Bivalent Mical/EHBP Rab binding domain; A variety of different effector proteins interact specifically with GTP-bound Rab proteins and mediate their versatile roles in membrane trafficking, including budding of vesicles from a donor membrane, directed transport through the cell and finally tethering and fusion with a target membrane. The 'bivalent Mical/EHBP Rab binding' (bMERB) domain is a Rab effector domain that is present in proteins of the Mical and EHBP families, both known to act in endosomal trafficking. The bMERB domain displays a preference for Rab8 family proteins (Rab8, 10, 13 and 15) and at least some of the bMERB domains contain two separate binding sites for Rab-proteins, allowing Micals and EHBPs to bind two Rabs simultaneously. The strong similarity between the two binding sites within one bMRB domain strongly suggests an evolutionarily development via duplication of a common ancestor supersecondary structure element. The bMERB domain has a completely alpha-helical fold consisting of a central helix and N- and C-terminal helices folding back on this central helix.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966981474  1006 ELAALENEQKQIDTRAALVEKRLRYLMDtgrNTEEEEAMMQEWFMLVNKKNALIRRMNQLSLLEKEHDLERRYELLNREL 1085
Cdd:pfam12130    1 ELEEIEERQRELEERGVELEKALRGEMS---GDEEEEQLLQEWFKLVNEKNALVRRESELMYLAKEQDLEERQARLEQEL 77

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 966981474  1086 RAMLAIEDWQKTEAQKRREQLLLDELVALVNKRDALVRDLDAQEKQAEEEDEHL 1139
Cdd:pfam12130   78 RELMSKPDWLKTEEDKQREEELLEELVEIVEQRDALVDSLEEDRLREEEEDEEL 131

Bivalent Mical/EHBP Rab binding domain; A variety of different effector proteins interact specifically with GTP-bound Rab proteins and mediate their versatile roles in membrane trafficking, including budding of vesicles from a donor membrane, directed transport through the cell and finally tethering and fusion with a target membrane. The 'bivalent Mical/EHBP Rab binding' (bMERB) domain is a Rab effector domain that is present in proteins of the Mical and EHBP families, both known to act in endosomal trafficking. The bMERB domain displays a preference for Rab8 family proteins (Rab8, 10, 13 and 15) and at least some of the bMERB domains contain two separate binding sites for Rab-proteins, allowing Micals and EHBPs to bind two Rabs simultaneously. The strong similarity between the two binding sites within one bMRB domain strongly suggests an evolutionarily development via duplication of a common ancestor supersecondary structure element. The bMERB domain has a completely alpha-helical fold consisting of a central helix and N- and C-terminal helices folding back on this central helix.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966981474  1006 ELAALENEQKQIDTRAALVEKRLRYLMDtgrNTEEEEAMMQEWFMLVNKKNALIRRMNQLSLLEKEHDLERRYELLNREL 1085
Cdd:pfam12130    1 ELEEIEERQRELEERGVELEKALRGEMS---GDEEEEQLLQEWFKLVNEKNALVRRESELMYLAKEQDLEERQARLEQEL 77

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 966981474  1086 RAMLAIEDWQKTEAQKRREQLLLDELVALVNKRDALVRDLDAQEKQAEEEDEHL 1139
Cdd:pfam12130   78 RELMSKPDWLKTEEDKQREEELLEELVEIVEQRDALVDSLEEDRLREEEEDEEL 131

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 966981474   412 QSLLVWCKEVTKNY-RGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLN--PQDIKENNKKAYD-GFASIGISR-LLE 486
Cdd:pfam00307    5 KELLRWINSHLAEYgPGVRVTNFTTDLRDGLALCALLNKLAPGLVDKKKLNksEFDKLENINLALDvAEKKLGVPKvLIE 84

                           90       100
                   ....*....|....*....|....*...
gi 966981474   487 PSDMVLlaiPDKLTVMTYLYQIRAHFSG 514
Cdd:pfam00307   85 PEDLVE---GDNKSVLTYLASLFRRFQA 109

