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 568965359 437 ELNTTNEVFKQHKLNQNDQLLSVPDVINCLTTTYDGLEQLHKDLVNVPLCVDMCLNWLLNVYDTGRTGKIRVQSLKIGLM 516
Cdd:cd16247    1 DLNTTHSVFKQHKLTQNDQLLSVPDVINCLTTIYDGLEQKHKDLVNVPLCVDMCLNWLLNVYDTGRTGKIRVLSLKIGLM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 517 SLSKGLLEEKYRCLFKEVAGPTEMCDQRQLGLLLHDAIQIPRQLGEVAAFGGSNIEPSVRSCFQQNNNKPEISVKEFIDW 596
Cdd:cd16247   81 SLSKGLLEEKYRYLFKEVAGPGDTCDQRQLGLLLHDAIQIPRQLGEVAAFGGSNIEPSVRSCFQHANNKPEIDVKQFIDW 160

                 ..
gi 568965359 597 MH 598
Cdd:cd16247  161 MR 162

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 568965359  44 QKLCKDIQAEIDAHNDIFKSIDGNRQKMVKAlgNSEEATMLQHRLDDMNQRWNDLKAKSASIRAHLEASAEKWnRLLASL 123
Cdd:cd00176   39 LKKHEALEAELAAHEERVEALNELGEQLIEE--GHPDAEEIQERLEELNQRWEELRELAEERRQRLEEALDLQ-QFFRDA 115

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 124 EELIKWLNMKDEELkKQMPIGGDVPALQLQYDHCKVLRRELKEKEYSVLNAVDQARVFLADQPIEAPEEprrnpqsktel 203
Cdd:cd00176  116 DDLEQWLEEKEAAL-ASEDLGKDLESVEELLKKHKELEEELEAHEPRLKSLNELAEELLEEGHPDADEE----------- 183

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 568965359 204 tpeeraqkiakaMRKQSSEVREKWENLNAVTSNWQKQVGKAL 245
Cdd:cd00176  184 ------------IEEKLEELNERWEELLELAEERQKKLEEAL 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
                 ....*....|....*....|....*....
gi 568965359 372 PWQRSISHNKVPYYINHQTQTTCWDHPKM 400
Cdd:cd00201    3 GWEERWDPDGRVYYYNHNTKETQWEDPRE 31

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 568965359 437 ELNTTNEVFKQHKLNQNDQLLSVPDVINCLTTTYDGLEQLHKDLVNVPLCVDMCLNWLLNVYDTGRTGKIRVQSLKIGLM 516
Cdd:cd16247    1 DLNTTHSVFKQHKLTQNDQLLSVPDVINCLTTIYDGLEQKHKDLVNVPLCVDMCLNWLLNVYDTGRTGKIRVLSLKIGLM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 517 SLSKGLLEEKYRCLFKEVAGPTEMCDQRQLGLLLHDAIQIPRQLGEVAAFGGSNIEPSVRSCFQQNNNKPEISVKEFIDW 596
Cdd:cd16247   81 SLSKGLLEEKYRYLFKEVAGPGDTCDQRQLGLLLHDAIQIPRQLGEVAAFGGSNIEPSVRSCFQHANNKPEIDVKQFIDW 160

                 ..
gi 568965359 597 MH 598
Cdd:cd16247  161 MR 162

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 568965359 623 AKCNICKECPIVGFRYRSLKHFNYDVCQSCFFSGRTAKGHKLHYPMVEY 671
Cdd:cd02334    1 AKCNICKEFPITGFRYRCLKCFNYDLCQSCFFSGRTSKSHKNSHPMKEY 49

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 568965359  619 AKHQAKCNICKECPIVGFRYRSLKHFNYDVCQSCFFSgRTAKGHK 663
Cdd:pfam00569   1 IHKVYTCNGCSNDPSIGVRYHCLRCSDYDLCQSCFQT-HKGGNHQ 44

