Domain of unknown function (DUF4757); This presumed domain is functionally uncharacterized. This domain family is found in eukaryotes, and is typically between 145 and 166 amino acids in length. The family is found in association with pfam00412. There are two completely conserved residues (W and L) that may be functionally important.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   655 MLARKIQSWKLGTAVP----------PISFKPGPCSEADLQKWEAIWE-------ASRLRHRKRLMVERLFQKIYGENGS 717
Cdd:pfam15949    1 MLARRTSSSEPKSSVPfnqflpnksnQSAYVPAPLRKKRAEKEEDIRRswstrtqPSKVAYPPRQFVQRLFQKVSDDLGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   718 KSMSDVSAEDV-QNLRQVRYEEMQKIKSQLKEQDQKWQDDLAKWKNRRKSYTSDLQKKKEEREEIEKQALEKS----DRS 792
Cdd:pfam15949   81 KSMSDIRCEEEaQPLSQVRYEELQKIRNQLKEEEDKWQDDLARWKSRRRSASQDLIKKEEERKKIEKLMSGEGgdsnRRK 160

                          170
                   ....*....|
gi 568988027   793 SKTFREMLQD 802
Cdd:pfam15949  161 SKTFKEMVEE 170

LIM is a small protein-protein interaction domain, containing two zinc fingers; LIM domains are identified in a diverse group of proteins with wide variety of biological functions, including gene expression regulation, cell fate determination, cytoskeleton organization, tumor formation and development. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes. They perform their functions through interactions with other protein partners. LIM domains are 50-60 amino acids in size and share two characteristic highly conserved zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. The consensus sequence of LIM domain has been defined as C-x(2)-C-x(16,23)-H-x(2)-[CH]-x(2)-C-x(2)-C-x(16,21)-C-x(2,3)-[CHD] (where X denotes any amino acid).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027 1678 CSYCNN-ILGKgaaMIIETLGLSYHLHCFKCVSCGCDLGGSSSGaevrIRNHQLYCNDCY 1736
Cdd:cd08368     1 CAGCGKpIEGR---ELLRALGKKWHPECFKCAECGKPLGGDSFY----EKDGKPYCEKCY 53

Domain of unknown function (DUF4757); This presumed domain is functionally uncharacterized. This domain family is found in eukaryotes, and is typically between 145 and 166 amino acids in length. The family is found in association with pfam00412. There are two completely conserved residues (W and L) that may be functionally important.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   655 MLARKIQSWKLGTAVP----------PISFKPGPCSEADLQKWEAIWE-------ASRLRHRKRLMVERLFQKIYGENGS 717
Cdd:pfam15949    1 MLARRTSSSEPKSSVPfnqflpnksnQSAYVPAPLRKKRAEKEEDIRRswstrtqPSKVAYPPRQFVQRLFQKVSDDLGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   718 KSMSDVSAEDV-QNLRQVRYEEMQKIKSQLKEQDQKWQDDLAKWKNRRKSYTSDLQKKKEEREEIEKQALEKS----DRS 792
Cdd:pfam15949   81 KSMSDIRCEEEaQPLSQVRYEELQKIRNQLKEEEDKWQDDLARWKSRRRSASQDLIKKEEERKKIEKLMSGEGgdsnRRK 160

                          170
                   ....*....|
gi 568988027   793 SKTFREMLQD 802
Cdd:pfam15949  161 SKTFKEMVEE 170

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 568988027     17 EAQRWVEAVTEKNFE--TTDFRASLENGVLLCDLINKLKPGVV--KKINRLSTPIAGLDNINVFLRACEQIGLKEaQLFH 92
Cdd:smart00033    2 TLLRWVNSLLAEYDKppVTNFSSDLKDGVALCALLNSLSPGLVdkKKVAASLSRFKKIENINLALSFAEKLGGKV-VLFE 80

