DAG1_HUMAN » Dystroglycan

DAG1_HUMAN » Dystroglycan
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
DAG1_HUMAN » Dystroglycan » Dystrophin-associated glycoprotein 1;
Hydrophobic Thickness 38.8 ± 4.4 Å
Tilt Angle 2 ± 5°
ΔGtransfer -27.7 kcal/mol
ΔGfold -26.8 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 750-776 (746-779)
Pathways

Arrhythmogenic right ventricular cardiomyopathy (KEGG)

Dilated cardiomyopathy (KEGG)

ECM-receptor interaction (KEGG)

Hypertrophic cardiomyopathy (KEGG)

Viral myocarditis (KEGG)

PDB 1eg4 (P=881-895)
OPM none
Complexes none
Interactions

AGRIN, Complex: AGRIN:DAG1, PubMed

ITB1, Complex: ITB1:DAG1, PubMed

LARGE, Complex: DAG1:LARGE, PubMed

NICA, Complex: DAG1:NICA, PubMed

NICA, Complex: PSN1:NICA:DAG1, PubMed

SGCA, Complex: SGCA:DAG1, PubMed

SGCE, Complex: UTRO:SGCE:DAG1:CAV1:NOS3

Domains

AA: 606-895, PDBID: 1EG4, Subunit P, Seq Identity:100%, Dystroglycan (Dystrophin-associated glycoprotein 1)

UniProt annotation for DAG1_HUMAN » Dystroglycan
FUNCTION: The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, and epithelial polarization.

FUNCTION: 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 acts as a receptor for M.leprae in peripheral nerve Schwann cells but only in the presence of the G-domain of LAMA2, and for lymphocytic choriomeningitis virus, Old World Lassa fever virus, and clade C New World arenaviruses.

FUNCTION: 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.

SUBUNIT: 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 LARGE; the interaction enhances laminin binding (By similarity). Interacts with SGCD. 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. 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).

TISSUE SPECIFICITY: Expressed in a variety of fetal and adult tissues. In epidermal tissue, located to the basement membrane. Also expressed in keratinocytes and fibroblasts.

DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C9 (MDDGC9) OMIM: An autosomal recessive muscular dystrophy showing onset in early childhood, and associated with mental retardation without structural brain anomalies. mutations affecting the gene represented in this entry. MDDGC7 is caused by DAG1 mutations that interfere with normal post- translational processing, resulting in defective DAG1 glycosylation and impaired interactions with extracellular-matrix components. Other muscular dystrophy-dystroglycanopathies are caused by defects in enzymes involved in protein O-glycosylation.

UniProt features for DAG1_HUMAN » Dystroglycan
SIGNAL 1 29 Potential.
CHAIN 30 653 Alpha-dystroglycan.
CHAIN 654 895 Beta-dystroglycan.
DOMAIN 500 733 Peptidase S72.
REGION 30 408 Required for laminin recognition.
REGION 169 200 O-glycosylated at one site.
REGION 316 485 Mucin-like domain.
REGION 463 485 O-glycosylated at seven sites with GalNAc.
REGION 819 895 Required for interaction with CAV3.
REGION 880 895 Required for binding DMD and UTRN.
MOTIF 776 782 Nuclear localization signal.
MOTIF 889 892 PPXY motif.
SITE 653 654 Cleavage; by autolysis.
SITE 715 716 Cleavage; by MMP9.
DISULFID 182 264 Potential.
DISULFID 669 713 Potential.
Amino Acid Sequence for DAG1_HUMAN » Dystroglycan
MRMSVGLSLL LPLSGRTFLL LLSVVMAQSH WPSEPSEAVR DWENQLEASM HSVLSDLHEA VPTVVGIPDG TAVVGRSFRV TIPTDLIASS GDIIKVSAAG KEALPSWLHW DSQSHTLEGL PLDTDKGVHY ISVSATRLGA NGSHIPQTSS VFSIEVYPED HSELQSVRTA SPDPGEVVSS ACAADEPVTV LTVILDADLT KMTPKQRIDL LHRMRSFSEV ELHNMKLVPV VNNRLFDMSA FMAGPGNAKK VVENGALLSW KLGCSLNQNS VPDIHGVEAP AREGAMSAQL GYPVVGWHIA NKKPPLPKRV RRQIHATPTP VTAIGPPTTA IQEPPSRIVP TPTSPAIAPP TETMAPPVRD PVPGKPTVTI RTRGAIIQTP TLGPIQPTRV SEAGTTVPGQ IRPTMTIPGY VEPTAVATPP TTTTKKPRVS TPKPATPSTD STTTTTRRPT KKPRTPRPVP RVTTKVSITR LETASPPTRI RTTTSGVPRG GEPNQRPELK NHIDRVDAWV GTYFEVKIPS DTFYDHEDTT TDKLKLTLKL REQQLVGEKS WVQFNSNSQL MYGLPDSSHV GKHEYFMHAT DKGGLSAVDA FEIHVHRRPQ GDRAPARFKA KFVGDPALVL NDIHKKIALV KKLAFAFGDR NCSTITLQNI TRGSIVVEWT NNTLPLEPCP KEQIAGLSRR IAEDDGKPRP AFSNALEPDF KATSITVTGS GSCRHLQFIP VVPPRRVPSE APPTEVPDRD PEKSSEDDVY LHTVIPAVVV AAILLIAGII AMICYRKKRK GKLTLEDQAT FIKKGVPIIF ADELDDSKPP PSSSMPLILQ EEKAPLPPPE YPNQSVPETT PLNQDTMGEY TPLRDEDPNA PPYQPPPPFT APMEGKGSRP KNMTPYRSPP PYVPP