DAG1_CANLF
ID DAG1_CANLF Reviewed; 892 AA.
AC Q9TSZ6;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Dystroglycan 1 {ECO:0000250|UniProtKB:Q14118};
DE AltName: Full=Dystroglycan {ECO:0000303|PubMed:10720570};
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10720570; DOI=10.1101/gr.10.3.295;
RA Leeb T., Neumann S., Deppe A., Breen M., Brenig B.;
RT "Genomic organization of the dog dystroglycan gene DAG1 locus on chromosome
RT 20q15.1-q15.2.";
RL Genome Res. 10:295-301(2000).
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 (By similarity). Also acts as a receptor
CC for laminin 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 (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 -!- 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 {ECO:0000250}. Postsynaptic cell membrane {ECO:0000250}. Note=The
CC monomeric form translocates to the nucleus via the action of importins
CC and depends on RAN. Nuclear transport is inhibited by Tyr-892
CC phosphorylation. In skeletal muscle, this phosphorylated form locates
CC to a vesicular internal membrane compartment. In muscle cells,
CC sarcolemma localization requires the presence of ANK2, while
CC localization to costameres requires the presence of ANK3. Localizes to
CC neuromuscular junctions (NMJs) in the presence of ANK2 (By similarity).
CC In peripheral nerves, localizes to the Schwann cell membrane.
CC Colocalizes with ERM proteins in Schwann-cell microvilli (By
CC similarity). {ECO:0000250}.
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 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-314, Thr-316 and Thr-376 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 -!- 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; AJ012166; CAB62568.1; -; Genomic_DNA.
DR RefSeq; NP_001029164.1; NM_001033992.1.
DR RefSeq; XP_005632375.1; XM_005632318.2.
DR RefSeq; XP_005632376.1; XM_005632319.2.
DR AlphaFoldDB; Q9TSZ6; -.
DR SMR; Q9TSZ6; -.
DR STRING; 9612.ENSCAFP00000016488; -.
DR MEROPS; S72.001; -.
DR PaxDb; Q9TSZ6; -.
DR PRIDE; Q9TSZ6; -.
DR Ensembl; ENSCAFT00030025431; ENSCAFP00030022207; ENSCAFG00030013738.
DR Ensembl; ENSCAFT00845045847; ENSCAFP00845035994; ENSCAFG00845025980.
DR GeneID; 476623; -.
DR KEGG; cfa:476623; -.
DR CTD; 1605; -.
DR VEuPathDB; HostDB:ENSCAFG00845025980; -.
DR eggNOG; KOG3781; Eukaryota.
DR GeneTree; ENSGT00390000008429; -.
DR HOGENOM; CLU_007629_2_0_1; -.
DR InParanoid; Q9TSZ6; -.
DR OMA; NQNMPET; -.
DR OrthoDB; 163609at2759; -.
DR TreeFam; TF328370; -.
DR Reactome; R-CFA-3000178; ECM proteoglycans.
DR Reactome; R-CFA-5173105; O-linked glycosylation.
DR Reactome; R-CFA-9010553; Regulation of expression of SLITs and ROBOs.
DR Proteomes; UP000002254; Chromosome 20.
DR Bgee; ENSCAFG00000011207; Expressed in cardiac muscle of left ventricle and 46 other tissues.
DR GO; GO:0005604; C:basement membrane; IBA:GO_Central.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0070938; C:contractile ring; IEA:Ensembl.
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:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0030175; C:filopodium; IEA:Ensembl.
DR GO; GO:0005925; C:focal adhesion; IEA:Ensembl.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0033268; C:node of Ranvier; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
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; IEA:Ensembl.
DR GO; GO:0051393; F:alpha-actinin binding; IEA:Ensembl.
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:0042169; F:SH2 domain binding; IEA:Ensembl.
DR GO; GO:0008307; F:structural constituent of muscle; IEA:Ensembl.
DR GO; GO:0015631; F:tubulin binding; IEA:Ensembl.
DR GO; GO:0017166; F:vinculin binding; IEA:Ensembl.
DR GO; GO:0001618; F:virus receptor activity; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
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:0071679; P:commissural neuron axon guidance; IEA:Ensembl.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IEA:Ensembl.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IEA:Ensembl.
DR GO; GO:0034453; P:microtubule anchoring; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; IEA:Ensembl.
DR GO; GO:0010470; P:regulation of gastrulation; IEA:Ensembl.
