DAG1
entrez
1605
canonical
uniprot
Q14118
canonical
ensembl
ENSG00000173402
resolver
ensp
ENSP00000312435
resolver
ensp
ENSP00000387859
resolver
ensp
ENSP00000388833
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ensp
ENSP00000401382
resolver
ensp
ENSP00000401805
resolver
ensp
ENSP00000405859
resolver
ensp
ENSP00000410145
resolver
ensp
ENSP00000412067
resolver
ensp
ENSP00000415321
resolver
ensp
ENSP00000501140
resolver
ensp
ENSP00000501165
resolver
ensp
ENSP00000513216
resolver
ensp
ENSP00000513217
resolver
ensp
ENSP00000513218
resolver
ensp
ENSP00000552518
resolver
ensp
ENSP00000552519
resolver
ensp
ENSP00000552520
resolver
ensp
ENSP00000552521
resolver
ensp
ENSP00000552522
resolver
ensp
ENSP00000552523
resolver
ensp
ENSP00000552524
resolver
ensp
ENSP00000552525
resolver
ensp
ENSP00000552526
resolver
ensp
ENSP00000552527
resolver
ensp
ENSP00000552528
resolver
ensp
ENSP00000552529
resolver
ensp
ENSP00000552530
resolver
ensp
ENSP00000552531
resolver
ensp
ENSP00000552532
resolver
ensp
ENSP00000552533
resolver
ensp
ENSP00000552534
resolver
ensp
ENSP00000552535
resolver
ensp
ENSP00000552536
resolver
ensp
ENSP00000552537
resolver
ensp
ENSP00000552538
resolver
ensp
ENSP00000552539
resolver
ensp
ENSP00000552540
resolver
ensp
ENSP00000552541
resolver
ensp
ENSP00000552542
resolver
ensp
ENSP00000552543
resolver
ensp
ENSP00000552544
resolver
ensp
ENSP00000552545
resolver
ensp
ENSP00000552546
resolver
ensp
ENSP00000606905
resolver
ensp
ENSP00000606906
resolver
ensp
ENSP00000606907
resolver
ensp
ENSP00000606908
resolver
ensp
ENSP00000606909
resolver
ensp
ENSP00000606910
resolver
ensp
ENSP00000606911
resolver
ensp
ENSP00000606912
resolver
ensp
ENSP00000606913
resolver
ensp
ENSP00000606914
resolver
ensp
ENSP00000606915
resolver
ensp
ENSP00000606916
resolver
ensp
ENSP00000606917
resolver
ensp
ENSP00000606918
resolver
ensp
ENSP00000606919
resolver
ensp
ENSP00000606920
resolver
ensp
ENSP00000606921
resolver
ensp
ENSP00000606922
resolver
ensp
ENSP00000606923
resolver
ensp
ENSP00000606924
resolver
ensp
ENSP00000636405
resolver
ensp
ENSP00000636406
resolver
ensp
ENSP00000636407
resolver
ensp
ENSP00000636408
resolver
ensp
ENSP00000636409
resolver
enst
ENST00000308775
resolver
enst
ENST00000418588
resolver
enst
ENST00000421560
resolver
enst
ENST00000428779
resolver
enst
ENST00000430636
resolver
enst
ENST00000431960
resolver
enst
ENST00000435508
resolver
enst
ENST00000452060
resolver
enst
ENST00000452317
resolver
enst
ENST00000466701
resolver
enst
ENST00000469139
resolver
enst
ENST00000496474
resolver
enst
ENST00000673708
resolver
enst
ENST00000697271
resolver
enst
ENST00000882459
resolver
enst
ENST00000882460
resolver
enst
ENST00000882461
resolver
enst
ENST00000882462
resolver
enst
ENST00000882463
resolver
enst
ENST00000882464
resolver
enst
ENST00000882465
resolver
enst
ENST00000882466
resolver
enst
ENST00000882467
resolver
enst
ENST00000882468
resolver
enst
ENST00000882469
resolver
enst
ENST00000882470
resolver
enst
ENST00000882471
resolver
enst
ENST00000882472
resolver
enst
ENST00000882473
resolver
enst
ENST00000882474
resolver
enst
ENST00000882475
resolver
enst