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 568965359 247 KLRDLQGAMDDLDADMKEVEAVRNGWKPVGDLliDSLQDHIEKTLAFREEIAPINLKVKTMNDLSSQLSPLDLHPSLKMS 326
Cdd:cd00176    1 KLQQFLRDADELEAWLSEKEELLSSTDYGDDL--ESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQ 78

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568965359 327 RQLDDLNMRWKLLQVSVDDRLKQLQEAHRDFGPSSQH 363
Cdd:cd00176   79 ERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDA 115

Spectrin repeats;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568965359    44 QKLCKDIQAEIDAHNDIFKSIDGNRQKMVKAlgNSEEATMLQHRLDDMNQRWNDLKAKSASIRAHLE 110
Cdd:smart00150  37 LKKHEAFEAELEAHEERVEALNELGEQLIEE--GHPDAEEIEERLEELNERWEELKELAEERRQKLE 101

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                           10        20        30
                   ....*....|....*....|....*....|...
gi 568965359   368 SVQLPWQRSISHNKVPYYINHQTQTTCWDHPKM 400
Cdd:smart00456   1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33

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 568965359  246 EKLRDLQGAMDDLDADMKEVEAVRNgWKPVGDLLiDSLQDHIEKTLAFREEIAPINLKVKTMNDLSSQLSPLDLHPSLKM 325
Cdd:pfam00435   1 LLLQQFFRDADDLESWIEEKEALLS-SEDYGKDL-ESVQALLKKHKALEAELAAHQDRVEALNELAEKLIDEGHYASEEI 78

                          90       100
                  ....*....|....*....|....*..
gi 568965359  326 SRQLDDLNMRWKLLQVSVDDRLKQLQE 352
Cdd:pfam00435  79 QERLEELNERWEQLLELAAERKQKLEE 105

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568965359   44 QKLCKDIQAEIDAHNDIFKSIDGNRQKMVKALGNSEEAtmLQHRLDDMNQRWNDLKAKSASIRAHLEA 111
Cdd:pfam00435  40 LKKHKALEAELAAHQDRVEALNELAEKLIDEGHYASEE--IQERLEELNERWEQLLELAAERKQKLEE 105

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 568965359 437 ELNTTNEVFKQHKLNQNDQLLSVPDVINCLTTTYDGLEQLHKDLVNVPLCVDMCLNWLLNVYDTGRTGKIRVQSLKIGLM 516
Cdd:cd16247    1 DLNTTHSVFKQHKLTQNDQLLSVPDVINCLTTIYDGLEQKHKDLVNVPLCVDMCLNWLLNVYDTGRTGKIRVLSLKIGLM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 517 SLSKGLLEEKYRCLFKEVAGPTEMCDQRQLGLLLHDAIQIPRQLGEVAAFGGSNIEPSVRSCFQQNNNKPEISVKEFIDW 596
Cdd:cd16247   81 SLSKGLLEEKYRYLFKEVAGPGDTCDQRQLGLLLHDAIQIPRQLGEVAAFGGSNIEPSVRSCFQHANNKPEIDVKQFIDW 160

                 ..
gi 568965359 597 MH 598
Cdd:cd16247  161 MR 162

EF-hand-like motif found in dystrophin; 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. It involves in maintaining the structural integrity of cells, as well as in the formation of the blood-brain barrier (BBB). The dystrophin 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, dystrophin contains two syntrophin binding sites (SBSs) and a long N-terminal extension that comprises two actin-binding calponin homology (CH) domains, approximately 24 spectrin repeats (SRs) and a WW domain. Mutations in dystrophin lead to Duchenne muscular dystrophy (DMD). Moreover, dystrophin deficiency is associated abnormal cerebral diffusion and perfusion, acute Trypanosoma cruzi infection.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 443 EVFKQHKLNQNDQLLSVPDVINCLTTTYDGLEQLHKDLVNVPLCVDMCLNWLLNVYDTGRTGKIRVQSLKIGLMSLSKGL 522
Cdd:cd16246    7 EALDQHNLKQNDQPMDILQIINCLTTIYDRLEQEHNNLVNVPLCVDMCLNWLLNVYDTGRTGRIRVLSFKTGIISLCKAH 86

