DAG1_HUMAN
ID DAG1_HUMAN Reviewed; 895 AA.
AC Q14118; A8K6M7; Q969J9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Dystroglycan 1 {ECO:0000312|HGNC:HGNC:2666};
DE AltName: Full=Dystroglycan {ECO:0000303|PubMed:8268918};
DE AltName: Full=Dystrophin-associated glycoprotein 1 {ECO:0000312|HGNC:HGNC:2666};
DE Contains:
DE RecName: Full=Alpha-dystroglycan;
DE Short=Alpha-DG;
DE Contains:
DE RecName: Full=Beta-dystroglycan;
DE Short=Beta-DG;
DE Flags: Precursor;
GN Name=DAG1 {ECO:0000312|HGNC:HGNC:2666};
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], TISSUE SPECIFICITY, AND VARIANT TRP-14.
RC TISSUE=Skeletal muscle;
RX PubMed=8268918; DOI=10.1093/hmg/2.10.1651;
RA Ibraghimov-Beskrovnaya O., Milatovich A., Ozcelik T., Yang B., Koepnick K.,
RA Francke U., Campbell K.P.;
RT "Human dystroglycan: skeletal muscle cDNA, genomic structure, origin of
RT tissue specific isoforms and chromosomal localization.";
RL Hum. Mol. Genet. 2:1651-1657(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TRP-14.
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT TRP-14.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TRP-14.
RC TISSUE=Muscle;
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 [6]
RP INTERACTION WITH DMD.
RX PubMed=7592992; DOI=10.1074/jbc.270.45.27305;
RA Jung D., Yang B., Meyer J., Chamberlain J.S., Campbell K.P.;
RT "Identification and characterization of the dystrophin anchoring site on
RT beta-dystroglycan.";
RL J. Biol. Chem. 270:27305-27310(1995).
RN [7]
RP FUNCTION (MICROBIAL INFECTION) AS RECEPTOR FOR MYCOBACTERIUM LEPRAE,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH LAMA2.
RX PubMed=9851927; DOI=10.1126/science.282.5396.2076;
RA Rambukkana A., Yamada H., Zanazzi G., Mathus T., Salzer J.L.,
RA Yurchenco P.D., Campbell K.P., Fischetti V.A.;
RT "Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium
RT leprae.";
RL Science 282:2076-2079(1998).
RN [8]
RP INTERACTION WITH UTRN.
RX PubMed=10767429; DOI=10.1016/s0014-5793(00)01400-9;
RA Tommasi di Vignano A., Di Zenzo G., Sudol M., Cesareni G., Dente L.;
RT "Contribution of the different modules in the utrophin carboxy-terminal
RT region to the formation and regulation of the DAP complex.";
RL FEBS Lett. 471:229-234(2000).
RN [9]
RP INTERACTION WITH CAV3.
RX PubMed=10988290; DOI=10.1074/jbc.m005321200;
RA Sotgia F., Lee J.K., Das K., Bedford M., Petrucci T.C., Macioce P.,
RA Sargiacomo M., Bricarelli F.D., Minetti C., Sudol M., Lisanti M.P.;
RT "Caveolin-3 directly interacts with the C-terminal tail of beta
RT -dystroglycan. Identification of a central WW-like domain within caveolin
RT family members.";
RL J. Biol. Chem. 275:38048-38058(2000).
RN [10]
RP PHOSPHORYLATION, AND INTERACTION WITH UTRN.
RX PubMed=10769203; DOI=10.1242/jcs.113.10.1717;
RA James M., Nuttall A., Ilsley J.L., Ottersbach K., Tinsley J.M., Sudol M.,
RA Winder S.J.;
RT "Adhesion-dependent tyrosine phosphorylation of (beta)-dystroglycan
RT regulates its interaction with utrophin.";
RL J. Cell Sci. 113:1717-1726(2000).
RN [11]
RP PHOSPHORYLATION, INTERACTION WITH FYN; CSK; NCK AND SHC, AND POSSIBLE
RP FUNCTION.
RX PubMed=11724572; DOI=10.1021/bi011247r;
RA Sotgia F., Lee H., Bedford M.T., Petrucci T., Sudol M., Lisanti M.P.;
RT "Tyrosine phosphorylation of beta-dystroglycan at its WW domain binding
RT motif, PPxY, recruits SH2 domain containing proteins.";
RL Biochemistry 40:14585-14592(2001).
RN [12]
RP PHOSPHORYLATION AT TYR-892, AND INTERACTION WITH DMD.
RX PubMed=11495720; DOI=10.1016/s0898-6568(01)00188-7;
RA Ilsley J.L., Sudol M., Winder S.J.;
RT "The interaction of dystrophin with beta-dystroglycan is regulated by
RT tyrosine phosphorylation.";
RL Cell. Signal. 13:625-632(2001).
RN [13]
RP GLYCOSYLATION, LIGAND-BINDING, AND ASSOCIATION WITH CONGENITAL MUSCULAR
RP DYSTROPHIES.
RX PubMed=12140558; DOI=10.1038/nature00837;
RA Michele D.E., Barresi R., Kanagawa M., Saito F., Cohn R.D., Satz J.S.,
RA Dollar J., Nishino I., Kelley R.I., Somer H., Straub V., Mathews K.D.,
RA Moore S.A., Campbell K.P.;
RT "Post-translational disruption of dystroglycan-ligand interactions in
RT congenital muscular dystrophies.";
RL Nature 418:417-422(2002).
RN [14]
RP PHOSPHORYLATION AT TYR-892, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP TYR-892.
RX PubMed=12795607; DOI=10.1021/bi0271289;
RA Sotgia F., Bonuccelli G., Bedford M., Brancaccio A., Mayer U., Wilson M.T.,
RA Campos-Gonzalez R., Brooks J.W., Sudol M., Lisanti M.P.;
RT "Localization of phospho-beta-dystroglycan (pY892) to an intracellular
RT vesicular compartment in cultured cells and skeletal muscle fibers in
RT vivo.";
RL Biochemistry 42:7110-7123(2003).
RN [15]
RP INTERACTION WITH AGR2 AND AGR3.
RX PubMed=12592373; DOI=10.1038/sj.bjc.6600740;
RA Fletcher G.C., Patel S., Tyson K., Adam P.J., Schenker M., Loader J.A.,
RA Daviet L., Legrain P., Parekh R., Harris A.L., Terrett J.A.;
RT "hAG-2 and hAG-3, human homologues of genes involved in differentiation,
RT are associated with oestrogen receptor-positive breast tumours and interact
RT with metastasis gene C4.4a and dystroglycan.";
RL Br. J. Cancer 88:579-585(2003).