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966981474  414 LLVWCKEVTKNYR-GVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQ--DIKENNKKAYD-GFASIGISRLLEPSD 489
Cdd:COG5069   130 LLLWCDEDTGGYKpEVDTFDFFRSWRDGLAFSALIHDSRPDTLDPNVLDLQkkNKALNNFQAFEnANKVIGIARLIGVED 209

                          90
                  ....*....|....*.
gi 966981474  490 MVLLAIPDKLTVMTYL 505
Cdd:COG5069   210 IVNVSIPDERSIMTYV 225

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966981474   943 KTQLQSFSQYIEN-RPEMKRQRS-IQEDTKKGNEEKAAITETQRKPSEDEVLNKG-----FKDTSQYVVGELAALENEQK 1015
Cdd:TIGR02169  743 EEDLSSLEQEIENvKSELKELEArIEELEEDLHKLEEALNDLEARLSHSRIPEIQaelskLEEEVSRIEARLREIEQKLN 822

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966981474  1016 QIDTRAALVEKRLRYLMDTGRNTEEEEAMMQEWFMLVNKKNA-----LIRRMNQLSLLEKEH-DLERRYELLNRELRAML 1089
Cdd:TIGR02169  823 RLTLEKEYLEKEIQELQEQRIDLKEQIKSIEKEIENLNGKKEeleeeLEELEAALRDLESRLgDLKKERDELEAQLRELE 902

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 966981474  1090 AIEDWQKTEAQKRREQLLLdelvaLVNKRDALVRDLDAQEKQAEEEDEHLERTLEQNKGKMAKKE 1154
Cdd:TIGR02169  903 RKIEELEAQIEKKRKRLSE-----LKAKLEALEEELSEIEDPKGEDEEIPEEELSLEDVQAELQR 962

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 966981474  409 NASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYDGFASIGISRLLEPS 488
Cdd:cd21198     1 SSGQDLLEWCQEVTKGYRGVKITNLTTSWRNGLAFCAILHHFRPDLIDFSSLSPHDIKENCKLAFDAAAKLGIPRLLDPA 80

                          90       100
                  ....*....|....*....|....*
gi 966981474  489 DMVLLAIPDKLTVMTYLYQIRAHFS 513
Cdd:cd21198    81 DMVLLSVPDKLSVMTYLHQIRAHFT 105

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 966981474  410 ASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYDGFAS-IGISRLLEPS 488
Cdd:cd22198     1 RPEELLSWCQEQTEGYRGVKVTDLTSSWRSGLALCAIIHRFRPDLIDFSSLDPENIAENNQLAFDVAEQeLGIPPVMTGQ 80

                          90       100
                  ....*....|....*....|....*
gi 966981474  489 DMVLLAIPDKLTVMTYLYQIRAHFS 513
Cdd:cd22198    81 EMASLAVPDKLSMVSYLSQFYEAFK 105

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 966981474  410 ASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYD-GFASIGISRLLEPS 488
Cdd:cd21253     2 GIKALQQWCRQQTEGYRDVKVTNMTTSWRDGLAFCAIIHRFRPDLIDFDSLSKENVYENNKLAFTvAEKELGIPALLDAE 81

                          90       100
                  ....*....|....*....|....
gi 966981474  489 DMVLLAIPDKLTVMTYLYQIRAHF 512
Cdd:cd21253    82 DMVALKVPDKLSILTYVSQYYNYF 105

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 966981474  405 GRKPNAsqsLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYDGFASIGISRL 484
Cdd:cd21199     7 GSKRNA---LLKWCQEKTQGYKGIDITNFSSSWNDGLAFCALLHSYLPDKIPYSELNPQDKRRNFTLAFKAAESVGIPTT 83

                          90       100
                  ....*....|....*....|....*...
gi 966981474  485 LEPSDMVLLAIPDKLTVMTYLYQIRAHF 512
Cdd:cd21199    84 LTIDEMVSMERPDWQSVMSYVTAIYKHF 111

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 966981474  410 ASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYDGFAS-IGISRLLEPS 488
Cdd:cd21194     3 AKDALLLWCQRKTAGYPGVNIQNFTTSWRDGLAFNALIHAHRPDLIDYNRLDPNDHLGNLNNAFDVAEQeLGIAKLLDAE 82