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568965359 523 LEEKYRCLFKEVAGPTEMCDQRQLGLLLHDAIQIPRQLGEVAAFGGSNIEPSVRSCFQQNNNKPEISVKEFIDWM 597
Cdd:cd16246   87 LEDKYRYLFKQVASSTGFCDQRRLGLLLHDAIQIPRQLGEVASFGGSNIEPSVRSCFQFANNKPEIEAALFLDWM 161

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 568965359 437 ELNTTNEVFKQHKLNQ-NDQLLSVPDVINCLTTTYDGLEQLHKDLVNVPLCVDMCLNWLLNVYDTGRTGKIRVQSLKIGL 515
Cdd:cd15901    1 DLSTVLSVFDRHGLSGsQDSVLDCEELETILTELYIKLNKRRPDLIDVPRASDLLLNWLLNLYDRNRTGCIRLLSVKIAL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 516 MSLSKGLLEEKYRCLFKEVAGPTEMCDQRQLGLLLHDAIQIPRQLGEVAAFGGSNIEPSVRSCFQQNNNKPEISVKEFID 595
Cdd:cd15901   81 ITLCAASLLDKYRYLFGQLADSSGFISRERLTQFLQDLLQIPDLIGESPAFGGHNVEAAVESCFQLARSRVGVSEDTFLS 160

                 ..
gi 568965359 596 WM 597
Cdd:cd15901  161 WL 162

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 568965359  523 LEEKYRCLFKEVAGPTEMCDQRQLGLLLHDAIQIPRQLGEVAAFGGsnIEPSVRSCFQQNNNKPEISVKEFIDWMHLEPQ 602
Cdd:pfam09069   1 LVDKYRYLFSQISDSNGLLDQSKLGLLLHELLQLPRQVGEVPAFGG--IEPSVRSCFEQVGGKPKITLNHFLDWLMSEPQ 78

                          90
                  ....*....|..
gi 568965359  603 SMVWLPVLHRVA 614
Cdd:pfam09069  79 SLVWLPVLHRLA 90

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 568965359  44 QKLCKDIQAEIDAHNDIFKSIDGNRQKMVKAlgNSEEATMLQHRLDDMNQRWNDLKAKSASIRAHLEASAEKWnRLLASL 123
Cdd:cd00176   39 LKKHEALEAELAAHEERVEALNELGEQLIEE--GHPDAEEIQERLEELNQRWEELRELAEERRQRLEEALDLQ-QFFRDA 115

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 124 EELIKWLNMKDEELkKQMPIGGDVPALQLQYDHCKVLRRELKEKEYSVLNAVDQARVFLADQPIEAPEEprrnpqsktel 203
Cdd:cd00176  116 DDLEQWLEEKEAAL-ASEDLGKDLESVEELLKKHKELEEELEAHEPRLKSLNELAEELLEEGHPDADEE----------- 183

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 568965359 204 tpeeraqkiakaMRKQSSEVREKWENLNAVTSNWQKQVGKAL 245
Cdd:cd00176  184 ------------IEEKLEELNERWEELLELAEERQKKLEEAL 213

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 568965359 443 EVFKQHKLNQND--QLLSVPDVINCLTTTYdglEQLHKDL-----VNVPLCVDMCLNWLLNVYDTGRTGKIRVQSLKIGL 515
Cdd:cd16244    7 EAFRENGLNTLDptTELSVSRLETLLSSIY---YQLNKRLptthqIDVDQSISLLLNWLLAAYDPEATGRLTVFSVKVAL 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 516 MSLSKGLLEEKYRCLFKEVAGPTEMCDQRQLGLLLHDAIQIPRQLGEVAAFGGSniEPSVRSCFQQNNnkpEISVKEFID 595
Cdd:cd16244   84 STLCAGKLVDKLRYIFSQISDSNGVLVFSKFEDFLREALKLPTAVFEGPSFGYN--ESAARSCFPGQS---KVTVNDFLD 158

