Q14118 (DAG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dystroglycan

Alternative name(s):
Dystrophin-associated glycoprotein 1

Cleaved into the following 2 chains:

1. Alpha-dystroglycan
   Short name=Alpha-DG
2. Beta-dystroglycan
   Short name=Beta-DG

Gene names

Name:

DAG1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	895 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.7 Ref.11 Ref.17 Ref.18 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. Ref.7 Ref.11 Ref.17 Ref.18 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. Ref.7 Ref.11 Ref.17 Ref.18
Subunit structure	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. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.15 Ref.16 Ref.21
Subcellular location	Alpha-dystroglycan: Secreted › extracellular space Ref.7 Ref.14 Ref.20 Ref.24. Beta-dystroglycan: Cell membrane; Single-pass type I membrane protein. Cytoplasm › cytoskeleton. Nucleus › nucleoplasm. Cell membrane › sarcolemma By similarity. Cell junction › synapse › postsynaptic 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. In peripheral nerves, localizes to the Schwann cell membrane. Colocalizes with ERM proteins in Schwann-cell microvilli. Ref.7 Ref.14 Ref.20 Ref.24
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. Ref.1 Ref.16
Post-translational modification	O- and N-glycosylated. 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-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 and is required for laminin binding. O-mannosylation is also required for binding lymphocytic choriomeningitis virus, Old World Lassa fever virus, and clade C New World arenaviruses. 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 beta subunit is N-glycosylated. Ref.10 Ref.11 Ref.12 Ref.14 Ref.24 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. 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.
Involvement in disease	Muscular dystrophy-dystroglycanopathy limb-girdle C7 (MDDGC7) [MIM:613818]: An autosomal recessive muscular dystrophy showing onset in early childhood, and associated with mental retardation without structural brain anomalies. Note: The disease is caused by 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. Ref.29
Sequence similarities	Contains 1 peptidase S72 domain.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cell junction Cell membrane Cytoplasm Cytoskeleton Membrane Nucleus Postsynaptic cell membrane Secreted Synapse
Coding sequence diversity	Polymorphism
Disease	Disease mutation Limb-girdle muscular dystrophy
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Host cell receptor for virus entry Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NLS-bearing substrate import into nucleus Inferred from direct assay Ref.24. Source: UniProtKB branching involved in salivary gland morphogenesis Inferred from electronic annotation. Source: Compara cytoskeletal anchoring at plasma membrane Inferred from mutant phenotype PubMed 18341635. Source: UniProtKB epithelial tube branching involved in lung morphogenesis Inferred from electronic annotation. Source: Compara membrane protein ectodomain proteolysis Inferred from direct assay Ref.21. Source: UniProtKB microtubule anchoring Inferred from mutant phenotype PubMed 18341635. Source: UniProtKB morphogenesis of an epithelial sheet Inferred from electronic annotation. Source: Compara myelination in peripheral nervous system Inferred from electronic annotation. Source: Compara negative regulation of MAPK cascade Inferred from mutant phenotype PubMed 19587235. Source: UniProtKB negative regulation of cell migration Inferred from mutant phenotype PubMed 19587235. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from mutant phenotype PubMed 19587235. Source: UniProtKB nerve maturation Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from direct assay Ref.17. Source: UniProtKB
Cellular_component	basement membrane Inferred from direct assay PubMed 19348877. Source: UniProtKB cell junction Inferred from electronic annotation. Source: UniProtKB-KW cell outer membrane Inferred from electronic annotation. Source: Compara contractile ring Inferred from direct assay PubMed 18341635. Source: UniProtKB cytoplasm Inferred from direct assay Ref.20. Source: UniProtKB cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell dystroglycan complex Inferred from electronic annotation. Source: Compara dystrophin-associated glycoprotein complex Inferred from direct assay PubMed 17993586. Source: UniProtKB extracellular space Inferred from direct assay PubMed 18201566. Source: UniProtKB filopodium Inferred from direct assay PubMed 18341635. Source: UniProtKB integral to membrane Inferred from direct assay PubMed 17628813. Source: UniProtKB lamellipodium Inferred from direct assay PubMed 18341635. Source: UniProtKB membrane raft Inferred from electronic annotation. Source: Compara node of Ranvier Inferred from electronic annotation. Source: Compara nucleoplasm Inferred from direct assay Ref.20. Source: UniProtKB postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell sarcolemma Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	SH2 domain binding Inferred from direct assay Ref.11. Source: UniProtKB actin binding Inferred from direct assay PubMed 18341635. Source: UniProtKB alpha-actinin binding Inferred from direct assay PubMed 18341635. Source: UniProtKB calcium ion binding Inferred from electronic annotation. Source: InterPro laminin-1 binding Inferred from sequence or structural similarity. Source: UniProtKB structural constituent of muscle Inferred from mutant phenotype PubMed 18691338. Source: UniProtKB tubulin binding Inferred from direct assay PubMed 18341635. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ank3	Q3T1J5	2	EBI-1755945,EBI-2133962	From a different organism.
NCK1	P16333	2	EBI-1755945,EBI-389883

