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 27-MAR-2024, entry version 215. 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 PRO_0000021066; P46939: UTRN; NbExp=3; IntAct=EBI-20738802, EBI-295856; 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; 138. DR ComplexPortal; CPX-2424; Dystrophin glycoprotein complex, skeletal muscle variant. DR ComplexPortal; CPX-2443; Dystrophin glycoprotein complex, neuromuscular junction variant. DR ComplexPortal; CPX-2453; Dystrophin glycoprotein complex, CNS variant. DR ComplexPortal; CPX-2454; Dystrophin glycoprotein complex, retinal outer plexiform layer variant. DR ComplexPortal; CPX-2455; Dystrophin glycoprotein complex, retinal inner limiting membrane variant. DR CORUM; Q14118; -. DR DIP; DIP-40928N; -. DR IntAct; Q14118; 74. 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 GlyCosmos; Q14118; 15 sites, 14 glycans. DR GlyGen; Q14118; 51 sites, 10 N-linked glycans (1 site), 6 O-linked glycans (39 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; 9606-ENSP00000442600; -. DR PeptideAtlas; Q14118; -. DR ProteomicsDB; 59825; -. DR Pumba; Q14118; -. DR TopDownProteomics; Q14118; -. DR Antibodypedia; 4283; 436 antibodies from 41 providers. DR DNASU; 1605; -. DR Ensembl; ENST00000308775.7; ENSP00000312435.2; ENSG00000173402.13. DR Ensembl; ENST00000418588.6; ENSP00000405859.2; ENSG00000173402.13. DR Ensembl; ENST00000421560.6; ENSP00000412067.2; ENSG00000173402.13. DR Ensembl; ENST00000428779.7; ENSP00000401382.3; ENSG00000173402.13. DR Ensembl; ENST00000430636.2; ENSP00000401805.2; ENSG00000173402.13. DR Ensembl; ENST00000431960.6; ENSP00000388833.2; ENSG00000173402.13. DR Ensembl; ENST00000435508.8; ENSP00000415321.4; ENSG00000173402.13. DR Ensembl; ENST00000452060.7; ENSP00000410145.3; ENSG00000173402.13. DR Ensembl; ENST00000452317.6; ENSP00000387859.2; ENSG00000173402.13. DR Ensembl; ENST00000466701.2; ENSP00000513216.1; ENSG00000173402.13. DR Ensembl; ENST00000469139.2; ENSP00000501165.2; ENSG00000173402.13. DR Ensembl; ENST00000496474.2; ENSP00000513217.1; ENSG00000173402.13. DR Ensembl; ENST00000673708.1; ENSP00000501140.1; ENSG00000173402.13. DR Ensembl; ENST00000697271.1; ENSP00000513218.1; ENSG00000173402.13. 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 AGR; HGNC:2666; -. 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; WRLGCSL; -. DR OrthoDB; 3598963at2759; -. 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 1168 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 215 other cell types or tissues. DR ExpressionAtlas; Q14118; baseline and differential. 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:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; 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:0098684; C:photoreceptor ribbon synapse; IEA:Ensembl. 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:0044877; F:protein-containing complex binding; IEA:Ensembl. 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: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:0003007; P:heart 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 phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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:0015031; P:protein transport; 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:0048167; P:regulation of synaptic plasticity; IEA:Ensembl. DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; IEA:Ensembl. DR GO; GO:0014850; P:response to muscle activity; 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 CDD; cd11305; alpha_DG_C; 1. DR CDD; cd11303; Dystroglycan_repeat; 2. DR DisProt; DP02765; -. DR Gene3D; 3.30.70.1040; Dystroglycan, domain 2; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. 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 PANTHER; PTHR21559:SF22; DYSTROGLYCAN 1; 1. DR PANTHER; PTHR21559; DYSTROGLYCAN-RELATED; 1. DR Pfam; PF18424; a_DG1_N2; 1. DR Pfam; PF05454; DAG1; 1. DR Pfam; PF05345; He_PIG; 1. DR SMART; SM00736; CADG; 2. DR SUPFAM; SSF49313; Cadherin-like; 2. DR SUPFAM; SSF111006; Dystroglycan, domain 2; 1. DR PROSITE; PS51699; SEA_DG; 1. DR Genevisible; Q14118; HS. 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 //