                          90
                  ....*....|....*..
gi 966981474  489 DmVLLAIPDKLTVMTYL 505
Cdd:cd21194    83 D-VDVARPDEKSIMTYV 98

N-terminal C2 in EEIG1 and EHBP1 proteins; This version of the C2 domain was initally identified in the vertebrate estrogen early-induced gene 1 (EEIG1), and its Drosophila ortholog required for uptake of dsRNA via the endocytotic machinery to induce RNAi silencing. It is also in C.elegans ortholog Sym-3 (SYnthetic lethal with Mec-3) and the mammalian protein EHBP1 (EH domain Binding Protein-1) that regulates endocytotic recycling and two plant proteins, RPG that regulates Rhizobium-directed polar growth and PMI1 (Plastid Movement Impaired 1) that is essential for intracellular movement of chloroplasts in response to blue light.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966981474    12 GKHASKFQFVASYQELMVECTkkwQPDKLVVVWtrrsRRKSSKAHSWQPGIKNPYRGVVVWPvpENIEITVTLFKDPHAE 91
Cdd:pfam10358    1 KKRKPKFQFVLTIHELQNLPL---VGGELFVKW----RRGDKKGSSGTTEKALVNNGRAIFN--EEFSIPVTLFLDKKGG 71

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966981474    92 EFEDKEWTFVIENESPSGRRKALATSSINMKQYASPMPTQTDVKLKFKplSKKVVSATLQFSLSCIFLREGKAT 165
Cdd:pfam10358   72 KYEEKLLEFSVYKVTKKGKKKVLGKASIDLAEYANLKKKPTTVRFLLK--KSSKKNATLSLSIQVLPLGEDPND 143

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 966981474  411 SQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYD-GFASIGISRLLEPSD 489
Cdd:cd21195     6 PSKLLTWCQQQTEGYQHVNVTDLTTSWRSGLALCAIIHRFRPELINFDSLNEDDAVENNQLAFDvAEREFGIPPVTTGKE 85

                          90       100
                  ....*....|....*....|....*
gi 966981474  490 MVLLAIPDKLTVMTYLYQIRAHFSG 514
Cdd:cd21195    86 MASAQEPDKLSMVMYLSKFYELFRG 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 966981474  407 KPNasqSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYD-GFASIGISRLL 485
Cdd:cd21250     5 RPN---KLLTWCQKQTEGYQNVNVTDLTTSWKSGLALCAIIHRFRPELIDFDSLNEDDAVKNNQLAFDvAEREFGIPPVT 81

                          90       100
                  ....*....|....*....|....*....
gi 966981474  486 EPSDMVLLAIPDKLTVMTYLYQIRAHFSG 514
Cdd:cd21250    82 TGKEMASAEEPDKLSMVMYLSKFYELFRG 110

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966981474  409 NASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYD-GFASIGISRLLEP 487
Cdd:cd21189     1 SAKEALLLWARRTTEGYPGVRVTNFTSSWRDGLAFNAIIHRNRPDLIDFRSVRNQSNRENLENAFNvAEKEFGVTRLLDP 80

                          90
                  ....*....|....*..
gi 966981474  488 SDmVLLAIPDKLTVMTY 504
Cdd:cd21189    81 ED-VDVPEPDEKSIITY 96

calponin homology (CH) domain found in the smoothelin family; The smoothelin family includes smoothelin and smoothelin-like proteins. Smoothelins are actin-binding cytoskeletal proteins that are abundantly expressed in healthy visceral (smoothelin-A) and vascular (smoothelin-B) smooth muscle. SMTNL1, also called calponin homology-associated smooth muscle protein (CHASM), plays a role in the regulation of contractile properties of both striated and smooth muscles. It can bind to calmodulin and tropomyosin. When it is unphosphorylated, SMTNL1 may inhibit myosin dephosphorylation. SMTNL2 is highly expressed in skeletal muscle and could be associated with differentiating myocytes. 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 966981474  412 QSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYDGFASIG-ISRLLEPSDM 490
Cdd:cd21200     4 QMLLEWCQAKTRGYEHVDITNFSSSWSDGMAFCALIHHFFPDAFDYSSLDPKNRRKNFELAFSTAEELAdIAPLLEVEDM 83

