EMD; NbExp=5; IntAct=EBI-10760388, EBI-489887;
CC Q8WXH0-4; Q9D666: Sun1; Xeno; NbExp=2; IntAct=EBI-6838657, EBI-6752574;
CC Q8WXH0-8; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12303825, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Nucleus outer membrane {ECO:0000305}; Single-pass
CC type IV membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC Sarcoplasmic reticulum membrane {ECO:0000305|PubMed:15671068}; Single-
CC pass type IV membrane protein {ECO:0000305}. Cell membrane
CC {ECO:0000305}; Single-pass membrane protein {ECO:0000305}. Cytoplasm,
CC cytoskeleton. Mitochondrion. Nucleus, nucleoplasm. Cytoplasm,
CC myofibril, sarcomere, Z line {ECO:0000305|PubMed:15671068}.
CC Note=Different isoform patterns are found in the different compartments
CC of the cell. The isoforms having the C-terminal transmembrane span can
CC be found in several organellar membranes like the nuclear envelope, the
CC sarcoplasmic reticulum of myoblasts, or the lamellipodia and focal
CC adhesions at the cell membrane. The largest part of the outer nuclear
CC membrane-associated protein is cytoplasmic, while its C-terminal part
CC is associated with the nuclear envelope, most probably the outer
CC nuclear membrane. Remains associated with the nuclear envelope during
CC its breakdown in mitotic cells. Shorter soluble isoforms can be found
CC in the cytoplasm and within the nucleus.
CC -!- SUBCELLULAR LOCATION: [Isoform 8]: Cell junction, focal adhesion
CC {ECO:0000269|PubMed:22768332}. Note=In U2OS cells.
CC {ECO:0000269|PubMed:22768332}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=13;
CC Name=1; Synonyms=Nesprin-2 Giant, NUANCE;
CC IsoId=Q8WXH0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WXH0-2; Sequence=VSP_007164, VSP_007166;
CC Name=3; Synonyms=epsilon2, JAM19;
CC IsoId=Q8WXH0-3; Sequence=VSP_007155;
CC Name=4; Synonyms=beta1;
CC IsoId=Q8WXH0-4; Sequence=VSP_007156;
CC Name=5; Synonyms=alpha1;
CC IsoId=Q8WXH0-5; Sequence=VSP_007157, VSP_007164, VSP_007165;
CC Name=6; Synonyms=alpha2;
CC IsoId=Q8WXH0-6; Sequence=VSP_007158, VSP_007165, VSP_007166;
CC Name=7; Synonyms=Gamma;
CC IsoId=Q8WXH0-7; Sequence=VSP_007154, VSP_007163;
CC Name=8; Synonyms=p32CH;
CC IsoId=Q8WXH0-8; Sequence=VSP_007161, VSP_007162;
CC Name=9; Synonyms=NUANCE-N-33;
CC IsoId=Q8WXH0-9; Sequence=VSP_007159, VSP_007160;
CC Name=10; Synonyms=beta2;
CC IsoId=Q8WXH0-10; Sequence=VSP_057484, VSP_007166;
CC Name=11; Synonyms=FLJ56122;
CC IsoId=Q8WXH0-11; Sequence=VSP_057483, VSP_057487;
CC Name=12; Synonyms=FLJ55476;
CC IsoId=Q8WXH0-12; Sequence=VSP_007157, VSP_007164;
CC Name=13; Synonyms=epsilon1, JAM28;
CC IsoId=Q8WXH0-13; Sequence=VSP_057485, VSP_057486;
CC -!- TISSUE SPECIFICITY: Widely expressed, with higher level in kidney,
CC adult and fetal liver, stomach and placenta. Weakly expressed in
CC skeletal muscle and brain. Isoform 5 is highly expressed in pancreas,
CC skeletal muscle and heart. {ECO:0000269|PubMed:15671068}.
CC -!- DOMAIN: The KASH domain mediates the nuclear envelope targeting.
CC {ECO:0000269|PubMed:18396275}.
CC -!- PTM: The disulfid bond with SUN2 is required for stability of the
CC SUN2:SYNE2/KASH2 LINC complex under tensile forces though not required
CC for the interaction. {ECO:0000269|PubMed:26244732}.
CC -!- DISEASE: Emery-Dreifuss muscular dystrophy 5, autosomal dominant
CC (EDMD5) [MIM:612999]: 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 -!- MISCELLANEOUS: [Isoform 3]: Produced by exon skipping that results in a
CC frameshift. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 8]: Lacks the spectrin repeats and KASH domain.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 13]: Detected only in ovary and early embryonic
CC cells. {ECO:0000269|PubMed:24718612}.
CC -!- SIMILARITY: Belongs to the nesprin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB84881.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB45729.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB55905.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF435010; AAL33547.1; -; mRNA.
DR EMBL; AF435011; AAL33548.1; -; mRNA.
DR EMBL; AY061757; AAL33800.1; -; mRNA.
DR EMBL; AY061758; AAL33801.1; -; mRNA.
DR EMBL; AY061759; AAL33802.1; -; mRNA.
DR EMBL; AY184204; AAO27772.1; -; mRNA.
DR EMBL; AY184205; AAO27773.1; -; mRNA.
DR EMBL; AF495911; AAN60443.1; -; mRNA.
DR EMBL; JQ754367; AFN44385.1; -; mRNA.
DR EMBL; AL117404; CAB55905.2; ALT_INIT; mRNA.
DR EMBL; AK074055; BAB84881.1; ALT_INIT; mRNA.
DR EMBL; AK090430; BAC03411.1; -; mRNA.
DR EMBL; AK095241; BAC04506.1; -; mRNA.
DR EMBL; AK297874; BAG60199.1; -; mRNA.
DR EMBL; AK298465; BAG60678.1; -; mRNA.
