Dystroglycan (Dystrophin-associated glycoprotein 1); Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in human. The protein product is cleaved into two non-covalently associated subunits, [alpha] (N-terminal) and [beta] (C-terminal). In skeletal muscle the dystroglycan complex works as a transmembrane linkage between the extracellular matrix and the cytoskeleton. [alpha]-dystroglycan is extracellular and binds to merosin ([alpha]-2 laminin) in the basement membrane, while [beta]-dystroglycan is a transmembrane protein and binds to dystrophin, which is a large rod-like cytoskeletal protein, absent in Duchenne muscular dystrophy patients. Dystrophin binds to intracellular actin cables. In this way, the dystroglycan complex, which links the extracellular matrix to the intracellular actin cables, is thought to provide structural integrity in muscle tissues. The dystroglycan complex is also known to serve as an agrin receptor in muscle, where it may regulate agrin-induced acetylcholine receptor clustering at the neuromuscular junction. There is also evidence which suggests the function of dystroglycan as a part of the signal transduction pathway because it is shown that Grb2, a mediator of the Ras-related signal pathway, can interact with the cytoplasmic domain of dystroglycan. In general, aberrant expression of dystrophin-associated protein complex underlies the pathogenesis of Duchenne muscular dystrophy, Becker muscular dystrophy and severe childhood autosomal recessive muscular dystrophy. Interestingly, no genetic disease has been described for either [alpha]- or [beta]-dystroglycan. Dystroglycan is widely distributed in non-muscle tissues as well as in muscle tissues. During epithelial morphogenesis of kidney, the dystroglycan complex is shown to act as a receptor for the basement membrane. Dystroglycan expression in mouse brain and neural retina has also been reported. However, the physiological role of dystroglycan in non-muscle tissues has remained unclear.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102   641 FFFKAYLSIKHERFNADLQRK--FVERVAKLNGDPTTGQIQIRSITthhdSDGTIVNFYNTTLyrKHNSCREKEVAMTRS 718
Cdd:pfam05454   1 VFFKAKFSGDHERVNNDIHKKilLVKKLAFAFGDRNSSTITLRSIT----KGSIIVEWTNNTL--PHEPCPKEQVAGLSK 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102   719 VYLNSDLSLREAAKRALGPELNLTNFSVVPFSICHHTENIDTNQLDYIPSR------PEEPTHKSSFGEDYMITFVWPIV 792
Cdd:pfam05454  75 KILDSDGSPREAFKNALEPEFKLTNISVVGSGSCRHTEFIPTNQLDYIPSRtpptgtPDRPTEKSSEDDVYLHTVIPAVV 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102   793 IIVAMLVAASIIACCLHwcRQRSGKMELgdeEERKSFRAKGIPVIFQDEYEE-KPEIGNKSPVILKDEKPPLLPPSYNTS 871
Cdd:pfam05454 155 VAAILLIAGIIAMICYR--KKRKGKLTL---EDQATFIKKGVPIIFADELDDsKPPPSSSMPLILKEEKPPLPPPEYPNQ 229

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 45551102   872 NM------------------NGDNDVDDYVPPPSVVVGGREVRGKSPATPSYRKPPPYVSP 914
Cdd:pfam05454 230 NVpettplnqdllgeytplrDEDPNAPPYQPPPPFTAPMEGKGSRPKNMTPYRSPPPYVPP 290

Cadherin-like repeat domain of alpha dystroglycan; Dystroglycan is a glycoprotein widely distributed in skeletal muscle and other tissues; the pre-protein is cleaved into two subunits (alpha and beta) that form a complex which links the extracellular matrix to the cytoskeleton. Cadherin-like dystroglycan repeats are present in the extracellular alpha-dystroglycan subunit, which binds to the alpha-2-laminin G-domain in the basement membrane as part of the dystrophin-dystroglycan-complex (DGC). DGC has been shown to interact with other etxtracellular matrix components as well, such as perlecan and m-agrin, suggesting that the complex may play various different roles depending on the extracellular ligand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102 537 MPRNQVDRVNASLGQLLVYKVPADTFYDANDN-QLTLTLKTrdhlelSPRHWLQFDSKNEEFYGIPKSGDIGSEEYLLVA 615
Cdd:cd11303   1 SPLWGIPDLVAVVGRLFTYKIPPDTFSGNGDTyQVSEAGKD------DLPSWLQFDSSSRTLYGLPLSDDVGVHYISVTA 74