ENST00000882476
resolver
enst
ENST00000882477
resolver
enst
ENST00000882478
resolver
enst
ENST00000882479
resolver
enst
ENST00000882480
resolver
enst
ENST00000882481
resolver
enst
ENST00000882482
resolver
enst
ENST00000882483
resolver
enst
ENST00000882484
resolver
enst
ENST00000882485
resolver
enst
ENST00000882486
resolver
enst
ENST00000882487
resolver
enst
ENST00000936846
resolver
enst
ENST00000936847
resolver
enst
ENST00000936848
resolver
enst
ENST00000936849
resolver
enst
ENST00000936850
resolver
enst
ENST00000936851
resolver
enst
ENST00000936852
resolver
enst
ENST00000936853
resolver
enst
ENST00000936854
resolver
enst
ENST00000936855
resolver
enst
ENST00000936856
resolver
enst
ENST00000936857
resolver
enst
ENST00000936858
resolver
enst
ENST00000936859
resolver
enst
ENST00000936860
resolver
enst
ENST00000936861
resolver
enst
ENST00000936862
resolver
enst
ENST00000936863
resolver
enst
ENST00000936864
resolver
enst
ENST00000936865
resolver
enst
ENST00000966346
resolver
enst
ENST00000966347
resolver
enst
ENST00000966348
resolver
enst
ENST00000966349
resolver
enst
ENST00000966350
resolver
genesymbol
DAG1
resolver
hgnc
HGNC:2666
resolver
uniprot
A8K6M7
resolver
uniprot
Q969J9
resolver
uniprot_entry
DAG1_HUMAN
resolver
uniprot_sec
A8K6M7
resolver
uniprot_sec
Q969J9
resolver
amino_acid_sequence
MRMSVGLSLLLPLSGRTFLLLLSVVMAQSHWPSEPSEAVRDWENQLEASMHSVLSDLHEAVPTVVGIPDGTAVVGRSFRVTIPTDLIASSGDIIKVSAAGKEALPSWLHWDSQSHTLEGLPLDTDKGVHYISVSATRLGANGSHIPQTSSVFSIEVYPEDHSELQSVRTASPDPGEVVSSACAADEPVTVLTVILDADLTKMTPKQRIDLLHRMRSFSEVELHNMKLVPVVNNRLFDMSAFMAGPGNAKKVVENGALLSWKLGCSLNQNSVPDIHGVEAPAREGAMSAQLGYPVVGWHIANKKPPLPKRVRRQIHATPTPVTAIGPPTTAIQEPPSRIVPTPTSPAIAPPTETMAPPVRDPVPGKPTVTIRTRGAIIQTPTLGPIQPTRVSEAGTTVPGQIRPTMTIPGYVEPTAVATPPTTTTKKPRVSTPKPATPSTDSTTTTTRRPTKKPRTPRPVPRVTTKVSITRLETASPPTRIRTTTSGVPRGGEPNQRPELKNHIDRVDAWVGTYFEVKIPSDTFYDHEDTTTDKLKLTLKLREQQLVGEKSWVQFNSNSQLMYGLPDSSHVGKHEYFMHATDKGGLSAVDAFEIHVHRRPQGDRAPARFKAKFVGDPALVLNDIHKKIALVKKLAFAFGDRNCSTITLQNITRGSIVVEWTNNTLPLEPCPKEQIAGLSRRIAEDDGKPRPAFSNALEPDFKATSITVTGSGSCRHLQFIPVVPPRRVPSEAPPTEVPDRDPEKSSEDDVYLHTVIPAVVVAAILLIAGIIAMICYRKKRKGKLTLEDQATFIKKGVPIIFADELDDSKPPPSSSMPLILQEEKAPLPPPEYPNQSVPETTPLNQDTMGEYTPLRDEDPNAPPYQPPPPFTAPMEGKGSRPKNMTPYRSPPPYVPP
uniprot
proteins
disease_involvement
DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C9 (MDDGC9) [MIM:613818]: An autosomal recessive muscular dystrophy showing onset in early childhood, and associated with intellectual disability without structural brain anomalies. {ECO:0000269|PubMed:21388311, ECO:0000269|PubMed:25503980}. Note=The disease is caused by variants 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.; DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A9 (MDDGA9) [MIM:616538]: An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound intellectual disability, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. {ECO:0000269|PubMed:24052401, ECO:0000269|PubMed:25934851}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: The dystroglycan complex is involved in a number of signaling events and processes including laminin deposition and extracellular matrix