DAG1_MOUSE
ID DAG1_MOUSE Reviewed; 893 AA.
AC Q62165; Q61094; Q61141; Q61497;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2001, sequence version 4.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Dystroglycan 1 {ECO:0000312|MGI:MGI:101864};
DE AltName: Full=Dystroglycan {ECO:0000303|PubMed:9175728};
DE AltName: Full=Dystrophin-associated glycoprotein 1 {ECO:0000312|MGI:MGI:101864};
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|MGI:MGI:101864};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISRUPTION PHENOTYPE, FUNCTION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=129/SvJ;
RX PubMed=9175728; DOI=10.1093/hmg/6.6.831;
RA Williamson R.A., Henry M.D., Daniels K.J., Hrstka R.F., Lee J.C.,
RA Sunada Y., Ibraghimov-Beskrovnaya O., Campbell K.P.;
RT "Dystroglycan is essential for early embryonic development: disruption of
RT Reichert's membrane in Dag1-null mice.";
RL Hum. Mol. Genet. 6:831-841(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-650.
RC TISSUE=Skeletal muscle;
RX PubMed=9057818; DOI=10.1016/s0945-053x(05)80032-0;
RA Brancaccio A., Ruegg M.A., Engel J.;
RT "Cloning and sequencing of mouse skeletal muscle alpha-dystroglycan.";
RL Matrix Biol. 14:681-685(1995).
RN [4]
RP SEQUENCE REVISION TO 142-143.
RA Brancaccio A.;
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 352-650, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/10; TISSUE=Skeletal muscle;
RX PubMed=7833916; DOI=10.1093/hmg/3.9.1589;
RA Gorecki D.C., Derry J.M.J., Barnard E.A.;
RT "Dystroglycan: brain localisation and chromosome mapping in the mouse.";
RL Hum. Mol. Genet. 3:1589-1597(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 620-893.
RC STRAIN=C57BL/6J; TISSUE=Decidua;
RX PubMed=8872465; DOI=10.1093/hmg/5.9.1259;
RA Yotsumoto S., Fujiwara H., Horton J.H., Mosby T.A., Wang X., Cui Y.,
RA Ko M.S.H.;
RT "Cloning and expression analyses of mouse dystroglycan gene: specific
RT expression in maternal decidua at the peri-implantation stage.";
RL Hum. Mol. Genet. 5:1259-1267(1996).
RN [7]
RP DISULFIDE BOND.
RX PubMed=9917844; DOI=10.1111/j.1749-6632.1998.tb10119.x;
RA Brancaccio A., Jeno P., Engel J.;
RT "A single disulfide bridge (Cys182-Cys264) is crucial for alpha-
RT dystroglycan N-terminal domain stability.";
RL Ann. N. Y. Acad. Sci. 857:228-231(1998).
RN [8]
RP INTERACTION WITH SGCD.
RX PubMed=9864373; DOI=10.1083/jcb.143.7.2033;
RA Chan Y.-M., Boennemann C.G., Lidov H.G.W., Kunkel L.M.;
RT "Molecular organization of sarcoglycan complex in mouse myotubes in
RT culture.";
RL J. Cell Biol. 143:2033-2044(1998).
RN [9]
RP PHOSPHORYLATION, 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 [10]
RP IDENTIFICATION IN A COMPLEX WITH DRP2; PRX; DMD AND UTRN, AND TISSUE
RP SPECIFICITY.
RX PubMed=11430802; DOI=10.1016/s0896-6273(01)00327-0;
RA Sherman D.L., Fabrizi C., Gillespie C.S., Brophy P.J.;
RT "Specific disruption of a Schwann cell dystrophin-related protein complex
RT in a demyelinating neuropathy.";
RL Neuron 30:677-687(2001).
RN [11]
RP DEVELOPMENTAL STAGE.
RX PubMed=12670716; DOI=10.1016/s0169-328x(03)00055-x;
RA Henion T.R., Qu Q., Smith F.I.;
RT "Expression of dystroglycan, fukutin and POMGnT1 during mouse cerebellar
RT development.";
RL Brain Res. Mol. Brain Res. 112:177-181(2003).