                 ..
gi 568965359 596 WM 597
Cdd:cd16244  159 VM 160

Zinc-binding domain, present in Dystrophin, CREB-binding protein; Putative zinc-binding domain present in dystrophin-like proteins, and CREB-binding protein/p300 homologues. The ZZ in dystrophin appears to bind calmodulin. A missense mutation of one of the conserved cysteines in dystrophin results in a patient with Duchenne muscular dystrophy.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 568965359   620 KHQAKCNICKEcPIVGFRYRSLKHFNYDVCQSCFFSGRTAKGHK 663
Cdd:smart00291   2 HHSYSCDTCGK-PIVGVRYHCLVCPDYDLCQSCFAKGSAGGEHS 44

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 568965359 494 LLNVYDTGRTGKIRVQSLKIGLMSLSKGLLEEKYRCLFK----EVAGPTEMCDQRQLGLLLHDAIQIPRQLGEVAAFGgs 569
Cdd:cd16243   58 LFRLYDREQTGFVSLRSVEAALIALSGDTLSAKYRALFQlyesGQGGSSGSITRSGLRVLLQDLSQIPAVVQESHVFG-- 135

                         90       100
                 ....*....|....*....|....*...
gi 568965359 570 NIEPSVRSCFQQNNNkPEISVKEFIDWM 597
Cdd:cd16243  136 NVETAVRSCFSGVLT-ASISEEHFLSWL 162

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 568965359 443 EVFKQHKLNQND--QLLSVPDVINCLTTTYdglEQLHKDL-----VNVPLCVDMCLNWLLNVYDTGRTGKIRVQSLKIGL 515
Cdd:cd16249    7 EALRENALNNLDpnTELNVARLEAVLSTIF---YQLNKRMptthqINVEQSISLLLNFLLAAFDPEGHGKISVFAVKMAL 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 516 MSLSKGLLEEKYRCLFKEVAGPTEMCDQRQLGLLLHDAIQIPRQLGEVAAFGGSniEPSVRSCFQQnnnKPEISVKEFID 595
Cdd:cd16249   84 ATLCGGKIMDKLRYIFSMISDSNGVMVYGRYDQFLREVLKLPTAVFEGPSFGYT--EQSARSCFSQ---QKKVTLNGFLD 158

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 568965359 443 EVFKQHKLNQNDQL--LSVPDVINCLTTTYdglEQLHKDL-----VNVPLCVDMCLNWLLNVYDTGRTGKIRVQSLKIGL 515
Cdd:cd16250    7 EAFRDNGLNTLDHSteISVSRLETIISSIY---YQLNKRLpsthqISVEQSISLLLNFMIAAYDSEGHGKLTVFSVKAML 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 516 MSLSKGLLEEKYRCLFKEVAGPTEMCDQRQLGLLLHDAIQIPRQLGEVAAFGGSniEPSVRSCFQQnnnKPEISVKEFID 595
Cdd:cd16250   84 ATMCGGKILDKLRYTFSQMSDSNGLMIFLKFDQFLREVLKLPTAVFEGPSFGYT--EHSVRTCFPQ---QKKIMLNMFLD 158

                 ..
gi 568965359 596 WM 597
Cdd:cd16250  159 TM 160

Spectrin repeats;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568965359    44 QKLCKDIQAEIDAHNDIFKSIDGNRQKMVKAlgNSEEATMLQHRLDDMNQRWNDLKAKSASIRAHLE 110
Cdd:smart00150  37 LKKHEAFEAELEAHEERVEALNELGEQLIEE--GHPDAEEIEERLEELNERWEELKELAEERRQKLE 101

Spectrin repeats;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359   251 LQGAMDDLDADMKEVEAVRNGWKPVGDLliDSLQDHIEKTLAFREEIAPINLKVKTMNDLSSQLSPLDLHPSLKMSRQLD 330
Cdd:smart00150   3 FLRDADELEAWLEEKEQLLASEDLGKDL--ESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERLE 80

                           90       100
                   ....*....|....*....|.
gi 568965359   331 DLNMRWKLLQVSVDDRLKQLQ 351
Cdd:smart00150  81 ELNERWEELKELAEERRQKLE 101