RN [16]
RP PROTEOLYTIC PROCESSING OF THE BETA SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=15175026; DOI=10.1111/j.0022-202x.2004.22605.x;
RA Herzog C., Has C., Franzke C.W., Echtermeyer F.G., Schlotzer-Schrehardt U.,
RA Kroger S., Gustafsson E., Fassler R., Bruckner-Tuderman L.;
RT "Dystroglycan in skin and cutaneous cells: beta-subunit is shed from the
RT cell surface.";
RL J. Invest. Dermatol. 122:1372-1380(2004).
RN [17]
RP GLYCOSYLATION, FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH
RP LYMPHOCYCTIC CHORIOMENINGITIS VIRUS GLYCOPROTEIN.
RX PubMed=16254364; DOI=10.1128/jvi.79.22.14297-14308.2005;
RA Imperiali M., Thoma C., Pavoni E., Brancaccio A., Callewaert N.,
RA Oxenius A.;
RT "O Mannosylation of alpha-dystroglycan is essential for lymphocytic
RT choriomeningitis virus receptor function.";
RL J. Virol. 79:14297-14308(2005).
RN [18]
RP DISULFIDE BOND.
RX PubMed=17212656; DOI=10.1111/j.1365-2443.2006.01033.x;
RA Watanabe N., Sasaoka T., Noguchi S., Nishino I., Tanaka T.;
RT "Cys669-Cys713 disulfide bridge formation is a key to dystroglycan cleavage
RT and subunit association.";
RL Genes Cells 12:75-88(2007).
RN [19]
RP GLYCOSYLATION, AND FUNCTION (MICROBIAL INFECTION) AS RECEPTOR FOR OLD WORLD
RP AND CLADE C NEW WORLD ARENAVIRUSES.
RX PubMed=17360738; DOI=10.1128/jvi.02574-06;
RA Rojek J.M., Spiropoulou C.F., Campbell K.P., Kunz S.;
RT "Old World and clade C New World arenaviruses mimic the molecular mechanism
RT of receptor recognition used by alpha-dystroglycan's host-derived
RT ligands.";
RL J. Virol. 81:5685-5695(2007).
RN [20]
RP AUTOCATALYTIC CLEAVAGE AT GLY-653, GLYCOSYLATION, LIGAND-BINDING, AND
RP MUTAGENESIS OF SER-654.
RX PubMed=17905726; DOI=10.1096/fj.07-8354com;
RA Akhavan A., Crivelli S.N., Singh M., Lingappa V.R., Muschler J.L.;
RT "SEA domain proteolysis determines the functional composition of
RT dystroglycan.";
RL FASEB J. 22:612-621(2008).
RN [21]
RP SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, GLYCOSYLATION AT ASN-661, AND
RP MUTAGENESIS OF SER-654; THR-663; 777-LYS--LYS-780; 793-LYS-LYS-794;
RP LYS-823; 828-PRO-PRO-829 AND TYR-831.
RX PubMed=18764929; DOI=10.1111/j.1600-0854.2008.00822.x;
RA Oppizzi M.L., Akhavan A., Singh M., Fata J.E., Muschler J.L.;
RT "Nuclear translocation of beta-dystroglycan reveals a distinctive
RT trafficking pattern of autoproteolyzed mucins.";
RL Traffic 9:2063-2072(2008).
RN [22]
RP PROTEOLYTIC PROCESSING OF BETA SUBUNIT, PROTEOLYTIC CLEAVAGE AT HIS-715,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19946898; DOI=10.1002/iub.273;
RA Bozzi M., Inzitari R., Sbardell D., Monaco S., Pavoni E., Gioia M.,
RA Marini S., Morlacchi S., Sciandra F., Castagnola M., Giardina B.,
RA Brancaccio A., Coletta M.;
RT "Enzymatic processing of beta-dystroglycan recombinant ectodomain by MMP-9:
RT identification of the main cleavage site.";
RL IUBMB Life 61:1143-1152(2009).
RN [23]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS], AND STRUCTURE OF CARBOHYDRATES.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=19838169; DOI=10.1038/nmeth.1392;
RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G.,
RA Larson G.;
RT "Enrichment of glycopeptides for glycan structure and attachment site
RT identification.";
RL Nat. Methods 6:809-811(2009).
RN [24]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH LASSA VIRUS
RP GLYCOPROTEIN.
RX PubMed=19324387; DOI=10.1016/j.virol.2009.02.042;
RA Kunz S.;
RT "Receptor binding and cell entry of Old World arenaviruses reveal novel
RT aspects of virus-host interaction.";
RL Virology 387:245-249(2009).
RN [25]
RP STRUCTURE OF CARBOHYDRATES, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP GLYCOSYLATION AT THR-367; THR-369; THR-372 AND THR-455.
RX PubMed=20507882; DOI=10.1093/glycob/cwq082;
RA Nilsson J., Nilsson J., Larson G., Grahn A.;
RT "Characterization of site-specific O-glycan structures within the mucin-
RT like domain of {alpha}-dystroglycan from human skeletal muscle.";
RL Glycobiology 20:1160-1169(2010).
RN [26]
RP PHOSPHORYLATION AT TYR-892, NUCLEAR LOCALIZATION SIGNAL, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF 777-LYS--LYS-782; ARG-779; LYS-780 AND
RP TYR-892.
RX PubMed=20512930; DOI=10.1002/jcb.22581;
RA Lara-Chacon B., de Leon M.B., Leocadio D., Gomez P., Fuentes-Mera L.,
RA Martinez-Vieyra I., Ortega A., Jans D.A., Cisneros B.;
RT "Characterization of an Importin alpha/beta-recognized nuclear localization
RT signal in beta-dystroglycan.";
RL J. Cell. Biochem. 110:706-717(2010).
RN [27]
RP GLYCOSYLATION AT THR-379; THR-381 AND THR-388, PHOSPHORYLATION AT THR-379,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=20044576; DOI=10.1126/science.1180512;
RA Yoshida-Moriguchi T., Yu L., Stalnaker S.H., Davis S., Kunz S., Madson M.,
RA Oldstone M.B., Schachter H., Wells L., Campbell K.P.;
RT "O-mannosyl phosphorylation of alpha-dystroglycan is required for laminin
RT binding.";
RL Science 327:88-92(2010).
RN [28]
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 [29]
RP GLYCOSYLATION AT THR-317 AND THR-319, PHOSPHORYLATION AT THR-317 AND
RP THR-319, AND MUTAGENESIS OF 317-THR--THR-319 AND 328-THR-THR-329.
