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Protein

Dystroglycan

Gene

Dag1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sacrolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, and epithelial polarization.
Alpha-dystroglycan is an extracellular peripheral glycoprotein that acts as a receptor for both extracellular matrix proteins containing laminin-G domains, and for certain adenoviruses. Receptor for laminin-2 (LAMA2) and agrin in peripheral nerve Schwann cells. Also receptor for lymphocytic choriomeningitis virus, Old World Lassa fever virus, and clade C New World arenaviruses.
Beta-dystroglycan is a transmembrane protein that plays important roles in connecting the extracellular matrix to the cytoskeleton. Acts as a cell adhesion receptor in both muscle and non-muscle tissues. Receptor for both DMD and UTRN and, through these interactions, scaffolds axin to the cytoskeleton. Also functions in cell adhesion-mediated signaling and implicated in cell polarity (By similarity).By similarity3 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processHost-virus interaction

Enzyme and pathway databases

ReactomeiR-MMU-3000178 ECM proteoglycans
R-MMU-5173105 O-linked glycosylation
R-MMU-9010553 Regulation of expression of SLITs and ROBOs

Protein family/group databases

MEROPSiS72.001

Names & Taxonomyi

Protein namesi
Recommended name:
Dystroglycan
Alternative name(s):
Dystrophin-associated glycoprotein 1
Cleaved into the following 2 chains:
Alpha-dystroglycan
Short name:
Alpha-DG
Beta-dystroglycan
Short name:
Beta-DG
Gene namesi
Name:Dag1
Synonyms:Dag-1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:101864 Dag1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini652 – 751ExtracellularSequence analysisAdd BLAST100
Transmembranei752 – 772HelicalSequence analysisAdd BLAST21
Topological domaini773 – 893CytoplasmicSequence analysisAdd BLAST121

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Nucleus, Postsynaptic cell membrane, Secreted, Synapse

Pathology & Biotechi

Disruption phenotypei

Homozygous null mice embryos exhibit gross developmental abnormalities, beginning around 6.5 days of gestation, in the Reichert's membrane, an extraembryonic basement membrane. In peripheral nerves, ablation of DAG1 from 4 week-old mice causes abnormalities in nerve structure and function including mildly impaired sorting of axons, dysmyelination, axonal loss and aberrant nerve conduction. Laminin-binding is lost and there is disruption of the Schwann cell dystroglycan complex.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi796 – 798IIF → AAA: Complete loss of ANK3-binding. 1 Publication3
Mutagenesisi800 – 801DE → AA: Complete loss of ANK3-binding. 1 Publication2
Mutagenesisi803 – 804DD → AA: Major reduction in ANK3-binding. 1 Publication2

Chemistry databases

ChEMBLiCHEMBL3739252

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000002106728 – 651Alpha-dystroglycanAdd BLAST624
ChainiPRO_0000021068652 – 893Beta-dystroglycanAdd BLAST242

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi139N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi180 ↔ 262Combined sources2 Publications
Glycosylationi315O-linked (Man6P...) threonineBy similarity1
Glycosylationi317O-linked (Man6P...) threonineBy similarity1
Glycosylationi377O-linked (Man6P...) threonineBy similarity1
Glycosylationi639N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi647N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi659N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi667 ↔ 711By similarity
Modified residuei788PhosphothreonineCombined sources1
Modified residuei890Phosphotyrosine; by SRCBy similarity1