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 568965359  372 PWQRSISHNKVPYYINHQTQTTCWDHP 398
Cdd:pfam00397   4 GWEERWDPDGRVYYYNHETGETQWEKP 30

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 568965359 625 CNICKECPIVGFRYRSLKHFNYDVCQSCFFSGRTAKGHKLHYPM 668
Cdd:cd02338    3 CDGCGKSNFTGRRYKCLICYDYDLCADCYDSGVTTERHLFDHPM 46

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359    78 SEEATMLQHRLDDMNQRWNDLKAKSASIRAH------------------------LEASAEKWNRLLASLEELIKWLNMK 133
Cdd:TIGR02169  673 PAELQRLRERLEGLKRELSSLQSELRRIENRldelsqelsdasrkigeiekeieqLEQEEEKLKERLEELEEDLSSLEQE 752

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359   134 DEELKKQMP-IGGDVPALQLQ-----------YDHCKVLRRELKEKEYSVLNAVdQARVFLADQPIEAPEEPRrnpQSKT 201
Cdd:TIGR02169  753 IENVKSELKeLEARIEELEEDlhkleealndlEARLSHSRIPEIQAELSKLEEE-VSRIEARLREIEQKLNRL---TLEK 828

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359   202 ELTPEERAQKIAK--AMRKQSSEVREKWENLN-------AVTSNWQKQVGKALEKLRDLQGAMDDLDADMKEVEAVRNGW 272
Cdd:TIGR02169  829 EYLEKEIQELQEQriDLKEQIKSIEKEIENLNgkkeeleEELEELEAALRDLESRLGDLKKERDELEAQLRELERKIEEL 908

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359   273 KPVGDLLIDSLQDHIEKTLAFREEIAPINLKVKTMNDLSSQLSPLdlhPSLKMSRQ--------LDDLNMRWKLLQVSVD 344
Cdd:TIGR02169  909 EAQIEKKRKRLSELKAKLEALEEELSEIEDPKGEDEEIPEEELSL---EDVQAELQrveeeiraLEPVNMLAIQEYEEVL 985

                          330
                   ....*....|
gi 568965359   345 DRLKQLQEAH 354
Cdd:TIGR02169  986 KRLDELKEKR 995

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359    40 SPRYQKLCKDIQAEIDAHNDIFKSIDGNRQKMVKALGN-SEEATMLQHRLDDMNQRWNDLKaksasirahleasaEKWNR 118
Cdd:TIGR00618  523 PGPLTRRMQRGEQTYAQLETSEEDVYHQLTSERKQRASlKEQMQEIQQSFSILTQCDNRSK--------------EDIPN 588

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359   119 LLASLEELIKWLNMKDEELKKQMpiggdvpalqlqydhcKVLRRELKEKEYsvlnAVDQARVFLADQPIEAPEEPRRNPQ 198
Cdd:TIGR00618  589 LQNITVRLQDLTEKLSEAEDMLA----------------CEQHALLRKLQP----EQDLQDVRLHLQQCSQELALKLTAL 648

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359   199 SKTELT-PEERAQKIAKAMRKQSSEVREKWENLNAVTSNWQKQVGKALEKLRDLQGAMDDLDADMKEVEAVRNGWKPVGD 277
Cdd:TIGR00618  649 HALQLTlTQERVREHALSIRVLPKELLASRQLALQKMQSEKEQLTYWKEMLAQCQTLLRELETHIEEYDREFNEIENASS 728

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359   278 LLIDSLQ---DHIEKTLAFREEIAPINLKVKTMNDL-SSQLSPLDLHPSLKMSRQLDDLNMRWKLLQVSVDDrLKQLQEA 353
Cdd:TIGR00618  729 SLGSDLAareDALNQSLKELMHQARTVLKARTEAHFnNNEEVTAALQTGAELSHLAAEIQFFNRLREEDTHL-LKTLEAE 807