                        90       100
                ....*....|....*....|....*
gi 45551102 616 EDSG--GLSAHDALVVVVSPAPKRD 638
Cdd:cd11303  75 EDKGsaGSQASDVFSIDVHPEPHPE 99

Dystroglycan (Dystrophin-associated glycoprotein 1); Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in human. The protein product is cleaved into two non-covalently associated subunits, [alpha] (N-terminal) and [beta] (C-terminal). In skeletal muscle the dystroglycan complex works as a transmembrane linkage between the extracellular matrix and the cytoskeleton. [alpha]-dystroglycan is extracellular and binds to merosin ([alpha]-2 laminin) in the basement membrane, while [beta]-dystroglycan is a transmembrane protein and binds to dystrophin, which is a large rod-like cytoskeletal protein, absent in Duchenne muscular dystrophy patients. Dystrophin binds to intracellular actin cables. In this way, the dystroglycan complex, which links the extracellular matrix to the intracellular actin cables, is thought to provide structural integrity in muscle tissues. The dystroglycan complex is also known to serve as an agrin receptor in muscle, where it may regulate agrin-induced acetylcholine receptor clustering at the neuromuscular junction. There is also evidence which suggests the function of dystroglycan as a part of the signal transduction pathway because it is shown that Grb2, a mediator of the Ras-related signal pathway, can interact with the cytoplasmic domain of dystroglycan. In general, aberrant expression of dystrophin-associated protein complex underlies the pathogenesis of Duchenne muscular dystrophy, Becker muscular dystrophy and severe childhood autosomal recessive muscular dystrophy. Interestingly, no genetic disease has been described for either [alpha]- or [beta]-dystroglycan. Dystroglycan is widely distributed in non-muscle tissues as well as in muscle tissues. During epithelial morphogenesis of kidney, the dystroglycan complex is shown to act as a receptor for the basement membrane. Dystroglycan expression in mouse brain and neural retina has also been reported. However, the physiological role of dystroglycan in non-muscle tissues has remained unclear.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102   641 FFFKAYLSIKHERFNADLQRK--FVERVAKLNGDPTTGQIQIRSITthhdSDGTIVNFYNTTLyrKHNSCREKEVAMTRS 718
Cdd:pfam05454   1 VFFKAKFSGDHERVNNDIHKKilLVKKLAFAFGDRNSSTITLRSIT----KGSIIVEWTNNTL--PHEPCPKEQVAGLSK 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102   719 VYLNSDLSLREAAKRALGPELNLTNFSVVPFSICHHTENIDTNQLDYIPSR------PEEPTHKSSFGEDYMITFVWPIV 792
Cdd:pfam05454  75 KILDSDGSPREAFKNALEPEFKLTNISVVGSGSCRHTEFIPTNQLDYIPSRtpptgtPDRPTEKSSEDDVYLHTVIPAVV 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102   793 IIVAMLVAASIIACCLHwcRQRSGKMELgdeEERKSFRAKGIPVIFQDEYEE-KPEIGNKSPVILKDEKPPLLPPSYNTS 871
Cdd:pfam05454 155 VAAILLIAGIIAMICYR--KKRKGKLTL---EDQATFIKKGVPIIFADELDDsKPPPSSSMPLILKEEKPPLPPPEYPNQ 229

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 45551102   872 NM------------------NGDNDVDDYVPPPSVVVGGREVRGKSPATPSYRKPPPYVSP 914
Cdd:pfam05454 230 NVpettplnqdllgeytplrDEDPNAPPYQPPPPFTAPMEGKGSRPKNMTPYRSPPPYVPP 290

Cadherin-like repeat domain of alpha dystroglycan; Dystroglycan is a glycoprotein widely distributed in skeletal muscle and other tissues; the pre-protein is cleaved into two subunits (alpha and beta) that form a complex which links the extracellular matrix to the cytoskeleton. Cadherin-like dystroglycan repeats are present in the extracellular alpha-dystroglycan subunit, which binds to the alpha-2-laminin G-domain in the basement membrane as part of the dystrophin-dystroglycan-complex (DGC). DGC has been shown to interact with other etxtracellular matrix components as well, such as perlecan and m-agrin, suggesting that the complex may play various different roles depending on the extracellular ligand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102 537 MPRNQVDRVNASLGQLLVYKVPADTFYDANDN-QLTLTLKTrdhlelSPRHWLQFDSKNEEFYGIPKSGDIGSEEYLLVA 615
Cdd:cd11303   1 SPLWGIPDLVAVVGRLFTYKIPPDTFSGNGDTyQVSEAGKD------DLPSWLQFDSSSRTLYGLPLSDDVGVHYISVTA 74