RX PubMed=21987822; DOI=10.1073/pnas.1114836108;
RA Hara Y., Kanagawa M., Kunz S., Yoshida-Moriguchi T., Satz J.S.,
RA Kobayashi Y.M., Zhu Z., Burden S.J., Oldstone M.B., Campbell K.P.;
RT "Like-acetylglucosaminyltransferase (LARGE)-dependent modification of
RT dystroglycan at Thr-317/319 is required for laminin binding and arenavirus
RT infection.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:17426-17431(2011).
RN [30]
RP GLYCOSYLATION AT THR-379, AND MUTAGENESIS OF 311-ARG--ILE-370;
RP 368-VAL--ARG-461 AND THR-379.
RX PubMed=23723439; DOI=10.1093/glycob/cwt043;
RA Nakagawa N., Takematsu H., Oka S.;
RT "HNK-1 sulfotransferase-dependent sulfation regulating laminin-binding
RT glycans occurs in the post-phosphoryl moiety on alpha-dystroglycan.";
RL Glycobiology 23:1066-1074(2013).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-790, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [32]
RP GLYCOSYLATION AT THR-63, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23234360; DOI=10.1021/pr300963h;
RA Halim A., Ruetschi U., Larson G., Nilsson J.;
RT "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT of human cerebrospinal fluid glycoproteins.";
RL J. Proteome Res. 12:573-584(2013).
RN [33]
RP GLYCOSYLATION AT THR-317 AND THR-319, PHOSPHORYLATION AT THR-317 AND
RP THR-319, AND MUTAGENESIS OF 317-THR--THR-319.
RX PubMed=24256719; DOI=10.1038/srep03288;
RA Yagi H., Nakagawa N., Saito T., Kiyonari H., Abe T., Toda T., Wu S.W.,
RA Khoo K.H., Oka S., Kato K.;
RT "AGO61-dependent GlcNAc modification primes the formation of functional
RT glycans on alpha-dystroglycan.";
RL Sci. Rep. 3:3288-3288(2013).
RN [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-790, AND IDENTIFICATION BY
RP 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 [35]
RP INVOLVEMENT IN MDDGC9, VARIANT MDDGC9 MET-192, AND CHARACTERIZATION OF
RP VARIANT MDDGC9 MET-192.
RX PubMed=21388311; DOI=10.1056/nejmoa1006939;
RA Hara Y., Balci-Hayta B., Yoshida-Moriguchi T., Kanagawa M.,
RA Beltran-Valero de Bernabe D., Gundesli H., Willer T., Satz J.S.,
RA Crawford R.W., Burden S.J., Kunz S., Oldstone M.B., Accardi A., Talim B.,
RA Muntoni F., Topaloglu H., Dincer P., Campbell K.P.;
RT "A dystroglycan mutation associated with limb-girdle muscular dystrophy.";
RL N. Engl. J. Med. 364:939-946(2011).
RN [36]
RP INVOLVEMENT IN MDDGA9, AND VARIANT MDDGA9 PHE-669.
RX PubMed=24052401; DOI=10.1007/s10048-013-0374-9;
RA Geis T., Marquard K., Roedl T., Reihle C., Schirmer S., von Kalle T.,
RA Bornemann A., Hehr U., Blankenburg M.;
RT "Homozygous dystroglycan mutation associated with a novel muscle-eye-brain
RT disease-like phenotype with multicystic leucodystrophy.";
RL Neurogenetics 14:205-213(2013).
RN [37]
RP INVOLVEMENT IN MDDGC9, VARIANTS MDDGC9 ILE-74 AND ASN-111, AND
RP CHARACTERIZATION OF VARIANTS MDDGC9 ILE-74 AND ASN-111.
RX PubMed=25503980; DOI=10.1212/wnl.0000000000001162;
RA Dong M., Noguchi S., Endo Y., Hayashi Y.K., Yoshida S., Nonaka I.,
RA Nishino I.;
RT "DAG1 mutations associated with asymptomatic hyperCKemia and
RT hypoglycosylation of alpha-dystroglycan.";
RL Neurology 84:273-279(2015).
RN [38]
RP INVOLVEMENT IN MDDGA9.
RX PubMed=25934851; DOI=10.1212/wnl.0000000000001615;
RA Riemersma M., Mandel H., van Beusekom E., Gazzoli I., Roscioli T., Eran A.,
RA Gershoni-Baruch R., Gershoni M., Pietrokovski S., Vissers L.E.,
RA Lefeber D.J., Willemsen M.A., Wevers R.A., van Bokhoven H.;
RT "Absence of alpha- and beta-dystroglycan is associated with Walker-Warburg
RT syndrome.";
RL Neurology 84:2177-2182(2015).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 881-895.
RX PubMed=10932245; DOI=10.1038/77923;
RA Huang X., Poy F., Zhang R., Joachimiak A., Sudol M., Eck M.J.;
RT "Structure of a WW domain containing fragment of dystrophin in complex with
RT beta-dystroglycan.";
RL Nat. Struct. Biol. 7:634-638(2000).
RN [40] {ECO:0007744|PDB:5GGP}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 316-325 IN COMPLEX WITH POMGNT1.
RX PubMed=27493216; DOI=10.1073/pnas.1525545113;
RA Kuwabara N., Manya H., Yamada T., Tateno H., Kanagawa M., Kobayashi K.,
RA Akasaka-Manya K., Hirose Y., Mizuno M., Ikeguchi M., Toda T.,
RA Hirabayashi J., Senda T., Endo T., Kato R.;
RT "Carbohydrate-binding domain of the POMGnT1 stem region modulates O-
RT mannosylation sites of alpha-dystroglycan.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:9280-9285(2016).
RN [41] {ECO:0007744|PDB:5LLK}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 52-315, AND DISULFIDE BONDS.
RX PubMed=28781947; DOI=10.1002/2211-5463.12259;
RA Covaceuszach S., Bozzi M., Bigotti M.G., Sciandra F., Konarev P.V.,
RA Brancaccio A., Cassetta A.;
RT "Structural flexibility of human alpha-dystroglycan.";
RL FEBS Open Bio 7:1064-1077(2017).
CC -!- FUNCTION: The dystroglycan complex is involved in a number of processes
CC including laminin and basement membrane assembly, sarcolemmal
CC stability, cell survival, peripheral nerve myelination, nodal
CC structure, cell migration, and epithelial polarization.
CC -!- FUNCTION: [Alpha-dystroglycan]: Extracellular peripheral glycoprotein
CC that acts as a receptor for extracellular matrix proteins containing
CC laminin-G domains. Receptor for laminin-2 (LAMA2) and agrin in
CC peripheral nerve Schwann cells. Also acts as a receptor for laminin
CC LAMA5 (By similarity). {ECO:0000250|UniProtKB:O18738}.
