calponin homology (CH) domain found in EH domain-binding protein 1-like protein 1 and similar proteins; EHBP1L1 may 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 subfamily 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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFDGFAALGVSRLLEPA 1290
Cdd:cd21255     1 SSSQSLLEWCQEVTAGYRGVRVTNFTTSWRNGLAFCAILHHFHPDLVDYESLDPLDIKENNKKAFEAFASLGVPRLLEPA 80

                          90       100
                  ....*....|....*....|....*
gi 167736351 1291 DMVLLSVPDKLIVMTYLCQIRAFCT 1315
Cdd:cd21255    81 DMVLLPIPDKLIVMTYLCQLRAHFT 105

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 167736351    12 GKRAAKFQFVACYHELVLECTkkwQPDKLVVVWTRRNrricSKAHSWQPGIQNPYRGTVVWmvPENVDISVTLYRDPHVD 91
Cdd:pfam10358    1 KKRKPKFQFVLTIHELQNLPL---VGGELFVKWRRGD----KKGSSGTTEKALVNNGRAIF--NEEFSIPVTLFLDKKGG 71

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 167736351    92 QYETKEWTFIIENESKGQRK-VLATVDVNLAHHAGPVPAQVPLRLRLKPKSVKvvHAELSLTLSGVLLREGRAT 164
Cdd:pfam10358   72 KYEEKLLEFSVYKVTKKGKKkVLGKASIDLAEYANLKKKPTTVRFLLKKSSKK--NATLSLSIQVLPLGEDPND 143

calponin homology (CH) domain found in EH domain-binding protein 1-like protein 1 and similar proteins; EHBP1L1 may 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 subfamily 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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFDGFAALGVSRLLEPA 1290
Cdd:cd21255     1 SSSQSLLEWCQEVTAGYRGVRVTNFTTSWRNGLAFCAILHHFHPDLVDYESLDPLDIKENNKKAFEAFASLGVPRLLEPA 80

                          90       100
                  ....*....|....*....|....*
gi 167736351 1291 DMVLLSVPDKLIVMTYLCQIRAFCT 1315
Cdd:cd21255    81 DMVLLPIPDKLIVMTYLCQLRAHFT 105

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 167736351    12 GKRAAKFQFVACYHELVLECTkkwQPDKLVVVWTRRNrricSKAHSWQPGIQNPYRGTVVWmvPENVDISVTLYRDPHVD 91
Cdd:pfam10358    1 KKRKPKFQFVLTIHELQNLPL---VGGELFVKWRRGD----KKGSSGTTEKALVNNGRAIF--NEEFSIPVTLFLDKKGG 71

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 167736351    92 QYETKEWTFIIENESKGQRK-VLATVDVNLAHHAGPVPAQVPLRLRLKPKSVKvvHAELSLTLSGVLLREGRAT 164
Cdd:pfam10358   72 KYEEKLLEFSVYKVTKKGKKkVLGKASIDLAEYANLKKKPTTVRFLLKKSSKK--NATLSLSIQVLPLGEDPND 143

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 167736351   1216 LLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDP----LNIKQNNKQAFDGFAALGVSR-LLEPA 1290
Cdd:smart00033    3 LLRWVNSLLAEYDKPPVTNFSSDLKDGVALCALLNSLSPGLVDKKKVAAslsrFKKIENINLALSFAEKLGGKVvLFEPE 82

                            90
                    ....*....|....*..
gi 167736351   1291 DMVLLSvPDKLIVMTYL 1307
Cdd:smart00033   83 DLVEGP-KLILGVIWTL 98

K+-dependent Na+/Ca+ exchanger; [Transport and binding proteins, Cations and iron carrying compounds]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167736351   329 EDPPTGMGSSGETQAQISSQEGTEAHEARPEPDIEVRGSKDSLGGERSKVEEEDTGDRPgASGAGNREKNTKKSDTTAGE 408
Cdd:TIGR00927  628 GDLSKGDVAEAEHTGERTGEEGERPTEAEGENGEESGGEAEQEGETETKGENESEGEIP-AERKGEQEGEGEIEAKEADH 706

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167736351   409 AGESSElHQVDAEHKSKVQHRATEGP-EAAGPTPKARLGDTPEAPPRSAQRRMGVRTQEEAPSDlNPPPAEPEEHLGDLr 487
Cdd:TIGR00927  707 KGETEA-EEVEHEGETEAEGTEDEGEiETGEEGEEVEDEGEGEAEGKHEVETEGDRKETEHEGE-TEAEGKEDEDEGEI- 783