RN [12]
RP DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=12843252; DOI=10.1523/jneurosci.23-13-05520.2003;
RA Previtali S.C., Nodari A., Taveggia C., Pardini C., Dina G., Villa A.,
RA Wrabetz L., Quattrini A., Feltri M.L.;
RT "Expression of laminin receptors in schwann cell differentiation: evidence
RT for distinct roles.";
RL J. Neurosci. 23:5520-5530(2003).
RN [13]
RP FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND LIGAND-BINDING.
RX PubMed=12797959; DOI=10.1016/s0896-6273(03)00301-5;
RA Saito F., Moore S.A., Barresi R., Henry M.D., Messing A., Ross-Barta S.E.,
RA Cohn R.D., Williamson R.A., Sluka K.A., Sherman D.L., Brophy P.J.,
RA Schmelzer J.D., Low P.A., Wrabetz L., Feltri M.L., Campbell K.P.;
RT "Unique role of dystroglycan in peripheral nerve myelination, nodal
RT structure, and sodium channel stabilization.";
RL Neuron 38:747-758(2003).
RN [14]
RP TISSUE SPECIFICITY.
RX PubMed=16709410; DOI=10.1016/j.febslet.2006.05.010;
RA McDearmon E.L., Combs A.C., Sekiguchi K., Fujiwara H., Ervasti J.M.;
RT "Brain alpha-dystroglycan displays unique glycoepitopes and preferential
RT binding to laminin-10/11.";
RL FEBS Lett. 580:3381-3385(2006).
RN [15]
RP INTERACTION WITH ANK3, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 796-ILE--PHE-798; 800-ASP-GLU-801 AND 803-ASP-ASP-804.
RX PubMed=19109891; DOI=10.1016/j.cell.2008.10.018;
RA Ayalon G., Davis J.Q., Scotland P.B., Bennett V.;
RT "An ankyrin-based mechanism for functional organization of dystrophin and
RT dystroglycan.";
RL Cell 135:1189-1200(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-788, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [17]
RP TISSUE SPECIFICITY.
RX PubMed=25757569; DOI=10.1096/fj.14-261453;
RA Suh J., Moncaster J.A., Wang L., Hafeez I., Herz J., Tanzi R.E.,
RA Goldstein L.E., Guenette S.Y.;
RT "FE65 and FE65L1 amyloid precursor protein-binding protein compound null
RT mice display adult-onset cataract and muscle weakness.";
RL FASEB J. 29:2628-2639(2015).
RN [18]
RP STRUCTURE OF CARBOHYDRATES, LIGAND-BINDING, ADENOVIRUS BINDING, AND
RP 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 [19]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 58-303 IN COMPLEX WITH LIGAND, AND
RP DISULFIDE BOND.
RX PubMed=15326183; DOI=10.1074/jbc.c400353200;
RA Bozic D., Sciandra F., Lamba D., Brancaccio A.;
RT "The structure of the N-terminal region of murine skeletal muscle alpha-
RT dystroglycan discloses a modular architecture.";
RL J. Biol. Chem. 279:44812-44816(2004).
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, and for certain adenoviruses. Receptor for laminin-2
CC (LAMA2) and agrin in peripheral nerve Schwann cells. Also acts as a
CC receptor for laminin LAMA5 (By similarity).
CC {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 (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:12797959,
CC ECO:0000269|PubMed:12843252, ECO:0000269|PubMed:9175728}.
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 (PubMed:11430802). Interacts with POMGNT1 (By similarity).
CC {ECO:0000250|UniProtKB:Q14118, ECO:0000250|UniProtKB:Q28685,
CC ECO:0000269|PubMed:11430802, ECO:0000269|PubMed:11495720,
CC ECO:0000269|PubMed:15326183, ECO:0000269|PubMed:19109891,
CC ECO:0000269|PubMed:9864373}.
