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 442619934  745 SMSTACESFDRHGLRAQNDKLIDIPDMTTVLHSLYVTIDK-----IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGL 819
Cdd:cd16242     1 SLSTAIEAFDQHGLRAQNDKLIDVPDMITCLTTIYEALEEehptlVNVPLCVDLCLNWLLNVYDSGRSGKIRVLSFKVGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  820 VLLCKGHLEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGSNIEPSVRSCLEQAGISQEaidgnqdi 899
Cdd:cd16242    81 VLLCNAHLEEKYRYLFSLIADPNGCVDQRRLGLLLHDCIQIPRQLGEVAAFGGSNIEPSVRSCFEKAGEKPE-------- 152

                         170
                  ....*....|..
gi 442619934  900 sIELQHFLGWLQ 911
Cdd:cd16242   153 -ISAAHFLDWLK 163

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  286 LQSFDRAMDQFLAFLSETETLCENAE-----SDIERNPLMFKDLQSEIETHRVVYDRLDGTGRKLLGSltSQEDAVMLQR 360
Cdd:cd00176     2 LQQFLRDADELEAWLSEKEELLSSTDygddlESVEALLKKHEALEAELAAHEERVEALNELGEQLIEE--GHPDAEEIQE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  361 RLDEMNQRWNNLKSKSIAIRNRLESNSEHWNaLLLSLRELTEWVIRKDTELSTLGLGPvrgDAVSLQKQLDDHKAFRRQL 440
Cdd:cd00176    80 RLEELNQRWEELRELAEERRQRLEEALDLQQ-FFRDADDLEQWLEEKEAALASEDLGK---DLESVEELLKKHKELEEEL 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  441 EDKRPIVESNLTSGRQYIaneaavsdtsdteanhdsdsrymsaEEQSRELTRSIRREVGKLSEQWNNLIDRSDNWKHRLD 520
Cdd:cd00176   156 EAHEPRLKSLNELAEELL-------------------------EEGHPDADEEIEEKLEELNERWEELLELAEERQKKLE 210

                  ...
gi 442619934  521 EYM 523
Cdd:cd00176   211 EAL 213

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 442619934  678 KPPWERATTAANVPYYIDHERETTHWDHPEM 708
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  542 KMRQFQKILEDLSSRVALAEQTKTSWLPPSSVGEANEQMQQLQRLRDKMTTASALLDDCNEqqsffTANQVLVPTPCLS- 620
Cdd:cd00176     1 KLQQFLRDADELEAWLSEKEELLSSTDYGDDLESVEALLKKHEALEAELAAHEERVEALNE-----LGEQLIEEGHPDAe 75

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 442619934  621 ----KLEDLNTRMKLLQIAMDERQKVLCQAGAQQTH 652
Cdd:cd00176    76 eiqeRLEELNQRWEELRELAEERRQRLEEALDLQQF 111

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 442619934  745 SMSTACESFDRHGLRAQNDKLIDIPDMTTVLHSLYVTIDK-----IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGL 819
Cdd:cd16242     1 SLSTAIEAFDQHGLRAQNDKLIDVPDMITCLTTIYEALEEehptlVNVPLCVDLCLNWLLNVYDSGRSGKIRVLSFKVGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  820 VLLCKGHLEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGSNIEPSVRSCLEQAGISQEaidgnqdi 899
Cdd:cd16242    81 VLLCNAHLEEKYRYLFSLIADPNGCVDQRRLGLLLHDCIQIPRQLGEVAAFGGSNIEPSVRSCFEKAGEKPE-------- 152

                         170
                  ....*....|..
gi 442619934  900 sIELQHFLGWLQ 911
Cdd:cd16242   153 -ISAAHFLDWLK 163

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        40
                  ....*....|....*....|....*....|....*....|....*....
gi 442619934  936 AKCNICKEYPIVGFRYRCLKCFNFDMCQKCFFFGRNAKNHKLTHPMHEY 984
Cdd:cd02334     1 AKCNICKEFPITGFRYRCLKCFNYDLCQSCFFSGRTSKSHKNSHPMKEY 49

