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FLASH GENE

Symbol

DAG1

contributors: mct/shn - updated : 12/01/2015

HGNC name	dystroglycan 1 (dystrophin-associated glycoprotein 1)
HGNC id	2666

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DEL3P21 chromosome 3p21 microdeletion SCARMD4 severe childhood muscular dystrophy 4
Location	3p21.31      Physical location : 49.506.145 - 49.573.046
Synonym name	dystrophin-associated glycoprotein 1, cleaved into the following 2 chains
	dystrophin-associated glycoprotein-1
	alpha-dystroglycan
	beta-dystroglycan
Synonym symbol(s)	156DAG, A3a, AGRNR, DAG, MDDGC7

DNA

TYPE	functioning gene
STRUCTURE	65.49 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - D3S1581 - D3S2384 - DAG1 - D3S3629 - D3S2456 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004393 3 splicing 5543 NP_004384 - 895 - - preproprotein NM_001165928 5 splicing 5904 NP_001159400 - 895 - - preproprotein NM_001177643 3 splicing 5594 NP_001171114 - 895 - - NM_001177637 4 splicing 5663 NP_001171108 - 895 - - NM_001177636 5 splicing 5825 NP_001171107 - 895 - - NM_001177635 4 splicing 5436 NP_001171106 - 895 - - NM_001177634 6 splicing 5847 NP_001171105 - 895 - - NM_001177644 3 splicing 5683 NP_001171115 - 895 - - NM_001177642 4 splicing 5595 NP_001171113 - 895 - - NM_001177641 4 splicing 5690 NP_001171112 - 895 - - NM_001177640 4 splicing 5600 NP_001171111 - 895 - - NM_001177639 4 splicing 5384 NP_001171110 - 895 - - NM_001177638 4 splicing 5694 NP_001171109 - 895 - -

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Nervous brain       highly Reproductive male system prostate     highly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial         Muscular striatum cardiac     Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Nervous epithelial cell Skin/Tegument melanocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	dystroglycan-type cadherin-like domain
	one peptidase S72 domain

conjugated

GlycoP

isoforms

Precursor

T precursor of the 43kDa DYS associated transmembrane glycoprotein DAG beta (dystroglycan beta)

HOMOLOGY

interspecies	ortholog to DAG1, pan troglodytes
	ortholog to Dag1, Mus musculus
	ortholog to Dag1, Rattus norvegicus
	ortholog to dag1, danio rerio

Homologene

FAMILY

CATEGORY

receptor

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,cytoskeleton
text	alpha DG is secreted whereas beta-DG is localized at the cytoskeleton
	localized at costameres and neuromuscular junctions in the sarcolemma of skeletal muscle (Ayalon 2008)

basic FUNCTION	required for the development of Reichert's membrane
	required for the formation of a basement membrane in embryoid bodies
	necessary for myofibre survival and synapse differentiation or stability
	acting as a Schwann cell receptor for mycobacterium leprae, in the presence of the G domain of LAMA2
	major organizer of extracellular matrix proteins, of the neuromuscular function and of synaptic components
	playing a role in the regulation of the actin cytoskeleton, transduction of signals from the extracellular matrix to the cytoskeleton and regulation of the cell morphology
	a key signaling component in the Notch pathway
	necessary for Laminin enhancement of filopodial formation, process outgrowth, and process branching in differentiating oligodendroglia

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	a 156kDa extracellular component DAG alpha (dystroglycan alpha) membrane associated through a non covalent interaction with the extracellular domain of DAG beta
	bound to laminin 2 (alpha 2,beta 1,gamma 1) and to agrin and perlecan, multifunctional protein critical in the formation of extracellular matrix in cells contacting basement membranes
	connecting the intracellular cytoskeleton to ECM and protecting muscle from mechanical injury
	receptor for lymphocytic choriomeningitis virus and Lassa fever virus

INTERACTION

DNA

RNA

small molecule	metal binding,
	ions Ca2+ binding

protein	agrin
	laminin A/B1/B2 and merosin M/B1/B2
	laminin-1
	dystrophin
	Biglycan
	utrophin
	growth factor receptor 2, Grb2
	Caveolin-3
	rapsyn RING-H2 domain
	AGR2 and AGR3
	AGR
	DAG1 function requires xylosyl- and glucuronyltransferase activities of LARGE to bind laminin-G domain-containing ECM ligands
	CHST10 suppressed the glycosylation and reduced the ligand binding activity of DAG1
	sulfate transfer induced by CHST10 plays a regulatory role in the formation of functional glycans DAG1
	GYLTL1B regulates functional DAG1 glycosylation in prostate cancer cell lines
	POMGNT2 might encode O-GlcNAc transferase that specifically glycosylates DAG1
	interacts with DAG1 and controls motility and mechanical properties of Schwann cells
	POMGNT1 stem region modulates O-mannosylation sites of DAG1, by its carbohydrate-binding domain
	TRAPPC11 and another membrane trafficking protein, GOSR2, implicated in DAG1 hypoglycosylation

cell & other

REGULATION

activated by

activated MUSK binding dystroglycan is regulated by alternative mRNA splicing of agrin

Other	precursor of the 43kDa DYS associated transmembrane glycoprotein DAG beta (dystroglycan beta)
	O-mannosyl phosphorylation is required for laminin binding, and when defective, may have a role in congenital muscular dystrophy (Yoshida-Moriguchi 2010)

ASSOCIATED DISORDERS

corresponding disease(s)

SCARMD4 , DEL3P21

Susceptibility

Variant & Polymorphism

Candidate gene	defect of dystroglycan glycosylation may be a factor in cancer progression (de Bernabé 2009)
	candidate gene for the site of mutation in autosomal recessive muscular dystrophies
Marker
Therapy target

ANIMAL & CELL MODELS

	Heterozygous Dag1neo2 mice are viable and fertile but homozygous Dag1neo2 embryos exhibit gross developmental abnormalities beginning around 6.5 days of gestation that is due to a disruption of Reichert's membrane
	chimaeric mice generated with ES cells targeted for both dystroglycan alleles have skeletal muscles essentially devoid of dystroglycans and develop a progressive muscle pathology with many disrupted neuromuscular junctions
	brain-selective deletion of dystroglycan in mice is sufficient to cause congenital muscular dystrophie-like brain malformations, including disarray of cerebral cortical layering, fusion of cerebral hemispheres and cerebellar folia, and aberrant migration of granule cells
	striated muscle-specific disruption of the mouse Dag1 gene results in loss of the dystrophin-glycoprotein complex in differentiated muscle and a remarkably mild muscular dystrophy with hypertrophy and without tissue fibrosis
	mouse harboring the Dag1 Thr192Met mutation display muscular dystrophy and cognitive impairment
	Dg morpholino knockdown leads to disruption of epidermal differentiation by affecting the intercalation of multiciliated cells, deposition of laminin, and organization of fibronectin in the extracellular matrix
	disruption of dystroglycan-Laminin interactions result in decreased filopodial number and length, decreased process length, and decreased numbers of primary and secondary processes