CC -!- INTERACTION:
CC PRO_0000021067; Q4VBE4: Egflam; NbExp=2; IntAct=EBI-2025154, EBI-2025048;
CC -!- SUBCELLULAR LOCATION: [Alpha-dystroglycan]: Secreted, extracellular
CC space {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Beta-dystroglycan]: Cell membrane {ECO:0000250};
CC Single-pass type I membrane protein {ECO:0000250}. Cytoplasm,
CC cytoskeleton. Nucleus, nucleoplasm. Cell membrane, sarcolemma.
CC Postsynaptic cell membrane. Note=The monomeric form translocates to the
CC nucleus via the action of importins and depends on RAN. Nuclear
CC transport is inhibited by Tyr-892 phosphorylation. In skeletal muscle,
CC this phosphorylated form locates to a vesicular internal membrane
CC compartment. In muscle cells, sarcolemma localization requires the
CC presence of ANK2, while localization to costameres requires the
CC presence of ANK3. Localizes to neuromuscular junctions (NMJs). In adult
CC muscle, NMJ localization depends upon ANK2 presence, but not in newborn
CC animals. In peripheral nerves, localizes to the Schwann cell membrane.
CC Colocalizes with ERM proteins in Schwann-cell microvilli.
CC -!- TISSUE SPECIFICITY: Detected in brain and kidney (at protein level)
CC (PubMed:16709410). Detected in sciatic nerve (at protein level)
CC (PubMed:11430802). Expressed in neurons and muscle cells (at protein
CC level) (PubMed:25757569). Expressed in a variety of tissues. In brain,
CC expressed in the hippocampal formation, the olfactory bulb, the
CC cerebellum and the thalamus. In the peripheral nerve system, expressed
CC in Schwann cells. {ECO:0000269|PubMed:11430802,
CC ECO:0000269|PubMed:12843252, ECO:0000269|PubMed:16709410,
CC ECO:0000269|PubMed:25757569, ECO:0000269|PubMed:7833916,
CC ECO:0000269|PubMed:9175728}.
CC -!- DEVELOPMENTAL STAGE: Broadly expressed in late embryonic and early
CC postnatal cerebellar neurons, including premigratory granule neurons of
CC the external granule cell layer, but expression is largely down-
CC regulated. Weak expression in Purkinje cells throughout development.
CC Alpha- and beta-DG proteins are also present on the Bergmann glial
CC scaffolds used by granule cells during early postnatal radial
CC migration. In the peripheral nerve system, expression briefly precedes
CC and parallels myelination. First expressed at 18.5 dpc in spinal roots,
CC dorsal root ganglions and nerve trunks. At P1, at the onset of
CC myelination, expressed in motor roots. At P5 and P15, expression
CC progressively increases in sensory roots and peripheral nerves. Between
CC postnatal 2 weeks and 18 months, localizes at the nodes of Ranvier as
CC well as at the Schwann cell outer membrane.
CC {ECO:0000269|PubMed:12670716, ECO:0000269|PubMed:12797959,
CC ECO:0000269|PubMed:12843252}.
CC -!- PTM: [Alpha-dystroglycan]: O-glycosylated (PubMed:20044576). POMGNT1
CC catalyzes the initial addition of N-acetylglucosamine, giving rise to
CC the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety and thus providing the
CC necessary basis for the addition of further carbohydrate moieties.
CC Heavily O-glycosylated comprising of up to two thirds of its mass and
CC the carbohydrate composition differs depending on tissue type. Mucin-
CC type O-glycosylation is important for ligand binding activity. O-
CC mannosylation is found in high abundance in both brain and muscle where
CC the most abundant glycan is Sia-alpha-2-3-Gal-beta-1-4-Glc-NAc-beta-1-
CC 2-Man. In muscle, glycosylation on Thr-315, Thr-317, Thr-379 by a
CC phosphorylated O-mannosyl glycan with the structure 2-(N-acetylamido)-
CC 2-deoxygalactosyl-beta-1,3-2-(N-acetylamido)-2-deoxyglucosyl-beta-1,4-
CC 6-phosphomannose is mediated by like-acetylglucosaminyltransferase
CC (LARGE1) protein amd is required for laminin binding. O-glycosylated in
CC the N-terminal region with a core 1 or possibly core 8 glycan. The
CC brain form displays a unique glycosylation pattern which is absent in
CC other tissues; this form shows enhanced binding to laminin LAMA5
CC compared to the skeletal muscle form (By similarity).