                    ....*.
gi 568988027     93 PGDLQD 98
Cdd:smart00033   81 PEDLVE 86

LIM is a small protein-protein interaction domain, containing two zinc fingers; LIM domains are identified in a diverse group of proteins with wide variety of biological functions, including gene expression regulation, cell fate determination, cytoskeleton organization, tumor formation and development. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes. They perform their functions through interactions with other protein partners. LIM domains are 50-60 amino acids in size and share two characteristic highly conserved zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. The consensus sequence of LIM domain has been defined as C-x(2)-C-x(16,23)-H-x(2)-[CH]-x(2)-C-x(2)-C-x(16,21)-C-x(2,3)-[CHD] (where X denotes any amino acid).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027 1678 CSYCNN-ILGKgaaMIIETLGLSYHLHCFKCVSCGCDLGGSSSGaevrIRNHQLYCNDCY 1736
Cdd:cd08368     1 CAGCGKpIEGR---ELLRALGKKWHPECFKCAECGKPLGGDSFY----EKDGKPYCEKCY 53

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568988027   1116 FGFTI---KWDISGIFVASVEQGSPAEFSQLQVDDEILAINNTKFSYKDTKkwEEVMANAQETGNLVMDVRR 1184
Cdd:smart00228   14 LGFSLvggKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHL--EAVDLLKKAGGKVTLTVLR 83

Calponin [Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   17 EAQRWVEAVTEKNFETT-DFRASLENGVLLCDLINKLKPGVVKkINRLSTPIAGLDNINVFLRACEQIGLKEAQLFHPGD 95
Cdd:COG5199    17 EVTLWIETVLGEKFEPPgDLLSLLKDGVRLCRILNEASPLDIK-YKESKMPFVQMENISSFINGLKKLRVPEYELFQTND 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 568988027   96 LQDLSNrvtvkqeetdrrLKNVLITLYWLGRKAQSNPYYNGPYL 139
Cdd:COG5199    96 LFEAKD------------LRQVVICLYSLSRYAQKERMFSGPFL 127

PDZ domain; PDZ domains are found in diverse signaling proteins.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 568988027  1116 FGFTIK----WDISGIFVASVEQGSPAEFSQLQVDDEILAINNTKFS 1158
Cdd:pfam00595   12 LGFSLKggsdQGDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVE 58

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027  1085 RGSPLREVSRSLDQFSDmrvsiNQTPGNKPVFGFT-------------IKWDISGIFVASVEQGSPAEFSQLQVDDEILA 1151
Cdd:TIGR02037  314 RKGKEKTITVTLGASPE-----EQASSSNPFLGLTvanlspeirkelrLKGDVKGVVVTKVVSGSPAARAGLQPGDVILS 388

                           90       100       110
                   ....*....|....*....|....*....|...
gi 568988027  1152 INNTkfSYKDTKKWEEVMANAQETGNLVMDVRR 1184
Cdd:TIGR02037  389 VNQQ--PVSSVAELRKVLARAKKGGRVALLILR 419

calponin homology (CH) domain found in LIM domain only protein 7 and similar proteins; This family includes LIM domain only protein 7 (LMO-7) and LIM and calponin homology domains-containing protein 1 (LIMCH1), and similar proteins. LMO-7, also called F-box only protein 20, or LOMP, is a transcription regulator for expression of many Emery-Dreifuss muscular dystrophy (EDMD)-relevant genes. It binds to alpha-actinin and AF6/afadin at adherens junctions for epithelial cell-cell adhesion. LIMCH1 acts as an actin stress fiber-associated protein that activates the non-muscle myosin IIa complex by promoting the phosphorylation of its regulatory subunit MRLC/MYL9. It positively regulates actin stress fiber assembly and stabilizes focal adhesions, and therefore negatively regulates cell spreading and cell migration. Members of this family contain a single copy of the CH domain at the N-terminus. CH domains are actin filament (F-actin) binding motifs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   14 AFAEAQRWVEAVTEKNFETTDFRASLENGVLLCDLINKLKPGVVKKINRLSTPIAGLDNINVFLRACEQIGLKEAQLFHP 93
Cdd:cd21208     1 ALKEARTWIEAVTGKKFPSDDFRESLEDGILLCELINAIKPGSIKKINRLPTPIAGLDNLNLFLKACEDLGLKDSQLFDP 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 568988027   94 GDLQDLSNRVT---VKQEETDRRLKNVLITLYWLGRKAQ 129
Cdd:cd21208    81 TDLQDLSNRRIathVRKKEDERRLKNVAITLYWLGRAAR 119