assembly, acetylcholine receptor clustering, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, epithelial polarization, and epithelium branching morphogenesis (By similarity). Required for the formation of photoreceptor ribbon synapses, and long-term maintenance of inhibitory synapses in cerebellar Purkinje cells (By similarity). Also involved in the positive regulation of cartilage formation through agrin (AGRN) binding and up-regulation of SOX9, a transcription factor that plays a key role in chondrocytes differentiation (PubMed:26290588). {ECO:0000250|UniProtKB:Q62165, ECO:0000269|PubMed:26290588}.; FUNCTION: [Alpha-dystroglycan]: Extracellular peripheral glycoprotein that acts as a receptor for extracellular matrix proteins containing laminin-G domains. As a receptor for laminin is involved in extracellular matrix assembly, and activation of the PI3K/AKT pathway regulating cell apoptotic signals in muscle (By similarity). Binding of laminin LAMA1 to alpha-dystroglycan also initiates a signaling cascade in which Src kinases, c-Src or c-Fyn, phosphorylate syntrophin modifying its interaction with the adapter protein GRB2; this triggers recruitment of guanyl-nucleotide exchange factor SOS1 and activation of RAC1, finally resulting in c-Jun phosphorylation by MAPK8/JNK1 (By similarity). As a receptor for laminin LAMA1 is also involved in epithelium branching morphogenesis in salivary glang and lung (By similarity). Receptor for laminin-2 (LAMA2) and agrin in peripheral nerve Schwann cells (By similarity). Also acts as a receptor for laminin LAMA5 (By similarity). In muscle cells, it is a receptor for laminin-1 (also known as laminin-111 or EHS laminin) and is involved in the stimulation of agrin-induced acetylcholine receptor (AChR) clustering, and formation of the synaptic basement membrane. It is required for acetylcholinesterase (AChE) localization at the neuromuscular junctions (NMJ) through its binding with perlecan (HSPG2) and is, therefore, involved in the down-regulation of colinergic synaptic transmission (By similarity). In the retina, it is required for the formation of photoreceptor ribbon synapses through its interaction with pikachurin (EGFLAM) (By similarity). Involved in the positive regulation of cartilage formation through agrin (AGRN) binding and up-regulation of SOX9, a transcription factor that plays a key role in chondrocytes differentiation (PubMed:26290588). {ECO:0000250|UniProtKB:O18738, ECO:0000250|UniProtKB:Q28685, ECO:0000250|UniProtKB:Q62165, ECO:0000269|PubMed:26290588}.; FUNCTION: [Beta-dystroglycan]: 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.; FUNCTION: [Alpha-dystroglycan]: (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus glycoprotein and class C new-world arenaviruses (PubMed:16254364, PubMed:17360738, PubMed:19324387). Acts as a Schwann cell receptor for Mycobacterium leprae, the causative organism of leprosy, but only in the presence of the G-domain of LAMA2 (PubMed:9851927). {ECO:0000269|PubMed:16254364, ECO:0000269|PubMed:17360738, ECO:0000269|PubMed:19324387, ECO:0000269|PubMed:9851927}.