                        90       100
                ....*....|....*....|....*
gi 45551102 616 EDSG--GLSAHDALVVVVSPAPKRD 638
Cdd:cd11303  75 EDKGsaGSQASDVFSIDVHPEPHPE 99

Dystroglycan-type cadherin-like domains; Cadherin-homologous domains present in metazoan dystroglycans and alpha/epsilon sarcoglycans, yeast Axl2p and in a very large protein from magnetotactic bacteria. Likely to bind calcium ions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102    309 TRLQKLAVTSGKAFTFHVLPETFYDAeDQGNLRLALTDKDGHELKanSWLQFNADKRELYGLPLDDTVSRWQYRLSATDS 388
Cdd:smart00736   2 NAIGDQTATEGESFSYTIPSSTFTDA-DGDTLTYSATLSDGSALP--SWLSFDSDTGTLSGTPTNSDVGSLSLKVTATDS 78

                           90
                   ....*....|....*.
gi 45551102    389 GNASVTETVEISVQQH 404
Cdd:smart00736  79 SGASASDTFTITVVNT 94

Putative Ig domain; This alignment represents the conserved core region of ~90 residue repeat found in several haemagglutinins and other cell surface proteins. Sequence similarities to (pfam02494) and (pfam00801) suggest an Ig-like fold (personal obs:C. Yeats). So this family may be similar in function to the (pfam02639) and (pfam02638) domains. This domain is also found in the WisP family of proteins of Tropheryma whipplei.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102   305 PIIKTRLQKLAVTSGKAFTFHVLPETFYDAEDQGNLRLALTDKDGHelkANSWLQFNADKRELYGLPLDDTVSRWQYRLS 384
Cdd:pfam05345   1 PPVVTSPADQTATVGTPYSFTLSASGGSDPYGGSTVTYSTTATGGA---LPSGLTLNSSTGTISGTPTSVQPGTYTFTVT 77

                          90
                  ....*....|....*..
gi 45551102   385 ATDSGNASVTETVEISV 401
Cdd:pfam05345  78 ATDSSGLSSSTTFTLTV 94

Dystroglycan (Dystrophin-associated glycoprotein 1); Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in human. The protein product is cleaved into two non-covalently associated subunits, [alpha] (N-terminal) and [beta] (C-terminal). In skeletal muscle the dystroglycan complex works as a transmembrane linkage between the extracellular matrix and the cytoskeleton. [alpha]-dystroglycan is extracellular and binds to merosin ([alpha]-2 laminin) in the basement membrane, while [beta]-dystroglycan is a transmembrane protein and binds to dystrophin, which is a large rod-like cytoskeletal protein, absent in Duchenne muscular dystrophy patients. Dystrophin binds to intracellular actin cables. In this way, the dystroglycan complex, which links the extracellular matrix to the intracellular actin cables, is thought to provide structural integrity in muscle tissues. The dystroglycan complex is also known to serve as an agrin receptor in muscle, where it may regulate agrin-induced acetylcholine receptor clustering at the neuromuscular junction. There is also evidence which suggests the function of dystroglycan as a part of the signal transduction pathway because it is shown that Grb2, a mediator of the Ras-related signal pathway, can interact with the cytoplasmic domain of dystroglycan. In general, aberrant expression of dystrophin-associated protein complex underlies the pathogenesis of Duchenne muscular dystrophy, Becker muscular dystrophy and severe childhood autosomal recessive muscular dystrophy. Interestingly, no genetic disease has been described for either [alpha]- or [beta]-dystroglycan. Dystroglycan is widely distributed in non-muscle tissues as well as in muscle tissues. During epithelial morphogenesis of kidney, the dystroglycan complex is shown to act as a receptor for the basement membrane. Dystroglycan expression in mouse brain and neural retina has also been reported. However, the physiological role of dystroglycan in non-muscle tissues has remained unclear.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102   641 FFFKAYLSIKHERFNADLQRK--FVERVAKLNGDPTTGQIQIRSITthhdSDGTIVNFYNTTLyrKHNSCREKEVAMTRS 718
Cdd:pfam05454   1 VFFKAKFSGDHERVNNDIHKKilLVKKLAFAFGDRNSSTITLRSIT----KGSIIVEWTNNTL--PHEPCPKEQVAGLSK 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102   719 VYLNSDLSLREAAKRALGPELNLTNFSVVPFSICHHTENIDTNQLDYIPSR------PEEPTHKSSFGEDYMITFVWPIV 792
Cdd:pfam05454  75 KILDSDGSPREAFKNALEPEFKLTNISVVGSGSCRHTEFIPTNQLDYIPSRtpptgtPDRPTEKSSEDDVYLHTVIPAVV 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102   793 IIVAMLVAASIIACCLHwcRQRSGKMELgdeEERKSFRAKGIPVIFQDEYEE-KPEIGNKSPVILKDEKPPLLPPSYNTS 871
Cdd:pfam05454 155 VAAILLIAGIIAMICYR--KKRKGKLTL---EDQATFIKKGVPIIFADELDDsKPPPSSSMPLILKEEKPPLPPPEYPNQ 229