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 29	29	Potential
	Chain	30 – 653	624	Alpha-dystroglycan		PRO_0000021065
	Chain	654 – 895	242	Beta-dystroglycan		PRO_0000021066
Regions
	Topological domain	654 – 749	96	Extracellular Potential
	Transmembrane	750 – 775	26	Helical; Potential
	Topological domain	776 – 895	120	Cytoplasmic Potential
	Domain	500 – 733	234	Peptidase S72
	Region	30 – 408	379	Required for laminin recognition
	Region	169 – 200	32	O-glycosylated at one site
	Region	316 – 485	170	Mucin-like domain
	Region	463 – 485	23	O-glycosylated at seven sites with GalNAc
	Region	819 – 895	77	Required for interaction with CAV3
	Region	880 – 895	16	Required for binding DMD and UTRN
	Motif	776 – 782	7	Nuclear localization signal Ref.24
	Motif	889 – 892	4	PPXY motif
	Compositional bias	317 – 484	168	Thr-rich
	Compositional bias	809 – 895	87	Pro-rich
Sites
	Site	653 – 654	2	Cleavage; by autolysis
	Site	715 – 716	2	Cleavage; by MMP9
Amino acid modifications
	Modified residue	892	1	Phosphotyrosine; by SRC Ref.12 Ref.14 Ref.24
	Glycosylation	63	1	O-linked (GalNAc...) Ref.27
	Glycosylation	141	1	N-linked (GlcNAc...) Potential
	Glycosylation	367	1	O-linked (Hex...) Ref.23
	Glycosylation	369	1	O-linked (Hex...) Ref.23
	Glycosylation	372	1	O-linked (Hex...) Ref.23
	Glycosylation	379	1	O-linked (Man6P...) Ref.25
	Glycosylation	381	1	O-linked (Hex...) Ref.25
	Glycosylation	388	1	O-linked (Hex...) Ref.25
	Glycosylation	455	1	O-linked (GalNAc...) Ref.23
	Glycosylation	641	1	N-linked (GlcNAc...) Potential
	Glycosylation	649	1	N-linked (GlcNAc...) Potential
	Glycosylation	661	1	N-linked (GlcNAc...) Potential
	Disulfide bond	182 ↔ 264		Potential
	Disulfide bond	669 ↔ 713		Potential
Natural variations
	Natural variant	14	1	S → W. Ref.1 Ref.2 Ref.4 Ref.5 Corresponds to variant rs2131107 [ dbSNP | Ensembl ].		VAR_024335
	Natural variant	192	1	T → M in MDDGC7; results in impaired interaction with LARGE and incomplete DAG1 glycosylation. Ref.29		VAR_065266
Experimental info
	Mutagenesis	654	1	S → A: Abolishes autoproteolysis and enhances laminin-binding. Ref.19 Ref.20
	Mutagenesis	663	1	T → A: Reduced N-linked glycosylation. No change in nuclear trnslocation. Ref.20
	Mutagenesis	776 – 782	7	RKKRKGK → AKKRKGA: Moderate reduction in nuclear accumulation.
	Mutagenesis	777 – 782	6	KKRKGK → AARKGA: About 50% reduction in nuclear accumulation. Ref.24
	Mutagenesis	777 – 782	6	KKRKGK → RKKAAGA: Drastic reduction in nuclear accumulation. Ref.24
