first calponin homology (CH) domain found in the alpha-actinin family; The alpha-actinin (ACTN) family includes alpha-actinin-1, -2, -3, and -4. They are F-actin cross-linking proteins which are thought to anchor actin to a variety of intracellular structures. ACTN1 mutations cause congenital macrothrombocytopenia. ACTN2 mutations are associated with cardiomyopathies, as well as skeletal muscle disorder. ACTN3 is critical in anchoring the myofibrillar actin filaments and plays a key role in muscle contraction. ACTN4 is associated with cell motility and cancer invasion. It is probably involved in vesicular trafficking via its association with the CART complex, which is necessary for efficient transferrin receptor recycling but not for epidermal growth factor receptor (EGFR) degradation. Members of this family contain two copies of the CH domain. This model corresponds to the first CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668  31 AWEKQQKKTFTAWCNSHLRKAGTAIDNIEEDFRNGLKLMLLLEVISGETLPKPDRGKMRFHKIANVNKALDFIASKGVHL 110
Cdd:cd21214    1 AWEKQQRKTFTAWCNSHLRKAGTQIENIEEDFRDGLKLMLLLEVISGERLPKPERGKMRFHKIANVNKALDFIASKGVKL 80

                         90       100
                 ....*....|....*....|....*
gi 320541668 111 VSIGAEEIVDGNLKMTLGMIWTIIL 135
Cdd:cd21214   81 VSIGAEEIVDGNLKMTLGMIWTIIL 105

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 320541668 398 LAQKFKHKADAHEDWTRGKEEMLQSQDFRQcKLNELKALKKKHEAFESDLAAHQDRVEQIAAIAQELNTLEYHDCVSVNA 477
Cdd:cd00176    1 KLQQFLRDADELEAWLSEKEELLSSTDYGD-DLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQE 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668 478 RCQRICDQWDRLGALTQRRRTALDEAERILEKI-DILHLEfakraapfnNWLDGTREDLVDMFIVHTMEEIQGLIQAHDQ 556
Cdd:cd00176   80 RLEELNQRWEELRELAEERRQRLEEALDLQQFFrDADDLE---------QWLEEKEAALASEDLGKDLESVEELLKKHKE 150

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 320541668 557 FKATLGEADKEFNLIVNLVREVESIVKQHqipgglENPYTTLTANDMTRKWSDVRQLVPQRDQTLANEL 625
Cdd:cd00176  151 LEEELEAHEPRLKSLNELAEELLEEGHPD------ADEEIEEKLEELNERWEELLELAEERQKKLEEAL 213

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 320541668 516 EFAKRAAPFNNWLDGTREDLVDMFIVHTMEEIQGLIQAHDQFKATLGEADKEFNlivNLVREVESIVKQHQIpgglENPY 595
Cdd:cd00176    4 QFLRDADELEAWLSEKEELLSSTDYGDDLESVEALLKKHEALEAELAAHEERVE---ALNELGEQLIEEGHP----DAEE 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668 596 TTLTANDMTRKWSDVRQLVPQRDQTLANELRKQQNNEMLRRqfaekaniVGPWIERQMDAVTAIGMG-LQGSLEDQLHRL 674
Cdd:cd00176   77 IQERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADD--------LEQWLEEKEAALASEDLGkDLESVEELLKKH 148

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 320541668 675 KEYEQAVYAYKPNIEELEKIHQAVQESMIFEN-RYTNYTMETLRVGWEQLLTSINRNINEVENQI 738
Cdd:cd00176  149 KELEEELEAHEPRLKSLNELAEELLEEGHPDAdEEIEEKLEELNERWEELLELAEERQKKLEEAL 213

