EF-hand-like motif found in the dystrophin/dystrobrevin/dystrotelin family; The dystrophin/dystrobrevin/dystrotelin family has been characterized by a compact cluster of domains comprising four EF-hand-like motifs and a ZZ-domain, followed by a looser region with two coiled-coils. Dystrophin is the founder member of this family. It is a sub-membrane cytoskeletal protein associated with the inner surface membrane. Dystrophin and its close paralog utrophin have a large N-terminal extension of actin-binding CH domains, up to 24 spectrin repeats, and a WW domain. Its further paralog, dystrophin-related protein 2 (DRP-2), retains only two of the spectrin repeats. Dystrophin, utrophin or DRP2 can form the core of a membrane-bound complex consisting of dystroglycan, sarcoglycans and syntrophins, known as the dystrophin-glycoprotein complex (DGC) that plays an important role in brain development and disease, as well as in the prevention of muscle damage. Dystrobrevins, including alpha- and beta-dystrobrevin, lack the large N-terminal extension found in dystrophin, but alpha-dystrobrevin has a characteristic C-terminal extension. Dystrobrevins are part of the DGC. They physically associate with members of the dystrophin family and with the syntrophins through their homologous C-terminal coiled coil motifs. In contrast, dystrotelins lack both the large N-terminal extension found in dystrophin and the obvious syntrophin-binding sites (SBSs). Dystrotelins are not critical for mammalian development. They may be involved in other forms of cytokinesis. Moreover, dystrotelin is unable to heterodimerize with members of the dystrophin or dystrobrevin families, or to homodimerize.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47201247   1 SDPGGCLLVLSVKAMLATLCGGKLVDKLRYVFSQVSDSNGVLVQSKFDAFLREALKLPTAVYEGPSFGYAQASTRPCFPQ 80
Cdd:cd16244  68 PEATGRLTVFSVKVALSTLCAGKLVDKLRYIFSQISDSNGVLVFSKFEDFLREALKLPTAVFEGPSFGYNESAARSCFPG 147

                        90
                ....*....|...
gi 47201247  81 QKRVTVNMFLDIL 93
Cdd:cd16244 148 QSKVTVNDFLDVM 160

EF-hand-like motif found in dystrobrevins and similar proteins; Dystrobrevins are part of the dystrophin-glycoprotein complex (DGC). They physically associate with members of the dystrophin family and with the syntrophins through their homologous C-terminal coiled coil motifs. The family includes two paralogs dystrobrevins, alpha- and beta-dystrobrevin, both of which are cytoplasmic components of the dystrophin-associated protein complex that function as scaffold proteins in signal transduction and intracellular transport. Absence of alpha- and beta-dystrobrevin causes cerebellar synaptic defects and abnormal motor behavior. The dystrobrevins subfamily has been characterized by a compact cluster of domains comprising four EF-hand-like motifs and a ZZ-domain, followed by a looser region with two coiled-coils. These domains are believed to be involved in protein-protein interactions. In addition, dystrobrevins contain one or two syntrophin binding sites (SBSs).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47201247   1 SDPGGCLLVLSVKAMLATLCGGKLVDKLRYVFSQVSDSNGVLVQSKFDAFLREALKLPTAVYEGPSFGYAQASTRPCFPQ 80
Cdd:cd16244  68 PEATGRLTVFSVKVALSTLCAGKLVDKLRYIFSQISDSNGVLVFSKFEDFLREALKLPTAVFEGPSFGYNESAARSCFPG 147

                        90
                ....*....|...
gi 47201247  81 QKRVTVNMFLDIL 93
Cdd:cd16244 148 QSKVTVNDFLDVM 160

Zinc finger, ZZ type. Zinc finger present in dystrophin and dystrobrevin. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Dystrophin attaches actin filaments to an integral membrane glycoprotein complex in muscle cells. The ZZ domain in dystrophin has been shown to be essential for binding to the membrane protein beta-dystroglycan.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 47201247 119 TSCSYCRTNGMTGFRYRCLRCRGYQLCQNCFWRGNAA 155
Cdd:cd02334   1 AKCNICKEFPITGFRYRCLKCFNYDLCQSCFFSGRTS 37

Zinc finger, ZZ type; Zinc finger present in dystrophin, CBP/p300. ZZ in dystrophin binds calmodulin. Putative zinc finger; binding not yet shown. Four to six cysteine residues in its sequence are responsible for coordinating zinc ions, to reinforce the structure.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 47201247   114 HVFHPTSCSYCRTNGmtgFRYRCLRCRGYQLCQNCF 149
Cdd:pfam00569   3 KVYTCNGCSNDPSIG---VRYHCLRCSDYDLCQSCF 35