Domain of unknown function (DUF4757); This presumed domain is functionally uncharacterized. This domain family is found in eukaryotes, and is typically between 145 and 166 amino acids in length. The family is found in association with pfam00412. There are two completely conserved residues (W and L) that may be functionally important.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   655 MLARKIQSWKLGTAVP----------PISFKPGPCSEADLQKWEAIWE-------ASRLRHRKRLMVERLFQKIYGENGS 717
Cdd:pfam15949    1 MLARRTSSSEPKSSVPfnqflpnksnQSAYVPAPLRKKRAEKEEDIRRswstrtqPSKVAYPPRQFVQRLFQKVSDDLGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   718 KSMSDVSAEDV-QNLRQVRYEEMQKIKSQLKEQDQKWQDDLAKWKNRRKSYTSDLQKKKEEREEIEKQALEKS----DRS 792
Cdd:pfam15949   81 KSMSDIRCEEEaQPLSQVRYEELQKIRNQLKEEEDKWQDDLARWKSRRRSASQDLIKKEEERKKIEKLMSGEGgdsnRRK 160

                          170
                   ....*....|
gi 568988027   793 SKTFREMLQD 802
Cdd:pfam15949  161 SKTFKEMVEE 170

calponin homology (CH) domain found in Drosophila melanogaster muscle-specific protein 20 (dMP20) and similar domains; This subfamily contains Drosophila melanogaster muscle-specific protein 20 (dMP20), Echinococcus granulosus myophilin, Dictyostelium discoideum Rac guanine nucleotide exchange factor B (also called Trix), and similar proteins. dMP20 is present only in the synchronous muscles of D. melanogaster. It may be involved in the system linking the nerve impulse with the contraction or the relaxation process. Trix is involved in the regulation of the late steps of the endocytic pathway. dMP20 contains a single copy of the CH domain, while Trix (triple CH-domain array exchange factor) contains three, two type 3 CH domains which are included in this model, and one type 1 CH domain that is not included in this subfamily, but is part of the superfamily. CH domains are actin filament (F-actin) binding motifs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   16 AEAQRWVEAVTEKNFET-TDFRASLENGVLLCDLINKLKPGVVKKINRLSTPIAGLDNINVFLRACEQIGLKEAQLFHPG 94
Cdd:cd21207     8 AEALDWIEAVTGEKLDDgKDYEDVLKDGVILCKLINILKPGSVKKINTSKMAFKLMENIENFLTACKGYGVPKTDLFQTV 87

                          90       100       110
                  ....*....|....*....|....*....|..
gi 568988027   95 DLQDLSNrvtvkqeetdrrLKNVLITLYWLGR 126
Cdd:cd21207    88 DLYEKKN------------IPQVTNCLFALGR 107

Domain of unknown function (DUF4757); This presumed domain is functionally uncharacterized. This domain family is found in eukaryotes, and is typically between 145 and 166 amino acids in length. The family is found in association with pfam00412. There are two completely conserved residues (W and L) that may be functionally important.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568988027   242 MSYRRISAIEPKSALPFNRFLPNKSKQPSYVPAPLRKKRPDKHEDNRRSW-----ASPVYTETDGTFS 304
Cdd:pfam15949    1 MLARRTSSSEPKSSVPFNQFLPNKSNQSAYVPAPLRKKRAEKEEDIRRSWstrtqPSKVAYPPRQFVQ 68

calponin homology (CH) domain found in the calponin family; Calponin is an actin filament-associated regulatory protein expressed in smooth muscle and many types of non-muscle cells. There are three calponin isoforms, calponin-1, -2, -3. All of them are actin-binding proteins with functions in inhibiting actin-activated myosin ATPase and stabilizing the actin cytoskeleton. Calponin-1 is specifically expressed in smooth muscle cells and plays a role in fine-tuning smooth muscle contractility. Calponin-2 is expressed in both smooth muscle and non-muscle cells and regulates multiple actin cytoskeleton-based functions. Calponin-3 is expressed in the brain and participates in actin cytoskeleton-based activities in embryonic development and myogenesis. 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 568988027   16 AEAQRWVEAVTEKNFeTTDFRASLENGVLLCDLINKLKPGVVKKINRLSTPIAGLDNINVFLRACEQIGLKEAQLFHPGD 95
Cdd:cd21211     6 AELRTWIEGVTGLSI-GPNFQKGLKDGIILCELINKLQPGSVKKINESMQNWHQLENIGNFIKAIVSYGMKPHDIFEAND 84