first calponin homology (CH) domain found in the alpha-actinin family; The alpha-actinin (ACTN) family includes alpha-actinin-1, -2, -3, and -4. They are F-actin cross-linking proteins which are thought to anchor actin to a variety of intracellular structures. ACTN1 mutations cause congenital macrothrombocytopenia. ACTN2 mutations are associated with cardiomyopathies, as well as skeletal muscle disorder. ACTN3 is critical in anchoring the myofibrillar actin filaments and plays a key role in muscle contraction. ACTN4 is associated with cell motility and cancer invasion. It is probably involved in vesicular trafficking via its association with the CART complex, which is necessary for efficient transferrin receptor recycling but not for epidermal growth factor receptor (EGFR) degradation. Members of this family contain two copies of the CH domain. This model corresponds to the first CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668  31 AWEKQQKKTFTAWCNSHLRKAGTAIDNIEEDFRNGLKLMLLLEVISGETLPKPDRGKMRFHKIANVNKALDFIASKGVHL 110
Cdd:cd21214    1 AWEKQQRKTFTAWCNSHLRKAGTQIENIEEDFRDGLKLMLLLEVISGERLPKPERGKMRFHKIANVNKALDFIASKGVKL 80

                         90       100
                 ....*....|....*....|....*
gi 320541668 111 VSIGAEEIVDGNLKMTLGMIWTIIL 135
Cdd:cd21214   81 VSIGAEEIVDGNLKMTLGMIWTIIL 105

Ca2+ insensitive EF hand; EF hands are helix-loop-helix binding motifs involved in the regulation of many cellular processes. EF hands usually bind to Ca2+ ions which causes a major conformational change that allows the protein to interact with its designated targets. This domain corresponds to an EF hand which has partially or entirely lost its calcium-binding properties. The calcium insensitive EF hand is still able to mediate protein-protein recognition.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 320541668  825 DTDTAEQVIDSFRILAADKPYILPDELRRELPPDQAEYCIQRMPPYKGP--NGVPGALDYMSFSTALYG 891
Cdd:pfam08726   1 DTDTAEQVEASFRALAGGKPYVTEEDLRRELTPDQAEYCIARMPPYSGPdgDSVPGAYDYVSFSEALFG 69

Calponin homology (CH) domain; The CH domain is found in both cytoskeletal proteins and signal transduction proteins. The CH domain is involved in actin binding in some members of the family. However in calponins there is evidence that the CH domain is not involved in its actin binding activity. Most member proteins have from two to four copies of the CH domain, however some proteins such as calponin have only a single copy.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668  147 MTAKEGLLLWCQRKTAPYK-NVNVQNFHLSFKDGLAFCALIHRHRPDLIDYAKLSKD--NPLENLNTAFDVAEKYLDIPR 223
Cdd:pfam00307   1 LELEKELLRWINSHLAEYGpGVRVTNFTTDLRDGLALCALLNKLAPGLVDKKKLNKSefDKLENINLALDVAEKKLGVPK 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 320541668  224 ML-DPDDLINtpkPDERAIMTYVSCYYHAFQG 254
Cdd:pfam00307  81 VLiEPEDLVE---GDNKSVLTYLASLFRRFQA 109

Calponin homology domain; Actin binding domains present in duplicate at the N-termini of spectrin-like proteins (including dystrophin, alpha-actinin). These domains cross-link actin filaments into bundles and networks. A calponin homology domain is predicted in yeasst Cdc24p.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668   151 EGLLLWCQRKTAPYKNVNVQNFHLSFKDGLAFCALIHRHRPDLIDYAKLSKD----NPLENLNTAFDVAEKYLDIPRMLD 226
Cdd:smart00033   1 KTLLRWVNSLLAEYDKPPVTNFSSDLKDGVALCALLNSLSPGLVDKKKVAASlsrfKKIENINLALSFAEKLGGKVVLFE 80

                           90       100
                   ....*....|....*....|
gi 320541668   227 PDDlINTPKPDERAIMTYVS 246
Cdd:smart00033  81 PED-LVEGPKLILGVIWTLI 99