	Mutagenesis	777 – 780	4	KKRK → NPGE: Abolishes nuclear translocation. Ref.20
	Mutagenesis	779	1	R → A: Significant reduction in nuclear accumulation.
	Mutagenesis	780	1	K → A: Significant reduction in nuclear accumulation.
	Mutagenesis	793 – 794	2	KK → TA: Abolishes nuclear translocation.
	Mutagenesis	823	1	K → A: No change in nuclear location. Ref.20
	Mutagenesis	828 – 829	2	PP → AA: No change in nuclear location.
	Mutagenesis	831	1	Y → A: No change in nuclear location. Ref.20
	Mutagenesis	892	1	Y → A: Abolishes phosphorylation. No change in plasma membrane location. Ref.14 Ref.24
	Mutagenesis	892	1	Y → E: Redistributes to a vesicular internal membrane compartment. Ref.14 Ref.24
	Mutagenesis	892	1	Y → F: Abolishes phosphorylation. Increase in nuclear location. Ref.14 Ref.24
	Sequence conflict	163	1	E → D in AAA81779. Ref.1
	Sequence conflict	248	1	A → P in AAA81779. Ref.1
	Sequence conflict	319	1	T → A in BAF84381. Ref.2
	Sequence conflict	871	1	A → V in AAA81779. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q14118 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: 3AF6CBB0DCF91962	FASTA	895	97,441
	10 20 30 40 50 60 MRMSVGLSLL LPLSGRTFLL LLSVVMAQSH WPSEPSEAVR DWENQLEASM HSVLSDLHEA 70 80 90 100 110 120 VPTVVGIPDG TAVVGRSFRV TIPTDLIASS GDIIKVSAAG KEALPSWLHW DSQSHTLEGL 130 140 150 160 170 180 PLDTDKGVHY ISVSATRLGA NGSHIPQTSS VFSIEVYPED HSELQSVRTA SPDPGEVVSS 190 200 210 220 230 240 ACAADEPVTV LTVILDADLT KMTPKQRIDL LHRMRSFSEV ELHNMKLVPV VNNRLFDMSA 250 260 270 280 290 300 FMAGPGNAKK VVENGALLSW KLGCSLNQNS VPDIHGVEAP AREGAMSAQL GYPVVGWHIA 310 320 330 340 350 360 NKKPPLPKRV RRQIHATPTP VTAIGPPTTA IQEPPSRIVP TPTSPAIAPP TETMAPPVRD 370 380 390 400 410 420 PVPGKPTVTI RTRGAIIQTP TLGPIQPTRV SEAGTTVPGQ IRPTMTIPGY VEPTAVATPP 430 440 450 460 470 480 TTTTKKPRVS TPKPATPSTD STTTTTRRPT KKPRTPRPVP RVTTKVSITR LETASPPTRI 490 500 510 520 530 540 RTTTSGVPRG GEPNQRPELK NHIDRVDAWV GTYFEVKIPS DTFYDHEDTT TDKLKLTLKL 550 560 570 580 590 600 REQQLVGEKS WVQFNSNSQL MYGLPDSSHV GKHEYFMHAT DKGGLSAVDA FEIHVHRRPQ 610 620 630 640 650 660 GDRAPARFKA KFVGDPALVL NDIHKKIALV KKLAFAFGDR NCSTITLQNI TRGSIVVEWT 670 680 690 700 710 720 NNTLPLEPCP KEQIAGLSRR IAEDDGKPRP AFSNALEPDF KATSITVTGS GSCRHLQFIP 730 740 750 760 770 780 VVPPRRVPSE APPTEVPDRD PEKSSEDDVY LHTVIPAVVV AAILLIAGII AMICYRKKRK 790 800 810 820 830 840 GKLTLEDQAT FIKKGVPIIF ADELDDSKPP PSSSMPLILQ EEKAPLPPPE YPNQSVPETT 850 860 870 880 890 PLNQDTMGEY TPLRDEDPNA PPYQPPPPFT APMEGKGSRP KNMTPYRSPP PYVPP

