helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336    3 QELTAENEKLVDEKTILETSFHQHRERAEQLSQENEKLMNLLQErvKNEEPTTQEGKIIELEQKCTGI-LEQGRFEREKL 81
Cdd:TIGR04523 228 NQLKDNIEKKQQEINEKTTEISNTQTQLNQLKDEQNKIKKQLSE--KQKELEQNNKKIKELEKQLNQLkSEISDLNNQKE 305

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336   82 LNIQQQLTCSLRKVEEENQGA-------LEMIKRLKEENEKLNEFLELERHNNNMMAKTLEECRVTLEGLKMENGSLKSH 154
Cdd:TIGR04523 306 QDWNKELKSELKNQEKKLEEIqnqisqnNKIISQLNEQISQLKKELTNSESENSEKQRELEEKQNEIEKLKKENQSYKQE 385

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336  155 LQGEKQKAT--EASAVEQTAESCEVQEMLKVARAEKDLLELSCNELRQELLKANGEIKHVSSLLAKVEKDYSYLKEICDH 232
Cdd:TIGR04523 386 IKNLESQINdlESKIQNQEKLNQQKDEQIKKLQQEKELLEKEIERLKETIIKNNSEIKDLTNQDSVKELIIKNLDNTRES 465

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336  233 QAEQLSRTS------------------------LKLQEKASESDAEIKDMKETIFELEDQVEQHRAVKLHNNQLISELES 288
Cdd:TIGR04523 466 LETQLKVLSrsinkikqnleqkqkelkskekelKKLNEEKKELEEKVKDLTKKISSLKEKIEKLESEKKEKESKISDLED 545

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336  289 sviKLEEQKSDLER-QLKTLTKQMKEETEEWRRFQADLQTAVVVANDIKCEAQQELRTVKRKLLEEEEKNARLQKELGDV 367
Cdd:TIGR04523 546 ---ELNKDDFELKKeNLEKEIDEKNKEIEELKQTQKSLKKKQEEKQELIDQKEKEKKDLIKEIEEKEKKISSLEKELEKA 622

                  .
gi 194391336  368 Q 368
Cdd:TIGR04523 623 K 623

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 194391336  562 RNALLKWCQKKTQGY-ANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKR--NLLLAFEAAE-SVGIKPSLE 637
Cdd:pfam00307   4 EKELLRWINSHLAEYgPGVRVTNFTTDLRDGLALCALLNKLAPGLVDKKKLNKSEFDKleNINLALDVAEkKLGVPKVLI 83

                          90       100
                  ....*....|....*....|....*...
gi 194391336  638 LSEMLYTdrPDWQSVMQYVAQIYKYFET 665
Cdd:pfam00307  84 EPEDLVE--GDNKSVLTYLASLFRRFQA 109

Ca2+-binding actin-bundling protein fimbrin/plastin (EF-Hand superfamily) [Cytoskeleton];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336 560 SKRNALLKWCQKKTQGYAN-IDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQ--EKKRNLLLAFEAAE-SVGIKPS 635
Cdd:COG5069  125 TKHINLLLWCDEDTGGYKPeVDTFDFFRSWRDGLAFSALIHDSRPDTLDPNVLDLQkkNKALNNFQAFENANkVIGIARL 204

                         90       100       110
                 ....*....|....*....|....*....|
gi 194391336 636 LELSEMLYTDRPDWQSVMQYVAQIYKYFET 665
Cdd:COG5069  205 IGVEDIVNVSIPDERSIMTYVSWYIIRFGL 234

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336 106 IKRLKEENEKLNEFLELErhnnnmmaKTLEECRVTLEGLKMEngslksHLQGEKQKAtEASAVEQTAESCEVQEMLKVAR 185
Cdd:COG1196  202 LEPLERQAEKAERYRELK--------EELKELEAELLLLKLR------ELEAELEEL-EAELEELEAELEELEAELAELE 266

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336 186 AEKDLLELSCNELRQELLKANGEIKHVSSLLAKVEKDYSYLKEicdhQAEQLSRTSLKLQEKASESDAEIKDMKETIFEL 265
Cdd:COG1196  267 AELEELRLELEELELELEEAQAEEYELLAELARLEQDIARLEE----RRRELEERLEELEEELAELEEELEELEEELEEL 342

