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 442619930  473 SMSTACESFDRHGLRAQNDKLIDIPDMTTVLHSLYVTIDK-----IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGL 547
Cdd:cd16242     1 SLSTAIEAFDQHGLRAQNDKLIDVPDMITCLTTIYEALEEehptlVNVPLCVDLCLNWLLNVYDSGRSGKIRVLSFKVGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619930  548 VLLCKGHLEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGSNIEPSVRSCLEQAGISQEaidgnqdi 627
Cdd:cd16242    81 VLLCNAHLEEKYRYLFSLIADPNGCVDQRRLGLLLHDCIQIPRQLGEVAAFGGSNIEPSVRSCFEKAGEKPE-------- 152

                         170
                  ....*....|..
gi 442619930  628 sIELQHFLGWLQ 639
Cdd:cd16242   153 -ISAAHFLDWLK 163

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 442619930  406 KPPWERATTAANVPYYIDHERETTHWDHPEM 436
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

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 442619930   835 AAMDAEQREELEAIIRDLEEENANLQAE---YQQLCSKEQSGMPEDSNGMqhsSSSMTGLSGQGEQGQDMMAEAKLLRQH 911
Cdd:TIGR02168  833 IAATERRLEDLEEQIEELSEDIESLAAEieeLEELIEELESELEALLNER---ASLEEALALLRSELEELSEELRELESK 909

                           90       100       110
                   ....*....|....*....|....*....|.
gi 442619930   912 KGRLEARMQILEDHNRQLEAQLQRLRQLLDE 942
Cdd:TIGR02168  910 RSELRRELEELREKLAQLELRLEGLEVRIDN 940

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 442619930  473 SMSTACESFDRHGLRAQNDKLIDIPDMTTVLHSLYVTIDK-----IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGL 547
Cdd:cd16242     1 SLSTAIEAFDQHGLRAQNDKLIDVPDMITCLTTIYEALEEehptlVNVPLCVDLCLNWLLNVYDSGRSGKIRVLSFKVGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619930  548 VLLCKGHLEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGSNIEPSVRSCLEQAGISQEaidgnqdi 627
Cdd:cd16242    81 VLLCNAHLEEKYRYLFSLIADPNGCVDQRRLGLLLHDCIQIPRQLGEVAAFGGSNIEPSVRSCFEKAGEKPE-------- 152

                         170
                  ....*....|..
gi 442619930  628 sIELQHFLGWLQ 639
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 442619930  664 AKCNICKEYPIVGFRYRCLKCFNFDMCQKCFFFGRNAKNHKLTHPMHEY 712
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 442619930   661 KHQAKCNICKEYPIVGFRYRCLKCFNFDMCQKCfFFGRNAKNHK 704
Cdd:pfam00569    2 HKVYTCNGCSNDPSIGVRYHCLRCSDYDLCQSC-FQTHKGGNHQ 44

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

                            10        20        30
                    ....*....|....*....|....*....|...
gi 442619930    404 SVKPPWERATTAANVPYYIDHERETTHWDHPEM 436
Cdd:smart00456    1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33

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 442619930  270 KMRQFQKILEDLSSRVALAEQTKTSWLPPSSVGEANEQMQQLQRLRDKMTTASALLDDCNEqqsffTANQVLVPTPCLS- 348
Cdd:cd00176     1 KLQQFLRDADELEAWLSEKEELLSSTDYGDDLESVEALLKKHEALEAELAAHEERVEALNE-----LGEQLIEEGHPDAe 75

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 442619930  349 ----KLEDLNTRMKLLQIAMDERQKVLCQAGAQQTH 380
Cdd:cd00176    76 eiqeRLEELNQRWEELRELAEERRQRLEEALDLQQF 111

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 442619930   269 EKMRQFQKILEDLSSRVALAEQTKTSWLPPSSVGEANEQMQQLQRLRDKMTTASALLDDCNEQQSFFTANQVLVPTPCLS 348
Cdd:pfam00435    1 LLLQQFFRDADDLESWIEEKEALLSSEDYGKDLESVQALLKKHKALEAELAAHQDRVEALNELAEKLIDEGHYASEEIQE 80