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 320541668  397 HLAQKFKHKADAHEDWTRGKEEMLQSQDFRQcKLNELKALKKKHEAFESDLAAHQDRVEQIAAIAQELNTLEYHDCVSVN 476
Cdd:pfam00435   1 LLLQQFFRDADDLESWIEEKEALLSSEDYGK-DLESVQALLKKHKALEAELAAHQDRVEALNELAEKLIDEGHYASEEIQ 79

                          90       100
                  ....*....|....*....|....*.
gi 320541668  477 ARCQRICDQWDRLGALTQRRRTALDE 502
Cdd:pfam00435  80 ERLEELNERWEQLLELAAERKQKLEE 105

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 320541668 280 EEYERLASDLLEWIRRTMPWLNSRQADNSLAGVQKKLEEYRTYRR--KHKPPRVEQkakletnFNTLQTKLRLSNRPAYL 357
Cdd:cd00176    3 QQFLRDADELEAWLSEKEELLSSTDYGDDLESVEALLKKHEALEAelAAHEERVEA-------LNELGEQLIEEGHPDAE 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668 358 PTEgKTVSDISNSWKGL-ELAEKafeewllaetmRLERLEHLAQKFKHKADAH--EDWTRGKEEMLQSQDFRQcKLNELK 434
Cdd:cd00176   76 EIQ-ERLEELNQRWEELrELAEE-----------RRQRLEEALDLQQFFRDADdlEQWLEEKEAALASEDLGK-DLESVE 142

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668 435 ALKKKHEAFESDLAAHQDRVEQIAAIAQEL-NTLEYHDCVSVNARCQRICDQWDRLGALTQRRRTALDEA 503
Cdd:cd00176  143 ELLKKHKELEEELEAHEPRLKSLNELAEELlEEGHPDADEEIEEKLEELNERWEELLELAEERQKKLEEA 212

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 320541668 753 EFRSSFNHFDKNRTGRLSPEEFKSCLVSLGysigkDRQGDLDFQRILAVVDPNNTGYVHFDAFLDFMT 820
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAALKSLG-----EGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

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 320541668  634 LRRQFAEKANIVGPWIERQMDAVTAIGMGLQ-GSLEDQLHRLKEYEQAVYAYKPNIEELEKIHQAVQESMIFENRYTNYT 712
Cdd:pfam00435   2 LLQQFFRDADDLESWIEEKEALLSSEDYGKDlESVQALLKKHKALEAELAAHQDRVEALNELAEKLIDEGHYASEEIQER 81

                          90       100
                  ....*....|....*....|....
gi 320541668  713 METLRVGWEQLLTSINRNINEVEN 736
Cdd:pfam00435  82 LEELNERWEQLLELAAERKQKLEE 105

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 320541668  752 NEFRSSFNHFDKNRTGRLSPEEFKSCLVSLGYSIGKDRQgdlDFQRILAVVDPNNTGYVHFDAFLDFMT 820
Cdd:pfam13499   2 EKLKEAFKLLDSDGDGYLDVEELKKLLRKLEEGEPLSDE---EVEELFKEFDLDKDGRISFEEFLELYS 67

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.

                           10        20
                   ....*....|....*....|....*....
gi 320541668   753 EFRSSFNHFDKNRTGRLSPEEFKSCLVSL 781
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

first calponin homology (CH) domain found in the alpha-actinin family; The alpha-actinin (ACTN) family includes alpha-actinin-1, -2, -3, and -4. They are F-actin cross-linking proteins which are thought to anchor actin to a variety of intracellular structures. ACTN1 mutations cause congenital macrothrombocytopenia. ACTN2 mutations are associated with cardiomyopathies, as well as skeletal muscle disorder. ACTN3 is critical in anchoring the myofibrillar actin filaments and plays a key role in muscle contraction. ACTN4 is associated with cell motility and cancer invasion. It is probably involved in vesicular trafficking via its association with the CART complex, which is necessary for efficient transferrin receptor recycling but not for epidermal growth factor receptor (EGFR) degradation. Members of this family contain two copies of the CH domain. This model corresponds to the first CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668  31 AWEKQQKKTFTAWCNSHLRKAGTAIDNIEEDFRNGLKLMLLLEVISGETLPKPDRGKMRFHKIANVNKALDFIASKGVHL 110
Cdd:cd21214    1 AWEKQQRKTFTAWCNSHLRKAGTQIENIEEDFRDGLKLMLLLEVISGERLPKPERGKMRFHKIANVNKALDFIASKGVKL 80