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336 266 EDQVEQHRAVKLHNNQLISELESSVIKLEEQKSDLERQLKTLTKQMKEETEEWRRFQADLQTAVVVANDIKcEAQQELRT 345
Cdd:COG1196  343 EEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALL-ERLERLEE 421

                        250
                 ....*....|....*....
gi 194391336 346 VKRKLLEEEEKNARLQKEL 364
Cdd:COG1196  422 ELEELEEALAELEEEEEEE 440

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336   25 QHRERAEQLSQENEKLMNLLQERVKNEEPTTQEgkiiELEQKCTgilEQGRFEREKLLNIQQQLTCSLRKVEEENQGALE 104
Cdd:PTZ00121 1428 EEKKKADEAKKKAEEAKKADEAKKKAEEAKKAE----EAKKKAE---EAKKADEAKKKAEEAKKADEAKKKAEEAKKKAD 1500

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336  105 MIKRLKEENEKLNEFLELERHNNNMMAKTLEECRVTLEGLKMEngslkshlqgEKQKATEASAVEQTAESCEVQEMLKVA 184
Cdd:PTZ00121 1501 EAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKADEAKKAE----------EKKKADELKKAEELKKAEEKKKAEEAK 1570

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336  185 RAEKD--LLELSCNELRQELLKANGEIKHVSSLLAKVEKDYSYLKEICDHQAEQLSrtslKLQEKASESDAEIKDMKETI 262
Cdd:PTZ00121 1571 KAEEDknMALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELK----KAEEEKKKVEQLKKKEAEEK 1646

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336  263 FELEDQVEQHRAVKLHNNQLISELESSVIKLEEQKSDLE----------------RQLKTLTKQMKEETEEWRRFQADLQ 326
Cdd:PTZ00121 1647 KKAEELKKAEEENKIKAAEEAKKAEEDKKKAEEAKKAEEdekkaaealkkeaeeaKKAEELKKKEAEEKKKAEELKKAEE 1726

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 194391336  327 TAVVVANDIKCEAQQELRTVKRKLLEEEEKN--ARLQKELGDVQGHGRVVTSRAAPPPVDEEPESSEVD 393
Cdd:PTZ00121 1727 ENKIKAEEAKKEAEEDKKKAEEAKKDEEEKKkiAHLKKEEEKKAEEIRKEKEAVIEEELDEEDEKRRME 1795

calponin homology (CH) domain found in the cytospin family; The cytospin family includes cytospin-A and cytospin-B. Cytospin-A, also called renal carcinoma antigen NY-REN-22, sperm antigen with calponin homology and coiled-coil domains 1-like, or SPECC1-like (SPECC1L) protein, is involved in cytokinesis and spindle organization. It may play a role in actin cytoskeleton organization and microtubule stabilization and hence, is required for proper cell adhesion and migration. Cytospin-B, also called nuclear structure protein 5 (NSP5), sperm antigen HCMOGT-1, or sperm antigen with calponin homology and coiled-coil domains 1 (SPECC1), is a novel fusion partner to PDGFRB in juvenile myelomonocytic leukemia with translocation t(5;17)(q33;p11.2). Members of this family contain 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 194391336 553 LAREYGGSKRNALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAESVGI 632
Cdd:cd21199    1 LARRYGGSKRNALLKWCQEKTQGYKGIDITNFSSSWNDGLAFCALLHSYLPDKIPYSELNPQDKRRNFTLAFKAAESVGI 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 194391336 633 KPSLELSEMLYTDRPDWQSVMQYVAQIYKYFE 664
Cdd:cd21199   81 PTTLTIDEMVSMERPDWQSVMSYVTAIYKHFE 112

second 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 second CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336 560 SKRNALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAE-SVGIKPSLEL 638
Cdd:cd21216   10 SAKEGLLLWCQRKTAPYKNVNVQNFHTSWKDGLAFCALIHRHRPDLLDYDKLRKDDPRENLNLAFDVAEkHLDIPKMLDA 89

                         90       100
                 ....*....|....*....|....*
gi 194391336 639 SEMLYTDRPDWQSVMQYVAQIYKYF 663
Cdd:cd21216   90 EDIVNTPRPDERSVMTYVSCYYHAF 114

calponin homology (CH) domain found in the EH domain-binding protein (EHBP) family; 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. EHBP1 is associated with aggressive prostate cancer and insulin-stimulated trafficking and cell migration. EHBP1L1 may also act as Rab effector protein and play a role in vesicle trafficking. It coordinates Rab8 and Bin1 to regulate apical-directed transport in polarized epithelial cells. Members of this family contain 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 194391336 565 LLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAESVGIKPSLELSEMLYT 644
Cdd:cd21198    6 LLEWCQEVTKGYRGVKITNLTTSWRNGLAFCAILHHFRPDLIDFSSLSPHDIKENCKLAFDAAAKLGIPRLLDPADMVLL 85