Post-translational modificationi

O- and N-glycosylated (By similarity). POMGNT1 catalyzes the initial addition of N-acetylglucosamine, giving rise to the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety and thus providing the necessary basis for the addition of further carbohydrate moieties. Alpha-dystroglycan is heavily O-glycosylated comprising of up to two thirds of its mass and the carbohydrate composition differs depending on tissue type. Mucin-type O-glycosylation is important for ligand binding activity. O-mannosylation of alpha-DAG1 is found in high abundance in both brain and muscle where the most abundant glycan is Sia-alpha-2-3-Gal-beta-1-4-Glc-NAc-beta-1-2-Man. In muscle, glycosylation on Thr-315, Thr-317, Thr-379 by a phosphorylated O-mannosyl glycan with the structure 2-(N-acetylamido)-2-deoxygalactosyl-beta-1,3-2-(N-acetylamido)-2-deoxyglucosyl-beta-1,4-6-phosphomannose is mediated by like-acetylglucosaminyltransferase (LARGE1) protein amd is required for laminin binding. O-glycosylated in the N-terminal region with a core 1 or possibly core 8 glycan. The beta subunit is N-glycosylated (By similarity).By similarity1 Publication
Autolytic cleavage produces the alpha and beta subunits. In cutaneous cells, as well as in certain pathological conditions, shedding of beta-dystroglcan can occur releasing a peptide of about 30 kDa (By similarity).By similarity
SRC-mediated phosphorylation of the PPXY motif of the beta subunit recruits SH2 domain-containing proteins, but inhibits binding to WWW domain-containing proteins, DMD and UTRN. This phosphorylation also inhibits nuclear entry (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei651 – 652Cleavage; by autolysisBy similarity2
Sitei713 – 714Cleavage; by MMP9By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ62165
MaxQBiQ62165
PaxDbiQ62165
PeptideAtlasiQ62165
PRIDEiQ62165

PTM databases

iPTMnetiQ62165
PhosphoSitePlusiQ62165
SwissPalmiQ62165

Miscellaneous databases

PMAP-CutDBiQ62165

Expressioni

Tissue specificityi

Detected in sciatic nerve (at protein level) (PubMed:11430802). Expressed in a variety of tissues. In brain, expressed in the hippocampal formation, the olfactory bulb, the cerebellum and the thalamus. In the peripheral nerve system, expressed in Schwann cells.4 Publications

Developmental stagei

Broadly expressed in late embryonic and early postnatal cerebellar neurons, including premigratory granule neurons of the external granule cell layer, but expression is largely down-regulated. Weak expression in Purkinje cells throughout development. Alpha- and beta-DG proteins are also present on the Bergmann glial scaffolds used by granule cells during early postnatal radial migration. In the peripheral nerve system, expression briefly precedes and parallels myelination. First expressed at E18.5 in spinal roots, dorsal root ganglions and nerve trunks. At P1, at the onset of myelination, expressed in motor roots. At P5 and P15, expression progressively increases in sensory roots and peripheral nerves. Between postnatal 2 weeks and 18 months, localizes at the nodes of Ranvier as well as at the Schwann cell outer membrane.3 Publications

Gene expression databases

BgeeiENSMUSG00000039952
CleanExiMM_DAG1
ExpressionAtlasiQ62165 baseline and differential
GenevisibleiQ62165 MM

Interactioni

Subunit structurei

Monomer. Heterodimer of alpha- and beta-dystroglycan subunits which are the central components of the dystrophin-glycoprotein complex. This complex then can form a dystrophin-associated glycoprotein complex (DGC) which is composed of three subcomplexes: a cytoplasmic complex comprised of DMD (or UTRN), DTNA and a number of syntrophins, such as SNTB1, SNTB2, SNTG1 and SNTG2, the transmembrane dystroglycan complex, and the sarcoglycan-sarcospan complex. Interacts (via the N-terminal of alphaDAG1) with LARGE1; the interaction enhances laminin binding (By similarity). Interacts with SGCD. Interacts with AGR2 and AGR3. Interacts (betaDAG1) with DMD; the interaction is inhibited by phosphorylation on the PPXY motif. Interacts (betaDAG1, via its PPXY motif) with UTRN (via its WWW and ZZ domains); the interaction is inhibited by phosphorylation on the PPXY motif. Interacts (betaDAG1, via its phosphorylated PPXY motif) with the SH2 domain-containing proteins, FYN, CSK, NCK and SHC. Interacts (betaDAG1) with CAV3 (via a central WW-like domain); the interaction disrupts the binding of DMD. BetaDAG1 directly interacts with ANK3, but not with ANK2; this interaction does not interfere with DMD-binding and is required for retention at costameres (By similarity). Identified in a dystroglycan complex that contains at least PRX, DRP2, UTRN, DMD and DAG1 (PubMed:11430802). Interacts with POMGNT1 (By similarity).By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199048, 7 interactors
CORUMiQ62165
IntActiQ62165, 7 interactors
MINTiQ62165
STRINGi10090.ENSMUSP00000079294