uniprot
proteins
mass_dalton
97441
uniprot
proteins
mutagenesis
MUTAGEN 311..370; /note="Missing: Abolishes LARGE1-dependent glycosylation, CHST10-dependent sulfation and consequent binding to laminin; when associated with A-379."; /evidence="ECO:0000269|PubMed:23723439"; MUTAGEN 317..319; /note="TPT->APA: Impaired laminin-binding."; /evidence="ECO:0000269|PubMed:21987822, ECO:0000269|PubMed:24256719"; MUTAGEN 328..329; /note="TT->AA: Does not affect laminin-binding."; /evidence="ECO:0000269|PubMed:21987822"; MUTAGEN 368..461; /note="Missing: Retains the capacity to bind laminin."; /evidence="ECO:0000269|PubMed:23723439"; MUTAGEN 379; /note="T->A: Abolishes LARGE1-dependent glycosylation, CHST10-dependent sulfation and consequent binding to laminin; when associated with 311-R--I-370 del."; /evidence="ECO:0000269|PubMed:23723439"; MUTAGEN 654; /note="S->A: Abolishes autoproteolysis and enhances laminin-binding."; /evidence="ECO:0000269|PubMed:17905726, ECO:0000269|PubMed:18764929"; MUTAGEN 663; /note="T->A: Reduced N-linked glycosylation. No change in nuclear translocation."; /evidence="ECO:0000269|PubMed:18764929"; MUTAGEN 776..782; /note="RKKRKGK->AKKRKGA: Moderate reduction in nuclear accumulation."; MUTAGEN 777..782; /note="KKRKGK->AARKGA: About 50% reduction in nuclear accumulation."; /evidence="ECO:0000269|PubMed:20512930"; MUTAGEN 777..782; /note="KKRKGK->RKKAAGA: Drastic reduction in nuclear accumulation."; /evidence="ECO:0000269|PubMed:20512930"; MUTAGEN 777..780; /note="KKRK->NPGE: Abolishes nuclear translocation."; /evidence="ECO:0000269|PubMed:18764929"; MUTAGEN 779; /note="R->A: Significant reduction in nuclear accumulation."; /evidence="ECO:0000269|PubMed:20512930"; MUTAGEN 780; /note="K->A: Significant reduction in nuclear accumulation."; /evidence="ECO:0000269|PubMed:20512930"; MUTAGEN 793..794; /note="KK->TA: Abolishes nuclear translocation."; /evidence="ECO:0000269|PubMed:18764929"; MUTAGEN 823; /note="K->A: No change in nuclear location."; /evidence="ECO:0000269|PubMed:18764929"; MUTAGEN 828..829; /note="PP->AA: No change in nuclear location."; /evidence="ECO:0000269|PubMed:18764929"; MUTAGEN 831; /note="Y->A: No change in nuclear location."; /evidence="ECO:0000269|PubMed:18764929"; MUTAGEN 892; /note="Y->A: Abolishes phosphorylation. No change in plasma membrane location."; /evidence="ECO:0000269|PubMed:12795607, ECO:0000269|PubMed:20512930"; MUTAGEN 892; /note="Y->E: Redistributes to a vesicular internal membrane compartment."; /evidence="ECO:0000269|PubMed:12795607, ECO:0000269|PubMed:20512930"; MUTAGEN 892; /note="Y->F: Abolishes phosphorylation. Increase in nuclear location."; /evidence="ECO:0000269|PubMed:12795607, ECO:0000269|PubMed:20512930
uniprot
proteins
post_translational_modification
PTM: [Alpha-dystroglycan]: O-glycosylated. 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 (PubMed:27493216). 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 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 (LARGE1) protein and is required for laminin binding (PubMed:20044576, PubMed:21987822, PubMed:23723439, PubMed:24256719). Glycosylation by LARGE1 is also required for perlecan binding (By similarity). The O-glycosyl hexose on Thr-367, Thr-369, Thr-372, Thr-381 and Thr-388 is probably mannose. O-glycosylated in the N-terminal region with a core 1 or possibly core 8 glycan. The brain form displays a unique glycosylation pattern which is absent in other tissues; this form shows enhanced binding to laminin LAMA5 compared to the skeletal muscle form (By