CC -!- FUNCTION: [Beta-dystroglycan]: Transmembrane protein that plays
CC important roles in connecting the extracellular matrix to the
CC cytoskeleton. Acts as a cell adhesion receptor in both muscle and non-
CC muscle tissues. Receptor for both DMD and UTRN and, through these
CC interactions, scaffolds axin to the cytoskeleton. Also functions in
CC cell adhesion-mediated signaling and implicated in cell polarity.
CC -!- FUNCTION: [Alpha-dystroglycan]: (Microbial infection) Acts as a
CC receptor for lassa virus and lymphocytic choriomeningitis virus
CC glycoprotein and class C new-world arenaviruses (PubMed:16254364,
CC PubMed:19324387, PubMed:17360738). Acts as a Schwann cell receptor for
CC Mycobacterium leprae, the causative organism of leprosy, but only in
CC the presence of the G-domain of LAMA2 (PubMed:9851927).
CC {ECO:0000269|PubMed:16254364, ECO:0000269|PubMed:17360738,
CC ECO:0000269|PubMed:19324387, ECO:0000269|PubMed:9851927}.
CC -!- SUBUNIT: Monomer. Heterodimer of alpha- and beta-dystroglycan subunits
CC which are the central components of the dystrophin-glycoprotein
CC complex. This complex then can form a dystrophin-associated
CC glycoprotein complex (DGC) which is composed of three subcomplexes: a
CC cytoplasmic complex comprised of DMD (or UTRN), DTNA and a number of
CC syntrophins, such as SNTB1, SNTB2, SNTG1 and SNTG2, the transmembrane
CC dystroglycan complex, and the sarcoglycan-sarcospan complex. Interacts
CC (via the N-terminal of alphaDAG1) with LARGE1; the interaction enhances
CC laminin binding (By similarity). Interacts with SGCD. Interacts with
CC AGR2 and AGR3. Interacts (betaDAG1) with DMD; the interaction is
CC inhibited by phosphorylation on the PPXY motif. Interacts (betaDAG1,
CC via its PPXY motif) with UTRN (via its WWW and ZZ domains); the
CC interaction is inhibited by phosphorylation on the PPXY motif.
CC Interacts (betaDAG1, via its phosphorylated PPXY motif) with the SH2
CC domain-containing proteins, FYN, CSK, NCK and SHC. Interacts (betaDAG1)
CC with CAV3 (via a central WW-like domain); the interaction disrupts the
CC binding of DMD. BetaDAG1 directly interacts with ANK3, but not with
CC ANK2; this interaction does not interfere with DMD-binding and is
CC required for retention at costameres (By similarity). Identified in a
CC dystroglycan complex that contains at least PRX, DRP2, UTRN, DMD and
CC DAG1 (By similarity). Interacts with POMGNT1 (PubMed:27493216).
CC {ECO:0000250|UniProtKB:Q28685, ECO:0000250|UniProtKB:Q62165,
CC ECO:0000269|PubMed:10767429, ECO:0000269|PubMed:10769203,
CC ECO:0000269|PubMed:10988290, ECO:0000269|PubMed:11495720,
CC ECO:0000269|PubMed:11724572, ECO:0000269|PubMed:12592373,
CC ECO:0000269|PubMed:27493216, ECO:0000269|PubMed:7592992}.
CC -!- SUBUNIT: (Microbial infection) Interacts with lassa virus and
CC lymphocytic choriomeningitis virus glycoprotein (PubMed:16254364,
CC PubMed:19324387). {ECO:0000269|PubMed:16254364,
CC ECO:0000269|PubMed:19324387}.
CC -!- SUBUNIT: (Microbial infection) Interacts with surface molecules of
CC mycobacterium leprae. {ECO:0000269|PubMed:9851927}.
CC -!- INTERACTION:
CC Q14118; P16333: NCK1; NbExp=2; IntAct=EBI-1755945, EBI-389883;
CC Q14118; Q3T1J5: Ank3; Xeno; NbExp=2; IntAct=EBI-1755945, EBI-2133962;
CC PRO_0000021065; PRO_0000021066 [Q14118]: DAG1; NbExp=4; IntAct=EBI-20738807, EBI-20738802;
CC -!- SUBCELLULAR LOCATION: [Alpha-dystroglycan]: Secreted, extracellular
CC space.
CC -!- SUBCELLULAR LOCATION: [Beta-dystroglycan]: Cell membrane
CC {ECO:0000269|PubMed:18764929}; Single-pass type I membrane protein.
CC Cytoplasm, cytoskeleton. Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:18764929}. Cell membrane, sarcolemma {ECO:0000250}.
CC Postsynaptic cell membrane {ECO:0000250}. Note=The monomeric form
CC translocates to the nucleus via the action of importins and depends on
CC RAN. Nuclear transport is inhibited by Tyr-892 phosphorylation. In
CC skeletal muscle, this phosphorylated form locates to a vesicular
CC internal membrane compartment. In muscle cells, sarcolemma localization
CC requires the presence of ANK2, while localization to costameres
CC requires the presence of ANK3. Localizes to neuromuscular junctions
CC (NMJs) in the presence of ANK2 (By similarity). In peripheral nerves,
CC localizes to the Schwann cell membrane. Colocalizes with ERM proteins
CC in Schwann-cell microvilli. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in a variety of fetal and adult tissues.
CC In epidermal tissue, located to the basement membrane. Also expressed
CC in keratinocytes and fibroblasts. {ECO:0000269|PubMed:15175026,
CC ECO:0000269|PubMed:8268918}.
CC -!- PTM: [Alpha-dystroglycan]: O-glycosylated. POMGNT1 catalyzes the
CC initial addition of N-acetylglucosamine, giving rise to the
CC GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety and thus providing the
CC necessary basis for the addition of further carbohydrate moieties
CC (PubMed:27493216). Heavily O-glycosylated comprising of up to two
CC thirds of its mass and the carbohydrate composition differs depending
CC on tissue type. Mucin-type O-glycosylation is important for ligand
CC binding activity. O-mannosylation is found in high abundance in both
CC brain and muscle where the most abundant glycan is Sia-alpha-2-3-Gal-
CC beta-1-4-Glc-NAc-beta-1-2-Man. In muscle, glycosylation on Thr-317,
CC Thr-319 and Thr-379 by a phosphorylated O-mannosyl glycan with the
CC structure 2-(N-acetylamido)-2-deoxygalactosyl-beta-1,3-2-(N-
CC acetylamido)-2-deoxyglucosyl-beta-1,4-6-phosphomannose is mediated by
CC like-acetylglucosaminyltransferase (LARGE1) protein and is required for
CC laminin binding (PubMed:20044576, PubMed:21987822, PubMed:24256719,
CC PubMed:23723439). The O-glycosyl hexose on Thr-367, Thr-369, Thr-372,
CC Thr-381 and Thr-388 is probably mannose. O-glycosylated in the N-
CC terminal region with a core 1 or possibly core 8 glycan. The brain form
CC displays a unique glycosylation pattern which is absent in other
CC tissues; this form shows enhanced binding to laminin LAMA5 compared to
CC the skeletal muscle form (By similarity).