DR EMBL; AL162832; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355094; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359235; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC042134; AAH42134.1; -; mRNA.
DR EMBL; BC071873; AAH71873.1; -; mRNA.
DR EMBL; BM805144; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CD654909; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AB023228; BAA76855.3; -; mRNA.
DR EMBL; AL080133; CAB45729.1; ALT_INIT; mRNA.
DR CCDS; CCDS41963.1; -. [Q8WXH0-1]
DR CCDS; CCDS45124.1; -. [Q8WXH0-5]
DR CCDS; CCDS45125.1; -. [Q8WXH0-6]
DR CCDS; CCDS9761.2; -. [Q8WXH0-2]
DR PIR; T12520; T12520.
DR PIR; T17215; T17215.
DR RefSeq; NP_055995.4; NM_015180.4. [Q8WXH0-1]
DR RefSeq; NP_878914.1; NM_182910.2. [Q8WXH0-6]
DR RefSeq; NP_878917.1; NM_182913.2. [Q8WXH0-5]
DR RefSeq; NP_878918.2; NM_182914.2. [Q8WXH0-2]
DR PDB; 4DXS; X-ray; 2.71 A; B=6857-6885.
DR PDB; 4FI9; X-ray; 3.05 A; B=6872-6885.
DR PDB; 6XF1; X-ray; 2.80 A; A/C=1425-1649.
DR PDBsum; 4DXS; -.
DR PDBsum; 4FI9; -.
DR PDBsum; 6XF1; -.
DR SMR; Q8WXH0; -.
DR BioGRID; 116830; 164.
DR CORUM; Q8WXH0; -.
DR DIP; DIP-53409N; -.
DR ELM; Q8WXH0; -.
DR IntAct; Q8WXH0; 63.
DR MINT; Q8WXH0; -.
DR STRING; 9606.ENSP00000350719; -.
DR CarbonylDB; Q8WXH0; -.
DR GlyGen; Q8WXH0; 6 sites, 2 O-linked glycans (6 sites).
DR iPTMnet; Q8WXH0; -.
DR PhosphoSitePlus; Q8WXH0; -.
DR SwissPalm; Q8WXH0; -.
DR BioMuta; SYNE2; -.
DR DMDM; 116242809; -.
DR EPD; Q8WXH0; -.
DR jPOST; Q8WXH0; -.
DR MassIVE; Q8WXH0; -.
DR MaxQB; Q8WXH0; -.
DR PaxDb; Q8WXH0; -.
DR PeptideAtlas; Q8WXH0; -.
DR PRIDE; Q8WXH0; -.
DR ProteomicsDB; 70449; -.
DR ProteomicsDB; 75044; -. [Q8WXH0-1]
DR ProteomicsDB; 75045; -. [Q8WXH0-2]
DR ProteomicsDB; 75046; -. [Q8WXH0-3]
DR ProteomicsDB; 75047; -. [Q8WXH0-4]
DR ProteomicsDB; 75048; -. [Q8WXH0-5]
DR ProteomicsDB; 75049; -. [Q8WXH0-6]
DR ProteomicsDB; 75050; -. [Q8WXH0-7]
DR ProteomicsDB; 75051; -. [Q8WXH0-8]
DR ProteomicsDB; 75052; -. [Q8WXH0-9]
DR Antibodypedia; 189; 189 antibodies from 23 providers.
DR DNASU; 23224; -.
DR Ensembl; ENST00000341472.9; ENSP00000344528.5; ENSG00000054654.20. [Q8WXH0-8]
DR Ensembl; ENST00000344113.8; ENSP00000341781.4; ENSG00000054654.20. [Q8WXH0-1]
DR Ensembl; ENST00000358025.7; ENSP00000350719.3; ENSG00000054654.20. [Q8WXH0-2]
DR Ensembl; ENST00000458046.6; ENSP00000391937.2; ENSG00000054654.20. [Q8WXH0-5]
DR Ensembl; ENST00000555002.6; ENSP00000450831.2; ENSG00000054654.20. [Q8WXH0-2]
DR GeneID; 23224; -.
DR KEGG; hsa:23224; -.
DR MANE-Select; ENST00000555002.6; ENSP00000450831.2; NM_182914.3; NP_878918.2. [Q8WXH0-2]
DR UCSC; uc001xgk.4; human. [Q8WXH0-1]
DR UCSC; uc001xgr.5; human.
DR CTD; 23224; -.
DR DisGeNET; 23224; -.
DR GeneCards; SYNE2; -.
DR HGNC; HGNC:17084; SYNE2.
DR HPA; ENSG00000054654; Tissue enhanced (skeletal).
DR MalaCards; SYNE2; -.
DR MIM; 608442; gene.
DR MIM; 612999; phenotype.
DR neXtProt; NX_Q8WXH0; -.
DR OpenTargets; ENSG00000054654; -.
DR Orphanet; 98853; Autosomal dominant Emery-Dreifuss muscular dystrophy.
DR PharmGKB; PA128394613; -.
DR VEuPathDB; HostDB:ENSG00000054654; -.
DR eggNOG; KOG0516; Eukaryota.
DR GeneTree; ENSGT00940000154656; -.
DR HOGENOM; CLU_000034_2_0_1; -.
DR InParanoid; Q8WXH0; -.
DR OMA; AEHGKYQ; -.
DR PhylomeDB; Q8WXH0; -.
DR TreeFam; TF329280; -.
DR PathwayCommons; Q8WXH0; -.
DR Reactome; R-HSA-1221632; Meiotic synapsis.
DR SignaLink; Q8WXH0; -.
DR SIGNOR; Q8WXH0; -.
DR BioGRID-ORCS; 23224; 10 hits in 1078 CRISPR screens.
DR ChiTaRS; SYNE2; human.