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|.
gi 568965359   354 HRDFGPSSQHFLSTSVQLPWQRSIS-HNKVPyyINHQTQTT 393
Cdd:TIGR00618  808 IGQEIPSDEDILNLQCETLVQEEEQfLSRLE--EKSATLGE 846

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359    22 SLQKVVVLLHRLQRMAVSSPRYQKLCKDIQAEIDAhndIFKSIDGNRQKMVKAlgnSEEATMLQHRLDDMNQRWNDLKAK 101
Cdd:TIGR02168  230 LVLRLEELREELEELQEELKEAEEELEELTAELQE---LEEKLEELRLEVSEL---EEEIEELQKELYALANEISRLEQQ 303

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359   102 SASIR-----------------AHLEASAEKWNRLLASLEELIKWLNMKDEELKKQMP-IGGDVPALQLQYDHCKVLRRE 163
Cdd:TIGR02168  304 KQILRerlanlerqleeleaqlEELESKLDELAEELAELEEKLEELKEELESLEAELEeLEAELEELESRLEELEEQLET 383

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359   164 LKEKEYSVLNAVDQ--ARVFLADQPIEAPEEPRRNPQSKTELTPEERAQKIAKAMRKQSSEVREKWENLNAVTSNWQKQV 241
Cdd:TIGR02168  384 LRSKVAQLELQIASlnNEIERLEARLERLEDRRERLQQEIEELLKKLEEAELKELQAELEELEEELEELQEELERLEEAL 463

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568965359   242 GKALEKLRDLQGAMDDLDADMKEVEAvrngwkpvgdlLIDSLQDHIEKTLAFREEIAPINLKVKTMNDLSSQLS 315
Cdd:TIGR02168  464 EELREELEEAEQALDAAERELAQLQA-----------RLDSLERLQENLEGFSEGVKALLKNQSGLSGILGVLS 526

chromosome segregation protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 101 KSASIRAHLEASAEKWNRLLASLEELIKWLNMKDEELKKQMPI--GGDVPALQLQYDHCKVLRRELKEKEysvlnaVDQA 178
Cdd:PRK01156 466 KSNHIINHYNEKKSRLEEKIREIEIEVKDIDEKIVDLKKRKEYleSEEINKSINEYNKIESARADLEDIK------IKIN 539

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 179 RvfLADQPIEApeeprrnpqskTELTPEERAQKIAKAMRKqssevREKWENLNAVTS-----NWQKQVGKALEKLRDLQG 253
Cdd:PRK01156 540 E--LKDKHDKY-----------EEIKNRYKSLKLEDLDSK-----RTSWLNALAVISlidieTNRSRSNEIKKQLNDLES 601

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568965359 254 AMDDLDADM---------------KEVEAVRNGWKPVGDL--LIDSLQDHIEKtlaFREEIAPINLKVKTMNDLSSQLSp 316
Cdd:PRK01156 602 RLQEIEIGFpddksyidksireieNEANNLNNKYNEIQENkiLIEKLRGKIDN---YKKQIAEIDSIIPDLKEITSRIN- 677

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 568965359 317 lDLHPSLKMSR-QLDDLNM---RWKLLQVSVDDRLKQLQEAHRD 356
Cdd:PRK01156 678 -DIEDNLKKSRkALDDAKAnraRLESTIEILRTRINELSDRIND 720

Zinc finger, ZZ type. Zinc finger present in Drosophila ref(2)P, NBR1, Human sequestosome 1 and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Drosophila ref(2)P appears to control the multiplication of sigma rhabdovirus. NBR1 (Next to BRCA1 gene 1 protein) interacts with fasciculation and elongation protein zeta-1 (FEZ1) and calcium and integrin binding protein (CIB), and may function in cell signalling pathways. Sequestosome 1 is a phosphotyrosine independent ligand for the Lck SH2 domain and binds noncovalently to ubiquitin via its UBA domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 568965359 627 ICKEC--PIVGFRYRSLKHFNYDVCQSCffsgrTAKG-HKLHyPMV 669
Cdd:cd02340    2 ICDGCqgPIVGVRYKCLVCPDYDLCESC-----EAKGvHPEH-AML 41