                         90
                 ....*....|....*....
gi 194391336 645 DRPDWQSVMQYVAQIYKYF 663
Cdd:cd21198   86 SVPDKLSVMTYLHQIRAHF 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 194391336 563 NALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAES-VGIKPSLELSEM 641
Cdd:cd22198    3 EELLSWCQEQTEGYRGVKVTDLTSSWRSGLALCAIIHRFRPDLIDFSSLDPENIAENNQLAFDVAEQeLGIPPVMTGQEM 82

                         90       100
                 ....*....|....*....|..
gi 194391336 642 LYTDRPDWQSVMQYVAQIYKYF 663
Cdd:cd22198   83 ASLAVPDKLSMVSYLSQFYEAF 104

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 194391336 560 SKRNALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAE-SVGIKPSLEl 638
Cdd:cd21248    2 SAKDALLLWCQMKTAGYPNVNVRNFTTSWRDGLAFNALIHKHRPDLIDYDKLSKSNALYNLQNAFNVAEqKLGLTKLLD- 80

                         90       100
                 ....*....|....*....|....*
gi 194391336 639 SEMLYTDRPDWQSVMQYVAQIYKYF 663
Cdd:cd21248   81 PEDVNVEQPDEKSIITYVVTYYHYF 105

second calponin homology (CH) domain found in spectrin beta chain, erythrocytic (SPTB) and similar proteins; 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. SPTB, also called beta-I spectrin, may be involved in anaemia pathogenesis. SPTB 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 194391336 560 SKRNALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAE-SVGIKPSLEl 638
Cdd:cd21319    5 SAKDALLLWCQMKTAGYPNVNVTNFTSSWKDGLAFNALIHKHRPDLVDFGKLKKSNARHNLEHAFNVAErQLGITKLLD- 83

                         90       100
                 ....*....|....*....|....*
gi 194391336 639 SEMLYTDRPDWQSVMQYVAQIYKYF 663
Cdd:cd21319   84 PEDVFTENPDEKSIITYVVAFYHYF 108

calponin homology (CH) domain found in smoothelin-A and similar proteins; Smoothelins are actin-binding cytoskeletal proteins that are abundantly expressed in healthy visceral (smoothelin-A) and vascular (smoothelin-B) smooth muscle. This model corresponds to the single CH domain of smoothelin-A. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336 560 SKRNALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAES-VGIKPSLEL 638
Cdd:cd21258    1 SIKQMLLDWCRAKTRGYEHVDIQNFSSSWSDGMAFCALVHNFFPDAFDYSQLSPQNRRQNFEVAFSAAEMlADCVPLVEV 80

                         90       100
                 ....*....|....*....|....*.
gi 194391336 639 SEMLYT-DRPDWQSVMQYVAQIYKYF 663
Cdd:cd21258   81 EDMMIMgKKPDSKCVFTYVQSLYNHL 106

calponin homology (CH) domain found in MICAL-like protein 2 and similar proteins; MICAL-like protein 2 (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 subfamily 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 194391336 564 ALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAES-VGIKPSLELSEML 642
Cdd:cd21253    5 ALQQWCRQQTEGYRDVKVTNMTTSWRDGLAFCAIIHRFRPDLIDFDSLSKENVYENNKLAFTVAEKeLGIPALLDAEDMV 84

                         90       100
                 ....*....|....*....|..
gi 194391336 643 YTDRPDWQSVMQYVAQIYKYFE 664
Cdd:cd21253   85 ALKVPDKLSILTYVSQYYNYFH 106

second calponin homology (CH) domain found in spectrin beta chain, non-erythrocytic 5 (SPTBN5) and similar proteins; 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. SPTBN5, also called beta-V spectrin, is a mammalian ortholog of Drosophila beta H spectrin that may play a crucial role as a longer actin-membrane cross-linker or to fulfill the need for greater extensible flexibility than can be provided by the other smaller conventional spectrins. SPTBN5 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 194391336 560 SKRNALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAES-VGIKPSLEl 638
Cdd:cd21249    4 SAKEALLIWCQRKTAGYTNVNVQDFSRSWRDGLAFNALIHAHRPDLIDYGSLRPDRPLYNLANAFLVAEQeLGISQLLD- 82