References

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[1]	"Human dystroglycan: skeletal muscle cDNA, genomic structure, origin of tissue specific isoforms and chromosomal localization." Ibraghimov-Beskrovnaya O., Milatovich A., Ozcelik T., Yang B., Koepnick K., Francke U., Campbell K.P. Hum. Mol. Genet. 2:1651-1657(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT TRP-14. Tissue: Skeletal muscle.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TRP-14. Tissue: Placenta.
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT TRP-14.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TRP-14. Tissue: Muscle.
[6]	"Identification and characterization of the dystrophin anchoring site on beta-dystroglycan." Jung D., Yang B., Meyer J., Chamberlain J.S., Campbell K.P. J. Biol. Chem. 270:27305-27310(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DMD.
[7]	"Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae." Rambukkana A., Yamada H., Zanazzi G., Mathus T., Salzer J.L., Yurchenco P.D., Campbell K.P., Fischetti V.A. Science 282:2076-2079(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS RECEPTOR FOR MYCOBACTERIUM LEPRAE, SUBCELLULAR LOCATION, INTERACTION WITH LAMA2.
[8]	"Contribution of the different modules in the utrophin carboxy-terminal region to the formation and regulation of the DAP complex." Tommasi di Vignano A., Di Zenzo G., Sudol M., Cesareni G., Dente L. FEBS Lett. 471:229-234(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UTRN.
[9]	"Caveolin-3 directly interacts with the C-terminal tail of beta -dystroglycan. Identification of a central WW-like domain within caveolin family members." Sotgia F., Lee J.K., Das K., Bedford M., Petrucci T.C., Macioce P., Sargiacomo M., Bricarelli F.D., Minetti C., Sudol M., Lisanti M.P. J. Biol. Chem. 275:38048-38058(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CAV3.
[10]	"Adhesion-dependent tyrosine phosphorylation of (beta)-dystroglycan regulates its interaction with utrophin." James M., Nuttall A., Ilsley J.L., Ottersbach K., Tinsley J.M., Sudol M., Winder S.J. J. Cell Sci. 113:1717-1726(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH UTRN.
[11]	"Tyrosine phosphorylation of beta-dystroglycan at its WW domain binding motif, PPxY, recruits SH2 domain containing proteins." Sotgia F., Lee H., Bedford M.T., Petrucci T., Sudol M., Lisanti M.P. Biochemistry 40:14585-14592(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH FYN; CSK; NCK AND SHC, POSSIBLE FUNCTION.
[12]	"The interaction of dystrophin with beta-dystroglycan is regulated by tyrosine phosphorylation." Ilsley J.L., Sudol M., Winder S.J. Cell. Signal. 13:625-632(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-892, INTERACTION WITH DMD.
[13]	"Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies." Michele D.E., Barresi R., Kanagawa M., Saito F., Cohn R.D., Satz J.S., Dollar J., Nishino I., Kelley R.I., Somer H., Straub V., Mathews K.D., Moore S.A., Campbell K.P. Nature 418:417-422(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, LIGAND-BINDING, ASSOCIATION WITH CONGENITAL MUSCULAR DYSTROPHIES.
[14]	"Localization of phospho-beta-dystroglycan (pY892) to an intracellular vesicular compartment in cultured cells and skeletal muscle fibers in vivo." Sotgia F., Bonuccelli G., Bedford M., Brancaccio A., Mayer U., Wilson M.T., Campos-Gonzalez R., Brooks J.W., Sudol M., Lisanti M.P. Biochemistry 42:7110-7123(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-892, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-892.
[15]	"hAG-2 and hAG-3, human homologues of genes involved in differentiation, are associated with oestrogen receptor-positive breast tumours and interact with metastasis gene C4.4a and dystroglycan." Fletcher G.C., Patel S., Tyson K., Adam P.J., Schenker M., Loader J.A., Daviet L., Legrain P., Parekh R., Harris A.L., Terrett J.A. Br. J. Cancer 88:579-585(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AGR2 AND AGR3.
[16]	"Dystroglycan in skin and cutaneous cells: beta-subunit is shed from the cell surface." Herzog C., Has C., Franzke C.W., Echtermeyer F.G., Schlotzer-Schrehardt U., Kroger S., Gustafsson E., Fassler R., Bruckner-Tuderman L. J. Invest. Dermatol. 122:1372-1380(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF THE BETA SUBUNIT, TISSUE SPECIFICITY.