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167736351   488 darpagQEKGSAEVRGKVPAIGRAGPEQGSSARAASAGPQVSCVQTVPSDGQGvKSRDQRAQEAEVGESRVLETEAEwvp 567
Cdd:TIGR00927  784 ------QAGEDGEMKGDEGAEGKVEHEGETEAGEKDEHEGQSETQADDTEVKD-ETGEQELNAENQGEAKQDEKGVD--- 853

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 167736351   568 weviGTSKTDAGIPESLDTEAGTAESEILEAQESEAARSEGLEP 611
Cdd:TIGR00927  854 ----GGGGSDGGDSEEEEEEEEEEEEEEEEEEEEEEEEEENEEP 893

DNA polymerase III subunits gamma and tau; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167736351  300 PTPAPRLRKGSDAPSSPVPCSGDEVPNTSEDPPTGMGSSGETQAQISSQEGTEAHEARPEPdievrgskdslGGERSKVE 379
Cdd:PRK07764  590 PAPGAAGGEGPPAPASSGPPEEAARPAAPAAPAAPAAPAPAGAAAAPAEASAAPAPGVAAP-----------EHHPKHVA 658

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167736351  380 EEDTGDRPGASGAGnrekntkksdtTAGEAGESSELHQVDAEHKSkvQHRATEGPEAAGPTPKARLGDTPEAPPRSAQRR 459
Cdd:PRK07764  659 VPDASDGGDGWPAK-----------AGGAAPAAPPPAPAPAAPAA--PAGAAPAQPAPAPAATPPAGQADDPAAQPPQAA 725

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167736351  460 MGVRTQEEAPSDLNPPPAEPEEHLGDLRDARPAGQEkgsaevrgkvPAIGRAGPEQGSSARAASAGPQVSCVQTVPSDGq 539
Cdd:PRK07764  726 QGASAPSPAADDPVPLPPEPDDPPDPAGAPAQPPPP----------PAPAPAAAPAAAPPPSPPSEEEEMAEDDAPSMD- 794

                         250       260
                  ....*....|....*....|...
gi 167736351  540 gvksrDQRAQEAEVGESRVLETE 562
Cdd:PRK07764  795 -----DEDRRDAEEVAMELLEEE 812

calponin homology (CH) domain found in EH domain-binding protein 1-like protein 1 and similar proteins; EHBP1L1 may 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 subfamily 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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFDGFAALGVSRLLEPA 1290
Cdd:cd21255     1 SSSQSLLEWCQEVTAGYRGVRVTNFTTSWRNGLAFCAILHHFHPDLVDYESLDPLDIKENNKKAFEAFASLGVPRLLEPA 80

                          90       100
                  ....*....|....*....|....*
gi 167736351 1291 DMVLLSVPDKLIVMTYLCQIRAFCT 1315
Cdd:cd21255    81 DMVLLPIPDKLIVMTYLCQLRAHFT 105

calponin homology (CH) domain found in EH domain-binding protein 1 and similar proteins; 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. Members of this subfamily 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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFDGFAALGVSRLLEPA 1290
Cdd:cd21254     1 NASQSLLAWCKEVTKGYRGVKITNFTTSWRNGLAFCAILHHFRPDLIDYKSLNPHDIKENNKKAYDGFASLGISRLLEPS 80

                          90       100
                  ....*....|....*....|....*..
gi 167736351 1291 DMVLLSVPDKLIVMTYLCQIRAFCTGQ 1317
Cdd:cd21254    81 DMVLLAVPDKLTVMTYLYQIRAHFSGQ 107

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 167736351  1561 ELQALEQEQGQIDGRAAEVEKQLRSLMEsgaNRLQEEVLIQEWFTLVNKKNALIRRQDQLQLLIEEQDLERRFELLSREL 1640
Cdd:pfam12130    1 ELEEIEERQRELEERGVELEKALRGEMS---GDEEEEQLLQEWFKLVNEKNALVRRESELMYLAKEQDLEERQARLEQEL 77

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 167736351  1641 RAMLAIEEWQKTVAQQHREQLLLEELVSLVNQRDELVRDLDQKERIALEEDERL 1694
Cdd:pfam12130   78 RELMSKPDWLKTEEDKQREEELLEELVEIVEQRDALVDSLEEDRLREEEEDEEL 131