                         90       100
                 ....*....|....*....|....*
gi 194391336 639 SEMLYTDRPDWQSVMQYVAQIYKYF 663
Cdd:cd21249   83 PEDVAVPHPDERSIMTYVSLYYHYF 107

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 194391336 561 KRNALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAE-SVGIKPSLELS 639
Cdd:cd21197    1 KIQALLRWCRRQCEGYPGVNITNLTSSFRDGLAFCAILHRHRPELIDFHSLKKDNWLENNRLAFRVAEtSLGIPALLDAE 80

                         90       100
                 ....*....|....*....|....
gi 194391336 640 EMLYTDRPDWQSVMQYVAQIYKYF 663
Cdd:cd21197   81 DMVTMHVPDRLSIITYVSQYYNHF 104

calponin homology (CH) domain found in molecule interacting with CasL protein 2 (MICAL-2), MICAL-3, and similar proteins; Molecule interacting with CasL protein (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. In addition, MICAL functions to interact with Rab13 and Rab8 to coordinate the assembly of tight junctions and adherens junctions in epithelial cells. Thus, MICAL is also called junctional Rab13-binding protein (JRAB). Members of this family, which includes MICAL-2, MICAL-3, and similar proteins, contain one CH domain. CH domains are actin filament (F-actin) binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194391336 558 GGSKRNALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAE-SVGIKPSL 636
Cdd:cd21195    2 GDIRPSKLLTWCQQQTEGYQHVNVTDLTTSWRSGLALCAIIHRFRPELINFDSLNEDDAVENNQLAFDVAErEFGIPPVT 81

                         90       100
                 ....*....|....*....|....*...
gi 194391336 637 ELSEMLYTDRPDWQSVMQYVAQIYKYFE 664
Cdd:cd21195   82 TGKEMASAQEPDKLSMVMYLSKFYELFR 109

calponin homology (CH) domain found in molecule interacting with CasL protein 3; MICAL-3 is a [F-actin]-monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2). MICAL-3 seems to act as a Rab effector protein and plays a role in vesicle trafficking. It is involved in exocytic vesicle tethering and fusion. MICAL3 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 194391336 560 SKRNALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAE-SVGIKPSLEL 638
Cdd:cd21251    5 ARSSKLLGWCQRQTEGYAGVNVTDLTMSWKSGLALCAIIHRYRPDLIDFDSLDEQDVEKNNQLAFDIAEkEFGISPIMTG 84

                         90       100
                 ....*....|....*....|....*.
gi 194391336 639 SEMLYTDRPDWQSVMQYVAQIYKYFE 664
Cdd:cd21251   85 KEMASVGEPDKLSMVMYLTQFYEMFK 110

calponin homology (CH) domain found in molecule interacting with CasL protein 2; MICAL-2 is a nuclear [F-actin]-monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2). MICAL-2 acts as a key regulator of the serum response factor (SRF) signaling pathway elicited by nerve growth factor and serum. It mediates oxidation and subsequent depolymerization of nuclear actin, leading to the increased MKL1/MRTF-A presence in the nucleus, promoting SRF:MKL1/MRTF-A-dependent gene transcription. MICAL-2 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 194391336 561 KRNALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAE-SVGIKPSLELS 639
Cdd:cd21250    5 RPNKLLTWCQKQTEGYQNVNVTDLTTSWKSGLALCAIIHRFRPELIDFDSLNEDDAVKNNQLAFDVAErEFGIPPVTTGK 84

                         90       100
                 ....*....|....*....|....
gi 194391336 640 EMLYTDRPDWQSVMQYVAQIYKYF 663
Cdd:cd21250   85 EMASAEEPDKLSMVMYLSKFYELF 108

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 194391336  562 RNALLKWCQKKTQGY-ANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKR--NLLLAFEAAE-SVGIKPSLE 637
Cdd:pfam00307   4 EKELLRWINSHLAEYgPGVRVTNFTTDLRDGLALCALLNKLAPGLVDKKKLNKSEFDKleNINLALDVAEkKLGVPKVLI 83