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  178 QRFEAKRLELEKWLARMEQRAERMGTIATTADIlEAQQKEQKSFHAELHQNKQHFDIFNELTQKLIAVYPnDDTTRIKKM 257
Cdd:cd00176     3 QQFLRDADELEAWLSEKEELLSSTDYGDDLESV-EALLKKHEALEAELAAHEERVEALNELGEQLIEEGH-PDAEEIQER 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  258 TEVINQRYANLNSGVINRGKQLHAAvHSLQSFDRAMDQFLAFLSETETLC---------ENAESDIERnplmFKDLQSEI 328
Cdd:cd00176    81 LEELNQRWEELRELAEERRQRLEEA-LDLQQFFRDADDLEQWLEEKEAALasedlgkdlESVEELLKK----HKELEEEL 155

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 442619934  329 ETHRVVYDRLDGTGRKLLGSLTSQEDAVmLQRRLDEMNQRWNNLKSKSIAIRNRLES 385
Cdd:cd00176   156 EAHEPRLKSLNELAEELLEEGHPDADEE-IEEKLEELNERWEELLELAEERQKKLEE 211

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        40
                   ....*....|....*....|....*....|....*....|....
gi 442619934   933 KHQAKCNICKEYPIVGFRYRCLKCFNFDMCQKCfFFGRNAKNHK 976
Cdd:pfam00569    2 HKVYTCNGCSNDPSIGVRYHCLRCSDYDLCQSC-FQTHKGGNHQ 44

Spectrin repeats;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934    178 QRFEAKRLELEKWLARMEQRAERMGtIATTADILEAQQKEQKSFHAELHQNKQHFDIFNELTQKLIAVYPnDDTTRIKKM 257
Cdd:smart00150    1 QQFLRDADELEAWLEEKEQLLASED-LGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGH-PDAEEIEER 78

                            90       100
                    ....*....|....*....|..
gi 442619934    258 TEVINQRYANLNSGVINRGKQL 279
Cdd:smart00150   79 LEELNERWEELKELAEERRQKL 100

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 442619934  678 KPPWERATTAANVPYYIDHERETTHWDHPEM 708
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.

                           10        20
                   ....*....|....*....|....*...
gi 442619934   679 PPWERATTAANVPYYIDHERETTHWDHP 706
Cdd:pfam00397    3 PGWEERWDPDGRVYYYNHETGETQWEKP 30

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934   284 HSLQSFDRAMDQFLAFLSETETLceNAESDIERNP-----LM--FKDLQSEIETHRVVYDRLDGTGRKLLGSLTSQEDAV 356
Cdd:pfam00435    1 LLLQQFFRDADDLESWIEEKEAL--LSSEDYGKDLesvqaLLkkHKALEAELAAHQDRVEALNELAEKLIDEGHYASEEI 78

                           90       100
                   ....*....|....*....|....*...
gi 442619934   357 mlQRRLDEMNQRWNNLKSKSIAIRNRLE 384
Cdd:pfam00435   79 --QERLEELNERWEQLLELAAERKQKLE 104

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  542 KMRQFQKILEDLSSRVALAEQTKTSWLPPSSVGEANEQMQQLQRLRDKMTTASALLDDCNEqqsffTANQVLVPTPCLS- 620
Cdd:cd00176     1 KLQQFLRDADELEAWLSEKEELLSSTDYGDDLESVEALLKKHEALEAELAAHEERVEALNE-----LGEQLIEEGHPDAe 75

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 442619934  621 ----KLEDLNTRMKLLQIAMDERQKVLCQAGAQQTH 652
Cdd:cd00176    76 eiqeRLEELNQRWEELRELAEERRQRLEEALDLQQF 111