DR GeneWiki; SYNE2; -.
DR GenomeRNAi; 23224; -.
DR Pharos; Q8WXH0; Tbio.
DR PRO; PR:Q8WXH0; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8WXH0; protein.
DR Bgee; ENSG00000054654; Expressed in ventricular zone and 202 other tissues.
DR ExpressionAtlas; Q8WXH0; baseline and differential.
DR Genevisible; Q8WXH0; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031527; C:filopodium membrane; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0031258; C:lamellipodium membrane; IDA:UniProtKB.
DR GO; GO:0034993; C:meiotic nuclear membrane microtubule tethering complex; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0031981; C:nuclear lumen; 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:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:CACAO.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030018; C:Z disc; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IEA:InterPro.
DR GO; GO:0140444; F:cytoskeleton-nuclear membrane anchor activity; IDA:GO_Central.
DR GO; GO:0051642; P:centrosome localization; IMP:UniProtKB.
DR GO; GO:0007097; P:nuclear migration; IMP:UniProtKB.
DR GO; GO:0031022; P:nuclear migration along microfilament; ISS:UniProtKB.
DR GO; GO:0021817; P:nucleokinesis involved in cell motility in cerebral cortex radial glia guided migration; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:1902017; P:regulation of cilium assembly; IEA:Ensembl.
DR CDD; cd00014; CH; 2.
DR CDD; cd00176; SPEC; 5.
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 InterPro; IPR030266; SYNE2.
DR PANTHER; PTHR47535:SF6; PTHR47535:SF6; 1.
DR Pfam; PF00307; CH; 2.
DR Pfam; PF10541; KASH; 1.
DR Pfam; PF00435; Spectrin; 3.
DR SMART; SM00033; CH; 2.
DR SMART; SM01249; KASH; 1.
DR SMART; SM00150; SPEC; 18.
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; Acetylation; Actin-binding; Alternative splicing;
KW Cell junction; Cell membrane; Coiled coil; Cytoplasm; Cytoskeleton;
KW Disease variant; Disulfide bond; Emery-Dreifuss muscular dystrophy;
KW Membrane; Mitochondrion; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Sarcoplasmic reticulum; Transmembrane; Transmembrane helix.
FT CHAIN 1..6885
FT /note="Nesprin-2"
FT /id="PRO_0000163592"
FT TOPO_DOM 1..6834
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385"
FT TRANSMEM 6835..6855
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385"
FT TOPO_DOM 6856..6885
FT /note="Perinuclear space"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385"
FT DOMAIN 31..136
FT /note="Calponin-homology (CH) 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT DOMAIN 181..286
FT /note="Calponin-homology (CH) 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT REPEAT 297..378
FT /note="Spectrin 1"
FT REPEAT 379..472
FT /note="Spectrin 2"
FT REPEAT 473..575
FT /note="Spectrin 3"
FT REPEAT 576..680
FT /note="Spectrin 4"
FT REPEAT 735..838
FT /note="Spectrin 5"
FT REPEAT 839..932
FT /note="Spectrin 6"
FT REPEAT 933..1034
FT /note="Spectrin 7"
FT REPEAT 1121..1212
FT /note="Spectrin 8"
FT REPEAT 1263..1323
FT /note="Spectrin 9"
FT REPEAT 1324..1419
FT /note="Spectrin 10"
FT REPEAT 1420..1524
FT /note="Spectrin 11"
FT REPEAT 1525..1636
FT /note="Spectrin 12"
FT REPEAT 1637..1738
FT /note="Spectrin 13"
FT REPEAT 1739..1830
FT /note="Spectrin 14"
FT REPEAT 1831..1938
FT /note="Spectrin 15"
FT REPEAT 1939..2036
FT /note="Spectrin 16"
FT REPEAT 2037..2132
FT /note="Spectrin 17"
FT REPEAT 2133..2243
FT /note="Spectrin 18"
FT REPEAT 2244..2360
FT /note="Spectrin 19"
FT REPEAT 2432..2513
FT /note="Spectrin 20"
FT REPEAT 2514..2620
FT /note="Spectrin 21"
FT REPEAT 2621..2717
FT /note="Spectrin 22"
FT REPEAT 2718..2831
FT /note="Spectrin 23"
FT REPEAT 2832..2933
FT /note="Spectrin 24"
FT REPEAT 2934..3036
FT /note="Spectrin 25"
FT REPEAT 3037..3142
FT /note="Spectrin 26"
FT REPEAT 3143..3248
FT /note="Spectrin 27"