similarity). {ECO:0000250|UniProtKB:O18738, ECO:0000269|PubMed:12140558, ECO:0000269|PubMed:16254364, ECO:0000269|PubMed:17360738, ECO:0000269|PubMed:17905726, ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:20044576, ECO:0000269|PubMed:20507882, ECO:0000269|PubMed:21987822, ECO:0000269|PubMed:23234360, ECO:0000269|PubMed:24256719, ECO:0000269|PubMed:27493216}.; PTM: [Alpha-dystroglycan]: (Microbial infection) O-mannosylation is required for binding lymphocytic choriomeningitis virus, Old World Lassa fever virus, and clade C New World arenaviruses. {ECO:0000269|PubMed:16254364, ECO:0000269|PubMed:17360738}.; PTM: [Beta-dystroglycan]: N-glycosylated. {ECO:0000269|PubMed:18764929}.; PTM: Autolytic cleavage produces the alpha and beta subunits. In cutaneous cells, as well as in certain pathological conditions, shedding of beta-dystroglycan can occur releasing a peptide of about 30 kDa. {ECO:0000269|PubMed:15175026, ECO:0000269|PubMed:17905726, ECO:0000269|PubMed:18764929, ECO:0000269|PubMed:19946898}.; PTM: 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.
uniprot
proteins
pubmed
10767429
uniprot
proteins
pubmed
10769203
uniprot
proteins
pubmed
10932245
uniprot
proteins
pubmed
10988290
uniprot
proteins
pubmed
11495720
uniprot
proteins
pubmed
11724572
uniprot
proteins
pubmed
12140558
uniprot
proteins
pubmed
12592373
uniprot
proteins
pubmed
12795607
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15175026
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16254364
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
17212656
uniprot
proteins
pubmed
17360738
uniprot
proteins
pubmed
17905726
uniprot
proteins
pubmed
18764929
uniprot
proteins
pubmed
19324387
uniprot
proteins
pubmed
19838169
uniprot
proteins
pubmed
19946898
uniprot
proteins
pubmed
20044576
uniprot
proteins
pubmed
20507882
uniprot
proteins
pubmed
20512930
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21388311
uniprot
proteins
pubmed
21987822
uniprot
proteins
pubmed
22205389
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23234360
uniprot
proteins
pubmed
23723439
uniprot
proteins
pubmed
24052401
uniprot
proteins
pubmed
24256719
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25503980
uniprot
proteins
pubmed
25934851
uniprot
proteins
pubmed
26290588
uniprot
proteins
pubmed
26848865
uniprot
proteins
pubmed
27493216
uniprot
proteins
pubmed
28781947
uniprot
proteins
pubmed
7592992
uniprot
proteins
pubmed
8268918
uniprot
proteins
pubmed
9851927
uniprot
proteins
sequence_length
895
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Alpha-dystroglycan]: Secreted, extracellular space {ECO:0000269|PubMed:9851927}. Secreted, extracellular space, extracellular matrix, basement membrane {ECO:0000250|UniProtKB:Q62165}. Synapse {ECO:0000250|UniProtKB:Q62165}. Note=Localized to inhibitory synapses in the cerebellar cortex. {ECO:0000250|UniProtKB:Q62165}.; SUBCELLULAR LOCATION: [Beta-dystroglycan]: Cell membrane {ECO:0000269|PubMed:18764929, ECO:0000269|PubMed:26848865}; Single-pass type I membrane protein. Cytoplasm, cytoskeleton. Nucleus, nucleoplasm {ECO:0000269|PubMed:18764929}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:Q62165}. Synapse {ECO:0000250|UniProtKB:Q62165}. Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q62165}. 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). In peripheral nerves, localizes to the Schwann cell membrane. Colocalizes with ERM proteins in Schwann-cell microvilli. Localized to inhibitory synapses in the cerebellar cortex. {ECO:0000250|UniProtKB:Q62165}.
uniprot
proteins
transmembrane_region
TRANSMEM 750..775; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins