DAG1_BOVIN
ID DAG1_BOVIN Reviewed; 895 AA.
AC O18738;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Dystroglycan 1 {ECO:0000250|UniProtKB:Q14118};
DE AltName: Full=Dystroglycan {ECO:0000303|PubMed:8798547};
DE AltName: Full=Dystrophin-associated glycoprotein 1 {ECO:0000250|UniProtKB:Q14118};
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:0000250|UniProtKB:Q14118};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shimizu H.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP LIGAND-BINDING, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=8798547; DOI=10.1074/jbc.271.38.23418;
RA Yamada H., Denzer A.J., Hori H., Tanaka T., Anderson L.V., Fujita S.,
RA Fukuta-Ohi H., Shimizu T., Ruegg M.A., Matsumura K.;
RT "Dystroglycan is a dual receptor for agrin and laminin-2 in Schwann cell
RT membrane.";
RL J. Biol. Chem. 271:23418-23423(1996).
RN [3]
RP STRUCTURE OF CARBOHYDRATES, AND LIGAND BINDING.
RX PubMed=8999917; DOI=10.1074/jbc.272.4.2156;
RA Chiba A., Matsumura K., Yamada H., Inazu T., Shimizu T., Kusunoki S.,
RA Kanazawa I., Kobata A., Endo T.;
RT "Structures of sialylated O-linked oligosaccharides of bovine peripheral
RT nerve alpha-dystroglycan. The role of a novel O-mannosyl-type
RT oligosaccharide in the binding of alpha-dystroglycan with laminin.";
RL J. Biol. Chem. 272:2156-2162(1997).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=10075729; DOI=10.1074/jbc.274.12.8240;
RA Saito F., Masaki T., Kamakura K., Anderson L.V.B., Fujita S.,
RA Fukuta-Ohi H., Sunada Y., Shimizu T., Matsumura K.;
RT "Characterization of the transmembrane molecular architecture of the
RT dystroglycan complex in Schwann cells.";
RL J. Biol. Chem. 274:8240-8246(1999).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND GLYCOSYLATION.
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).
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. {ECO:0000250}.
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 (PubMed:8798547). Also acts as a
CC receptor for laminin LAMA5 (PubMed:16709410).
CC {ECO:0000269|PubMed:16709410, ECO:0000269|PubMed:8798547}.
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}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q14118, ECO:0000250|UniProtKB:Q28685,
CC ECO:0000250|UniProtKB:Q62165}.
CC -!- INTERACTION:
CC O18738; P19137: Lama1; Xeno; NbExp=2; IntAct=EBI-8522926, EBI-7176628;
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. Cytoplasm, cytoskeleton. Nucleus,
CC nucleoplasm. Cell membrane, sarcolemma {ECO:0000250}. Postsynaptic cell
CC membrane {ECO:0000250}. 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 the
CC presence of ANK2 (By similarity). Colocalizes with ERM proteins in
CC Schwann-cell microvilli (By similarity). In peripheral nerves,
CC localizes to the Schwann cell membrane. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in brain (at protein level)
CC (PubMed:16709410). Expressed in the myelin sheath of peripheral nerves
CC (PubMed:8798547). {ECO:0000269|PubMed:16709410,
CC ECO:0000269|PubMed:8798547}.
CC -!- PTM: [Alpha-dystroglycan]: O-glycosylated (PubMed:8999917,
CC PubMed:16709410). POMGNT1 catalyzes the initial addition of N-
CC acetylglucosamine, giving rise to the GlcNAc(beta1-2)Man(alpha1-)O-
CC Ser/Thr moiety and thus providing the necessary basis for the addition
CC of further carbohydrate moieties. Heavily O-glycosylated comprising of
CC up to two thirds of its mass and the carbohydrate composition differs
CC depending on tissue type. Mucin-type O-glycosylation is important for
CC ligand binding activity. O-mannosylation is found in high abundance in
CC both brain and muscle where the most abundant glycan is Sia-alpha-2-3-
CC Gal-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 amd is required for
CC laminin binding. O-glycosylated in the N-terminal region with a core 1
CC or possibly core 8 glycan. The brain form displays a unique
CC glycosylation pattern which is absent in other tissues; this form shows
CC enhanced binding to laminin LAMA5 compared to the skeletal muscle form
CC (PubMed:16709410). {ECO:0000250|UniProtKB:Q14118,
CC ECO:0000269|PubMed:16709410, ECO:0000269|PubMed:8999917}.
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}.
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DR EMBL; AB009079; BAA23650.1; -; mRNA.
DR RefSeq; NP_776587.1; NM_174162.1.
DR AlphaFoldDB; O18738; -.
DR SMR; O18738; -.
DR BioGRID; 158770; 4.
DR IntAct; O18738; 4.
DR MINT; O18738; -.