FT REPEAT 3249..3352
FT /note="Spectrin 28"
FT REPEAT 3353..3465
FT /note="Spectrin 29"
FT REPEAT 3466..3573
FT /note="Spectrin 30"
FT REPEAT 3574..3679
FT /note="Spectrin 31"
FT REPEAT 3680..3777
FT /note="Spectrin 32"
FT REPEAT 3778..3880
FT /note="Spectrin 33"
FT REPEAT 3881..3986
FT /note="Spectrin 34"
FT REPEAT 3987..4086
FT /note="Spectrin 35"
FT REPEAT 4229..4348
FT /note="Spectrin 36"
FT REPEAT 4520..4639
FT /note="Spectrin 37"
FT REPEAT 4640..4727
FT /note="Spectrin 38"
FT REPEAT 4728..4837
FT /note="Spectrin 39"
FT REPEAT 4838..4943
FT /note="Spectrin 40"
FT REPEAT 4944..5051
FT /note="Spectrin 41"
FT REPEAT 5052..5164
FT /note="Spectrin 42"
FT REPEAT 5165..5266
FT /note="Spectrin 43"
FT REPEAT 5267..5391
FT /note="Spectrin 44"
FT REPEAT 5392..5487
FT /note="Spectrin 45"
FT REPEAT 5488..5589
FT /note="Spectrin 46"
FT REPEAT 5590..5704
FT /note="Spectrin 47"
FT REPEAT 5705..5799
FT /note="Spectrin 48"
FT REPEAT 5800..5907
FT /note="Spectrin 49"
FT REPEAT 5908..6017
FT /note="Spectrin 50"
FT REPEAT 6018..6135
FT /note="Spectrin 51"
FT REPEAT 6136..6243
FT /note="Spectrin 52"
FT REPEAT 6244..6355
FT /note="Spectrin 53"
FT REPEAT 6461..6549
FT /note="Spectrin 54"
FT REPEAT 6550..6665
FT /note="Spectrin 55"
FT REPEAT 6666..6782
FT /note="Spectrin 56"
FT DOMAIN 6826..6885
FT /note="KASH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385"
FT REGION 1..286
FT /note="Actin-binding"
FT REGION 1042..1084
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2368..2394
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4073..4162
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4184..4232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4335..4363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4416..4448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 6354..6508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 6769..6824
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 6872..6885
FT /note="Sufficient for interaction with SUN2"
FT /evidence="ECO:0000269|PubMed:22632968"
FT COILED 297..6782
FT /evidence="ECO:0000255"
FT COMPBIAS 1042..1062
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4118..4132
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4184..4213
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4335..4354
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 6354..6386
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 6425..6439
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 6479..6493
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 6804..6819
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 841
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 955
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 2781
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 4108
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 5785
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 6361
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 6384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZWQ0"
FT MOD_RES 6411
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZWQ0"
FT MOD_RES 6428
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZWQ0"
FT MOD_RES 6429
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZWQ0"
FT MOD_RES 6430
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZWQ0"
FT MOD_RES 6459
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT DISULFID 6862
FT /note="Interchain (with C-563 in SUN2)"
FT /evidence="ECO:0000269|PubMed:22632968,
FT ECO:0000305|PubMed:26244732"
FT VAR_SEQ 1..6469
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:11792814,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_007158"
FT VAR_SEQ 1..6434
FT /note="Missing (in isoform 11)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057483"
FT VAR_SEQ 1..6366