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:0098942; P:retrograde trans-synaptic signaling by trans-synaptic protein complex; IEA:Ensembl.
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 3: Inferred from homology;
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..27
FT /evidence="ECO:0000255"
FT CHAIN 28..650
FT /note="Alpha-dystroglycan"
FT /id="PRO_0000021063"
FT CHAIN 651..892
FT /note="Beta-dystroglycan"
FT /id="PRO_0000021064"
FT TOPO_DOM 28..750
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 751..771
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 772..892
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 600..709
FT /note="Peptidase S72"
FT REGION 30..405
FT /note="Required for laminin recognition"
FT /evidence="ECO:0000250"
FT REGION 46..68
FT /note="O-glycosylated at one site"
FT /evidence="ECO:0000250"
FT REGION 313..482
FT /note="Mucin-like domain"
FT /evidence="ECO:0000250"
FT REGION 378..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 460..482
FT /note="O-glycosylated at seven sites with GalNAc"
FT /evidence="ECO:0000250"
FT REGION 721..742
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 816..892
FT /note="Required for interaction with CAV3"
FT /evidence="ECO:0000250"
FT REGION 820..892
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 877..892
FT /note="Required for binding DMD and UTRN"
FT /evidence="ECO:0000250"
FT MOTIF 773..779
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 886..889
FT /note="PPXY motif"
FT /evidence="ECO:0000250"
FT COMPBIAS 378..399
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 413..446
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 465..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 855..870
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 650..651
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT SITE 712..713
FT /note="Cleavage; by MMP9"
FT /evidence="ECO:0000250"
FT MOD_RES 787
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT MOD_RES 889
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 314
FT /note="O-linked (Man6P...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT CARBOHYD 316
FT /note="O-linked (Man6P...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT CARBOHYD 376
FT /note="O-linked (Man6P...) threonine"
FT /evidence="ECO:0000250"
FT CARBOHYD 638
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 646
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 658
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 179..261
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT DISULFID 666..710
FT /evidence="ECO:0000250|UniProtKB:Q14118"
SQ SEQUENCE 892 AA; 97192 MW; 0228FAFD471CD5F3 CRC64;
MRMSAGLSLL LPLWGRTFLL LLSVAMAQSH WPSEAGRDWE NQLEASMHSV LSDLHEAVPT
VVGIPDGIAV VGRSFRVTIP MDLIASNGEL VKVSAVGKEV LPSWLHWDPQ SHTLEGLPLD
TDKGVHYISV SATRLGANGS HVPQTSSVFS IEVYPEDHSE PQSVRAASPD PAEVVSSACA
ADEPVTVLTV ILDADLTKMT PKQRIDLLHR MRSFSEVELH NMKLVPVVNN RLFDMSAFMA
GPGNAKKVVE NGALLSWKLG CSLNQNNVPD IHGVEAPARE GAMSAQLGYP VVGWHIANKK
PPIPKRIRRQ IHATPTPVTA IGPPTTAIQE PPSRIVPTPT SPAIAPPTET MAPPVRDPVP
GKPTVTIRTR GAIIQTPTLG PIQPTRVSEA GTTVPGQIRP TMTIPGYVEP TAVATPPTTT
TKKPRVSTPK PATPSTDSST TTTRRPTKKP RTPRPVPRVT TKAPITRLET ASPPTRIRTT
TSGVPRGGEP NQRPELKNHI DRVDAWVGTY FEVKIPSDTF YDHEDTTTDK LKLTLKLREQ
QLVGEKSWVQ FNSNSQLMYG LPDSSHVGKH EYFMHATDKG GLSAVDAFEI HVHKRPQGDR
APARFKAKFM GDPVPVVNDI HKKISLVKKL AFAFGDRNCS TITLQNITRG SILVEWTNNT
LPLEPCPKEQ IMALSQRIAE DNGKPRAAFS NALEPDFQAS SIAVTGSGSC RHLQFIPVAP
PRRVPSEVPS TDVPDRDPEK SSEDDVYLHT VIPAVVVAAI LLIAGIIAMI CYRKKRKGKL
TLEDQATFIK KGVPIIFADE LDDSKPPPSS SMPLILQEEK APLPPPEYPN QSVPETTPLN
QDTVGEYTPL REEDPNAPPY QPPPPFTAPM EGKGSRPKNM TPYRSPPPYV PP