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 442619934  745 SMSTACESFDRHGLRAQNDKLIDIPDMTTVLHSLYVTIDK-----IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGL 819
Cdd:cd16242     1 SLSTAIEAFDQHGLRAQNDKLIDVPDMITCLTTIYEALEEehptlVNVPLCVDLCLNWLLNVYDSGRSGKIRVLSFKVGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  820 VLLCKGHLEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGSNIEPSVRSCLEQAGISQEaidgnqdi 899
Cdd:cd16242    81 VLLCNAHLEEKYRYLFSLIADPNGCVDQRRLGLLLHDCIQIPRQLGEVAAFGGSNIEPSVRSCFEKAGEKPE-------- 152

                         170
                  ....*....|..
gi 442619934  900 sIELQHFLGWLQ 911
Cdd:cd16242   153 -ISAAHFLDWLK 163

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 442619934  746 MSTACESFDRHGLRAQNDKLIDIPDMTTVLHSLYVTIDK-----IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGLV 820
Cdd:cd15901     2 LSTVLSVFDRHGLSGSQDSVLDCEELETILTELYIKLNKrrpdlIDVPRASDLLLNWLLNLYDRNRTGCIRLLSVKIALI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  821 LLCKGHLEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGSNIEPSVRSCLEQAGISQEaidgnqdis 900
Cdd:cd15901    82 TLCAASLLDKYRYLFGQLADSSGFISRERLTQFLQDLLQIPDLIGESPAFGGHNVEAAVESCFQLARSRVG--------- 152

                         170
                  ....*....|.
gi 442619934  901 IELQHFLGWLQ 911
Cdd:cd15901   153 VSEDTFLSWLL 163

EF hand; Members of this family adopt a helix-loop-helix motif, as per other EF hand domains. However, since they do not contain the canonical pattern of calcium binding residues found in many EF hand domains, they do not bind calcium ions. The main function of this domain is the provision of specificity in beta-dystroglycan recognition, though in dystrophin it serves an additional role: stabilization of the WW domain (pfam00397), enhancing dystroglycan binding.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934   709 IELMKGLADLNEIRFSAYRTAMKLRSVQKRLALDRISMSTACESFDRHGLRA-QNDKLIDIPDMTTVLHSLYVTIDK--- 784
Cdd:pfam09068    1 TELMQELQDFNNIRFAAYRTAMKLRALQKRLNLDLVDLWNLIEAFDEHGLNSlENDLLLSVSELEALLSSIYFALNKrkp 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 442619934   785 ----IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGLVLLC 823
Cdd:pfam09068   81 tthqINVPLSVDLLLNWLLNVYDPERTGKIRVLSFKVALATLC 123

EF-hand; Members of this family adopt a helix-loop-helix motif, as per other EF hand domains. However, since they do not contain the canonical pattern of calcium binding residues found in many EF hand domains, they do not bind calcium ions. The main function of this domain is the provision of specificity in beta-dystroglycan recognition, though in dystrophin it serves an additional role: stabilization of the WW domain (pfam00397), enhancing dystroglycan binding.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934   827 LEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGsnIEPSVRSCLEQAGISQEaidgnqdisIELQHF 906
Cdd:pfam09069    1 LVDKYRYLFSQISDSNGLLDQSKLGLLLHELLQLPRQVGEVPAFGG--IEPSVRSCFEQVGGKPK---------ITLNHF 69

                           90       100
                   ....*....|....*....|
gi 442619934   907 LGWLQHEPQSLVWLPVLHRL 926
Cdd:pfam09069   70 LDWLMSEPQSLVWLPVLHRL 89

EF-hand-like motif found in Drosophila melanogaster discontinuous actin hexagon (DAH) and similar proteins; DAH, the product of the dah (discontinuous actin hexagon) gene, is a Drosophila homolog to vertebrate dystrotelin. It is tightly membrane-associated and highly phosphorylated in a time-dependent fashion. DAH plays an essential role in the process of cellularization, and is associated with vesicles that convene at the cleavage furrow. The absence of DAH leads the severe disruption of the cleavage furrows around the nuclei and development stalls. DAH 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  745 SMSTACESFDRHGLR-AQNDKLIDIPDMTTVLHSLYVTIDK-----IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVG 818
Cdd:cd16245     1 PLKLIMGVFDRHQLSnSENNLCLPPDELEAVLHDIYFAAEKlgnfnIDVDLATELLANLFLNVFDPERKKSISVLELKVF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 442619934  819 LVLLCKGHLEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGSNIEPSVRSCLEQ 885
Cdd:cd16245    81 LTLLCGSSLQEKYLYLFQLLADHNNCVSRKRLEALLKSLAKLLSYLGEDVAFGSHLIELAVEQCFEN 147