                          90       100
                  ....*....|....*....|....
gi 966981474  491 VLLAI-PDKLTVMTYLYQIRAHFS 513
Cdd:cd21200    84 VRMGNrPDWKCVFTYVQSLYRHLR 107

second calponin homology (CH) domain found in the synaptic nuclear envelope protein (SYNE) family; The SYNE family includes SYNE-1, -2 and calmin. 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) and SYNE-2 (also called nesprin-2, KASH domain-containing protein 2, KASH2, nuclear envelope spectrin repeat protein 2, nucleus and actin connecting element protein, or protein NUANCE) may act redundantly. They are multi-isomeric modular proteins which form a linking network between organelles and the actin cytoskeleton to maintain subcellular spatial organization. They also act as components of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, which is involved in the connection between the nuclear lamina and the cytoskeleton. Calmin, also called calponin-like transmembrane domain protein, is a protein with calponin homology (CH) and transmembrane domains expressed in maturing spermatogenic cells. It may be involved in the development and/or maintenance of neuronal functions. 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 966981474  407 KPNASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYDgFAS--IGISRL 484
Cdd:cd21192     1 QGSAEKALLKWVQAEIGKYYGIRVTDFDKSWRDGVAFLALIHAIRPDLVDMKTVKNRSPRDNLELAFR-IAEqhLNIPRL 79

                          90       100
                  ....*....|....*....|....*...
gi 966981474  485 LEPSDmVLLAIPDKLTVMTYLYQIRAHF 512
Cdd:cd21192    80 LEVED-VLVDKPDERSIMTYVSQFLRMF 106

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 966981474   412 QSLLVWCKEVTKNY-RGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLN--PQDIKENNKKAYD-GFASIGISR-LLE 486
Cdd:pfam00307    5 KELLRWINSHLAEYgPGVRVTNFTTDLRDGLALCALLNKLAPGLVDKKKLNksEFDKLENINLALDvAEKKLGVPKvLIE 84

                           90       100
                   ....*....|....*....|....*...
gi 966981474   487 PSDMVLlaiPDKLTVMTYLYQIRAHFSG 514
Cdd:pfam00307   85 PEDLVE---GDNKSVLTYLASLFRRFQA 109

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 966981474  409 NASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYD-GFASIGISRLLEP 487
Cdd:cd21319     5 SAKDALLLWCQMKTAGYPNVNVTNFTSSWKDGLAFNALIHKHRPDLVDFGKLKKSNARHNLEHAFNvAERQLGITKLLDP 84

                          90       100
                  ....*....|....*....|....*.
gi 966981474  488 SDmVLLAIPDKLTVMTYLYQIRAHFS 513
Cdd:cd21319    85 ED-VFTENPDEKSIITYVVAFYHYFS 109

second calponin homology (CH) domain found in dystonin and similar proteins; 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. Dystonin 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 966981474  409 NASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYDGFASIGISRLLEPS 488
Cdd:cd21239     1 SAKERLLLWSQQMTEGYTGIRCENFTTCWRDGRLFNAIIHKYRPDLIDMNTVAVQSNLANLEHAFYVAEKLGVTRLLDPE 80

                          90
                  ....*....|....*..
gi 966981474  489 DmVLLAIPDKLTVMTYL 505
Cdd:cd21239    81 D-VDVSSPDEKSVITYV 96

second calponin homology (CH) domain found in spectrin beta chain, non-erythrocytic 2 (SPTBN2) 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. SPTBN2, also called beta-III spectrin, or spinocerebellar ataxia 5 protein (SCA5), probably plays an important role in the neuronal membrane skeleton. Mutations in SPTBN2 is associated with spinocerebellar ataxia type 5. SPTBN2 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 966981474  407 KPNASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYD-GFASIGISRLL 485
Cdd:cd21321     3 KKSAKDALLLWCQMKTAGYPNVNVHNFTTSWRDGLAFNAIVHKHRPDLIDFETLKKSNAHYNLQNAFNvAEKELGLTKLL 82