                         90       100
                 ....*....|....*....|....*
gi 320541668 111 VSIGAEEIVDGNLKMTLGMIWTIIL 135
Cdd:cd21214   81 VSIGAEEIVDGNLKMTLGMIWTIIL 105

second calponin homology (CH) domain found in alpha-actinin-2; Alpha-actinin-2 (ACTN2), also called alpha-actinin skeletal muscle isoform 2, is an F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. ACTN2 is a bundling protein. Its mutations are associated with cardiomyopathies, as well as skeletal muscle disorder. It contains two copies of the CH domain. This model corresponds to the second CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668 139 IQDISVEEMTAKEGLLLWCQRKTAPYKNVNVQNFHLSFKDGLAFCALIHRHRPDLIDYAKLSKDNPLENLNTAFDVAEKY 218
Cdd:cd21288    1 IQDISVEETSAKEGLLLWCQRKTAPYRNVNIQNFHTSWKDGLGLCALIHRHRPDLIDYSKLNKDDPIGNINLAMEIAEKH 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 320541668 219 LDIPRMLDPDDLINTPKPDERAIMTYVSCYYHAFQGAQQAETAA 262
Cdd:cd21288   81 LDIPKMLDAEDIVNTPKPDERAIMTYVSCFYHAFAGAEQAETAA 124

second calponin homology (CH) domain found in alpha-actinin-1; Alpha-actinin-1 (ACTN1), also called alpha-actinin cytoskeletal isoform, or non-muscle alpha-actinin-1, is an F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. ACTN1 is a bundling protein. Its mutations cause congenital macrothrombocytopenia. It contains two copies of the CH domain. This model corresponds to the second CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668 139 IQDISVEEMTAKEGLLLWCQRKTAPYKNVNVQNFHLSFKDGLAFCALIHRHRPDLIDYAKLSKDNPLENLNTAFDVAEKY 218
Cdd:cd21287    1 IQDISVEETSAKEGLLLWCQRKTAPYKNVNIQNFHISWKDGLGFCALIHRHRPELIDYGKLRKDDPLTNLNTAFDVAEKY 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 320541668 219 LDIPRMLDPDDLINTPKPDERAIMTYVSCYYHAFQGAQQ 257
Cdd:cd21287   81 LDIPKMLDAEDIVGTARPDEKAIMTYVSSFYHAFSGAQK 119

second calponin homology (CH) domain found in the beta spectrin family; The beta spectrin family includes beta-I, -II, -III, -IV and -V spectrins. Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. Beta-I spectrin, also called spectrin beta chain, erythrocytic (SPTB), may be involved in anaemia pathogenesis. Beta-II spectrin, also called spectrin beta chain, non-erythrocytic 1 (SPTBN1), or fodrin beta chain, is a component of fodrin, which is the general spectrin-like protein that seems to be involved in secretion. Fodrin interacts with calmodulin in a calcium-dependent manner and is thus a candidate for the calcium-dependent movement of the cytoskeleton at the membrane. Beta-IV spectrin is also called spectrin, non-erythroid beta chain 3 (SPTBN3) or spectrin beta chain, non-erythrocytic 4 (SPTBN4). Its mutation associates with congenital myopathy, neuropathy, and central deafness. Beta-III spectrin is also called spectrin beta chain, non-erythrocytic 2 (SPTBN2), or spinocerebellar ataxia 5 protein (SCA5). Beta-V spectrin, also called spectrin beta chain, non-erythrocytic 5 (SPTBN5), is a mammalian ortholog of Drosophila beta H spectrin. Beta-III and Beta-V spectrins may play crucial roles as longer actin-membrane cross-linkers or fulfill the need for greater extensible flexibility than can be provided by the other smaller conventional spectrins. Members of this family contain two copies of the CH domain. This model corresponds to the second CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668 148 TAKEGLLLWCQRKTAPYKNVNVQNFHLSFKDGLAFCALIHRHRPDLIDYAKLSKDNPLENLNTAFDVAEKYLDIPRMLDP 227
Cdd:cd21194    2 SAKDALLLWCQRKTAGYPGVNIQNFTTSWRDGLAFNALIHAHRPDLIDYNRLDPNDHLGNLNNAFDVAEQELGIAKLLDA 81