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  178 QRFEAKRLELEKWLARMEQRAERMGTIATTADIlEAQQKEQKSFHAELHQNKQHFDIFNELTQKLIAVYPnDDTTRIKKM 257
Cdd:cd00176     3 QQFLRDADELEAWLSEKEELLSSTDYGDDLESV-EALLKKHEALEAELAAHEERVEALNELGEQLIEEGH-PDAEEIQER 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  258 TEVINQRYANLNSGVINRGKQLHAAvHSLQSFDRAMDQFLAFLSETETLC---------ENAESDIERnplmFKDLQSEI 328
Cdd:cd00176    81 LEELNQRWEELRELAEERRQRLEEA-LDLQQFFRDADDLEQWLEEKEAALasedlgkdlESVEELLKK----HKELEEEL 155

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 442619934  329 ETHRVVYDRLDGTGRKLLGSLTSQEDAVmLQRRLDEMNQRWNNLKSKSIAIRNRLES 385
Cdd:cd00176   156 EAHEPRLKSLNELAEELLEEGHPDADEE-IEEKLEELNERWEELLELAEERQKKLEE 211

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 442619934  751 ESFDRHGLRAQNDKL-IDIPDMTTVLHSLYVTIDK-------IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGLVLL 822
Cdd:cd16244     7 EAFRENGLNTLDPTTeLSVSRLETLLSSIYYQLNKrlptthqIDVDQSISLLLNWLLAAYDPEATGRLTVFSVKVALSTL 86

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 442619934  823 CKGHLEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGSniEPSVRSCLEQ 885
Cdd:cd16244    87 CAGKLVDKLRYIFSQISDSNGVLVFSKFEDFLREALKLPTAVFEGPSFGYN--ESAARSCFPG 147

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  802 YDSQRTGQIRVLSFKVGLVLLCKGHLEEKYRYLFRLVA----DTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGgsNIEP 877
Cdd:cd16243    62 YDREQTGFVSLRSVEAALIALSGDTLSAKYRALFQLYEsgqgGSSGSITRSGLRVLLQDLSQIPAVVQESHVFG--NVET 139

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 442619934  878 SVRSCLEQ---AGISQEaidgnqdisielqHFLGWLQ 911
Cdd:cd16243   140 AVRSCFSGvltASISEE-------------HFLSWLQ 163

Zinc finger, ZZ type. Zinc finger present in dystrophin, CBP/p300 and many other proteins. The ZZ motif coordinates one or two zinc ions and most likely participates in ligand binding or molecular scaffolding. Many proteins containing ZZ motifs have other zinc-binding motifs as well, and the majority serve as scaffolds in pathways involving acetyltransferase, protein kinase, or ubiqitin-related activity. ZZ proteins can be grouped into the following functional classes: chromatin modifying, cytoskeletal scaffolding, ubiquitin binding or conjugating, and membrane receptor or ion-channel modifying proteins.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 442619934  938 CNICKEyPIVGFRYRCLKCFNFDMCQKCFFfgRNAKNHKLTHPM 981
Cdd:cd02249     3 CDGCLK-PIVGVRYHCLVCEDFDLCSSCYA--KGKKGHPPDHSF 43

Zinc finger, ZZ type. Zinc finger present in potassium channel modulatory factor (PCMF) 1 and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Human potassium channel modulatory factor 1 or FIGC has been shown to possess intrinsic E3 ubiquitin ligase activity and to promote ubiquitination.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 442619934  938 CNICKEYPIVGFRYRCLKCFNFDMCQKCFFFGRNAKNHKLTHPM 981
Cdd:cd02338     3 CDGCGKSNFTGRRYKCLICYDYDLCADCYDSGVTTERHLFDHPM 46