CC {ECO:0000250|UniProtKB:O18738, ECO:0000250|UniProtKB:Q14118,
CC ECO:0000269|PubMed:20044576}.
CC -!- PTM: [Beta-dystroglycan]: N-glycosylated.
CC {ECO:0000250|UniProtKB:Q14118}.
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 (By similarity). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Homozygous null mice embryos exhibit gross
CC developmental abnormalities, beginning around 6.5 days of gestation, in
CC the Reichert's membrane, an extraembryonic basement membrane. In
CC peripheral nerves, ablation of DAG1 from 4 week-old mice causes
CC abnormalities in nerve structure and function including mildly impaired
CC sorting of axons, dysmyelination, axonal loss and aberrant nerve
CC conduction. Laminin-binding is lost and there is disruption of the
CC Schwann cell dystroglycan complex. {ECO:0000269|PubMed:12797959,
CC ECO:0000269|PubMed:9175728}.
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; U48854; AAA99779.2; -; Genomic_DNA.
DR EMBL; BC007150; AAH07150.1; -; mRNA.
DR EMBL; X86073; CAA60031.1; -; mRNA.
DR EMBL; Z34532; CAA84293.1; -; mRNA.
DR EMBL; U43512; AAC52853.1; -; mRNA.
DR CCDS; CCDS23518.1; -.
DR PIR; S59630; S59630.
DR RefSeq; NP_001263410.1; NM_001276481.1.
DR RefSeq; NP_001263411.1; NM_001276482.1.
DR RefSeq; NP_001263414.1; NM_001276485.1.
DR RefSeq; NP_001263415.1; NM_001276486.1.
DR RefSeq; NP_001263421.1; NM_001276492.1.
DR RefSeq; NP_001263422.1; NM_001276493.1.
DR RefSeq; NP_034147.1; NM_010017.4.
DR RefSeq; XP_006511699.1; XM_006511636.2.
DR PDB; 1U2C; X-ray; 2.30 A; A=58-303.
DR PDB; 4WIQ; X-ray; 1.59 A; A=50-313.
DR PDB; 5N30; X-ray; 1.80 A; A=50-312.
DR PDB; 5N4H; X-ray; 1.70 A; A=51-313.
DR PDBsum; 1U2C; -.
DR PDBsum; 4WIQ; -.
DR PDBsum; 5N30; -.
DR PDBsum; 5N4H; -.
DR AlphaFoldDB; Q62165; -.
DR BMRB; Q62165; -.
DR SMR; Q62165; -.
DR BioGRID; 199048; 17.
DR CORUM; Q62165; -.
DR IntAct; Q62165; 8.
DR MINT; Q62165; -.
DR STRING; 10090.ENSMUSP00000130626; -.
DR ChEMBL; CHEMBL3739252; -.
DR MEROPS; S72.001; -.
DR GlyConnect; 2270; 2 N-Linked glycans (2 sites).
DR GlyGen; Q62165; 7 sites, 2 N-linked glycans (2 sites).
DR iPTMnet; Q62165; -.
DR PhosphoSitePlus; Q62165; -.
DR SwissPalm; Q62165; -.
DR CPTAC; non-CPTAC-3909; -.
DR EPD; Q62165; -.
DR jPOST; Q62165; -.
DR MaxQB; Q62165; -.
DR PaxDb; Q62165; -.
DR PeptideAtlas; Q62165; -.
DR PRIDE; Q62165; -.
DR ProteomicsDB; 277942; -.