FT /note="Missing (in isoform 5 and isoform 12)"
FT /evidence="ECO:0000303|PubMed:11792814,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_007157"
FT VAR_SEQ 1..6217
FT /note="Missing (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:11792814"
FT /id="VSP_057484"
FT VAR_SEQ 1..6122
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11792814"
FT /id="VSP_007156"
FT VAR_SEQ 1..6030
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_007155"
FT VAR_SEQ 1..5850
FT /note="Missing (in isoform 13)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057485"
FT VAR_SEQ 1..3638
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:11792814"
FT /id="VSP_007154"
FT VAR_SEQ 263..285
FT /note="DVDVVDPDEKSIMTYVAQFLQYS -> DAWRSSALYRIYMPGTVSCASYL
FT (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007161"
FT VAR_SEQ 263..267
FT /note="DVDVV -> AYKNF (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:12118075"
FT /id="VSP_007159"
FT VAR_SEQ 268..6885
FT /note="Missing (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:12118075"
FT /id="VSP_007160"
FT VAR_SEQ 286..6885
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007162"
FT VAR_SEQ 3828
FT /note="Q -> QDSKCFRSGPRPNIYVSYYVTVIQ (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:11792814"
FT /id="VSP_007163"
FT VAR_SEQ 5851..5852
FT /note="IK -> MQ (in isoform 13)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057486"
FT VAR_SEQ 6435..6443
FT /note="EEGPYYSAL -> MTTKTLKAS (in isoform 11)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057487"
FT VAR_SEQ 6444
FT /note="S -> SDVEIPENPEAYLKMTTKTLKASS (in isoform 2, isoform
FT 5 and isoform 12)"
FT /evidence="ECO:0000303|PubMed:10231032,
FT ECO:0000303|PubMed:11792814, ECO:0000303|PubMed:14702039"
FT /id="VSP_007164"
FT VAR_SEQ 6664
FT /note="Q -> QGSKTRPRSDVLFFK (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:11792814,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_007165"
FT VAR_SEQ 6801
FT /note="Missing (in isoform 2, isoform 6 and isoform 10)"
FT /evidence="ECO:0000303|PubMed:10231032,
FT ECO:0000303|PubMed:11792814, ECO:0000303|PubMed:17974005"
FT /id="VSP_007166"
FT VARIANT 8
FT /note="P -> S (in dbSNP:rs2275017)"
FT /id="VAR_027947"
FT VARIANT 432
FT /note="S -> R (in dbSNP:rs35554503)"
FT /id="VAR_050238"
FT VARIANT 574
FT /note="I -> T (in dbSNP:rs9944035)"
FT /id="VAR_027948"
FT VARIANT 1393
FT /note="R -> W (in dbSNP:rs17751301)"
FT /id="VAR_050239"
FT VARIANT 1969
FT /note="M -> T (in dbSNP:rs4902264)"
FT /evidence="ECO:0000269|PubMed:12118075"
FT /id="VAR_050240"
FT VARIANT 2284
FT /note="A -> V (in dbSNP:rs4027402)"
FT /evidence="ECO:0000269|PubMed:12118075"
FT /id="VAR_050241"
FT VARIANT 2347
FT /note="A -> E (in dbSNP:rs34625768)"
FT /id="VAR_050242"
FT VARIANT 2358
FT /note="N -> S (in dbSNP:rs4027404)"
FT /id="VAR_027949"
FT VARIANT 2359
FT /note="S -> G (in dbSNP:rs7157465)"
FT /id="VAR_050243"
FT VARIANT 2359
FT /note="S -> N (in dbSNP:rs4027404)"
FT /evidence="ECO:0000269|PubMed:12118075"
FT /id="VAR_050244"
FT VARIANT 2394
FT /note="A -> T (in dbSNP:rs4027405)"
FT /id="VAR_027950"
FT VARIANT 2395
FT /note="A -> T (in dbSNP:rs4027405)"
FT /evidence="ECO:0000269|PubMed:12118075"
FT /id="VAR_050245"
FT VARIANT 2490
FT /note="V -> G (in dbSNP:rs34393543)"
FT /id="VAR_050246"
FT VARIANT 2564
FT /note="I -> V (in dbSNP:rs11628107)"
FT /id="VAR_050247"
FT VARIANT 2801
FT /note="G -> S (in dbSNP:rs1890908)"
FT /id="VAR_027951"
FT VARIANT 2802
FT /note="S -> G (in dbSNP:rs1890908)"
FT /evidence="ECO:0000269|PubMed:12118075"
FT /id="VAR_050248"
FT VARIANT 2942
FT /note="I -> V (in dbSNP:rs3829767)"
FT /evidence="ECO:0000269|PubMed:12118075"
FT /id="VAR_050249"
FT VARIANT 3026
FT /note="E -> D (in dbSNP:rs34843668)"
FT /id="VAR_050250"
FT VARIANT 3130
FT /note="N -> S (in dbSNP:rs11847087)"
FT /id="VAR_050251"
FT VARIANT 3253