                         90       100
                 ....*....|....*....|....*
gi 320541668 228 DDlINTPKPDERAIMTYVSCYYHAF 252
Cdd:cd21194   82 ED-VDVARPDEKSIMTYVASYYHYF 105

second calponin homology (CH) domain found in the beta-I spectrin-like subfamily; The beta-I spectrin-like family includes beta-I, -II, -III and -IV spectrins. Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. Beta-I spectrin, also called spectrin beta chain, erythrocytic (SPTB), may be involved in anaemia pathogenesis. Beta-II spectrin, also called spectrin beta chain, non-erythrocytic 1 (SPTBN1), or fodrin beta chain, is a component of fodrin, which is the general spectrin-like protein that seems to be involved in secretion. Fodrin interacts with calmodulin in a calcium-dependent manner and is thus a candidate for the calcium-dependent movement of the cytoskeleton at the membrane. Beta-III spectrin, also called spectrin beta chain, non-erythrocytic 2 (SPTBN2), or spinocerebellar ataxia 5 protein (SCA5), may play a crucial role as a longer actin-membrane cross-linker or fulfill the need for greater extensible flexibility than can be provided by the other smaller conventional spectrins. Beta-IV spectrin is also called spectrin, non-erythroid beta chain 3 (SPTBN3) or spectrin beta chain, non-erythrocytic 4 (SPTBN4). Its mutation associates with congenital myopathy, neuropathy, and central deafness. Members of this subfamily contain two copies of the CH domain. This model corresponds to the second CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668 148 TAKEGLLLWCQRKTAPYKNVNVQNFHLSFKDGLAFCALIHRHRPDLIDYAKLSKDNPLENLNTAFDVAEKYLDIPRMLDP 227
Cdd:cd21248    2 SAKDALLLWCQMKTAGYPNVNVRNFTTSWRDGLAFNALIHKHRPDLIDYDKLSKSNALYNLQNAFNVAEQKLGLTKLLDP 81

                         90       100
                 ....*....|....*....|....*
gi 320541668 228 DDlINTPKPDERAIMTYVSCYYHAF 252
Cdd:cd21248   82 ED-VNVEQPDEKSIITYVVTYYHYF 105

first calponin homology (CH) domain found in the beta spectrin family; The beta spectrin family includes beta-I, -II, -III, -IV and -V spectrins. Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. Beta-I spectrin, also called spectrin beta chain, erythrocytic (SPTB), may be involved in anaemia pathogenesis. Beta-II spectrin, also called spectrin beta chain, non-erythrocytic 1 (SPTBN1), or fodrin beta chain, is a component of fodrin, which is the general spectrin-like protein that seems to be involved in secretion. Fodrin interacts with calmodulin in a calcium-dependent manner and is thus a candidate for the calcium-dependent movement of the cytoskeleton at the membrane. Beta-IV spectrin is also called spectrin, non-erythroid beta chain 3 (SPTBN3) or spectrin beta chain, non-erythrocytic 4 (SPTBN4). Its mutation associates with congenital myopathy, neuropathy, and central deafness. Beta-III spectrin is also called spectrin beta chain, non-erythrocytic 2 (SPTBN2), or spinocerebellar ataxia 5 protein (SCA5). Beta-V spectrin, also called spectrin beta chain, non-erythrocytic 5 (SPTBN5), is a mammalian ortholog of Drosophila beta H spectrin. Beta-III and Beta-V spectrins may play crucial roles as longer actin-membrane cross-linkers or fulfill the need for greater extensible flexibility than can be provided by the other smaller conventional spectrins. Members of this family contain two copies of the CH domain. This model corresponds to the first CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668  36 QKKTFTAWCNSHLRKAGTAIDNIEEDFRNGLKLMLLLEVISGETLPKPDRGKMRFHKIANVNKALDFIASKgVHLVSIGA 115
Cdd:cd21193   17 QKKTFTKWINSFLEKANLEIGDLFTDLSDGKLLLKLLEIISGEKLGKPNRGRLRVQKIENVNKALAFLKTK-VRLENIGA 95