Structurei

Secondary structure

1893
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi68 – 71Combined sources4
Beta strandi76 – 79Combined sources4
Helixi82 – 85Combined sources4
Beta strandi91 – 96Combined sources6
Beta strandi99 – 101Combined sources3
Beta strandi106 – 109Combined sources4
Turni110 – 113Combined sources4
Beta strandi114 – 117Combined sources4
Helixi121 – 123Combined sources3
Beta strandi125 – 136Combined sources12
Beta strandi142 – 156Combined sources15
Beta strandi186 – 194Combined sources9
Helixi197 – 199Combined sources3
Helixi202 – 216Combined sources15
Helixi220 – 222Combined sources3
Beta strandi224 – 227Combined sources4
Beta strandi239 – 243Combined sources5
Beta strandi254 – 263Combined sources10
Turni266 – 268Combined sources3
Helixi273 – 281Combined sources9
Helixi283 – 288Combined sources6
Beta strandi292 – 300Combined sources9

3D structure databases

DisProtiDP00491
ProteinModelPortaliQ62165
SMRiQ62165
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ62165

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini601 – 710Peptidase S72Add BLAST110

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni28 – 406Required for laminin recognitionBy similarityAdd BLAST379
Regioni47 – 69O-glycosylated at one siteBy similarityAdd BLAST23
Regioni314 – 483Mucin-like domainBy similarityAdd BLAST170
Regioni461 – 483O-glycosylated at seven sites with GalNAcBy similarityAdd BLAST23
Regioni817 – 893Required for interaction with CAV3By similarityAdd BLAST77
Regioni878 – 893Required for binding DMD and UTRNBy similarityAdd BLAST16

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi774 – 780Nuclear localization signalBy similarity7
Motifi887 – 890PPXY motifBy similarity4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi316 – 475Pro-richAdd BLAST160
Compositional biasi807 – 893Pro-richAdd BLAST87

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3781 Eukaryota
ENOG410XQTU LUCA
GeneTreeiENSGT00390000008429
HOGENOMiHOG000072580
HOVERGENiHBG000078
InParanoidiQ62165
KOiK06265
OMAiAMICYRK
OrthoDBiEOG091G05R9
PhylomeDBiQ62165
TreeFamiTF328370