DR Antibodypedia; 4283; 374 antibodies from 41 providers.
DR DNASU; 13138; -.
DR Ensembl; ENSMUST00000080435; ENSMUSP00000079294; ENSMUSG00000039952.
DR Ensembl; ENSMUST00000166905; ENSMUSP00000128531; ENSMUSG00000039952.
DR Ensembl; ENSMUST00000171412; ENSMUSP00000130626; ENSMUSG00000039952.
DR Ensembl; ENSMUST00000191899; ENSMUSP00000142109; ENSMUSG00000039952.
DR GeneID; 13138; -.
DR KEGG; mmu:13138; -.
DR UCSC; uc009rox.2; mouse.
DR CTD; 1605; -.
DR MGI; MGI:101864; Dag1.
DR VEuPathDB; HostDB:ENSMUSG00000039952; -.
DR eggNOG; KOG3781; Eukaryota.
DR GeneTree; ENSGT00390000008429; -.
DR HOGENOM; CLU_007629_2_0_1; -.
DR InParanoid; Q62165; -.
DR OMA; NQNMPET; -.
DR OrthoDB; 163609at2759; -.
DR PhylomeDB; Q62165; -.
DR TreeFam; TF328370; -.
DR Reactome; R-MMU-3000178; ECM proteoglycans.
DR Reactome; R-MMU-5173105; O-linked glycosylation.
DR Reactome; R-MMU-9010553; Regulation of expression of SLITs and ROBOs.
DR BioGRID-ORCS; 13138; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Dag1; mouse.
DR EvolutionaryTrace; Q62165; -.
DR PRO; PR:Q62165; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q62165; protein.
DR Bgee; ENSMUSG00000039952; Expressed in sciatic nerve and 280 other tissues.
DR ExpressionAtlas; Q62165; baseline and differential.
DR Genevisible; Q62165; MM.
DR GO; GO:0005912; C:adherens junction; ISO:MGI.
DR GO; GO:0005604; C:basement membrane; IDA:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0070938; C:contractile ring; ISO:MGI.
DR GO; GO:0043034; C:costamere; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0016011; C:dystroglycan complex; IDA:MGI.
DR GO; GO:0016010; C:dystrophin-associated glycoprotein complex; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0030175; C:filopodium; ISO:MGI.
DR GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0030027; C:lamellipodium; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; IDA:MGI.
DR GO; GO:0033268; C:node of Ranvier; IMP:UniProtKB.
DR GO; GO:0034399; C:nuclear periphery; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0044853; C:plasma membrane raft; ISO:MGI.
DR GO; GO:0099524; C:postsynaptic cytosol; ISO:MGI.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042383; C:sarcolemma; IDA:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0051393; F:alpha-actinin binding; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0002162; F:dystroglycan binding; IPI:CAFA.
DR GO; GO:0043236; F:laminin binding; ISO:MGI.
DR GO; GO:0043237; F:laminin-1 binding; ISO:MGI.
DR GO; GO:0042169; F:SH2 domain binding; ISO:MGI.
DR GO; GO:0008307; F:structural constituent of muscle; ISO:MGI.
DR GO; GO:0015631; F:tubulin binding; ISO:MGI.
DR GO; GO:0017166; F:vinculin binding; ISO:MGI.
DR GO; GO:0001618; F:virus receptor activity; ISO:MGI.
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; IMP:MGI.
DR GO; GO:0060445; P:branching involved in salivary gland morphogenesis; IMP:MGI.
DR GO; GO:0016340; P:calcium-dependent cell-matrix adhesion; ISO:MGI.
DR GO; GO:0071397; P:cellular response to cholesterol; IEA:Ensembl.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:MGI.
DR GO; GO:0071679; P:commissural neuron axon guidance; IMP:MGI.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IMP:MGI.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISO:MGI.
DR GO; GO:0034453; P:microtubule anchoring; ISO:MGI.
DR GO; GO:0002011; P:morphogenesis of an epithelial sheet; IMP:MGI.
