DAG1_RABIT
ID DAG1_RABIT Reviewed; 895 AA.
AC Q28685;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Dystroglycan 1 {ECO:0000250|UniProtKB:Q14118};
DE AltName: Full=Dystroglycan {ECO:0000303|PubMed:15210115};
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 783-793, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Skeletal muscle;
RX PubMed=1741056; DOI=10.1038/355696a0;
RA Ibraghimov-Beskrovnaya O., Ervasti J.M., Leveille C.J., Slaughter C.A.,
RA Sernett S.W., Campbell K.P.;
RT "Primary structure of dystrophin-associated glycoproteins linking
RT dystrophin to the extracellular matrix.";
RL Nature 355:696-702(1992).
RN [2]
RP STRUCTURE OF CARBOHYDRATES.
RX PubMed=9838223; DOI=10.1016/s0304-4165(98)00114-7;
RA Sasaki T., Yamada H., Matsumura K., Shimizu T., Kobata A., Endo T.;
RT "Detection of O-mannosyl glycans in rabbit skeletal muscle alpha-
RT dystroglycan.";
RL Biochim. Biophys. Acta 1425:599-606(1998).
RN [3]
RP INTERACTION WITH LARGE1, AND LIGAND-BINDING.
RX PubMed=15210115; DOI=10.1016/j.cell.2004.06.003;
RA Kanagawa M., Saito F., Kunz S., Yoshida-Moriguchi T., Barresi R.,
RA Kobayashi Y.M., Muschler J., Dumanski J.P., Michele D.E., Oldstone M.B.,
RA Campbell K.P.;
RT "Molecular recognition by LARGE is essential for expression of functional
RT dystroglycan.";
RL Cell 117:953-964(2004).
RN [4]
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).
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. Interacts with SGCD. Interacts with AGR2 and AGR3.
CC Interacts (betaDAG1) with DMD; the interaction is inhibited by
CC phosphorylation on the PPXY motif. Interacts (betaDAG1, via its PPXY
CC motif) with UTRN (via its WWW and ZZ domains); the interaction is
CC inhibited by phosphorylation on the PPXY motif. Interacts (betaDAG1,
CC via its phosphorylated PPXY motif) with the SH2 domain-containing
CC proteins, FYN, CSK, NCK and SHC. Interacts (betaDAG1) with CAV3 (via a
CC central WW-like domain); the interaction disrupts the binding of DMD.
CC BetaDAG1 directly interacts with ANK3, but not with ANK2; this
CC interaction does not interfere with DMD-binding and is required for
CC retention at costameres (By similarity). Identified in a dystroglycan
CC complex that contains at least PRX, DRP2, UTRN, DMD and DAG1 (By
CC similarity). Interacts with POMGNT1 (By similarity).
CC {ECO:0000250|UniProtKB:Q14118, ECO:0000250|UniProtKB:Q62165,
CC ECO:0000269|PubMed:15210115}.
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 (By similarity). Localizes to neuromuscular junctions
CC (NMJs) in the presence of ANK2 (By similarity). Colocalizes with ERM
CC proteins in Schwann-cell microvilli (By similarity). In peripheral
CC nerves, localizes to the Schwann cell membrane. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in brain, cardiac muscle and skeletal
CC muscle (at protein level) (PubMed:16709410). Expressed in lung, brain,
CC liver, kidney, diaphragm and stomach (PubMed:1741056).
CC {ECO:0000269|PubMed:16709410, ECO:0000269|PubMed:1741056}.
CC -!- PTM: [Alpha-dystroglycan]: O-glycosylated (PubMed:9838223). 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-317, Thr-319 and 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:9838223}.
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; X64393; CAA45732.1; -; mRNA.
DR PIR; PN0662; PN0662.
DR PIR; PN0663; PN0663.
DR PIR; S20582; S20582.
DR RefSeq; NP_001095170.1; NM_001101700.1.
DR RefSeq; XP_017199133.1; XM_017343644.1.
DR RefSeq; XP_017199134.1; XM_017343645.1.
DR AlphaFoldDB; Q28685; -.
DR SMR; Q28685; -.
DR CORUM; Q28685; -.