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 45551102   872 NM------------------NGDNDVDDYVPPPSVVVGGREVRGKSPATPSYRKPPPYVSP 914
Cdd:pfam05454 230 NVpettplnqdllgeytplrDEDPNAPPYQPPPPFTAPMEGKGSRPKNMTPYRSPPPYVPP 290

Cadherin-like repeat domain of alpha dystroglycan; Dystroglycan is a glycoprotein widely distributed in skeletal muscle and other tissues; the pre-protein is cleaved into two subunits (alpha and beta) that form a complex which links the extracellular matrix to the cytoskeleton. Cadherin-like dystroglycan repeats are present in the extracellular alpha-dystroglycan subunit, which binds to the alpha-2-laminin G-domain in the basement membrane as part of the dystrophin-dystroglycan-complex (DGC). DGC has been shown to interact with other etxtracellular matrix components as well, such as perlecan and m-agrin, suggesting that the complex may play various different roles depending on the extracellular ligand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102 537 MPRNQVDRVNASLGQLLVYKVPADTFYDANDN-QLTLTLKTrdhlelSPRHWLQFDSKNEEFYGIPKSGDIGSEEYLLVA 615
Cdd:cd11303   1 SPLWGIPDLVAVVGRLFTYKIPPDTFSGNGDTyQVSEAGKD------DLPSWLQFDSSSRTLYGLPLSDDVGVHYISVTA 74

                        90       100
                ....*....|....*....|....*
gi 45551102 616 EDSG--GLSAHDALVVVVSPAPKRD 638
Cdd:cd11303  75 EDKGsaGSQASDVFSIDVHPEPHPE 99

Dystroglycan-type cadherin-like domains; Cadherin-homologous domains present in metazoan dystroglycans and alpha/epsilon sarcoglycans, yeast Axl2p and in a very large protein from magnetotactic bacteria. Likely to bind calcium ions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102    309 TRLQKLAVTSGKAFTFHVLPETFYDAeDQGNLRLALTDKDGHELKanSWLQFNADKRELYGLPLDDTVSRWQYRLSATDS 388
Cdd:smart00736   2 NAIGDQTATEGESFSYTIPSSTFTDA-DGDTLTYSATLSDGSALP--SWLSFDSDTGTLSGTPTNSDVGSLSLKVTATDS 78

                           90
                   ....*....|....*.
gi 45551102    389 GNASVTETVEISVQQH 404
Cdd:smart00736  79 SGASASDTFTITVVNT 94

Putative Ig domain; This alignment represents the conserved core region of ~90 residue repeat found in several haemagglutinins and other cell surface proteins. Sequence similarities to (pfam02494) and (pfam00801) suggest an Ig-like fold (personal obs:C. Yeats). So this family may be similar in function to the (pfam02639) and (pfam02638) domains. This domain is also found in the WisP family of proteins of Tropheryma whipplei.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45551102   305 PIIKTRLQKLAVTSGKAFTFHVLPETFYDAEDQGNLRLALTDKDGHelkANSWLQFNADKRELYGLPLDDTVSRWQYRLS 384
Cdd:pfam05345   1 PPVVTSPADQTATVGTPYSFTLSASGGSDPYGGSTVTYSTTATGGA---LPSGLTLNSSTGTISGTPTSVQPGTYTFTVT 77

                          90
                  ....*....|....*..
gi 45551102   385 ATDSGNASVTETVEISV 401
Cdd:pfam05345  78 ATDSSGLSSSTTFTLTV 94