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 167736351 1214 QSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFD-GFAALGVSRLLEPADM 1292
Cdd:cd21197     3 QALLRWCRRQCEGYPGVNITNLTSSFRDGLAFCAILHRHRPELIDFHSLKKDNWLENNRLAFRvAETSLGIPALLDAEDM 82

                          90
                  ....*....|....*...
gi 167736351 1293 VLLSVPDKLIVMTYLCQI 1310
Cdd:cd21197    83 VTMHVPDRLSIITYVSQY 100

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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFDGFAA-LGVSRLLEP 1289
Cdd:cd21194     2 SAKDALLLWCQRKTAGYPGVNIQNFTTSWRDGLAFNALIHAHRPDLIDYNRLDPNDHLGNLNNAFDVAEQeLGIAKLLDA 81

                          90
                  ....*....|....*...
gi 167736351 1290 ADmVLLSVPDKLIVMTYL 1307
Cdd:cd21194    82 ED-VDVARPDEKSIMTYV 98

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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFDGFAALG-VSRLLEP 1289
Cdd:cd21200     1 SIKQMLLEWCQAKTRGYEHVDITNFSSSWSDGMAFCALIHHFFPDAFDYSSLDPKNRRKNFELAFSTAEELAdIAPLLEV 80

                          90
                  ....*....|....*....
gi 167736351 1290 ADMVLLS-VPDKLIVMTYL 1307
Cdd:cd21200    81 EDMVRMGnRPDWKCVFTYV 99

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 167736351 1210 VSSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFD-GFAALGVSRLLE 1288
Cdd:cd21195     3 DIRPSKLLTWCQQQTEGYQHVNVTDLTTSWRSGLALCAIIHRFRPELINFDSLNEDDAVENNQLAFDvAEREFGIPPVTT 82

                          90       100
                  ....*....|....*....|.
gi 167736351 1289 PADMVLLSVPDKLIVMTYLCQ 1309
Cdd:cd21195    83 GKEMASAQEPDKLSMVMYLSK 103

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 167736351    12 GKRAAKFQFVACYHELVLECTkkwQPDKLVVVWTRRNrricSKAHSWQPGIQNPYRGTVVWmvPENVDISVTLYRDPHVD 91
Cdd:pfam10358    1 KKRKPKFQFVLTIHELQNLPL---VGGELFVKWRRGD----KKGSSGTTEKALVNNGRAIF--NEEFSIPVTLFLDKKGG 71

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 167736351    92 QYETKEWTFIIENESKGQRK-VLATVDVNLAHHAGPVPAQVPLRLRLKPKSVKvvHAELSLTLSGVLLREGRAT 164
Cdd:pfam10358   72 KYEEKLLEFSVYKVTKKGKKkVLGKASIDLAEYANLKKKPTTVRFLLKKSSKK--NATLSLSIQVLPLGEDPND 143

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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFDgfAA---LGVSRLL 1287
Cdd:cd21248     2 SAKDALLLWCQMKTAGYPNVNVRNFTTSWRDGLAFNALIHKHRPDLIDYDKLSKSNALYNLQNAFN--VAeqkLGLTKLL 79

                          90
                  ....*....|....*....
gi 167736351 1288 EPADmVLLSVPDKLIVMTY 1306
Cdd:cd21248    80 DPED-VNVEQPDEKSIITY 97

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 167736351 1212 SSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFD-GFAALGVSRLLEPA 1290
Cdd:cd21187     1 LEKTLLAWCRQSTRGYEQVDVKNFTTSWRDGLAFNALIHRHRPDLFDFDSLVKDSPESRLEHAFTvAHEHLGIEKLLDPE 80

                          90
                  ....*....|....*..
gi 167736351 1291 DmVLLSVPDKLIVMTYL 1307
Cdd:cd21187    81 D-VNVEQPDKKSILMYV 96

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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFDGFAAL-GVSRLLEP 1289
Cdd:cd21261     1 SIKQILLEWCRSKTIGYKNIDLQNFSSSWSDGMAFCALVHSFFPEAFDYDSLSPSNRKHNFELAFSMAEKLaNCDRLIEV 80

                          90
                  ....*....|....*....
gi 167736351 1290 ADMVLLS-VPDKLIVMTYL 1307
Cdd:cd21261    81 EDMMVMGrKPDPMCVFTYV 99