                         90       100
                 ....*....|....*....|.
gi 320541668 116 EEIVDGNLKMTLGMIWTIILR 136
Cdd:cd21193   96 EDIVDGNPRLILGLIWTIILR 116

first calponin homology (CH) domain found in the plectin/dystonin/MACF1 family; This family includes plectin, dystonin and microtubule-actin cross-linking factor 1, isoforms 1/2/3/5 (MACF1). Plectin, also called PCN, PLTN, hemidesmosomal protein 1 (HD1), or plectin-1, is a structural component of muscle. It interlinks intermediate filaments with microtubules and microfilaments, and anchors intermediate filaments to desmosomes or hemidesmosomes. It could also bind muscle proteins such as actin to membrane complexes in muscle. Dystonin, also called 230 kDa bullous pemphigoid antigen, 230/240 kDa bullous pemphigoid antigen, bullous pemphigoid antigen 1 (BPA or BPAG1), dystonia musculorum protein, or hemidesmosomal plaque protein, is a cytoskeletal linker protein that acts as an integrator of intermediate filaments, actin, and microtubule cytoskeleton networks. It is required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells, or keratin-containing intermediate filaments to hemidesmosomes in epithelial cells. MACF1, also called 620 kDa actin-binding protein (ABP620), actin cross-linking family protein 7 (ACF7), macrophin-1, or trabeculin-alpha, is a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. It facilitates actin-microtubule interactions at the cell periphery and couples the microtubule network to cellular junctions. Members of this family contain two copies of the CH domain. This model corresponds to the first CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668  36 QKKTFTAWCNSHLRKAGTAIDNIEEDFRNGLKLMLLLEVISGETLPKpDRGKMRFHKIANVNKALDFIASKGVHLVSIGA 115
Cdd:cd21188    4 QKKTFTKWVNKHLIKARRRVVDLFEDLRDGHNLISLLEVLSGESLPR-ERGRMRFHRLQNVQTALDFLKYRKIKLVNIRA 82

                         90       100
                 ....*....|....*....|..
gi 320541668 116 EEIVDGNLKMTLGMIWTIILRF 137
Cdd:cd21188   83 EDIVDGNPKLTLGLIWTIILHF 104

first calponin homology (CH) domain found in the beta-I spectrin-like subfamily; The beta-I spectrin-like family includes beta-I, -II, -III and -IV spectrins. Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. Beta-I spectrin, also called spectrin beta chain, erythrocytic (SPTB), may be involved in anaemia pathogenesis. Beta-II spectrin, also called spectrin beta chain, non-erythrocytic 1 (SPTBN1), or fodrin beta chain, is a component of fodrin, which is the general spectrin-like protein that seems to be involved in secretion. Fodrin interacts with calmodulin in a calcium-dependent manner and is thus a candidate for the calcium-dependent movement of the cytoskeleton at the membrane. Beta-III spectrin, also called spectrin beta chain, non-erythrocytic 2 (SPTBN2), or spinocerebellar ataxia 5 protein (SCA5), may play a crucial role as a longer actin-membrane cross-linker or fulfill the need for greater extensible flexibility than can be provided by the other smaller conventional spectrins. Beta-IV spectrin is also called spectrin, non-erythroid beta chain 3 (SPTBN3) or spectrin beta chain, non-erythrocytic 4 (SPTBN4). Its mutation associates with congenital myopathy, neuropathy, and central deafness. Members of this subfamily contain two copies of the CH domain. This model corresponds to the first CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668  33 EKQQKKTFTAWCNSHLRKAGTAIDNIEEDFRNGLKLMLLLEVISGETLPKPDRGKMRFHKIANVNKALDFIASKGVHLVS 112
Cdd:cd21246   14 EAVQKKTFTKWVNSHLARVGCRINDLYTDLRDGRMLIKLLEVLSGERLPKPTKGKMRIHCLENVDKALQFLKEQRVHLEN 93