DR DIP; DIP-679N; -.
DR IntAct; Q28685; 2.
DR MINT; Q28685; -.
DR STRING; 9986.ENSOCUP00000002981; -.
DR MEROPS; S72.001; -.
DR GlyConnect; 40; 4 O-Linked glycans.
DR PRIDE; Q28685; -.
DR Ensembl; ENSOCUT00000003437; ENSOCUP00000002981; ENSOCUG00000003439.
DR GeneID; 100009278; -.
DR KEGG; ocu:100009278; -.
DR CTD; 1605; -.
DR eggNOG; KOG3781; Eukaryota.
DR GeneTree; ENSGT00390000008429; -.
DR HOGENOM; CLU_007629_2_0_1; -.
DR InParanoid; Q28685; -.
DR OMA; NQNMPET; -.
DR OrthoDB; 163609at2759; -.
DR TreeFam; TF328370; -.
DR Proteomes; UP000001811; Chromosome 9.
DR Bgee; ENSOCUG00000003439; Expressed in upper lobe of left lung and 15 other tissues.
DR GO; GO:0005604; C:basement membrane; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0016010; C:dystrophin-associated glycoprotein complex; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
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:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
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:0043237; F:laminin-1 binding; IDA:UniProtKB.
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: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:0035556; P:intracellular signal transduction; IDA:CACAO.
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: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: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 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Membrane; Nucleus; Phosphoprotein;
KW Postsynaptic cell membrane; Reference proteome; Secreted; Signal; Synapse;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..653
FT /note="Alpha-dystroglycan"
FT /id="PRO_0000021069"
FT CHAIN 654..895
FT /note="Beta-dystroglycan"
FT /id="PRO_0000021070"
FT TOPO_DOM 654..749
FT /note="Extracellular"
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 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 348..369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 413..499
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 348..363
FT /note="Pro 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 468..490
FT /note="Polar 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; 97030 MW; C2B9E4733A0AB82A CRC64;
MRMSVGLSLL LPLWGRTFLL LLCVAVAQSH WPSEPSEAVR DWENQLEASM HSVLSDLHEA
LPTVVGIPDG TAVVGRSFRV TIPTDLIGSS GEVIKVSTAG KEVLPSWLHW DPQSHTLEGL
PLDTDKGVHY ISVSAAQLDA NGSHIPQTSS VFSIEVYPED HSEPQSVRAA SPDLGEAAAS
ACAAEEPVTV LTVILDADLT KMTPKQRIDL LHRMQSFSEV ELHNMKLVPV VNNRLFDMSA
FMAGPGNAKK VVENGALLSW KLGCSLNQNS VPDIRGVEAP AREGTMSAQL GYPVVGWHIA
NKKPPLPKRI RRQIHATPTP VTAIGPPTTA IQEPPSRIVP TPTSPAIAPP TETMAPPVRD
PVPGKPTVTT RTRGAIIQTP TLGPIQPTRV SDAGTVVSGQ IRATVTIPGY VEPTAVATPP
TTTTKKPRVS TPKPATPSTD SSATTTRRPT KKPRTPRPVP RVTTKAPITR LETASPPTRI
RTTTSGVPRG GEPNQRPELK NHIDRVDAWV GTYFEVKIPS DTFYDKEDTT TDKLKLTLKL
REQQLVGEKS WVQFNSNSQL MYGLPDSSHV GKHEYFMHAT DKGGLSAVDA FEIHVHKRPQ
GDKAPARFKA KFVGDPAPVV NDIHKKIALV KKLAFAFGDR NCSTVTLQNI TRGSIVVEWT
NNTLPLEPCP KEQITGLSRR IAEDNGQPRP AFTNALEPDF KATSIAITGS GSCRHLQFIP
VAPPGIPSSV TPPTEVPDRD PEKSSEDDVY LHTVIPAVVV AAILLIAGII AMICYRKKRK
GKLTLEDQAT FIKKGVPIIF ADELDDSKPP PSSSMPLILQ EEKAPLPPPE YPSQSVPETT
PLNQDTVGEY TPLRDEDPNA PPYQPPPPFT APMEGKGSRP KNMTPYRSPP PYVPP