                          90       100
                  ....*....|....*....|....*...
gi 966981474  486 EPSDmVLLAIPDKLTVMTYLYQIRAHFS 513
Cdd:cd21321    83 DPED-VNVDQPDEKSIITYVATYYHYFS 109

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966981474  412 QSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYDGFASIG-ISRLLEPSDM 490
Cdd:cd21259     4 QMLLDWCRAKTRGYENVDIQNFSSSWSDGMAFCALVHNFFPEAFDYSQLSPQNRRHNFEVAFSSAEKHAdCPQLLDVEDM 83

                          90
                  ....*....|....*
gi 966981474  491 VLLAIPDKLTVMTYL 505
Cdd:cd21259    84 VRMREPDWKCVYTYI 98

calponin homology (CH) domain found in smoothelin-like protein 2; Smoothelin-like protein 2 (SMTNL2) is highly expressed in skeletal muscle and could be associated with differentiating myocytes. 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 966981474  412 QSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYDGFASI-GISRLLEPSDM 490
Cdd:cd21261     4 QILLEWCRSKTIGYKNIDLQNFSSSWSDGMAFCALVHSFFPEAFDYDSLSPSNRKHNFELAFSMAEKLaNCDRLIEVEDM 83

                          90       100
                  ....*....|....*....|...
gi 966981474  491 VLLA-IPDKLTVMTYLYQIRAHF 512
Cdd:cd21261    84 MVMGrKPDPMCVFTYVQSLYNHL 106

second calponin homology (CH) domain found in synaptic nuclear envelope protein 2 (SYNE-2) and similar proteins; SYNE-2, also called nesprin-2, KASH domain-containing protein 2 (KASH2), nuclear envelope spectrin repeat protein 2, nucleus and actin connecting element protein, or protein NUANCE, is a multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain subcellular spatial organization. SYNE-2 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-2 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 966981474  407 KPNASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYD-GFASIGISRLL 485
Cdd:cd21244     3 KMSARKALLLWAQEQCAKVGSISVTDFKSSWRNGLAFLAIIHALRPGLVDMEKLKGRSNRENLEEAFRiAEQELKIPRLL 82

                          90       100
                  ....*....|....*....|..
gi 966981474  486 EPSDmVLLAIPDKLTVMTYLYQ 507
Cdd:cd21244    83 EPED-VDVVNPDEKSIMTYVAQ 103

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 966981474  409 NASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYD-GFASIGISRLLEP 487
Cdd:cd21320     2 SAKDALLLWCQMKTAGYPNVNIHNFTTSWRDGMAFNALIHKHRPDLIDFDKLKKSNAHYNLQNAFNlAEQHLGLTKLLDP 81

                          90       100
                  ....*....|....*....|....*.
gi 966981474  488 SDmVLLAIPDKLTVMTYLYQIRAHFS 513
Cdd:cd21320    82 ED-ISVDHPDEKSIITYVVTYYHYFS 106

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 966981474  409 NASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQDIKENNKKAYD-GFASIGISRLLEP 487
Cdd:cd21289    10 SAKEGLLLWCQRKTAPYRNVNVQNFHTSWKDGLALCALIHRHRPDLIDYAKLRKDDPIGNLNTAFEvAEKYLDIPKMLDA 89

                          90       100
                  ....*....|....*....|....*....
gi 966981474  488 SDMVLLAIPDKLTVMTYLYQIRAHFSGQE 516
Cdd:cd21289    90 EDIVNTPKPDEKAIMTYVSCFYHAFAGAE 118

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 966981474    414 LLVWCKEVTKNYRGVKITNFTTSWRNGLSFCAILHHFRPDLIDYKSLNPQ----DIKENNKKAYDGFASIGISR-LLEPS 488
Cdd:smart00033    3 LLRWVNSLLAEYDKPPVTNFSSDLKDGVALCALLNSLSPGLVDKKKVAASlsrfKKIENINLALSFAEKLGGKVvLFEPE 82

                            90       100
                    ....*....|....*....|
gi 966981474    489 DMVLLAiPDKLTVMTYLYQI 508
Cdd:smart00033   83 DLVEGP-KLILGVIWTLISL 101