CC {ECO:0000250|UniProtKB:O18738, ECO:0000269|PubMed:12140558,
CC ECO:0000269|PubMed:16254364, ECO:0000269|PubMed:17360738,
CC ECO:0000269|PubMed:17905726, ECO:0000269|PubMed:19838169,
CC ECO:0000269|PubMed:20044576, ECO:0000269|PubMed:20507882,
CC ECO:0000269|PubMed:21987822, ECO:0000269|PubMed:23234360,
CC ECO:0000269|PubMed:24256719, ECO:0000269|PubMed:27493216}.
CC -!- PTM: [Alpha-dystroglycan]: (Microbial infection) O-mannosylation is
CC required for binding lymphocytic choriomeningitis virus, Old World
CC Lassa fever virus, and clade C New World arenaviruses.
CC {ECO:0000269|PubMed:16254364, ECO:0000269|PubMed:17360738}.
CC -!- PTM: [Beta-dystroglycan]: N-glycosylated.
CC {ECO:0000269|PubMed:18764929}.
CC -!- PTM: Autolytic cleavage produces the alpha and beta subunits. In
CC cutaneous cells, as well as in certain pathological conditions,
CC shedding of beta-dystroglycan can occur releasing a peptide of about 30
CC kDa. {ECO:0000269|PubMed:15175026, ECO:0000269|PubMed:17905726,
CC ECO:0000269|PubMed:18764929, ECO:0000269|PubMed:19946898}.
CC -!- PTM: SRC-mediated phosphorylation of the PPXY motif of the beta subunit
CC recruits SH2 domain-containing proteins, but inhibits binding to WWW
CC domain-containing proteins, DMD and UTRN. This phosphorylation also
CC inhibits nuclear entry.
CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C9 (MDDGC9)
CC [MIM:613818]: An autosomal recessive muscular dystrophy showing onset
CC in early childhood, and associated with intellectual disability without
CC structural brain anomalies. {ECO:0000269|PubMed:21388311,
CC ECO:0000269|PubMed:25503980}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. MDDGC7 is caused by DAG1
CC mutations that interfere with normal post-translational processing,
CC resulting in defective DAG1 glycosylation and impaired interactions
CC with extracellular-matrix components. Other muscular dystrophy-
CC dystroglycanopathies are caused by defects in enzymes involved in
CC protein O-glycosylation.
CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain
CC and eye anomalies A9 (MDDGA9) [MIM:616538]: An autosomal recessive
CC disorder characterized by congenital muscular dystrophy associated with
CC cobblestone lissencephaly and other brain anomalies, eye malformations,
CC profound intellectual disability, and death usually in the first years
CC of life. Included diseases are the more severe Walker-Warburg syndrome
CC and the slightly less severe muscle-eye-brain disease.
CC {ECO:0000269|PubMed:24052401, ECO:0000269|PubMed:25934851}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Dystroglycan entry;
CC URL="https://en.wikipedia.org/wiki/Dystroglycan";
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DR EMBL; L19711; AAA81779.1; -; mRNA.
DR EMBL; AK291692; BAF84381.1; -; mRNA.
DR EMBL; AC104452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64989.1; -; Genomic_DNA.
DR EMBL; BC012740; AAH12740.1; -; mRNA.
DR EMBL; BC014616; AAH14616.1; -; mRNA.
DR CCDS; CCDS2799.1; -.
DR PIR; I54343; I54343.
DR RefSeq; NP_001159400.2; NM_001165928.3.
DR RefSeq; NP_001171105.1; NM_001177634.2.
DR RefSeq; NP_001171106.1; NM_001177635.2.
DR RefSeq; NP_001171107.1; NM_001177636.2.
DR RefSeq; NP_001171108.1; NM_001177637.2.
DR RefSeq; NP_001171109.1; NM_001177638.2.
DR RefSeq; NP_001171110.1; NM_001177639.2.
DR RefSeq; NP_001171111.1; NM_001177640.2.
DR RefSeq; NP_001171112.1; NM_001177641.2.
DR RefSeq; NP_001171113.1; NM_001177642.2.
DR RefSeq; NP_001171114.1; NM_001177643.2.
DR RefSeq; NP_001171115.1; NM_001177644.2.
DR RefSeq; NP_004384.4; NM_004393.5.
DR PDB; 1EG4; X-ray; 2.00 A; P=881-895.
DR PDB; 2MK7; NMR; -; A=419-427.
DR PDB; 5GGP; X-ray; 1.60 A; C/D=316-325.
DR PDB; 5LLK; X-ray; 1.80 A; A=52-315.
DR PDB; 6JJY; X-ray; 2.30 A; U=877-895.
DR PDB; 7E9K; X-ray; 2.05 A; C/F=369-389.
DR PDB; 7E9L; X-ray; 2.10 A; C=378-389.
DR PDBsum; 1EG4; -.
DR PDBsum; 2MK7; -.
DR PDBsum; 5GGP; -.
DR PDBsum; 5LLK; -.
DR PDBsum; 6JJY; -.
DR PDBsum; 7E9K; -.
DR PDBsum; 7E9L; -.
DR AlphaFoldDB; Q14118; -.
DR SMR; Q14118; -.
DR BioGRID; 107975; 127.
DR CORUM; Q14118; -.
DR DIP; DIP-40928N; -.
DR IntAct; Q14118; 73.
DR MINT; Q14118; -.
DR STRING; 9606.ENSP00000442600; -.
DR ChEMBL; CHEMBL3714399; -.
DR MEROPS; S72.001; -.
DR TCDB; 9.B.277.1.1; the dystroglycan (dg) family.
DR GlyConnect; 715; 9 N-Linked glycans (1 site), 1 O-Linked glycan (1 site).
DR GlyGen; Q14118; 20 sites, 10 N-linked glycans (1 site), 5 O-linked glycans (3 sites).
DR iPTMnet; Q14118; -.
DR PhosphoSitePlus; Q14118; -.
DR SwissPalm; Q14118; -.
DR BioMuta; DAG1; -.
DR DMDM; 229462879; -.
DR EPD; Q14118; -.
DR jPOST; Q14118; -.
DR MassIVE; Q14118; -.
DR MaxQB; Q14118; -.
DR PaxDb; Q14118; -.
DR PeptideAtlas; Q14118; -.
DR PRIDE; Q14118; -.
DR ProteomicsDB; 59825; -.
DR TopDownProteomics; Q14118; -.
DR Antibodypedia; 4283; 374 antibodies from 41 providers.
DR DNASU; 1605; -.
DR Ensembl; ENST00000308775.7; ENSP00000312435.2; ENSG00000173402.12.
DR Ensembl; ENST00000515359.6; ENSP00000440705.1; ENSG00000173402.12.
DR Ensembl; ENST00000538711.5; ENSP00000438421.1; ENSG00000173402.12.
DR Ensembl; ENST00000539901.5; ENSP00000439334.1; ENSG00000173402.12.
DR Ensembl; ENST00000541308.5; ENSP00000440590.1; ENSG00000173402.12.
DR Ensembl; ENST00000545947.5; ENSP00000442600.1; ENSG00000173402.12.
DR Ensembl; ENST00000673708.1; ENSP00000501140.1; ENSG00000173402.12.
DR GeneID; 1605; -.
DR KEGG; hsa:1605; -.
DR MANE-Select; ENST00000308775.7; ENSP00000312435.2; NM_004393.6; NP_004384.5.
DR UCSC; uc003cxc.5; human.
DR CTD; 1605; -.
DR DisGeNET; 1605; -.
DR GeneCards; DAG1; -.
DR HGNC; HGNC:2666; DAG1.
DR HPA; ENSG00000173402; Low tissue specificity.
DR MalaCards; DAG1; -.
DR MIM; 128239; gene.
DR MIM; 613818; phenotype.
DR MIM; 616538; phenotype.
DR neXtProt; NX_Q14118; -.
DR OpenTargets; ENSG00000173402; -.
DR Orphanet; 280333; Alpha-dystroglycan-related limb-girdle muscular dystrophy R16.
DR Orphanet; 370997; Muscle-eye-brain disease with bilateral multicystic leucodystrophy.
DR Orphanet; 899; Walker-Warburg syndrome.
DR PharmGKB; PA27138; -.
DR VEuPathDB; HostDB:ENSG00000173402; -.
DR eggNOG; KOG3781; Eukaryota.
DR GeneTree; ENSGT00390000008429; -.
DR HOGENOM; CLU_007629_2_0_1; -.
DR InParanoid; Q14118; -.
DR OMA; NQNMPET; -.
DR OrthoDB; 163609at2759; -.
DR PhylomeDB; Q14118; -.
DR TreeFam; TF328370; -.
DR PathwayCommons; Q14118; -.
DR Reactome; R-HSA-3000171; Non-integrin membrane-ECM interactions.
DR Reactome; R-HSA-3000178; ECM proteoglycans.
DR Reactome; R-HSA-5083628; Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3.
DR Reactome; R-HSA-5083629; Defective POMT2 causes MDDGA2, MDDGB2 and MDDGC2.
DR Reactome; R-HSA-5083633; Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1.
DR Reactome; R-HSA-5173105; O-linked glycosylation.
DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs.
DR Reactome; R-HSA-9619665; EGR2 and SOX10-mediated initiation of Schwann cell myelination.
DR SignaLink; Q14118; -.
DR SIGNOR; Q14118; -.
DR BioGRID-ORCS; 1605; 15 hits in 1088 CRISPR screens.
DR ChiTaRS; DAG1; human.
DR EvolutionaryTrace; Q14118; -.
DR GeneWiki; Dystroglycan; -.
DR GenomeRNAi; 1605; -.
DR Pharos; Q14118; Tbio.
DR PRO; PR:Q14118; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q14118; protein.
DR Bgee; ENSG00000173402; Expressed in olfactory bulb and 213 other tissues.
DR ExpressionAtlas; Q14118; baseline and differential.
DR Genevisible; Q14118; HS.
DR GO; GO:0005912; C:adherens junction; IEA:Ensembl.
DR GO; GO:0005604; C:basement membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0070938; C:contractile ring; IDA:UniProtKB.
DR GO; GO:0043034; C:costamere; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016011; C:dystroglycan complex; IBA:GO_Central.
DR GO; GO:0016010; C:dystrophin-associated glycoprotein complex; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0033268; C:node of Ranvier; IEA:Ensembl.
DR GO; GO:0034399; C:nuclear periphery; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0044853; C:plasma membrane raft; IEA:Ensembl.
DR GO; GO:0099524; C:postsynaptic cytosol; IEA:Ensembl.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042383; C:sarcolemma; IBA:GO_Central.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0051393; F:alpha-actinin binding; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0002162; F:dystroglycan binding; IEA:Ensembl.
DR GO; GO:0043236; F:laminin binding; IBA:GO_Central.
DR GO; GO:0043237; F:laminin-1 binding; ISS:UniProtKB.
DR GO; GO:0042169; F:SH2 domain binding; IDA:UniProtKB.
DR GO; GO:0008307; F:structural constituent of muscle; IMP:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB.
DR GO; GO:0017166; F:vinculin binding; IPI:UniProtKB.
DR GO; GO:0001618; F:virus receptor activity; IDA:FlyBase.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0060055; P:angiogenesis involved in wound healing; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0031103; P:axon regeneration; IEA:Ensembl.
DR GO; GO:0071711; P:basement membrane organization; IEA:Ensembl.
DR GO; GO:0060445; P:branching involved in salivary gland morphogenesis; IEA:Ensembl.
DR GO; GO:0016340; P:calcium-dependent cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0071397; P:cellular response to cholesterol; IEA:Ensembl.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0071679; P:commissural neuron axon guidance; IEA:Ensembl.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IEA:Ensembl.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:UniProtKB.
DR GO; GO:0034453; P:microtubule anchoring; IMP:UniProtKB.
DR GO; GO:0002011; P:morphogenesis of an epithelial sheet; IEA:Ensembl.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IBA:GO_Central.
DR GO; GO:0016203; P:muscle attachment; IBA:GO_Central.
DR GO; GO:0022011; P:myelination in peripheral nervous system; IEA:Ensembl.
DR GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0021675; P:nerve development; IBA:GO_Central.
DR GO; GO:0021682; P:nerve maturation; IEA:Ensembl.
DR GO; GO:1904261; P:positive regulation of basement membrane assembly involved in embryonic body morphogenesis; IMP:UniProtKB.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0031643; P:positive regulation of myelination; IEA:Ensembl.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0016476; P:regulation of embryonic cell shape; ISS:UniProtKB.
DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; IMP:UniProtKB.
DR GO; GO:0010470; P:regulation of gastrulation; IMP:UniProtKB.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IEA:Ensembl.
DR GO; GO:0050807; P:regulation of synapse organization; IEA:Ensembl.
DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; IEA:Ensembl.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR GO; GO:0098942; P:retrograde trans-synaptic signaling by trans-synaptic protein complex; IEA:Ensembl.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; IEA:Ensembl.
DR DisProt; DP02765; -.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 3.30.70.1040; -; 1.
DR IDEAL; IID00278; -.
DR InterPro; IPR027468; Alpha-dystroglycan_domain_2.
DR InterPro; IPR041631; Alpha_DG1_N2.
DR InterPro; IPR006644; Cadg.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR008465; DAG1_C.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR030398; SEA_DG_dom.
DR Pfam; PF18424; a_DG1_N2; 1.
DR Pfam; PF05454; DAG1; 1.
DR SMART; SM00736; CADG; 2.
DR SUPFAM; SSF111006; SSF111006; 1.
DR SUPFAM; SSF49313; SSF49313; 2.
DR PROSITE; PS51699; SEA_DG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Cell membrane;
KW Congenital muscular dystrophy; Cytoplasm; Cytoskeleton; Disease variant;
KW Disulfide bond; Dystroglycanopathy; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction;
KW Limb-girdle muscular dystrophy; Lissencephaly; Membrane; Nucleus;
KW Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome;
KW Secreted; Signal; Synapse; Transmembrane; Transmembrane helix.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..653
FT /note="Alpha-dystroglycan"
FT /id="PRO_0000021065"
FT CHAIN 654..895
FT /note="Beta-dystroglycan"
FT /id="PRO_0000021066"
FT TOPO_DOM 654..749
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 750..775
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 776..895
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 603..712
FT /note="Peptidase S72"
FT REGION 30..408
FT /note="Required for laminin recognition"
FT REGION 169..200
FT /note="O-glycosylated at one site"
FT REGION 316..485
FT /note="Mucin-like domain"
FT REGION 381..460
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 463..485
FT /note="O-glycosylated at seven sites with GalNAc"
FT REGION 478..498
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 724..746
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 819..895
FT /note="Required for interaction with CAV3"
FT /evidence="ECO:0000269|PubMed:10988290"
FT REGION 823..895
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 880..895
FT /note="Required for binding DMD and UTRN"
FT MOTIF 776..782
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:20512930"
FT MOTIF 889..892
FT /note="PPXY motif"
FT COMPBIAS 381..402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..449
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 732..746
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 858..873
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 653..654
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:17905726"
FT SITE 715..716
FT /note="Cleavage; by MMP9"
FT /evidence="ECO:0000269|PubMed:19946898"
FT MOD_RES 790
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 892
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:11495720,
FT ECO:0000269|PubMed:12795607, ECO:0000269|PubMed:20512930"
FT CARBOHYD 63
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:23234360"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 317
FT /note="O-linked (Man6P...) threonine"
FT /evidence="ECO:0000269|PubMed:21987822,
FT ECO:0000269|PubMed:24256719"
FT CARBOHYD 319
FT /note="O-linked (Man6P...) threonine"
FT /evidence="ECO:0000269|PubMed:21987822,
FT ECO:0000269|PubMed:24256719"
FT CARBOHYD 367
FT /note="O-linked (Hex...) threonine"
FT /evidence="ECO:0000269|PubMed:20507882"
FT CARBOHYD 369
FT /note="O-linked (Hex...) threonine"
FT /evidence="ECO:0000269|PubMed:20507882"
FT CARBOHYD 372
FT /note="O-linked (Hex...) threonine"
FT /evidence="ECO:0000269|PubMed:20507882"
FT CARBOHYD 379
FT /note="O-linked (Man6P...) threonine"
FT /evidence="ECO:0000269|PubMed:20044576,
FT ECO:0000269|PubMed:23723439"
FT CARBOHYD 381
FT /note="O-linked (Hex...) threonine"
FT /evidence="ECO:0000269|PubMed:20044576"
FT CARBOHYD 388
FT /note="O-linked (Hex...) threonine"
FT /evidence="ECO:0000269|PubMed:20044576"
FT CARBOHYD 455
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:20507882"
FT CARBOHYD 641
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 649
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 661
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18764929"
FT DISULFID 182..264
FT /evidence="ECO:0000269|PubMed:28781947,
FT ECO:0007744|PDB:5LLK"
FT DISULFID 669..713
FT /evidence="ECO:0000269|PubMed:17212656"
FT VARIANT 14
FT /note="S -> W (in dbSNP:rs2131107)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:8268918,
FT ECO:0000269|Ref.4"
FT /id="VAR_024335"
FT VARIANT 74
FT /note="V -> I (in MDDGC9; no effect on dystroglycan
FT expression; impairs alpha-dystroglycan glycosylation;
FT dbSNP:rs189360006)"
FT /evidence="ECO:0000269|PubMed:25503980"
FT /id="VAR_075809"
FT VARIANT 111
FT /note="D -> N (in MDDGC9; does not affect dystroglycan
FT expression; impairs alpha-dystroglycan glycosylation;
FT dbSNP:rs117209107)"
FT /evidence="ECO:0000269|PubMed:25503980"
FT /id="VAR_075810"
FT VARIANT 192
FT /note="T -> M (in MDDGC9; results in impaired interaction
FT with LARGE1 and incomplete DAG1 glycosylation;
FT dbSNP:rs193922955)"
FT /evidence="ECO:0000269|PubMed:21388311"
FT /id="VAR_065266"
FT VARIANT 669
FT /note="C -> F (in MDDGA9; dbSNP:rs797045023)"
FT /evidence="ECO:0000269|PubMed:24052401"
FT /id="VAR_075811"
FT MUTAGEN 311..370
FT /note="Missing: Abolishes LARGE1-dependent glycosylation,
FT CHST10-dependent sulfation and consequent binding to
FT laminin; when associated with A-379."
FT /evidence="ECO:0000269|PubMed:23723439"
FT MUTAGEN 317..319
FT /note="TPT->APA: Impaired laminin-binding."
FT /evidence="ECO:0000269|PubMed:21987822,
FT ECO:0000269|PubMed:24256719"
FT MUTAGEN 328..329
FT /note="TT->AA: Does not affect laminin-binding."
FT /evidence="ECO:0000269|PubMed:21987822"
FT MUTAGEN 368..461
FT /note="Missing: Retains the capacity to bind laminin."