FT /note="D -> H (in dbSNP:rs8010911)"
FT /evidence="ECO:0000269|PubMed:12118075"
FT /id="VAR_050252"
FT VARIANT 3309
FT /note="H -> R (in dbSNP:rs8010699)"
FT /evidence="ECO:0000269|PubMed:12118075"
FT /id="VAR_050253"
FT VARIANT 3523
FT /note="K -> Q (in dbSNP:rs35203186)"
FT /id="VAR_050254"
FT VARIANT 3982
FT /note="N -> H (in dbSNP:rs10137972)"
FT /id="VAR_050255"
FT VARIANT 4041
FT /note="R -> H (in dbSNP:rs17101661)"
FT /id="VAR_050256"
FT VARIANT 4912
FT /note="P -> A (in dbSNP:rs17766354)"
FT /id="VAR_050257"
FT VARIANT 4913
FT /note="E -> K (in dbSNP:rs12881815)"
FT /id="VAR_050258"
FT VARIANT 5086
FT /note="H -> Y (in dbSNP:rs2039475)"
FT /id="VAR_050259"
FT VARIANT 5186
FT /note="L -> M (in dbSNP:rs10151658)"
FT /evidence="ECO:0000269|PubMed:12118075,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_050260"
FT VARIANT 5547
FT /note="D -> N (in dbSNP:rs17179194)"
FT /id="VAR_050261"
FT VARIANT 5940
FT /note="V -> I (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036255"
FT VARIANT 6155
FT /note="A -> V (in dbSNP:rs2275014)"
FT /id="VAR_050262"
FT VARIANT 6200
FT /note="Y -> C (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036256"
FT VARIANT 6211
FT /note="T -> M (in EDMD5; dbSNP:rs36215895)"
FT /evidence="ECO:0000269|PubMed:17761684"
FT /id="VAR_062977"
FT VARIANT 6681
FT /note="K -> E (in dbSNP:rs35315070)"
FT /id="VAR_050263"
FT VARIANT 6697
FT /note="R -> W (in dbSNP:rs35700578)"
FT /id="VAR_050264"
FT MUTAGEN 6876
FT /note="L->A: Disrupts interaction with SUN2."
FT /evidence="ECO:0000269|PubMed:22632968"
FT MUTAGEN 6878
FT /note="Y->A: Disrupts interaction with SUN2."
FT /evidence="ECO:0000269|PubMed:22632968"
FT MUTAGEN 6883
FT /note="P->A: Disrupts interaction with SUN2."
FT /evidence="ECO:0000269|PubMed:22632968"
FT CONFLICT 668
FT /note="Missing (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 1087
FT /note="M -> T (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 3115
FT /note="F -> S (in Ref. 1; AAL33548)"
FT /evidence="ECO:0000305"
FT CONFLICT 3193
FT /note="E -> G (in Ref. 1; AAL33548)"
FT /evidence="ECO:0000305"
FT CONFLICT 3951
FT /note="Q -> L (in Ref. 2; AAL33802)"
FT /evidence="ECO:0000305"
FT CONFLICT 4001
FT /note="W -> Q (in Ref. 3; AAN60443)"
FT /evidence="ECO:0000305"
FT CONFLICT 4158
FT /note="S -> F (in Ref. 2; AAL33802 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 4209
FT /note="I -> T (in Ref. 2; AAL33802 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 4327
FT /note="E -> Q (in Ref. 2; AAL33802 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 4418
FT /note="N -> K (in Ref. 2; AAL33802 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 4713
FT /note="E -> G (in Ref. 1; AAL33548)"
FT /evidence="ECO:0000305"
FT CONFLICT 4733
FT /note="P -> S (in Ref. 2; AAL33802 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 4807
FT /note="N -> I (in Ref. 2; AAL33802 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 4826
FT /note="S -> P (in Ref. 2; AAL33802 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 5166
FT /note="E -> D (in Ref. 2; AAL33802 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 5646
FT /note="T -> A (in Ref. 2; AAL33802 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 5727
FT /note="K -> R (in Ref. 2; AAL33802 and 3)"
FT /evidence="ECO:0000305"
FT HELIX 1425..1451
FT /evidence="ECO:0007829|PDB:6XF1"
FT HELIX 1460..1492
FT /evidence="ECO:0007829|PDB:6XF1"
FT HELIX 1501..1556
FT /evidence="ECO:0007829|PDB:6XF1"
FT HELIX 1562..1564
FT /evidence="ECO:0007829|PDB:6XF1"
FT HELIX 1567..1586
FT /evidence="ECO:0007829|PDB:6XF1"
FT HELIX 1588..1606
FT /evidence="ECO:0007829|PDB:6XF1"
FT HELIX 1617..1646
FT /evidence="ECO:0007829|PDB:6XF1"
FT TURN 6867..6870
FT /evidence="ECO:0007829|PDB:4DXS"
FT STRAND 6871..6873
FT /evidence="ECO:0007829|PDB:4DXS"
FT STRAND 6875..6881