EF-hand-like motif found in dystrobrevins and similar proteins; Dystrobrevins are part of the dystrophin-glycoprotein complex (DGC). They physically associate with members of the dystrophin family and with the syntrophins through their homologous C-terminal coiled coil motifs. The family includes two paralogs dystrobrevins, alpha- and beta-dystrobrevin, both of which are cytoplasmic components of the dystrophin-associated protein complex that function as scaffold proteins in signal transduction and intracellular transport. Absence of alpha- and beta-dystrobrevin causes cerebellar synaptic defects and abnormal motor behavior. The dystrobrevins subfamily has been characterized by a compact cluster of domains comprising four EF-hand-like motifs and a ZZ-domain, followed by a looser region with two coiled-coils. These domains are believed to be involved in protein-protein interactions. In addition, dystrobrevins contain one or two syntrophin binding sites (SBSs).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47201247   1 SDPGGCLLVLSVKAMLATLCGGKLVDKLRYVFSQVSDSNGVLVQSKFDAFLREALKLPTAVYEGPSFGYAQASTRPCFPQ 80
Cdd:cd16244  68 PEATGRLTVFSVKVALSTLCAGKLVDKLRYIFSQISDSNGVLVFSKFEDFLREALKLPTAVFEGPSFGYNESAARSCFPG 147

                        90
                ....*....|...
gi 47201247  81 QKRVTVNMFLDIL 93
Cdd:cd16244 148 QSKVTVNDFLDVM 160

EF-hand-like motif found in beta-dystrobrevin; Beta-dystrobrevin, also termed dystrobrevin beta (DTN-B), is a dystrophin-related protein that is restricted to non-muscle tissues and is abundantly expressed in brain, lung, kidney, and liver. It may be involved in regulating chromatin dynamics, possibly playing a role in neuronal differentiation, through the interactions with the high mobility group HMG20 proteins iBRAF/HMG20a and BRAF35 /HMG20b. It also binds to and represses the promoter of synapsin I, a neuronal differentiation gene. Moreover, beta-dystrobrevin functions as a kinesin-binding receptor involved in brain development via the association with the extracellular matrix components pancortins. Furthermore, beta-dystrobrevin binds directly to dystrophin and is a cytoplasmic component of the dystrophin-associated glycoprotein complex, a multimeric protein complex that links the extracellular matrix to the cortical actin cytoskeleton and acts as a scaffold for signaling proteins such as protein kinase A. Absence of alpha- and beta-dystrobrevin causes cerebellar synaptic defects and abnormal motor behavior. Beta-dystrobrevin has a compact cluster of domains comprising four EF-hand-like motifs and a ZZ-domain, followed by a looser region with two coiled-coils. These domains are believed to be involved in protein-protein interactions. In addition, beta-dystrobrevin contain two syntrophin binding sites (SBSs).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47201247   1 SDPGGCLLVLSVKAMLATLCGGKLVDKLRYVFSQVSDSNGVLVQSKFDAFLREALKLPTAVYEGPSFGYAQASTRPCFPQ 80
Cdd:cd16250  68 SEGHGKLTVFSVKAMLATMCGGKILDKLRYTFSQMSDSNGLMIFLKFDQFLREVLKLPTAVFEGPSFGYTEHSVRTCFPQ 147

                        90
                ....*....|...
gi 47201247  81 QKRVTVNMFLDIL 93
Cdd:cd16250 148 QKKIMLNMFLDTM 160

EF-hand-like motif found in the dystrophin/dystrobrevin/dystrotelin family; The dystrophin/dystrobrevin/dystrotelin family has been characterized by a compact cluster of domains comprising four EF-hand-like motifs and a ZZ-domain, followed by a looser region with two coiled-coils. Dystrophin is the founder member of this family. It is a sub-membrane cytoskeletal protein associated with the inner surface membrane. Dystrophin and its close paralog utrophin have a large N-terminal extension of actin-binding CH domains, up to 24 spectrin repeats, and a WW domain. Its further paralog, dystrophin-related protein 2 (DRP-2), retains only two of the spectrin repeats. Dystrophin, utrophin or DRP2 can form the core of a membrane-bound complex consisting of dystroglycan, sarcoglycans and syntrophins, known as the dystrophin-glycoprotein complex (DGC) that plays an important role in brain development and disease, as well as in the prevention of muscle damage. Dystrobrevins, including alpha- and beta-dystrobrevin, lack the large N-terminal extension found in dystrophin, but alpha-dystrobrevin has a characteristic C-terminal extension. Dystrobrevins are part of the DGC. They physically associate with members of the dystrophin family and with the syntrophins through their homologous C-terminal coiled coil motifs. In contrast, dystrotelins lack both the large N-terminal extension found in dystrophin and the obvious syntrophin-binding sites (SBSs). Dystrotelins are not critical for mammalian development. They may be involved in other forms of cytokinesis. Moreover, dystrotelin is unable to heterodimerize with members of the dystrophin or dystrobrevin families, or to homodimerize.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47201247   5 GCLLVLSVKAMLATLCGGKLVDKLRYVFSQVSDSNGVLVQSKFDAFLREALKLPTAVYEGPSFG--YAQASTRPCFPQQ- 81
Cdd:cd15901  69 GCIRLLSVKIALITLCAASLLDKYRYLFGQLADSSGFISRERLTQFLQDLLQIPDLIGESPAFGghNVEAAVESCFQLAr 148