                           90       100
                   ....*....|....*....|...
gi 442619930   349 KLEDLNTRMKLLQIAMDERQKVL 371
Cdd:pfam00435   81 RLEELNERWEQLLELAAERKQKL 103

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 442619930  473 SMSTACESFDRHGLRAQNDKLIDIPDMTTVLHSLYVTIDK-----IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGL 547
Cdd:cd16242     1 SLSTAIEAFDQHGLRAQNDKLIDVPDMITCLTTIYEALEEehptlVNVPLCVDLCLNWLLNVYDSGRSGKIRVLSFKVGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619930  548 VLLCKGHLEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGSNIEPSVRSCLEQAGISQEaidgnqdi 627
Cdd:cd16242    81 VLLCNAHLEEKYRYLFSLIADPNGCVDQRRLGLLLHDCIQIPRQLGEVAAFGGSNIEPSVRSCFEKAGEKPE-------- 152

                         170
                  ....*....|..
gi 442619930  628 sIELQHFLGWLQ 639
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 442619930  474 MSTACESFDRHGLRAQNDKLIDIPDMTTVLHSLYVTIDK-----IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGLV 548
Cdd:cd15901     2 LSTVLSVFDRHGLSGSQDSVLDCEELETILTELYIKLNKrrpdlIDVPRASDLLLNWLLNLYDRNRTGCIRLLSVKIALI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442619930  549 LLCKGHLEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGSNIEPSVRSCLEQAGISQEaidgnqdis 628
Cdd:cd15901    82 TLCAASLLDKYRYLFGQLADSSGFISRERLTQFLQDLLQIPDLIGESPAFGGHNVEAAVESCFQLARSRVG--------- 152

                         170
                  ....*....|.
gi 442619930  629 IELQHFLGWLQ 639
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 442619930   437 IELMKGLADLNEIRFSAYRTAMKLRSVQKRLALDRISMSTACESFDRHGLRA-QNDKLIDIPDMTTVLHSLYVTIDK--- 512
Cdd:pfam09068    1 TELMQELQDFNNIRFAAYRTAMKLRALQKRLNLDLVDLWNLIEAFDEHGLNSlENDLLLSVSELEALLSSIYFALNKrkp 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 442619930   513 ----IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGLVLLC 551
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 442619930   555 LEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGsnIEPSVRSCLEQAGISQEaidgnqdisIELQHF 634
Cdd:pfam09069    1 LVDKYRYLFSQISDSNGLLDQSKLGLLLHELLQLPRQVGEVPAFGG--IEPSVRSCFEQVGGKPK---------ITLNHF 69

                           90       100
                   ....*....|....*....|
gi 442619930   635 LGWLQHEPQSLVWLPVLHRL 654
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 442619930  473 SMSTACESFDRHGLR-AQNDKLIDIPDMTTVLHSLYVTIDK-----IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVG 546
Cdd:cd16245     1 PLKLIMGVFDRHQLSnSENNLCLPPDELEAVLHDIYFAAEKlgnfnIDVDLATELLANLFLNVFDPERKKSISVLELKVF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 442619930  547 LVLLCKGHLEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGSNIEPSVRSCLEQ 613
Cdd:cd16245    81 LTLLCGSSLQEKYLYLFQLLADHNNCVSRKRLEALLKSLAKLLSYLGEDVAFGSHLIELAVEQCFEN 147

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 442619930    661 KHQAKCNICKEyPIVGFRYRCLKCFNFDMCQKCFFFGRNAKNHK 704
Cdd:smart00291    2 HHSYSCDTCGK-PIVGVRYHCLVCPDYDLCQSCFAKGSAGGEHS 44

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 442619930   661 KHQAKCNICKEYPIVGFRYRCLKCFNFDMCQKCfFFGRNAKNHK 704
Cdd:pfam00569    2 HKVYTCNGCSNDPSIGVRYHCLRCSDYDLCQSC-FQTHKGGNHQ 44

