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Protein

Dystroglycan

Gene

DAG1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.By similarity
Alpha-dystroglycan is an extracellular peripheral glycoprotein that acts as a receptor for extracellular matrix proteins containing laminin-G domains. Receptor for laminin-2 (LAMA2) and agrin in peripheral nerve Schwann cells (By similarity).By similarity
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 similarity

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • laminin binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

Beta-dystroglycan :
  • Cell membrane By similarity; Single-pass type I membrane protein
  • Cytoplasmcytoskeleton
  • Nucleusnucleoplasm
  • Cell membranesarcolemma By similarity
  • Cell junctionsynapsepostsynaptic cell membrane By similarity

  • Note: The monomeric form translocates to the nucleus via the action of importins and depends on RAN. Nuclear transport is inhibited by Tyr-892 phosphorylation. In skeletal muscle, this phosphorylated form locates to a vesicular internal membrane compartment. In muscle cells, sarcolemma localization requires the presence of ANK2, while localization to costameres requires the presence of ANK3. Localizes to neuromuscular junctions (NMJs) in the presence of ANK2 (By similarity). Colocalizes with ERM proteins in Schwann-cell microvilli (By similarity). In peripheral nerves, localizes to the Schwann cell membrane.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini654 – 74996ExtracellularSequence analysisAdd
BLAST
Transmembranei750 – 77526HelicalSequence analysisAdd
BLAST
Topological domaini776 – 895120CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929Sequence analysisAdd
BLAST
Chaini30 – 653624Alpha-dystroglycanPRO_0000021061Add
BLAST
Chaini654 – 895242Beta-dystroglycanPRO_0000021062Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi141 – 1411N-linked (GlcNAc...)Sequence analysis
Disulfide bondi182 ↔ 264By similarity
Glycosylationi317 – 3171O-linked (Man6P...)By similarity
Glycosylationi319 – 3191O-linked (Man6P...)By similarity
Glycosylationi379 – 3791O-linked (Man6P...)By similarity
Glycosylationi641 – 6411N-linked (GlcNAc...)Sequence analysis
Glycosylationi649 – 6491N-linked (GlcNAc...)Sequence analysis
Glycosylationi661 – 6611N-linked (GlcNAc...)Sequence analysis
Disulfide bondi669 ↔ 713By similarity
Modified residuei790 – 7901PhosphothreonineBy similarity
Modified residuei892 – 8921Phosphotyrosine; by SRCBy similarity

Post-translational modificationi

O- and N-glycosylated (By similarity). 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-317, Thr-319 and 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 (LARGE) 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 similarity
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)LengthDescriptionGraphical viewFeature identifierActions
Sitei653 – 6542Cleavage; by autolysisBy similarity
Sitei715 – 7162Cleavage; by MMP9By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO18738.
PRIDEiO18738.

Expressioni

Tissue specificityi

Expressed in the myelin sheath of peripheral nerves.1 Publication

Interactioni

Subunit structurei

Monomer (By similarity). 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 LARGE; the interaction enhances laminin binding (By similarity). Interacts with AGR2 and AGR3. Interacts (betaDAG1) with DMD; the interaction is inhibited by phosphorylaion 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 (By similarity). Interacts with SGCD. BetaDAG1 directly interacts with ANK3, but not with ANK2; this interaction does not interfere with DMD-binding and is required for retention at costameres. Identified in a dystroglycan complex that contains at least PRX, DRP2, UTRN, DMD and DAG1 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Lama1P191372EBI-8522926,EBI-7176628From a different organism.

GO - Molecular functioni

  • laminin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi158770. 4 interactions.
IntActiO18738. 4 interactions.
MINTiMINT-2635114.
STRINGi9913.ENSBTAP00000015385.

Structurei

3D structure databases

ProteinModelPortaliO18738.
SMRiO18738. Positions 61-305.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini603 – 712110Peptidase S72Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni30 – 408379Required for laminin recognitionBy similarityAdd
BLAST
Regioni49 – 7123O-glycosylated at one siteBy similarityAdd
BLAST
Regioni316 – 485170Mucin-like domainBy similarityAdd
BLAST
Regioni463 – 48523O-glycosylated at seven sites with GalNAcBy similarityAdd
BLAST
Regioni819 – 89577Required for interaction with CAV3By similarityAdd
BLAST
Regioni880 – 89516Required for binding DMD and UTRNBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi776 – 7827Nuclear localization signalBy similarity
Motifi889 – 8924PPXY motifBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi809 – 89587Pro-richAdd
BLAST

Sequence similaritiesi

Contains 1 peptidase S72 domain.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3781. Eukaryota.
ENOG410XQTU. LUCA.
HOGENOMiHOG000072580.
HOVERGENiHBG000078.
InParanoidiO18738.
KOiK06265.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
3.30.70.1040. 1 hit.
InterProiIPR027468. Alpha-dystroglycan_domain_2.
IPR006644. Cadg.
IPR015919. Cadherin-like.
IPR008465. DAG1.
IPR013783. Ig-like_fold.
IPR030398. SEA_DG_dom.
[Graphical view]
PfamiPF05454. DAG1. 1 hit.
[Graphical view]
SMARTiSM00736. CADG. 2 hits.
[Graphical view]
SUPFAMiSSF111006. SSF111006. 1 hit.
SSF49313. SSF49313. 2 hits.
PROSITEiPS51699. SEA_DG. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