                         90       100
                 ....*....|....*....|....
gi 320541668 113 IGAEEIVDGNLKMTLGMIWTIILR 136
Cdd:cd21246   94 MGSHDIVDGNHRLTLGLIWTIILR 117

first calponin homology (CH) domain found in Schizosaccharomyces pombe alpha-actinin-like protein 1 and similar proteins; Schizosaccharomyces pombe alpha-actinin-like protein 1 (SpAIN1) binds to actin and is involved in actin-ring formation and organization. It plays a role in cytokinesis and is involved in septation. Members of this family contain two copies of the CH domain. This model corresponds to the first CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668  32 WEKQQKKTFTAWCNSHLRKAGTAIDNIEEDFRNGLKLMLLLEVISGETLPKPD-RGKMRFHKIANVNKALDFIASKGVHL 110
Cdd:cd21215    1 WVDVQKKTFTKWLNTKLSSRGLSITDLVTDLSDGVRLIQLLEIIGDESLGRYNkNPKMRVQKLENVNKALEFIKSRGVKL 80

                         90       100
                 ....*....|....*....|....*..
gi 320541668 111 VSIGAEEIVDGNLKMTLGMIWTIILRF 137
Cdd:cd21215   81 TNIGAEDIVDGNLKLILGLLWTLILRF 107

calponin homology (CH) domain found in MICAL-like protein 1; MICAL-like protein 1 (MICAL-L1), also called molecule interacting with Rab13 (MIRab13), is a probable lipid-binding protein with higher affinity for phosphatidic acid, a lipid enriched in recycling endosome membranes. It is a tubular endosomal membrane hub that connects Rab35 and Arf6 with Rab8a. It may be involved in a late step of receptor-mediated endocytosis regulating endocytosed-EGF receptor trafficking. Alternatively, it may regulate slow endocytic recycling of endocytosed proteins back to the plasma membrane. MICAL-L1 may indirectly play a role in neurite outgrowth. It contains a single copy of the CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668 149 AKEGLLLWCQRKTAPYKNVNVQNFHLSFKDGLAFCALIHRHRPDLIDYAKLSKDNPLENLNTAFDVAEKYLDIPRMLDPD 228
Cdd:cd21252    1 ARRALQAWCRRQCEGYPGVEIRDLSSSFRDGLAFCAILHRHRPDLIDFDSLSKDNVYENNRLAFEVAERELGIPALLDPE 80

                         90       100
                 ....*....|....*....|....
gi 320541668 229 DLINTPKPDERAIMTYVSCYYHAF 252
Cdd:cd21252   81 DMVSMKVPDCLSIMTYVSQYYNHF 104