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; IMP:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:MGI.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0021675; P:nerve development; IBA:GO_Central.
DR GO; GO:0021682; P:nerve maturation; IMP:UniProtKB.
DR GO; GO:1904261; P:positive regulation of basement membrane assembly involved in embryonic body morphogenesis; ISO:MGI.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; ISO:MGI.
DR GO; GO:0031643; P:positive regulation of myelination; ISO:MGI.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; ISO:MGI.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:0010470; P:regulation of gastrulation; ISO:MGI.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0050807; P:regulation of synapse organization; IDA:SynGO.
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; IDA:SynGO.
DR GO; GO:0014044; P:Schwann cell development; IMP:UniProtKB.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; IEA:Ensembl.
DR DisProt; DP00491; -.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 3.30.70.1040; -; 1.
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; Cell membrane; Cytoplasm; Cytoskeleton; Disulfide bond;
KW Glycoprotein; Host-virus interaction; Membrane; Nucleus; Phosphoprotein;
KW Postsynaptic cell membrane; Reference proteome; Secreted; Signal; Synapse;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..651
FT /note="Alpha-dystroglycan"
FT /id="PRO_0000021067"
FT CHAIN 652..893
FT /note="Beta-dystroglycan"
FT /id="PRO_0000021068"
FT TOPO_DOM 652..751
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 752..772
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 773..893
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 601..710
FT /note="Peptidase S72"
FT REGION 28..406
FT /note="Required for laminin recognition"
FT /evidence="ECO:0000250"
FT REGION 47..69
FT /note="O-glycosylated at one site"
FT /evidence="ECO:0000250"
FT REGION 314..483
FT /note="Mucin-like domain"
FT /evidence="ECO:0000250"
FT REGION 379..498
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 461..483
FT /note="O-glycosylated at seven sites with GalNAc"
FT /evidence="ECO:0000250"
FT REGION 721..744
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 817..893
FT /note="Required for interaction with CAV3"
FT /evidence="ECO:0000250"
FT REGION 821..893
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 878..893
FT /note="Required for binding DMD and UTRN"
FT /evidence="ECO:0000250"
FT MOTIF 774..780
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 887..890
FT /note="PPXY motif"
FT /evidence="ECO:0000250"
FT COMPBIAS 379..400
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..447
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 466..488
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 856..871
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 651..652
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT SITE 713..714
FT /note="Cleavage; by MMP9"
FT /evidence="ECO:0000250"
FT MOD_RES 788
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 890
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 315
FT /note="O-linked (Man6P...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT CARBOHYD 317
FT /note="O-linked (Man6P...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT CARBOHYD 377
FT /note="O-linked (Man6P...) threonine"
FT /evidence="ECO:0000250"
FT CARBOHYD 639
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 647
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 659
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 180..262
FT /evidence="ECO:0000269|PubMed:15326183,
FT ECO:0000269|PubMed:9917844, ECO:0007744|PDB:1U2C,
FT ECO:0007744|PDB:4WIQ, ECO:0007744|PDB:5N30,
FT ECO:0007744|PDB:5N4H"
FT DISULFID 667..711
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT MUTAGEN 796..798
FT /note="IIF->AAA: Complete loss of ANK3-binding."
FT /evidence="ECO:0000269|PubMed:19109891"
FT MUTAGEN 800..801
FT /note="DE->AA: Complete loss of ANK3-binding."
FT /evidence="ECO:0000269|PubMed:19109891"
FT MUTAGEN 803..804
FT /note="DD->AA: Major reduction in ANK3-binding."