FT /evidence="ECO:0000269|PubMed:23723439"
FT MUTAGEN 379
FT /note="T->A: Abolishes LARGE1-dependent glycosylation,
FT CHST10-dependent sulfation and consequent binding to
FT laminin; when associated with 311-R--I-370 del."
FT /evidence="ECO:0000269|PubMed:23723439"
FT MUTAGEN 654
FT /note="S->A: Abolishes autoproteolysis and enhances
FT laminin-binding."
FT /evidence="ECO:0000269|PubMed:17905726,
FT ECO:0000269|PubMed:18764929"
FT MUTAGEN 663
FT /note="T->A: Reduced N-linked glycosylation. No change in
FT nuclear translocation."
FT /evidence="ECO:0000269|PubMed:18764929"
FT MUTAGEN 776..782
FT /note="RKKRKGK->AKKRKGA: Moderate reduction in nuclear
FT accumulation."
FT MUTAGEN 777..782
FT /note="KKRKGK->AARKGA: About 50% reduction in nuclear
FT accumulation."
FT /evidence="ECO:0000269|PubMed:20512930"
FT MUTAGEN 777..782
FT /note="KKRKGK->RKKAAGA: Drastic reduction in nuclear
FT accumulation."
FT /evidence="ECO:0000269|PubMed:20512930"
FT MUTAGEN 777..780
FT /note="KKRK->NPGE: Abolishes nuclear translocation."
FT /evidence="ECO:0000269|PubMed:18764929"
FT MUTAGEN 779
FT /note="R->A: Significant reduction in nuclear
FT accumulation."
FT /evidence="ECO:0000269|PubMed:20512930"
FT MUTAGEN 780
FT /note="K->A: Significant reduction in nuclear
FT accumulation."
FT /evidence="ECO:0000269|PubMed:20512930"
FT MUTAGEN 793..794
FT /note="KK->TA: Abolishes nuclear translocation."
FT /evidence="ECO:0000269|PubMed:18764929"
FT MUTAGEN 823
FT /note="K->A: No change in nuclear location."
FT /evidence="ECO:0000269|PubMed:18764929"
FT MUTAGEN 828..829
FT /note="PP->AA: No change in nuclear location."
FT /evidence="ECO:0000269|PubMed:18764929"
FT MUTAGEN 831
FT /note="Y->A: No change in nuclear location."
FT /evidence="ECO:0000269|PubMed:18764929"
FT MUTAGEN 892
FT /note="Y->A: Abolishes phosphorylation. No change in plasma
FT membrane location."
FT /evidence="ECO:0000269|PubMed:12795607,
FT ECO:0000269|PubMed:20512930"
FT MUTAGEN 892
FT /note="Y->E: Redistributes to a vesicular internal membrane
FT compartment."
FT /evidence="ECO:0000269|PubMed:12795607,
FT ECO:0000269|PubMed:20512930"
FT MUTAGEN 892
FT /note="Y->F: Abolishes phosphorylation. Increase in nuclear
FT location."
FT /evidence="ECO:0000269|PubMed:12795607,
FT ECO:0000269|PubMed:20512930"
FT CONFLICT 163
FT /note="E -> D (in Ref. 1; AAA81779)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="A -> P (in Ref. 1; AAA81779)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="T -> A (in Ref. 2; BAF84381)"
FT /evidence="ECO:0000305"
FT CONFLICT 871
FT /note="A -> V (in Ref. 1; AAA81779)"
FT /evidence="ECO:0000305"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:5LLK"
FT HELIX 84..87
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:5LLK"
FT TURN 112..115
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:5LLK"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 127..138
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 144..157
FT /evidence="ECO:0007829|PDB:5LLK"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 188..196
FT /evidence="ECO:0007829|PDB:5LLK"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:5LLK"
FT HELIX 204..218
FT /evidence="ECO:0007829|PDB:5LLK"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 256..265
FT /evidence="ECO:0007829|PDB:5LLK"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:5LLK"
FT HELIX 275..283
FT /evidence="ECO:0007829|PDB:5LLK"
FT HELIX 285..290
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 294..302
FT /evidence="ECO:0007829|PDB:5LLK"
FT STRAND 372..377
FT /evidence="ECO:0007829|PDB:7E9K"
FT STRAND 379..384
FT /evidence="ECO:0007829|PDB:7E9K"
SQ SEQUENCE 895 AA; 97441 MW; 3AF6CBB0DCF91962 CRC64;
MRMSVGLSLL LPLSGRTFLL LLSVVMAQSH WPSEPSEAVR DWENQLEASM HSVLSDLHEA
VPTVVGIPDG TAVVGRSFRV TIPTDLIASS GDIIKVSAAG KEALPSWLHW DSQSHTLEGL
PLDTDKGVHY ISVSATRLGA NGSHIPQTSS VFSIEVYPED HSELQSVRTA SPDPGEVVSS
ACAADEPVTV LTVILDADLT KMTPKQRIDL LHRMRSFSEV ELHNMKLVPV VNNRLFDMSA
FMAGPGNAKK VVENGALLSW KLGCSLNQNS VPDIHGVEAP AREGAMSAQL GYPVVGWHIA
NKKPPLPKRV RRQIHATPTP VTAIGPPTTA IQEPPSRIVP TPTSPAIAPP TETMAPPVRD
PVPGKPTVTI RTRGAIIQTP TLGPIQPTRV SEAGTTVPGQ IRPTMTIPGY VEPTAVATPP
TTTTKKPRVS TPKPATPSTD STTTTTRRPT KKPRTPRPVP RVTTKVSITR LETASPPTRI
RTTTSGVPRG GEPNQRPELK NHIDRVDAWV GTYFEVKIPS DTFYDHEDTT TDKLKLTLKL
REQQLVGEKS WVQFNSNSQL MYGLPDSSHV GKHEYFMHAT DKGGLSAVDA FEIHVHRRPQ
GDRAPARFKA KFVGDPALVL NDIHKKIALV KKLAFAFGDR NCSTITLQNI TRGSIVVEWT
NNTLPLEPCP KEQIAGLSRR IAEDDGKPRP AFSNALEPDF KATSITVTGS GSCRHLQFIP
VVPPRRVPSE APPTEVPDRD PEKSSEDDVY LHTVIPAVVV AAILLIAGII AMICYRKKRK
GKLTLEDQAT FIKKGVPIIF ADELDDSKPP PSSSMPLILQ EEKAPLPPPE YPNQSVPETT
PLNQDTMGEY TPLRDEDPNA PPYQPPPPFT APMEGKGSRP KNMTPYRSPP PYVPP