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 442619930  479 ESFDRHGLRA-QNDKLIDIPDMTTVLHSLYVTIDK-------IDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGLVLL 550
Cdd:cd16250     7 EAFRDNGLNTlDHSTEISVSRLETIISSIYYQLNKrlpsthqISVEQSISLLLNFMIAAYDSEGHGKLTVFSVKAMLATM 86

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 442619930  551 CKGHLEEKYRYLFRLVADTDRRADQRRLGLLLHDCIQVPRQLGEVAAFGGSniEPSVRSCLEQ 613
Cdd:cd16250    87 CGGKILDKLRYTFSQMSDSNGLMIFLKFDQFLREVLKLPTAVFEGPSFGYT--EHSVRTCFPQ 147

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 442619930  499 MTTVLHSL---YVTIDKIDLTLMLDLAINWILNVYDSQRTGQIRVLSFKVGLVLLCKGHLEEKYRYLFRLVADTDRRADQ 575
Cdd:cd16249    32 LSTIFYQLnkrMPTTHQINVEQSISLLLNFLLAAFDPEGHGKISVFAVKMALATLCGGKIMDKLRYIFSMISDSNGVMVY 111

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 442619930  576 RRLGLLLHDCIQVPRQLGEVAAFGGSniEPSVRSCLEQ 613
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 442619930  406 KPPWERATTAANVPYYIDHERETTHWDHPEM 436
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

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 442619930  665 KCNICKEYPIVGFRYRCLKCFNFDMCQKCFFFGRNAKNHKLTHP 708
Cdd:cd02335     2 HCDYCSKDITGTIRIKCAECPDFDLCLECFSAGAEIGKHRNDHN 45

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 442619930  666 CNICKEYPIVGFRYRCLKCFNFDMCQKCFFFGRNAKNHKLTHPMHE 711
Cdd:cd02345     3 CSACRKQDISGIRFPCQVCRDYSLCLGCYTKGRETKRHNSLHIMYE 48

Zinc finger, ZZ type. Zinc finger present in HERC2 and related proteins. HERC2 is a potential E3 ubiquitin protein ligase and/or guanine nucleotide exchange factor. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 442619930  665 KCNICKEYPIVGFRYRCLKCFNFDMCQKCFFFGRNAKNH 703
Cdd:cd02344     2 TCDGCQMFPINGPRFKCRNCDDFDFCENCFKTRKHNTRH 40

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 442619930  270 KMRQFQKILEDLSSRVALAEQTKTSWLPPSSVGEANEQMQQLQRLRDKMTTASALLDDCNEqqsffTANQVLVPTPCLS- 348
Cdd:cd00176     1 KLQQFLRDADELEAWLSEKEELLSSTDYGDDLESVEALLKKHEALEAELAAHEERVEALNE-----LGEQLIEEGHPDAe 75

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 442619930  349 ----KLEDLNTRMKLLQIAMDERQKVLCQAGAQQTH 380
Cdd:cd00176    76 eiqeRLEELNQRWEELRELAEERRQRLEEALDLQQF 111

Zinc finger, ZZ type. Zinc finger present in CBP/p300 and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. CREB-binding protein (CBP) is a large multidomain protein that provides binding sites for transcriptional coactivators, the role of the ZZ domain in CBP/p300 is unclear.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 442619930  666 CNICKEypIVGFRYRCLKCFNFDMCQKCFffgrNAKNHklTHPM 709
Cdd:cd02337     3 CNECKH--HVETRWHCTVCEDYDLCITCY----NTKNH--PHKM 38

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 442619930   269 EKMRQFQKILEDLSSRVALAEQTKTSWLPPSSVGEANEQMQQLQRLRDKMTTASALLDDCNEQQSFFTANQVLVPTPCLS 348
Cdd:pfam00435    1 LLLQQFFRDADDLESWIEEKEALLSSEDYGKDLESVQALLKKHKALEAELAAHQDRVEALNELAEKLIDEGHYASEEIQE 80

                           90       100
                   ....*....|....*....|...
gi 442619930   349 KLEDLNTRMKLLQIAMDERQKVL 371
Cdd:pfam00435   81 RLEELNERWEQLLELAAERKQKL 103