O18738-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRMSVGSAVP LPLWGRTFLL LLSVAVTQSH WPSEPSEAVR DWENQLEASM
60 70 80 90 100
HSALSDLHET VPTVVGIPDG TAVVGRSFRV TIPTDLIASN GEVIKVSAAG
110 120 130 140 150
KEALPSWLHW DPQSHTLEGL PLDTDKGVHY ISVSAARLGA NGSHVPQTSS
160 170 180 190 200
VFSIEVYPED HSEPQSLRAA SPDPGEVVSL VCAADEPVTV LTVILDADLT
210 220 230 240 250
KMTPKQRIDL LRRMRGFSEV EPHNMKLVPV VNNRLFDMSA FMAGPGNAKK
260 270 280 290 300
VVENGALLSW KLGCCLNQNS VPDIRGVEVP AREGAMSAQL GYPVVGWHIA
310 320 330 340 350
NKKPSLPKRI RRQIHATPTP VTAIGPPTTA IQEPPSRIVP TPTSPAIAPP
360 370 380 390 400
TETMAPPVRD PVPGKPTVTI RTRGAIIQTP TLGPIQPTRV SEAGTTVPSQ
410 420 430 440 450
IRPTMTIPGY MEPSTVTTPP TTTTKKPRVS TPRPATPSTD SSTTTTRRPT
460 470 480 490 500
KKPRTSRPVP RVTTKAPITR LETASPATRM RTTTSGVPHG GEPNQRPELK
510 520 530 540 550
NHIDRVDAWV GTYFEVKIPS DTFYDNEDTT TDKLKLTLKL REQQLVGEKS
560 570 580 590 600
WVQFNSNSQL MYGLPDSSHV GKHEYFMHAT DKGGLSAVDA FEIHVHRRPQ
610 620 630 640 650
GDKAPARFKA KLTGDPAAVT NDIHKKIALV KKLAFAFGDR NCSTITLQNI
660 670 680 690 700
TRGSIVVEWT NNTLPLEPCP KEQITALSRR IAEDDGKPRG AFVNALEPDF
710 720 730 740 750
QAMSITVTGS GSCRHLQFVP VAPPMRVPSE APATEVPDRD PEKSSEDDVY
760 770 780 790 800
LHTVIPAVVV AAILLIAGII AMICYRKKRK GKLTLEDQAT FIKKGVPIIF
810 820 830 840 850
ADELDDSKPP PSSSMPLILQ EEKAPLPPPE YPNQSMPETT PLNQDTVGEY
860 870 880 890
APLRDEDPSA PPYQPPPPFT APMEGKGSRP KNMTPYRSPP PYVPP
Length:895
Mass (Da):97,321
Last modified:January 1, 1998 - v1
Checksum:i400213A299630D11
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB009079 mRNA. Translation: BAA23650.1.
RefSeqiNP_776587.1. NM_174162.1.
UniGeneiBt.88492.

Genome annotation databases

GeneIDi281439.
KEGGibta:281439.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB009079 mRNA. Translation: BAA23650.1.
RefSeqiNP_776587.1. NM_174162.1.
UniGeneiBt.88492.

3D structure databases

ProteinModelPortaliO18738.
SMRiO18738. Positions 61-305.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi158770. 4 interactions.
IntActiO18738. 4 interactions.
MINTiMINT-2635114.
STRINGi9913.ENSBTAP00000015385.

Protein family/group databases

MEROPSiS72.001.

Proteomic databases

PaxDbiO18738.
PRIDEiO18738.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi281439.
KEGGibta:281439.

Organism-specific databases

CTDi1605.

Phylogenomic databases

eggNOGiKOG3781. Eukaryota.
ENOG410XQTU. LUCA.
HOGENOMiHOG000072580.
HOVERGENiHBG000078.
InParanoidiO18738.
KOiK06265.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
3.30.70.1040. 1 hit.
InterProiIPR027468. Alpha-dystroglycan_domain_2.
IPR006644. Cadg.
IPR015919. Cadherin-like.
IPR008465. DAG1.
IPR013783. Ig-like_fold.
IPR030398. SEA_DG_dom.
[Graphical view]
PfamiPF05454. DAG1. 1 hit.
[Graphical view]
SMARTiSM00736. CADG. 2 hits.
[Graphical view]
SUPFAMiSSF111006. SSF111006. 1 hit.
SSF49313. SSF49313. 2 hits.
PROSITEiPS51699. SEA_DG. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. Shimizu H.
    Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Dystroglycan is a dual receptor for agrin and laminin-2 in Schwann cell membrane."
    Yamada H., Denzer A.J., Hori H., Tanaka T., Anderson L.V., Fujita S., Fukuta-Ohi H., Shimizu T., Ruegg M.A., Matsumura K.
    J. Biol. Chem. 271:23418-23423(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: LIGAND-BINDING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  3. "Structures of sialylated O-linked oligosaccharides of bovine peripheral nerve alpha-dystroglycan. The role of a novel O-mannosyl-type oligosaccharide in the binding of alpha-dystroglycan with laminin."
    Chiba A., Matsumura K., Yamada H., Inazu T., Shimizu T., Kusunoki S., Kanazawa I., Kobata A., Endo T.
    J. Biol. Chem. 272:2156-2162(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE OF CARBOHYDRATES, LIGAND BINDING.
  4. "Characterization of the transmembrane molecular architecture of the dystroglycan complex in Schwann cells."
    Saito F., Masaki T., Kamakura K., Anderson L.V.B., Fujita S., Fukuta-Ohi H., Sunada Y., Shimizu T., Matsumura K.
    J. Biol. Chem. 274:8240-8246(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.

Entry informationi

Entry nameiDAG1_BOVIN
AccessioniPrimary (citable) accession number: O18738
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: June 8, 2016
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.