DR STRING; 9913.ENSBTAP00000015385; -.
DR MEROPS; S72.001; -.
DR GlyConnect; 39; 3 O-Linked glycans.
DR PaxDb; O18738; -.
DR PeptideAtlas; O18738; -.
DR PRIDE; O18738; -.
DR GeneID; 281439; -.
DR KEGG; bta:281439; -.
DR CTD; 1605; -.
DR eggNOG; KOG3781; Eukaryota.
DR InParanoid; O18738; -.
DR OrthoDB; 163609at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005604; C:basement membrane; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0016011; C:dystroglycan complex; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042383; C:sarcolemma; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0043236; F:laminin binding; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
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:0021675; P:nerve development; IBA:GO_Central.
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 Cell membrane; Cytoplasm; Cytoskeleton; Disulfide bond; Glycoprotein;
KW Membrane; Nucleus; Phosphoprotein; Postsynaptic cell membrane;
KW Reference proteome; Secreted; Signal; Synapse; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..653
FT /note="Alpha-dystroglycan"
FT /id="PRO_0000021061"
FT CHAIN 654..895
FT /note="Beta-dystroglycan"
FT /id="PRO_0000021062"
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 /evidence="ECO:0000250"
FT REGION 49..71
FT /note="O-glycosylated at one site"
FT /evidence="ECO:0000250"
FT REGION 316..485
FT /note="Mucin-like domain"
FT /evidence="ECO:0000250"
FT REGION 381..500
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 463..485
FT /note="O-glycosylated at seven sites with GalNAc"
FT /evidence="ECO:0000250"
FT REGION 724..747
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 819..895
FT /note="Required for interaction with CAV3"
FT /evidence="ECO:0000250"
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 /evidence="ECO:0000250"
FT MOTIF 776..782
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 889..892
FT /note="PPXY motif"
FT /evidence="ECO:0000250"
FT COMPBIAS 381..403
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..449
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 468..490
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 733..747
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:0000250"
FT SITE 715..716
FT /note="Cleavage; by MMP9"
FT /evidence="ECO:0000250"
FT MOD_RES 790
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT MOD_RES 892
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
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:0000250|UniProtKB:Q14118"
FT CARBOHYD 319
FT /note="O-linked (Man6P...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT CARBOHYD 379
FT /note="O-linked (Man6P...) threonine"
FT /evidence="ECO:0000250"
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:0000255"
FT DISULFID 182..264
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT DISULFID 669..713
FT /evidence="ECO:0000250|UniProtKB:Q14118"
SQ SEQUENCE 895 AA; 97321 MW; 400213A299630D11 CRC64;
MRMSVGSAVP LPLWGRTFLL LLSVAVTQSH WPSEPSEAVR DWENQLEASM HSALSDLHET
VPTVVGIPDG TAVVGRSFRV TIPTDLIASN GEVIKVSAAG KEALPSWLHW DPQSHTLEGL
PLDTDKGVHY ISVSAARLGA NGSHVPQTSS VFSIEVYPED HSEPQSLRAA SPDPGEVVSL
VCAADEPVTV LTVILDADLT KMTPKQRIDL LRRMRGFSEV EPHNMKLVPV VNNRLFDMSA
FMAGPGNAKK VVENGALLSW KLGCCLNQNS VPDIRGVEVP AREGAMSAQL GYPVVGWHIA
NKKPSLPKRI RRQIHATPTP VTAIGPPTTA IQEPPSRIVP TPTSPAIAPP TETMAPPVRD
PVPGKPTVTI RTRGAIIQTP TLGPIQPTRV SEAGTTVPSQ IRPTMTIPGY MEPSTVTTPP
TTTTKKPRVS TPRPATPSTD SSTTTTRRPT KKPRTSRPVP RVTTKAPITR LETASPATRM
RTTTSGVPHG GEPNQRPELK NHIDRVDAWV GTYFEVKIPS DTFYDNEDTT TDKLKLTLKL
REQQLVGEKS WVQFNSNSQL MYGLPDSSHV GKHEYFMHAT DKGGLSAVDA FEIHVHRRPQ
GDKAPARFKA KLTGDPAAVT NDIHKKIALV KKLAFAFGDR NCSTITLQNI TRGSIVVEWT
NNTLPLEPCP KEQITALSRR IAEDDGKPRG AFVNALEPDF QAMSITVTGS GSCRHLQFVP
VAPPMRVPSE APATEVPDRD PEKSSEDDVY LHTVIPAVVV AAILLIAGII AMICYRKKRK
GKLTLEDQAT FIKKGVPIIF ADELDDSKPP PSSSMPLILQ EEKAPLPPPE YPNQSMPETT
PLNQDTVGEY APLRDEDPSA PPYQPPPPFT APMEGKGSRP KNMTPYRSPP PYVPP