                        90
                ....*....|..
gi 47201247  82 KRVTV--NMFLD 91
Cdd:cd15901 149 SRVGVseDTFLS 160

EF-hand-like motif found in the dystrophins subfamily; This dystrophins subfamily includes dystrophin and its two paralogs, utrophin and DRP-2. Dystrophin is a large, submembrane cytoskeletal protein that is the main component of the dystrophin-glycoprotein complex (DGC) in skeletal muscle. It links the transmembrane DGC to the actin cytoskeleton through binding strongly to the cytoplasmic tail of beta-dystroglycan, the transmembrane subunit of a highly O-glycosylated cell-surface protein. Dystrophin also involves in maintaining the structural integrity of cells, as well as in the formation of the blood-brain barrier (BBB). Utrophin, also termed dystrophin-related protein 1 (DRP-1), is an autosomal dystrophin homologue that increases dystrophic muscle function and reduces pathology. It is broadly expressed at both the mRNA and protein levels, and occurs in the cerebrovascular endothelium. Utrophin forms the utrophin-glycoprotein complex (UGC) by interacting with the dystroglycans (DGs) and the sarcoglycan-dystroglycans, sarcoglycans and sarcospan (SG-SSPN) subcomplex. It may act as a scaffolding protein that stabilizes lipid microdomains and clusters mechanosensitive channel subunits, and link the F-actin cytoskeleton to the cell membrane via the associated glycoprotein complex. DRP-2 is mainly expressed in the vertebrate central nervous system (CNS). It is associated with brain membrane fractions and highly enriched in the postsynaptic density. DRP-2 plays a role in the organization of central cholinergic synapses. It interacts with dystroglycan and L-Periaxin to form a transmembrane complex, which plays a role in Schwann cell-basal lamina interactions and in the regulation of the terminal stages of myelination. The dystrophins subfamily has been characterized by a compact cluster of domains comprising a WW domain, four EF-hand-like motifs and a ZZ-domain, followed by two syntrophin binding sites (SBSs) and a looser region with two coiled-coils.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47201247   2 DPG--GCLLVLSVKAMLATLCGGKLVDKLRYVFSQVSDSNGVLVQSKFDAFLREALKLPTAVYEGPSFGYA--QASTRPC 77
Cdd:cd16242  64 DSGrsGKIRVLSFKVGLVLLCNAHLEEKYRYLFSLIADPNGCVDQRRLGLLLHDCIQIPRQLGEVAAFGGSniEPSVRSC 143

                        90
                ....*....|....*..
gi 47201247  78 FPQ---QKRVTVNMFLD 91
Cdd:cd16242 144 FEKageKPEISAAHFLD 160

EF-hand-like motif found in utrophin; Utrophin, also termed dystrophin-related protein 1 (DRP-1), is an autosomal dystrophin homologue that increases dystrophic muscle function and reduces pathology. It is broadly expressed at both the mRNA and protein levels, and occurs in the cerebrovascular endothelium. Utrophin forms the utrophin-glycoprotein complex (UGC) by interacting with the dystroglycans (DGs) and the sarcoglycan-dystroglycans, sarcoglycans and sarcospan (SG-SSPN) subcomplex. It may act as a scaffolding protein that stabilizes lipid microdomains and clusters mechanosensitive channel subunits, and link the F-actin cytoskeleton to the cell membrane via the associated glycoprotein complex. Like dystrophin, Utrophin has a compact cluster of domains comprising four EF-hand-like motifs and a ZZ-domain, followed by a looser region with two coiled-coils. These domains are believed to be involved in protein-protein interactions. In addition, it contains two syntrophin binding sites (SBSs) and a long N-terminal extension that comprises two actin-binding calponin homology (CH) domains, up to 24 spectrin repeats (SRs) and a WW domain. However, utrophin lacks the intrinsic microtubule binding activity of dystrophin SRs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47201247   5 GCLLVLSVKAMLATLCGGKLVDKLRYVFSQVSDSNGVLVQSKFDAFLREALKLPTAVYEGPSFGYA--QASTRPCFPQ-- 80
Cdd:cd16247  68 GKIRVLSLKIGLMSLSKGLLEEKYRYLFKEVAGPGDTCDQRQLGLLLHDAIQIPRQLGEVAAFGGSniEPSVRSCFQHan 147