[17]	"O Mannosylation of alpha-dystroglycan is essential for lymphocytic choriomeningitis virus receptor function." Imperiali M., Thoma C., Pavoni E., Brancaccio A., Callewaert N., Oxenius A. J. Virol. 79:14297-14308(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, FUNCTION AS RECEPTOR FOR LYMPHOCYCTIC CHORIOMENINGITIS VIRUS.
[18]	"Old World and clade C New World arenaviruses mimic the molecular mechanism of receptor recognition used by alpha-dystroglycan's host-derived ligands." Rojek J.M., Spiropoulou C.F., Campbell K.P., Kunz S. J. Virol. 81:5685-5695(2007) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, FUNCTION AS RECEPTOR FOR OLD WORLD AND CLADE C NEW WORLD ARENAVIRUSES.
[19]	"SEA domain proteolysis determines the functional composition of dystroglycan." Akhavan A., Crivelli S.N., Singh M., Lingappa V.R., Muschler J.L. FASEB J. 22:612-621(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING, CLEAVAGE AT GLY-653, GLYCOSYLATION, LIGAND-BINDING, MUTAGENESIS OF SER-654.
[20]	"Nuclear translocation of beta-dystroglycan reveals a distinctive trafficking pattern of autoproteolyzed mucins." Oppizzi M.L., Akhavan A., Singh M., Fata J.E., Muschler J.L. Traffic 9:2063-2072(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, MUTAGENESIS OF SER-654; THR-663; 777-LYS--LYS-780; 793-LYS-LYS-794; LYS-823; 828-PRO-PRO-829 AND TYR-831.
[21]	"Enzymatic processing of beta-dystroglycan recombinant ectodomain by MMP-9: identification of the main cleavage site." Bozzi M., Inzitari R., Sbardell D., Monaco S., Pavoni E., Gioia M., Marini S., Morlacchi S., Sciandra F., Castagnola M., Giardina B., Brancaccio A., Coletta M. IUBMB Life 61:1143-1152(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF BETA SUBUNIT, CLEAVAGE AT HIS-715, MASS SPECTROMETRY.
[22]	"Enrichment of glycopeptides for glycan structure and attachment site identification." Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G. Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS], STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY. Tissue: Cerebrospinal fluid.
[23]	"Characterization of site-specific O-glycan structures within the mucin-like domain of {alpha}-dystroglycan from human skeletal muscle." Nilsson J., Nilsson J., Larson G., Grahn A. Glycobiology 20:1160-1169(2010) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY, GLYCOSYLATION AT THR-367; THR-369; THR-372 AND THR-455.
[24]	"Characterization of an Importin alpha/beta-recognized nuclear localization signal in beta-dystroglycan." Lara-Chacon B., de Leon M.B., Leocadio D., Gomez P., Fuentes-Mera L., Martinez-Vieyra I., Ortega A., Jans D.A., Cisneros B. J. Cell. Biochem. 110:706-717(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-892, NUCLEAR LOCALIZATION SIGNAL, SUBCELLULAR LOCATION, MUTAGENESIS OF 777-LYS--LYS-782 AND TYR-892.
[25]	"O-mannosyl phosphorylation of alpha-dystroglycan is required for laminin binding." Yoshida-Moriguchi T., Yu L., Stalnaker S.H., Davis S., Kunz S., Madson M., Oldstone M.B., Schachter H., Wells L., Campbell K.P. Science 327:88-92(2010) [PubMed] [Europe PMC] [Abstract] Cited for: MASS SPECTROMETRY, GLYCOSYLATION AT THR-379; THR-381 AND THR-388.
[26]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]	"LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins." Halim A., Ruetschi U., Larson G., Nilsson J. J. Proteome Res. 12:573-584(2013) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-63, MASS SPECTROMETRY.
[28]	"Structure of a WW domain containing fragment of dystrophin in complex with beta-dystroglycan." Huang X., Poy F., Zhang R., Joachimiak A., Sudol M., Eck M.J. Nat. Struct. Biol. 7:634-638(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 881-895.
[29]	"A dystroglycan mutation associated with limb-girdle muscular dystrophy." Hara Y., Balci-Hayta B., Yoshida-Moriguchi T., Kanagawa M., Beltran-Valero de Bernabe D., Gundesli H., Willer T., Satz J.S., Crawford R.W., Burden S.J., Kunz S., Oldstone M.B., Accardi A., Talim B., Muntoni F., Topaloglu H., Dincer P., Campbell K.P. N. Engl. J. Med. 364:939-946(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MDDGC7 MET-192, CHARACTERIZATION OF VARIANT MDDGC7 MET-192.
+	Additional computationally mapped references.

