DAG1_PIG
ID DAG1_PIG Reviewed; 877 AA.
AC Q29243; I3LD20;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 07-JAN-2015, sequence version 2.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Dystroglycan 1 {ECO:0000250|UniProtKB:Q14118};
DE AltName: Full=Dystroglycan {ECO:0000250|UniProtKB:Q14118};
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 439-566.
RC TISSUE=Small intestine;
RX PubMed=8672129; DOI=10.1007/s003359900153;
RA Winteroe A.K., Fredholm M., Davies W.;
RT "Evaluation and characterization of a porcine small intestine cDNA library:
RT analysis of 839 clones.";
RL Mamm. Genome 7:509-517(1996).
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 of alpha-DAG1 is found in high abundance in both brain
CC and muscle where the most abundant glycan is Sia-alpha-2-3-Gal-beta-1-
CC 4-Glc-NAc-beta-1-2-Man. In muscle, glycosylation on Thr-317, Thr-319
CC and Thr-379 by a phosphorylated O-mannosyl glycan with the structure 2-
CC (N-acetylamido)-2-deoxygalactosyl-beta-1,3-2-(N-acetylamido)-2-
CC deoxyglucosyl-beta-1,4-6-phosphomannose is mediated by like-
CC 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 (By similarity). {ECO:0000250|UniProtKB:O18738,
CC 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; F14847; CAA23292.1; -; mRNA.
DR STRING; 9823.ENSSSCP00000021948; -.
DR PaxDb; Q29243; -.
DR PeptideAtlas; Q29243; -.
DR PRIDE; Q29243; -.
DR eggNOG; KOG3781; Eukaryota.
DR TreeFam; TF328370; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0043236; F:laminin binding; IBA:GO_Central.
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 2: Evidence at transcript 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..635
FT /note="Alpha-dystroglycan"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT /id="PRO_0000431681"
FT CHAIN 636..877
FT /note="Beta-dystroglycan"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT /id="PRO_0000431682"
FT TRANSMEM 732..757
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 585..694
FT /note="Peptidase S72"
FT /evidence="ECO:0000305"
FT REGION 30..408
FT /note="Required for laminin recognition"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT REGION 49..71
FT /note="O-glycosylated at one site"
FT /evidence="ECO:0000250"
FT REGION 316..468
FT /note="Mucin-like domain"
FT /evidence="ECO:0000250"
FT REGION 319..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 380..444
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 446..468
FT /note="O-glycosylated at seven sites with GalNAc"
FT /evidence="ECO:0000250"
FT REGION 458..480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 706..727
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 784..877
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 801..877
FT /note="Required for interaction with CAV3"
FT /evidence="ECO:0000250"
FT REGION 862..877
FT /note="Required for binding DMD and UTRN"
FT /evidence="ECO:0000250"
FT MOTIF 758..764
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 871..874
FT /note="PPXY motif"
FT /evidence="ECO:0000250"
FT COMPBIAS 338..363
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 417..431
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 458..473
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 840..855
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 635..636
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT SITE 697..698
FT /note="Cleavage; by MMP9"
FT /evidence="ECO:0000250"
FT MOD_RES 772
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT MOD_RES 874
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 623
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 631
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 643
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 182..264
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT DISULFID 651..695
FT /evidence="ECO:0000250|UniProtKB:Q14118"
FT CONFLICT 530
FT /note="V -> E (in Ref. 2; CAA23292)"
FT /evidence="ECO:0000305"
FT CONFLICT 563
FT /note="D -> G (in Ref. 2; CAA23292)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 877 AA; 95431 MW; 4F3714FFBBA16F8B CRC64;
MRMSAGLSLL IPLWGRTFLL LLSVAVTQSR WPSEPSDAVR DWENQLEASM HSVLSDLHEA
VPTVVGIPDG TAVVGRSFRV TIPTDLIASG GEIIKVSAAG KEALPSWLHW DPQSHTLEGL
PLDTDKGVHY ISVSAARLGA NGSHVPQTSS VFSIEVYPED HSEPQSVRAA SPDPGEVVSS
VCAADEPVTV LTVILDADLT KMIPKQRLDL LQRMQSFSEV ELHNMKLVPV VNNRLFDMSA
FMAGPGNAKK VIENGALLSW KLGCSLNQNS VPDIHGVEVP AREGAMSAQL GYPVVGWHIA
NKKPPLPKRI RRQIHATPTP VTAIGPPTTA IQEPPSRIVP TPTSPAIAPP TETMAPPVRD
PVPGKPTVTI RTRGAIFQTP TLGPIQPTRV SEAGTTVPGH IRPTMTIPGY LEPTAVATPP
TPTTKNPRVS XPTKKPRTPR PVPRVTTKAP ITRLETASPP TRIRTTTSGL PRGEPNQRPE
LKNHIDRVDA WVGTYFEVKI PSDTFYDNED TTTDKLKLTL KLREQQLVGV KSWVQFNSNS
QLMYGLPDSS HVGKHEYFMH ATDKGGLSAV DAFEIHVHRR PQGDRAPARF TAKFVGDPAP
VVNDIHKKIA LVKKLAFAFG DRNCSTITLQ NITRGSIVVE WTNNTLPLEP CPKEQITGLS
RRIAEDDGKP RAAFSNALEP DFKAMSIAVT GSGSCRHLQF VPVAPPKRVP SEAPPTEVPD
RDPEKSSEDD VYLHTVIPAV VVAAILLIAG IIAMICYRKK RKGKLTLEDQ ATFIKKGVPI
IFADELDDSK PPPSSSMPLI LQEEKAPLPP PEYPNQSVPE TTPLNQDTVG EYTPLRDEDP
NAPPYQPPPP FTAPMEGKGS RPKNMTPYRS PPPYVPP