FT /evidence="ECO:0007829|PDB:4DXS"
SQ SEQUENCE 6885 AA; 796442 MW; 3D37E27B080ADBD8 CRC64;
MASSPELPTE DEQGSWGIDD LHISLQAEQE DTQKKAFTCW INSQLARHTS PSVISDLFTD
IKKGHVLLDL LEVLSGQQLP RDKGSNTFQC RINIEHALTF LRNRSIKLIN IHVTDIIDGN
PSIILGLIWT IILHFHIEKL AQTLSCNYNQ PSLDDVSVVD SSPASSPPAK KCSKVQARWQ
MSARKALLLW AQEQCATYES VNVTDFKSSW RNGMAFLAII HALRPDLIDM KSVKHRSNKD
NLREAFRIAE QELKIPRLLE PEDVDVVDPD EKSIMTYVAQ FLQYSKDAPG TGEEAQGKVK
DAMGWLTLQK EKLQKLLKDS ENDTYFKKYN SLLSFMESFN EEKKSFLDVL SIKRDLDELD
KDHLQLREAW DGLDHQINAW KIKLNYALPP PLHQTEAWLQ EVEELMDEDL SASQDHSQAV
TLIQEKMTLF KSLMDRFEHH SNILLTFENK DENHLPLVPP NKLEEMKRRI NNILEKKFIL
LLEFHYYKCL VLGLVDEVKS KLDIWNIKYG SRESVELLLE DWHKFIEEKE FLARLDTSFQ
KCGEIYKNLA GECQNINKQY MMVKSDVCMY RKNIYNVKST LQKVLACWAT YVENLRLLRA
CFEETKKEEI KEVPFETLAQ WNLEHATLNE AGNFLVEVSN DVVGSSISKE LRRLNKRWRK
LVSKTQLEMN LPLMIKKQDQ PTFDNSGNIL SKEEKATVEF STDMSVELPE NYNQNIKAGE
KHEKENEEFT GQLKVAKDVE KLIGQVEIWE AEAKSVLDQD DVDTSMEESL KHLIAKGSMF
DELMARSEDM LQMDIQNISS QESFQHVLTT GLQAKIQEAK EKVQINVVKL IAALKNLTDV
SPDLDIRLKM EESQKELESY MMRAQQLLGQ RESPGELISK HKEALIISNT KSLAKYLKAV
EELKNNVTED IKMSLEEKSR DVCAKWESLH HELSLYVQQL KIDIEKGKLS DNILKLEKQI
NKEKKLIRRG RTKGLIKEHE ACFSEEGCLY QLNHHMEVLR ELCEELPSQK SQQEVKRLLK
DYEQKIERLL KCASEIHMTL QPTAGGTSKN EGTITTSENR GGDPHSEAPF AKSDNQPSTE
KAMEPTMKFS LASVLRPLQE ESIMEKDYSA SINSLLERYD TYRDILEHHL QNNKFRITSD
FSSEEDRSSS CLQAKLTDLQ VIKNETDARW KEFEIISLKL ENHVNDIKKP FVIKERDTLK
ERERELQMTL NTRMESLETA LRLVLPVEKA SLLLCGSDLP LHKMAIQGFH LIDADRIYQH
LRNIQDSIAK QIEICNRLEE PGNFVLKELH PFDLHAMQNI ILKYKTQFEG MNHRVQRSED
TLKALEDFLA SLRTAKLSAE PVTDLSASDT QVAQENTLTV KNKEGEIHLM KDKAKHLDKC
LKMLDMSFKD AERGDDTSCE NLLDAFSIKL SETHGYGVQE EFTEENKLLE ACIFKNNELL
KNIQDVQSQI SKIGLKDPTV PAVKHRKKSL IRLDKVLDEY EEEKRHLQEM ANSLPHFKDG
REKTVNQQCQ NTVVLWENTK ALVTECLEQC GRVLELLKQY QNFKSILTTL IQKEESVISL
QASYMGKENL KKRIAEIEIV KEEFNEHLEV VDKINQVCKN LQFYLNKMKT FEEPPFEKEA
NIIVDRWLDI NEKTEDYYEN LGRALALWDK LFNLKNVIDE WTEKALQKME LHQLTEEDRE
RLKEELQVHE QKTSEFSRRV AEIQFLLQSS EIPLELQVME SSILNKMEHV QKCLTGESNC
HALSGSTAEL REDLDQAKTQ IGMTESLLKA LSPSDSLEIF TKLEEIQQQI LQQKHSMILL
ENQIGCLTPE LSELKKQYES VSDLFNTKKS VLQDHFSKLL NDQCKNFNDW FSNIKVNLKE
CFESSETKKS VEQKLQKLSD FLTLEGRNSK IKQVDSVLKH VKKHLPKAHV KELISWLVGQ
EFELEKMESI CQARAKELED SLQQLLRLQD DHRNLRKWLT NQEEKWKGME EPGEKTELFC
QALARKREQF ESVAQLNNSL KEYGFTEEEE IIMEATCLMD RYQTLLRQLS EIEEEDKLLP
TEDQSFNDLA HDVIHWIKEI KESLMVLNSS EGKMPLEERI QKIKEIILLK PEGDARIETI
MKQAESSEAP LVQKTLTDIS NQWDNTLHLA STYLSHQEKL LLEGEKYLQS KEDLRLMLIE
LKKKQEAGFA LQHGLQEKKA QLKIYKKFLK KAQDLTSLLK ELKSQGNYLL ECTKNPSFSE
EPWLEIKHLH ESLLQQLQDS VQNLDGHVRE HDSYQVCVTD LNTTLDNFSK EFVSFSDKPV
DQIAVEEKLQ KLQELENRLS LQDGTLKKIL ALAKSVKQNT SSVGQKIIKD DIKSLQCKQK
DLENRLASAK QEMECCLNSI LKSKRSTEKK GKFTLPGREK QATSDVQEST QESAAVEKLE
EDWEINKDSA VEMAMSKQLS LNAQESMKNT EDERKVNELQ NQPLELDTML RNEQLEEIEK
LYTQLEAKKA AIKPLEQTEC LNKTETGALV LHNIGYSAQH LDNLLQALIT LKKNKESQYC
VLRDFQEYLA AVESSMKALL TDKESLKVGP LDSVTYLDKI KKFIASIEKE KDSLGNLKIK
WENLSNHVTD MDKKLLESQI KQLEHGWEQV EQQIQKKYSQ QVVEYDEFTT LMNKVQDTEI
SLQQQQQHLQ LRLKSPEERA GNQSMIALTT DLQATKHGFS VLKGQAELQM KRIWGEKEKK
NLEDGINNLK KQWETLEPLH LEAENQIKKC DIRNKMKETI LWAKNLLGEL NPSIPLLPDD
ILSQIRKCKV THDGILARQQ SVESLAEEVK DKVPSLTTYE GSDLNNTLED LRNQYQMLVL
KSTQRSQQLE FKLEERSNFF AIIRKFQLMV QESETLIIPR VETAATEAEL KHHHVTLEAS
QKELQEIDSG ISTHLQELTN IYEELNVFER LFLEDQLKNL KIRTNRIQRF IQNTCNEVEH
KIKFCRQFHE KTSALQEEAD SIQRNELLLN QEVNKGVKEE IYNLKDRLTA IKCCILQVLK
LKKVFDYIGL NWDFSQLDQL QTQVFEKEKE LEEKIKQLDT FEEEHGKYQA LLSKMRAIDL
QIKKMTEVVL KAPDSSPESR RLNAQILSQR IEKAKCLCDE IIKKLNENKT FDDSFKEKEI
LQIKLNAEEN DKLYKVLQNM VLELSPKELD EKNCQDKLET SLHVLNQIKS QLQQPLLINL
EIKHIQNEKD NCEAFQEQVW AEMCSIKAVT AIEKQREENS SEASDVETKL REFEDLQMQL
NTSIDLRTNV LNDAYENLTR YKEAVTRAVE SITSLEAIII PYRVDVGNPE ESLEMPLRKQ
EELESTVAHI QDLTEKLGMI SSPEAKLQLQ YTLQELVSKN SAMKEAFKAQ ETEAERYLEN
YKCYRKMEED IYTNLSKMET VLGQSMSSLP LSYREALERL EQSKALVSNL ISTKEELMKL