calponin homology (CH) domain found in the MICAL-like protein family; The MICAL-L family includes MICAL-L1 and MICAL-L2. MICAL-L1, also called molecule interacting with Rab13 (MIRab13), is a probable lipid-binding protein with higher affinity for phosphatidic acid, a lipid enriched in recycling endosome membranes. It is a tubular endosomal membrane hub that connects Rab35 and Arf6 with Rab8a. It may be involved in a late step of receptor-mediated endocytosis regulating endocytosed-EGF receptor trafficking. Alternatively, it may regulate slow endocytic recycling of endocytosed proteins back to the plasma membrane. MICAL-L1 may indirectly play a role in neurite outgrowth. MICAL-L2, also called junctional Rab13-binding protein (JRAB), or molecule interacting with CasL-like 2, acts as an effector of small Rab GTPases which is involved in junctional complexes assembly through the regulation of cell adhesion molecule transport to the plasma membrane, and actin cytoskeleton reorganization. It regulates the endocytic recycling of occludins, claudins, and E-cadherin to the plasma membrane and may thereby regulate the establishment of tight junctions and adherens junctions. Members of this family contain a single copy of CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668 149 AKEGLLLWCQRKTAPYKNVNVQNFHLSFKDGLAFCALIHRHRPDLIDYAKLSKDNPLENLNTAFDVAEKYLDIPRMLDPD 228
Cdd:cd21197    1 KIQALLRWCRRQCEGYPGVNITNLTSSFRDGLAFCAILHRHRPELIDFHSLKKDNWLENNRLAFRVAETSLGIPALLDAE 80

                         90       100
                 ....*....|....*....|....
gi 320541668 229 DLINTPKPDERAIMTYVSCYYHAF 252
Cdd:cd21197   81 DMVTMHVPDRLSIITYVSQYYNHF 104

calponin homology (CH) domain found in the MICAL and EHBP families; This group is composed of the molecule interacting with CasL protein (MICAL) and EH domain-binding protein (EHBP) families. MICAL is a large, multidomain, cytosolic protein with a single LIM domain, a calponin homology (CH) domain and a flavoprotein monooxygenase (MO) domain. In Drosophila, MICAL is expressed in axons, interacts with the neuronal A (PlexA) receptor and is required for Semaphorin 1a (Sema-1a)-PlexA-mediated repulsive axon guidance. The LIM and CH domains mediate interactions with the cytoskeleton, cytoskeletal adaptor proteins, and other signaling proteins. The flavoprotein MO is required for semaphorin-plexin repulsive axon guidance during axonal pathfinding in the Drosophila neuromuscular system. The EHBP family includes EHBP1 and EHBP1-like protein (EHBP1L1). EHBP1 is a regulator of endocytic recycling and may play a role in actin reorganization by linking clathrin-mediated endocytosis to the actin cytoskeleton. It may act as an effector of small GTPases, including RAB-10 (Rab10), and play a role in vesicle trafficking. EHBP proteins contain a single CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668 151 EGLLLWCQRKTAPYKNVNVQNFHLSFKDGLAFCALIHRHRPDLIDYAKLSKDNPLENLNTAFDVAEKYLDIPRMLDPDDL 230
Cdd:cd22198    3 EELLSWCQEQTEGYRGVKVTDLTSSWRSGLALCAIIHRFRPDLIDFSSLDPENIAENNQLAFDVAEQELGIPPVMTGQEM 82

                         90       100
                 ....*....|....*....|..
gi 320541668 231 INTPKPDERAIMTYVSCYYHAF 252
Cdd:cd22198   83 ASLAVPDKLSMVSYLSQFYEAF 104

second calponin homology (CH) domain found in synaptic nuclear envelope protein 1 (SYNE-1) and similar proteins; SYNE-1, also called nesprin-1, enaptin, KASH domain-containing protein 1 (KASH1), myocyte nuclear envelope protein 1 (MYNE-1), or nuclear envelope spectrin repeat protein 1, is a multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain subcellular spatial organization. SYNE-1 also acts as a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, which is involved in the connection between the nuclear lamina and the cytoskeleton. SYNE-1 contains two copies of the CH domain. This model corresponds to the second CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320541668 147 MTAKEGLLLWCQRKTAPYKNVNVQNFHLSFKDGLAFCALIHRHRPDLIDYAKLSKDNPLENLNTAFDVAEKYLDIPRMLD 226
Cdd:cd21243    4 GGAKKALLKWVQNAAAKRFGIEVKDFGPSWRDGVAFNAIIHSIRPDLVDMESLKRRSNRENLETAFTVAEKELGIPRLLD 83