Family and domain databases

Gene3Di2.60.40.10, 2 hits
3.30.70.1040, 1 hit
InterProiView protein in InterPro
IPR027468 Alpha-dystroglycan_domain_2
IPR006644 Cadg
IPR015919 Cadherin-like
IPR008465 DAG1
IPR013783 Ig-like_fold
IPR030398 SEA_DG_dom
PfamiView protein in Pfam
PF05454 DAG1, 1 hit
SMARTiView protein in SMART
SM00736 CADG, 2 hits
SUPFAMiSSF111006 SSF111006, 1 hit
SSF49313 SSF49313, 2 hits
PROSITEiView protein in PROSITE
PS51699 SEA_DG, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q62165-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSVDNWLLHP LWGQTFLLLL SVAVAQAHWP SEPSEAVRDW KNQLEASMHS
60 70 80 90 100
VLSDFQEAVP TVVGIPDGTA VVGRSFRVSI PTDLIASSGE IIKVSAAGKE
110 120 130 140 150
ALPSWLHWDP HSHILEGLPL DTDKGVHYIS VSAARLGANG SHVPQTSSVF
160 170 180 190 200
SIEVYPEDHN EPQSVRAASS DPGEVVPSAC AADEPVTVLT VILDADLTKM
210 220 230 240 250
TPKQRIDLLN RMQSFSEVEL HNMKLVPVVN NRLFDMSAFM AGPGNAKKVV
260 270 280 290 300
ENGALLSWKL GCSLNQNSVP DIRGVETPAR EGAMSAQLGY PVVGWHIANK
310 320 330 340 350
KPTLPKRLRR QIHATPTPVT AIGPPTTAIQ EPPSRIVPTP TSPAIAPPTE
360 370 380 390 400
TMAPPVRDPV PGKPTVTIRT RGAIIQTPTL GPIQPTRVSE AGTTVPGQIR
410 420 430 440 450
PTLTIPGYVE PTAVITPPTT TTKKPRVSTP KPATPSTDSS TTTTRRPTKK
460 470 480 490 500
PRTPRPVPRV TTKAPITRLE TASPPTRIRT TTSGVPRGGE PNQRPELKNH
510 520 530 540 550
IDRVDAWVGT YFEVKIPSDT FYDNEDTTTD KLKLTLKLRE QQLVGEKSWV
560 570 580 590 600
QFNSNSQLMY GLPDSSHVGK HEYFMHATDK GGLSAVDAFE IHVHKRPQGD
610 620 630 640 650
KAPARFKARL AGDPAPVVND IHKKIALVKK LAFAFGDRNC SSITLQNITR
660 670 680 690 700
GSIVVEWTNN TLPLEPCPKE QIIGLSRRIA DENGKPRPAF SNALEPDFKA
710 720 730 740 750
LSIAVTGSGS CRHLQFIPVA PPSPGSSAAP ATEVPDRDPE KSSEDDVYLH
760 770 780 790 800
TVIPAVVVAA ILLIAGIIAM ICYRKKRKGK LTLEDQATFI KKGVPIIFAD
810 820 830 840 850
ELDDSKPPPS SSMPLILQEE KAPLPPPEYP NQSMPETTPL NQDTVGEYTP
860 870 880 890
LRDEDPNAPP YQPPPPFTAP MEGKGSRPKN MTPYRSPPPY VPP
Length:893
Mass (Da):96,905
Last modified:July 11, 2001 - v4
Checksum:i59C081EA86AB0AC1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti448 – 450TKK → SKE in CAA84293 (PubMed:7833916).Curated3
Sequence conflicti599 – 600GD → PH in CAA84293 (PubMed:7833916).Curated2
Sequence conflicti643I → V in CAA60031 (PubMed:9057818).Curated1
Sequence conflicti643I → V in AAC52853 (PubMed:7833916).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U48854 Genomic DNA Translation: AAA99779.2
BC007150 mRNA Translation: AAH07150.1
X86073 mRNA Translation: CAA60031.1
Z34532 mRNA Translation: CAA84293.1
U43512 mRNA Translation: AAC52853.1
CCDSiCCDS23518.1
PIRiS59630
RefSeqiNP_001263410.1, NM_001276481.1
NP_001263411.1, NM_001276482.1
NP_001263414.1, NM_001276485.1
NP_001263415.1, NM_001276486.1
NP_001263421.1, NM_001276492.1
NP_001263422.1, NM_001276493.1
NP_034147.1, NM_010017.4
XP_006511699.1, XM_006511636.2
UniGeneiMm.491797
Mm.7524

Genome annotation databases

EnsembliENSMUST00000080435; ENSMUSP00000079294; ENSMUSG00000039952
ENSMUST00000166905; ENSMUSP00000128531; ENSMUSG00000039952
ENSMUST00000171412; ENSMUSP00000130626; ENSMUSG00000039952
ENSMUST00000191899; ENSMUSP00000142109; ENSMUSG00000039952
GeneIDi13138
KEGGimmu:13138
UCSCiuc009rox.2 mouse

Similar proteinsi

Entry informationi

Entry nameiDAG1_MOUSE
AccessioniPrimary (citable) accession number: Q62165
Secondary accession number(s): Q61094, Q61141, Q61497
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 11, 2001
Last modified: July 18, 2018
This is version 177 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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