                        90
                ....*....|..
gi 47201247  81 -QKRVTVNMFLD 91
Cdd:cd16247 148 nKPEIDVKQFID 159

EF-hand-like motif found in dystrophin-related protein 2 (DRP-2); DRP-2 is a dystrophin homologue mainly expressed in the vertebrate central nervous system (CNS). It is associated with brain membrane fractions and highly enriched in the postsynaptic density. DRP-2 plays a role in the organization of central cholinergic synapses. It interacts with dystroglycan and L-Periaxin to form a transmembrane complex, which plays a role in Schwann cell-basal lamina interactions and in the regulation of the terminal stages of myelination. Like dystrophin, DRP-2 has a compact cluster of domains comprising four EF-hand-like motifs and a ZZ-domain, followed by a looser region with two coiled-coils. These domains are believed to be involved in protein-protein interactions. In addition, it contains two syntrophin binding sites (SBSs) and a long N-terminal extension that comprises only two spectrin repeats (SRs) and a WW domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47201247   5 GCLLVLSVKAMLATLCGGKLVDKLRYVFSQVSDSNGVLVQSKFDAFLREALKLPTAVYEGPSFGYA--QASTRPCF---P 79
Cdd:cd16248  68 GKIRVLSFKTGIVCLCNADVKEKYQYLFSQVAGPGGQCDQRHLSLLLHEAIQIPRQLGEVAAFGGSnvEPSVRSCFrfaP 147

                        90
                ....*....|..
gi 47201247  80 QQKRVTVNMFLD 91
Cdd:cd16248 148 GKPVIELSQFLE 159

EF-hand-like motif found in dystrotelin and similar proteins; Dystrotelin is the vertebrate orthologue of Drosophila DAH, which is involved in the synchronised cellularization of thousands of nuclei in the syncytial early fly embryo (a specialised form of cytokinesis). Dystrotelin is mainly expressed in the developing central nervous system (CNS) and adult nervous and muscular tissues. Heterologously expressed dystrotelin protein localizes spontaneously to the cytoplasmic membrane, and possibly to the endoplasmic reticulum (ER). Dystrotelin is not critical for mammalian development. It may be involved in other forms of cytokinesis. Its N-terminal region contains a compact cluster of domains comprising four EF-hand-like motifs and a ZZ-domain, followed by a looser region with two coiled-coils. These domains are believed to be involved in protein-protein interactions. The C-terminal region is extremely divergent. Unlike other superfamily members, dystrophin or dystrobrevin, the residues directly involved in beta-dystroglycan binding are not conserved in dystrotelin, which makes it unlikely that dystrotelin interacts with this ligand. Moreover, dystrotelin is unable to heterodimerize with members of the dystrophin or dystrobrevin families, or to homodimerize.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 47201247   5 GCLLVLSVKAMLATLCGGKLVDKLRYVF----SQVSDSNGVLVQSKFDAFLREALKLPTAVYEGPSFGYAQASTRPCF 78
Cdd:cd16243  68 GFVSLRSVEAALIALSGDTLSAKYRALFqlyeSGQGGSSGSITRSGLRVLLQDLSQIPAVVQESHVFGNVETAVRSCF 145

Zinc finger, ZZ type; Zinc finger present in dystrophin, CBP/p300. ZZ in dystrophin binds calmodulin. Putative zinc finger; binding not yet shown. Four to six cysteine residues in its sequence are responsible for coordinating zinc ions, to reinforce the structure.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 47201247   114 HVFHPTSCSYCRTNGmtgFRYRCLRCRGYQLCQNCF 149
Cdd:pfam00569   3 KVYTCNGCSNDPSIG---VRYHCLRCSDYDLCQSCF 35

Zinc finger, ZZ type. Zinc finger present in Drosophila Mind bomb (D-mib) and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Mind bomb is an E3 ubiqitin ligase that has been shown to regulate signaling by the Notch ligand Delta in Drosophila melanogaster.

                        10        20
                ....*....|....*....|....*....
gi 47201247 121 CSYCRTNGMTGFRYRCLRCRGYQLCQNCF 149
Cdd:cd02339   3 CDTCRKQGIIGIRWKCAECPNYDLCTTCY 31