                          90       100
                  ....*....|....*....|....*...
gi 194391336  638 LSEMLYTdrPDWQSVMQYVAQIYKYFET 665
Cdd:pfam00307  84 EPEDLVE--GDNKSVLTYLASLFRRFQA 109

second calponin homology (CH) domain found in the dystrophin family; The dystrophin family includes dystrophin and its paralog, utrophin. Dystrophin, encoded by the DMD gene, is a large, submembrane cytoskeletal protein that is the main component of the dystrophin-glycoprotein complex (DGC) in skeletal muscles. 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 is also involved in maintaining the structural integrity of cells, as well as in the formation of the blood-brain barrier (BBB). Utrophin, also called dystrophin-related protein 1 (DRP-1), is an autosomal dystrophin homolog that increases dystrophic muscle function and reduces pathology. It is broadly expressed in both the mRNA and protein levels, and occurs in the cerebrovascular endothelium. Utrophin forms the utrophin-glycoprotein complex (UGC) by interacting with dystroglycans (DGs) and sarcoglycan-dystroglycans, as well as sarcoglycan and sarcospan (SG-SSPN) subcomplexes. 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. 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 194391336 565 LLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAA-ESVGIKPSLElSEMLY 643
Cdd:cd21187    5 LLAWCRQSTRGYEQVDVKNFTTSWRDGLAFNALIHRHRPDLFDFDSLVKDSPESRLEHAFTVAhEHLGIEKLLD-PEDVN 83

                         90
                 ....*....|....*...
gi 194391336 644 TDRPDWQSVMQYVAQIYK 661
Cdd:cd21187   84 VEQPDKKSILMYVTSLFQ 101

second calponin homology (CH) domain found in spectrin beta chain, non-erythrocytic 1 (SPTBN1) and similar proteins; 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. SPTBN1, also called beta-II spectrin, fodrin beta chain, or spectrin, non-erythroid beta chain 1, is also 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. SPTBN1 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 194391336 560 SKRNALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAES-VGIKPSLEl 638
Cdd:cd21320    2 SAKDALLLWCQMKTAGYPNVNIHNFTTSWRDGMAFNALIHKHRPDLIDFDKLKKSNAHYNLQNAFNLAEQhLGLTKLLD- 80

                         90       100
                 ....*....|....*....|....*
gi 194391336 639 SEMLYTDRPDWQSVMQYVAQIYKYF 663
Cdd:cd21320   81 PEDISVDHPDEKSIITYVVTYYHYF 105

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 194391336 558 GGSKRnALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAES-VGIkPSL 636
Cdd:cd21243    4 GGAKK-ALLKWVQNAAAKRFGIEVKDFGPSWRDGVAFNAIIHSIRPDLVDMESLKRRSNRENLETAFTVAEKeLGI-PRL 81

                         90       100
                 ....*....|....*....|....*..
gi 194391336 637 ELSEMLYTDRPDWQSVMQYVAQIYKYF 663
Cdd:cd21243   82 LDPEDVDVDKPDEKSIMTYVAQFLKKY 108

second calponin homology (CH) domain found in alpha-actinin-3; Alpha-actinin-3 (ACTN3), also called alpha-actinin skeletal muscle isoform 3, is an F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. ACTN3 is a bundling protein. It is critical in anchoring the myofibrillar actin filaments and plays a key role in muscle contraction. 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 194391336 560 SKRNALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPYQELNSQEKKRNLLLAFEAAES-VGIKPSLEL 638
Cdd:cd21289   10 SAKEGLLLWCQRKTAPYRNVNVQNFHTSWKDGLALCALIHRHRPDLIDYAKLRKDDPIGNLNTAFEVAEKyLDIPKMLDA 89

                         90       100
                 ....*....|....*....|....*
gi 194391336 639 SEMLYTDRPDWQSVMQYVAQIYKYF 663
Cdd:cd21289   90 EDIVNTPKPDEKAIMTYVSCFYHAF 114

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 194391336   563 NALLKWCQKKTQGYANIDITNFSSSWSDGLAFCALLHTYLPAHIPY----QELNSQEKKRNLLLAFEAAESVGIKPSLEL 638
Cdd:smart00033   1 KTLLRWVNSLLAEYDKPPVTNFSSDLKDGVALCALLNSLSPGLVDKkkvaASLSRFKKIENINLALSFAEKLGGKVVLFE 80