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 167736351 1216 LLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFD-GFAALGVSRLLEPADMVL 1294
Cdd:cd21250     9 LLTWCQKQTEGYQNVNVTDLTTSWKSGLALCAIIHRFRPELIDFDSLNEDDAVKNNQLAFDvAEREFGIPPVTTGKEMAS 88

                          90
                  ....*....|...
gi 167736351 1295 LSVPDKLIVMTYL 1307
Cdd:cd21250    89 AEEPDKLSMVMYL 101

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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFDGFAALG-VSRLLEP 1289
Cdd:cd21259     1 SIKQMLLDWCRAKTRGYENVDIQNFSSSWSDGMAFCALVHNFFPEAFDYSQLSPQNRRHNFEVAFSSAEKHAdCPQLLDV 80

                          90
                  ....*....|....*...
gi 167736351 1290 ADMVLLSVPDKLIVMTYL 1307
Cdd:cd21259    81 EDMVRMREPDWKCVYTYI 98

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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFDGFAALG-VSRLLEP 1289
Cdd:cd21258     1 SIKQMLLDWCRAKTRGYEHVDIQNFSSSWSDGMAFCALVHNFFPDAFDYSQLSPQNRRQNFEVAFSAAEMLAdCVPLVEV 80

                          90
                  ....*....|....*....
gi 167736351 1290 ADMVLL-SVPDKLIVMTYL 1307
Cdd:cd21258    81 EDMMIMgKKPDSKCVFTYV 99

second calponin homology (CH) domain found in spectrin beta chain, non-erythrocytic 4 (SPTBN4) 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. SPTBN4, also called beta-IV spectrin, or spectrin, non-erythroid beta chain 3 (SPTBN3), is a novel spectrin isolated as an interactor of the receptor tyrosine phosphatase-like protein ICA512. Its mutation associates with congenital myopathy, neuropathy, and central deafness. SPTBN4 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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFDGFAA-LGVSRLLEP 1289
Cdd:cd21322    17 SAKDALLLWCQMKTAGYPEVNIQNFTTSWRDGLAFNALIHRHRPDLIDFSKLTKSNATYNLQQAFNTAEQhLGLTKLLDP 96

                          90
                  ....*....|....*...
gi 167736351 1290 ADmVLLSVPDKLIVMTYL 1307
Cdd:cd21322    97 ED-VNMEAPDEKSIITYV 113

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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFD-GFAALGVSRLLEP 1289
Cdd:cd21192     3 SAEKALLKWVQAEIGKYYGIRVTDFDKSWRDGVAFLALIHAIRPDLVDMKTVKNRSPRDNLELAFRiAEQHLNIPRLLEV 82

                          90       100
                  ....*....|....*....|
gi 167736351 1290 ADmVLLSVPDKLIVMTYLCQ 1309
Cdd:cd21192    83 ED-VLVDKPDERSIMTYVSQ 101

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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFD-GFAALGVSRLLEP 1289
Cdd:cd21321     5 SAKDALLLWCQMKTAGYPNVNVHNFTTSWRDGLAFNAIVHKHRPDLIDFETLKKSNAHYNLQNAFNvAEKELGLTKLLDP 84

                          90
                  ....*....|....*...
gi 167736351 1290 ADmVLLSVPDKLIVMTYL 1307
Cdd:cd21321    85 ED-VNVDQPDEKSIITYV 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 167736351 1211 SSSQSLLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDPLNIKQNNKQAFD-GFAALGVSRLLEP 1289
Cdd:cd21320     2 SAKDALLLWCQMKTAGYPNVNIHNFTTSWRDGMAFNALIHKHRPDLIDFDKLKKSNAHYNLQNAFNlAEQHLGLTKLLDP 81

                          90
                  ....*....|....*...
gi 167736351 1290 ADmVLLSVPDKLIVMTYL 1307
Cdd:cd21320    82 ED-ISVDHPDEKSIITYV 98

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 167736351   1216 LLEWCQEVTNGYRGVCITNFTTSWRNGLAFCAILHRFYPDKIDYFSLDP----LNIKQNNKQAFDGFAALGVSR-LLEPA 1290
Cdd:smart00033    3 LLRWVNSLLAEYDKPPVTNFSSDLKDGVALCALLNSLSPGLVDKKKVAAslsrFKKIENINLALSFAEKLGGKVvLFEPE 82

                            90
                    ....*....|....*..
gi 167736351   1291 DMVLLSvPDKLIVMTYL 1307
Cdd:smart00033   83 DLVEGP-KLILGVIWTL 98