FT /evidence="ECO:0000269|PubMed:19109891"
FT CONFLICT 448..450
FT /note="TKK -> SKE (in Ref. 5; CAA84293)"
FT /evidence="ECO:0000305"
FT CONFLICT 599..600
FT /note="GD -> PH (in Ref. 5; CAA84293)"
FT /evidence="ECO:0000305"
FT CONFLICT 643
FT /note="I -> V (in Ref. 3; CAA60031 and 5; AAC52853)"
FT /evidence="ECO:0000305"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:4WIQ"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:4WIQ"
FT HELIX 82..85
FT /evidence="ECO:0007829|PDB:4WIQ"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:4WIQ"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:4WIQ"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:4WIQ"
FT TURN 110..113
FT /evidence="ECO:0007829|PDB:4WIQ"
FT STRAND 114..117
FT /evidence="ECO:0007829|PDB:4WIQ"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:4WIQ"
FT STRAND 125..136
FT /evidence="ECO:0007829|PDB:4WIQ"
FT STRAND 142..156
FT /evidence="ECO:0007829|PDB:4WIQ"
FT STRAND 186..194
FT /evidence="ECO:0007829|PDB:4WIQ"
FT HELIX 197..199
FT /evidence="ECO:0007829|PDB:4WIQ"
FT HELIX 202..216
FT /evidence="ECO:0007829|PDB:4WIQ"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:4WIQ"
FT STRAND 224..227
FT /evidence="ECO:0007829|PDB:4WIQ"
FT STRAND 239..243
FT /evidence="ECO:0007829|PDB:4WIQ"
FT STRAND 254..263
FT /evidence="ECO:0007829|PDB:4WIQ"
FT TURN 266..268
FT /evidence="ECO:0007829|PDB:4WIQ"
FT HELIX 273..281
FT /evidence="ECO:0007829|PDB:4WIQ"
FT HELIX 283..288
FT /evidence="ECO:0007829|PDB:4WIQ"
FT STRAND 292..300
FT /evidence="ECO:0007829|PDB:4WIQ"
SQ SEQUENCE 893 AA; 96905 MW; 59C081EA86AB0AC1 CRC64;
MSVDNWLLHP LWGQTFLLLL SVAVAQAHWP SEPSEAVRDW KNQLEASMHS VLSDFQEAVP
TVVGIPDGTA VVGRSFRVSI PTDLIASSGE IIKVSAAGKE ALPSWLHWDP HSHILEGLPL
DTDKGVHYIS VSAARLGANG SHVPQTSSVF SIEVYPEDHN EPQSVRAASS DPGEVVPSAC
AADEPVTVLT VILDADLTKM TPKQRIDLLN RMQSFSEVEL HNMKLVPVVN NRLFDMSAFM
AGPGNAKKVV ENGALLSWKL GCSLNQNSVP DIRGVETPAR EGAMSAQLGY PVVGWHIANK
KPTLPKRLRR QIHATPTPVT AIGPPTTAIQ EPPSRIVPTP TSPAIAPPTE TMAPPVRDPV
PGKPTVTIRT RGAIIQTPTL GPIQPTRVSE AGTTVPGQIR PTLTIPGYVE PTAVITPPTT
TTKKPRVSTP KPATPSTDSS TTTTRRPTKK PRTPRPVPRV TTKAPITRLE TASPPTRIRT
TTSGVPRGGE PNQRPELKNH IDRVDAWVGT YFEVKIPSDT FYDNEDTTTD KLKLTLKLRE
QQLVGEKSWV QFNSNSQLMY GLPDSSHVGK HEYFMHATDK GGLSAVDAFE IHVHKRPQGD
KAPARFKARL AGDPAPVVND IHKKIALVKK LAFAFGDRNC SSITLQNITR GSIVVEWTNN
TLPLEPCPKE QIIGLSRRIA DENGKPRPAF SNALEPDFKA LSIAVTGSGS CRHLQFIPVA
PPSPGSSAAP ATEVPDRDPE KSSEDDVYLH TVIPAVVVAA ILLIAGIIAM ICYRKKRKGK
LTLEDQATFI KKGVPIIFAD ELDDSKPPPS SSMPLILQEE KAPLPPPEYP NQSMPETTPL
NQDTVGEYTP LRDEDPNAPP YQPPPPFTAP MEGKGSRPKN MTPYRSPPPY VPP