Web resources

Wikipedia

Dystroglycan entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L19711 mRNA. Translation: AAA81779.1.
AK291692 mRNA. Translation: BAF84381.1.
AC104452 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64989.1.
BC012740 mRNA. Translation: AAH12740.1.
BC014616 mRNA. Translation: AAH14616.1.

IPI

IPI00028911.

PIR

I54343.

RefSeq

NP_001159400.2. NM_001165928.3.
NP_001171105.1. NM_001177634.2.
NP_001171106.1. NM_001177635.2.
NP_001171107.1. NM_001177636.2.
NP_001171108.1. NM_001177637.2.
NP_001171109.1. NM_001177638.2.
NP_001171110.1. NM_001177639.2.
NP_001171111.1. NM_001177640.2.
NP_001171112.1. NM_001177641.2.
NP_001171113.1. NM_001177642.2.
NP_001171114.1. NM_001177643.2.
NP_001171115.1. NM_001177644.2.
NP_004384.4. NM_004393.5.

UniGene

Hs.76111.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EG4	X-ray	2.00	P	881-895	[»]

ProteinModelPortal

Q14118.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-40928N.

IntAct

Q14118. 8 interactions.

MINT

MINT-5004541.

STRING

9606.ENSP00000312435.

Protein family/group databases

MEROPS

S72.001.

PTM databases

PhosphoSite

Q14118.

Polymorphism databases

DMDM

229462879.

Proteomic databases

PaxDb

Q14118.

PRIDE

Q14118.

Protocols and materials databases

DNASU

1605.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000308775; ENSP00000312435; ENSG00000173402.
ENST00000515359; ENSP00000440705; ENSG00000173402.
ENST00000538711; ENSP00000438421; ENSG00000173402.
ENST00000539901; ENSP00000439334; ENSG00000173402.
ENST00000541308; ENSP00000440590; ENSG00000173402.
ENST00000545947; ENSP00000442600; ENSG00000173402.

GeneID

1605.

KEGG

hsa:1605.

UCSC

uc003cxc.4. human.

Organism-specific databases

CTD

1605.

GeneCards

GC03P049482.

HGNC

HGNC:2666. DAG1.

HPA

CAB001960.
CAB016353.

MIM

128239. gene.
613818. phenotype.

neXtProt

NX_Q14118.

Orphanet

280333. Autosomal recessive limb-girdle muscular dystrophy - dystroglycanopathy type C7.

PharmGKB

PA27138.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG266557.

HOGENOM

HOG000072580.

HOVERGEN

HBG000078.

InParanoid

Q14118.

KO

K06265.

OMA

AMICYRK.

OrthoDB

EOG49S65X.

PhylomeDB

Q14118.

Gene expression databases

ArrayExpress

Q14118.

Bgee

Q14118.

CleanEx

HS_DAG1.

Genevestigator

Q14118.

GermOnline

ENSG00000173402. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 2 hits.

InterPro

IPR006644. Cadg.
IPR015919. Cadherin-like.
IPR008465. DAG1.
IPR013783. Ig-like_fold.
[Graphical view]

PANTHER

PTHR21559:SF9. PTHR21559:SF9. 1 hit.

Pfam

PF05454. DAG1. 1 hit.
[Graphical view]

SMART

SM00736. CADG. 2 hits.
[Graphical view]

SUPFAM

SSF49313. Cadherin. 2 hits.

ProtoNet

Search...

Other

ChiTaRS

DAG1. human.

EvolutionaryTrace

Q14118.

GenomeRNAi

1605.

NextBio

6586.

SOURCE

Search...

Entry information

Entry name

DAG1_HUMAN

Accession

Primary (citable) accession number: Q14118
Secondary accession number(s): A8K6M7, Q969J9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 5, 2009
Last modified:	May 1, 2013
This is version 128 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.