RQILRLLRLR CTENDGICLL KIVSALWEKW LSLLEAAKEW EMWCEELKQE WKFVSEEIER
EAIILDNLQE ELPEISKTKE AATTEELSEL LDCLCQYGEN VEKQQLLLTL LLQRIRSIQN
VPESSGAVET VPAFQEITSM KERCNKLLQK VQKNKELVQT EIQERHSFTK EIIALKNFFQ
QTTTSFQNMA FQDHPEKSEQ FEELQSILKK GKLTFENIME KLRIKYSEMY TIVPAEIESQ
VEECRKALED IDEKISNEVL KSSPSYAMRR KIEEINNGLH NVEKMLQQKS KNIEKAQEIQ
KKMWDELDLW HSKLNELDSE VQDIVEQDPG QAQEWMDNLM IPFQQYQQVS QRAECRTSQL
NKATVKMEEY SDLLKSTEAW IENTSHLLAN PADYDSLRTL SHHASTVQMA LEDSEQKHNL
LHSIFMDLED LSIIFETDEL TQSIQELSNQ VTALQQKIME SLPQIQRMAD DVVAIESEVK
SMEKRVSKIK TILLSKEIFD FSPEEHLKHG EVILENIRPM KKTIAEIVSY QVELRLPQTG
MKPLPVFQRT NQLLQDIKLL ENVTQEQNEL LKVVIKQTNE WDEEIENLKQ ILNNYSAQFS
LEHMSPDQAD KLPQLQGEIE RMEKQILSLN QRKEDLLVDL KATVLNLHQH LKQEQEGVER
DRLPAVTSEE GGVAERDASE RKLNRRGSMS YLAAVEEEVE ESSVKSDNGD EKAEPSPQSW
SSLWKHDKDM EEDRASSSSG TIVQEAYGKI STSDNSMAQI LTPDSLNTEQ GPECSLRPNQ
TEEGTTPPIE ADTLDSSDAQ GGLEPRVEKT RPEPTEVLHA CKTQVAELEL WLQQANVAVE
PETLNADMQQ VLEQQLVGCQ AMLTEIEHKV AFLLETCKDQ GLGDNGATQH EAEALSLKLK
TVKCNLEKVQ MMLQEKHSED QHPTILKKSS EPEHQEALQP VNLSELESIV TERPQFSRQK
DFQQQQVLEL KPMEQKDFIK FIEFNAKKMW PQYCQHDNDT TQESSASNQA SSPENDVPDS
ILSPQGQNGD KWQYLHHELS SKIKLPLPQL VEPQVSTNMG ILPSVTMYNF RYPTTEELKT
YTTQLEDLRQ EASNLQTQEN MTEEAYINLD KKLFELFLTL SQCLSSVEEM LEMPRLYRED
GSGQQVHYET LALELKKLYL ALSDKKGDLL KAMTWPGENT NLLLECFDNL QVCLEHTQAA
AVCRSKSLKA GLDYNRSYQN EIKRLYHQLI KSKTSLQQSL NEISGQSVAE QLQKADAYTV
ELENAESRVA KLRDEGERLH LPYALLQEVY KLEDVLDSMW GMLRARYTEL SSPFVTESQQ
DALLQGMVEL VKIGKEKLAH GHLKQTKSKV ALQAQIENHK VFFQKLVADM LLIQAYSAKI
LPSLLQNRET FWAEQVTEVK ILEEKSRQCG MKLQSLLQKW EEFDENYASL EKDLEILIST
LPSVSLVEET EERLVERISF YQQIKRNIGG KHARLYQTLN EGKQLVASVS CPELEGQIAK
LEEQWLSLNK KIDHELHRLQ ALLKHLLSYN RDSDQLTKWL ESSQHTLNYW KEQSLNVSQD
LDTIRSNINN FFEFSKEVDE KSSLKTAVIS IGNQLLHLKE TDTATLRASL AQFEQKWTML
ITQLPDIQEK LHQLQMEKLP SRKAITEMIS WMNNVEHQTS DEDSVHSPSS ASQVKHLLQK
HKEFRMEMDY KQWIVDFVNQ SLLQLSTCDV ESKRYERTEF AEHLGEMNRQ WHRVHGMLNR
KIQHLEQLLE SITESENKIQ ILNNWLEAQE ERLKTLQKPE SVISVQKLLL DCQDIENQLA
IKSKALDELK QSYLTLESGA VPLLEDTASR IDELFQKRSS VLTQVNQLKT SMQSVLQEWK
IYDQLYDEVN MMTIRFWYCM EHSKPVVLSL ETLRCQVENL QSLQDEAESS EGSWEKLQEV
IGKLKGLCPS VAEIIEEKCQ NTHKRWTQVN QAIADQLQKA QSLLQLWKAY SNAHGEAAAR
LKQQEAKFQQ LANISMSGNN LAEILPPALQ DIKELQHDVQ KTKEAFLQNS SVLDRLPQPA
ESSTHMLLPG PLHSLQRAAY LEKMLLVKAN EFEFVLSQFK DFGVRLESLK GLIMHEEENL
DRLHQQEKEN PDSFLNHVLA LTAQSPDIEH LNEVSLKLPL SDVAVKTLQN MNRQWIRATA
TALERCSELQ GIGLNEKFLY CCEKWIQLLE KIEEALKVDV ANSLPELLEQ QKTYKMLEAE
VSINQTIADS YVTQSLQLLD TTEIENRPEF ITEFSKLTDR WQNAVQGVRQ RKGDVDGLVR
QWQDFTTSVE NLFRFLTDTS HLLSAVKGQE RFSLYQTRSL IHELKNKEIH FQRRRTTCAL
TLEAGEKLLL TTDLKTKESV GRRISQLQDS WKDMEPQLAE MIKQFQSTVE TWDQCEKKIK
ELKSRLQVLK AQSEDPLPEL HEDLHNEKEL IKELEQSLAS WTQNLKELQT MKADLTRHVL
VEDVMVLKEQ IEHLHRQWED LCLRVAIRKQ EIEDRLNTWV VFNEKNKELC AWLVQMENKV
LQTADISIEE MIEKLQKDCM EEINLFSENK LQLKQMGDQL IKASNKSRAA EIDDKLNKIN
DRWQHLFDVI GSRVKKLKET FAFIQQLDKN MSNLRTWLAR IESELSKPVV YDVCDDQEIQ
KRLAEQQDLQ RDIEQHSAGV ESVFNICDVL LHDSDACANE TECDSIQQTT RSLDRRWRNI
CAMSMERRMK IEETWRLWQK FLDDYSRFED WLKSAERTAA CPNSSEVLYT SAKEELKRFE
AFQRQIHERL TQLELINKQY RRLARENRTD TASRLKQMVH EGNQRWDNLQ RRVTAVLRRL
RHFTNQREEF EGTRESILVW LTEMDLQLTN VEHFSESDAD DKMRQLNGFQ QEITLNTNKI
DQLIVFGEQL IQKSEPLDAV LIEDELEELH RYCQEVFGRV SRFHRRLTSC TPGLEDEKEA
SENETDMEDP REIQTDSWRK RGESEEPSSP QSLCHLVAPG HERSGCETPV SVDSIPLEWD
HTGDVGGSSS HEEDEEGPYY SALSGKSISD GHSWHVPDSP SCPEHHYKQM EGDRNVPPVP
PASSTPYKPP YGKLLLPPGT DGGKEGPRVL NGNPQQEDGG LAGITEQQSG AFDRWEMIQA
QELHNKLKIK QNLQQLNSDI SAITTWLKKT EAELEMLKMA KPPSDIQEIE LRVKRLQEIL
KAFDTYKALV VSVNVSSKEF LQTESPESTE LQSRLRQLSL LWEAAQGAVD SWRGGLRQSL
MQCQDFHQLS QNLLLWLASA KNRRQKAHVT DPKADPRALL ECRRELMQLE KELVERQPQV
DMLQEISNSL LIKGHGEDCI EAEEKVHVIE KKLKQLREQV SQDLMALQGT QNPASPLPSF
DEVDSGDQPP ATSVPAPRAK QFRAVRTTEG EEETESRVPG STRPQRSFLS RVVRAALPLQ
LLLLLLLLLA CLLPSSEEDY SCTQANNFAR SFYPMLRYTN GPPPT