Spectrin repeats;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934    178 QRFEAKRLELEKWLARMEQRAERMGtIATTADILEAQQKEQKSFHAELHQNKQHFDIFNELTQKLIAVYPnDDTTRIKKM 257
Cdd:smart00150    1 QQFLRDADELEAWLEEKEQLLASED-LGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGH-PDAEEIEER 78

                            90       100
                    ....*....|....*....|..
gi 442619934    258 TEVINQRYANLNSGVINRGKQL 279
Cdd:smart00150   79 LEELNERWEELKELAEERRQKL 100

EF-hand-like motif found in alpha-dystrobrevin; Alpha-dystrobrevin, also termed dystrobrevin alpha (DTN-A), or dystrophin-related protein 3 (DRP-3), is the mammalian ortholog of the Torpedo 87 kDa postsynaptic protein that tightly associates with dystrophin. It is a cytoplasmic protein expressed predominantly in skeletal muscle, heart, lung, and brain. Alpha-dystrobrevin has been implicated in the regulation of acetylcholine receptor (AChR) aggregate density and patterning. It is also essential in the pathogenesis of dystrophin-dependent muscular dystrophies. It plays a critical role in the full functionality of dystrophin through increasing dystrophin's binding to the dystrophin-glycoprotein complex (DGC), and provides protection during cardiac stress. Alpha-dystrobrevin binds to the intermediate filament proteins syncoilin and beta-synemin, thereby linking the dystrophin-associated protein complex (DAPC) to the intermediate filament network. Moreover, alpha-dystrobrevin involves in cell signaling via interaction with other proteins such as syntrophin, a modular adaptor protein that coordinates the assembly of the signaling proteins nitric oxide synthase, stress-activated protein kinase-3, and Grb2 to the DAPC. Furthermore, alpha-dystrobrevin plays an important role in muscle function, as well as in nuclear morphology maintenance through specific interaction with the nuclear lamina component lamin B1. In addition, alpha-dystrobrevin is required in dystrophin-associated protein scaffolding in brain. Absence of glial alpha-dystrobrevin causes abnormalities of the blood-brain barrier and progressive brain edema. Alpha-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, alpha-dystrobrevin contain two syntrophin binding sites (SBSs).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619934  771 MTTVLHSL---YVTIDKIDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGLVLLCKGHLEEKYRYLFRLVADTDRRADQ 847
Cdd:cd16249    32 LSTIFYQLnkrMPTTHQINVEQSISLLLNFLLAAFDPEGHGKISVFAVKMALATLCGGKIMDKLRYIFSMISDSNGVMVY 111

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 442619934  848 RRLGLLLHDCIQVPRQLGEVAAFGGSniEPSVRSCLEQ 885
Cdd:cd16249   112 GRYDQFLREVLKLPTAVFEGPSFGYT--EQSARSCFSQ 147

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 442619934  678 KPPWERATTAANVPYYIDHERETTHWDHPEM 708
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

Zinc finger, ZZ type. Zinc finger present in Drosophila dah and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Dah (discontinuous actin hexagon) is a membrane associated protein essential for cortical furrow formation in Drosophila.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 442619934  938 CNICKEYPIVGFRYRCLKCFNFDMCQKCFFFGRNAKNHKLTHPMHE 983
Cdd:cd02345     3 CSACRKQDISGIRFPCQVCRDYSLCLGCYTKGRETKRHNSLHIMYE 48

Zinc finger, ZZ type. Zinc finger present in ADA2, a putative transcriptional adaptor, and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 442619934  937 KCNICKEYPIVGFRYRCLKCFNFDMCQKCFFFGRNAKNHKLTHP 980
Cdd:cd02335     2 HCDYCSKDITGTIRIKCAECPDFDLCLECFSAGAEIGKHRNDHN 45