                          90
                  ....*....|.
gi 568988027   96 LQDLSNRVTVK 106
Cdd:cd21211    85 LFENGNMTQVQ 95

calponin homology (CH) domain found in calponin-3; Calponin-3 (CNN3), also called acidic isoform calponin, is an F-actin-binding protein that is expressed in the brain and has been shown to control dendritic spine morphology, density, and plasticity by regulating actin cytoskeletal reorganization and dynamics. 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 568988027   17 EAQRWVEAVTEKNFeTTDFRASLENGVLLCDLINKLKPGVVKKINRLSTPIAGLDNINVFLRACEQIGLKEAQLFHPGDL 96
Cdd:cd21284     9 ELRNWIEEVTGMSI-GENFQKGLKDGVILCELINKLQPGSIRKINESKLNWHQLENIGNFIKAIQAYGMKPHDIFEANDL 87

                          90
                  ....*....|
gi 568988027   97 QDLSNRVTVK 106
Cdd:cd21284    88 FENGNMTQVQ 97

calponin homology (CH) domain found in the IQ motif containing GTPase activating protein family; Members of the IQ motif containing GTPase activating protein (IQGAP) family are associated with the Ras GTP-binding protein and act as essential regulators of cytoskeletal function. There are three known IQGAP family members: IQGAP1, IQGAP2, and IQGAP3. They are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity. It lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3 regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   16 AEAQRWVEAVTEKNFE-TTDFRASLENGVLLCDLINKLKPGVVKKINrlsTPIAGL-----DNINVFLRACEQIGLKEAQ 89
Cdd:cd21206    11 EEAKQWIEACLNEELPpTTEFEEELRNGVVLAKLANKFAPKLVPLKK---IYDVGLqfrhtDNINHFLRALKKIGLPKIF 87

                          90
                  ....*....|..
gi 568988027   90 LFHPGDLQDLSN 101
Cdd:cd21206    88 HFETTDLYEKKN 99

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 568988027    20 RWVEAVTEKNFET---TDFRASLENGVLLCDLINKLKPGVVKKINRLSTPIAGLDNINVFLRACEQ-IGLKEAQLfhpgD 95
Cdd:pfam00307    9 RWINSHLAEYGPGvrvTNFTTDLRDGLALCALLNKLAPGLVDKKKLNKSEFDKLENINLALDVAEKkLGVPKVLI----E 84

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 568988027    96 LQDLsnrvtvkqeeTDRRLKNVLITLYWLGRKAQS 130
Cdd:pfam00307   85 PEDL----------VEGDNKSVLTYLASLFRRFQA 109

calponin homology (CH) domain found in the Pak Interactive eXchange factor family; Pak Interactive eXchange factor (PIX) proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX family, alpha-PIX and beta-PIX. Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6), is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7), plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. Both alpha-PIX and beta-PIX contain a single copy of the CH domain at the N-terminus. CH domains are actin filament (F-actin) binding motifs.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568988027   36 RASLENGVLLCDLINKLKPGVVKKInrLSTPIAG---LDNINVFLRACEQIGLKEAQLFHPGDL 96
Cdd:cd21202    31 SESLKNGVVLCRLVNRLKPGTVEKI--YDEPTTEeecLYNFESFLKACQELGILAEEIFDPNDL 92

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568988027   1116 FGFTI---KWDISGIFVASVEQGSPAEFSQLQVDDEILAINNTKFSYKDTKkwEEVMANAQETGNLVMDVRR 1184
Cdd:smart00228   14 LGFSLvggKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHL--EAVDLLKKAGGKVTLTVLR 83

calponin homology (CH) domain found in the growth arrest-specific protein 2 family; The growth arrest-specific protein 2 (GAS-2) family includes GAS-2, and GAS-2 like proteins, GAS2L1-3. GAS-2 may play a role in apoptosis by acting as a cell death substrate for caspases. GAS2L1 (also called GAS2-related protein on chromosome 22 or growth arrest-specific protein 2-like 1) and GAS2L2 (also called GAS2-related protein on chromosome 17 or growth arrest-specific protein 2-like 2) may be involved in the cross-linking of microtubules and microfilaments. GAS2L3, also called GAS2-like protein 3, is a cytoskeletal linker protein that may promote and stabilize the formation of the actin and microtubule network. Members of this family contain a single copy of the CH domain at the N-terminal region. CH domains are actin filament (F-actin) binding motifs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   20 RWVEAVTEKNFETTDFRASLENGVLLCDLINKL--------------KPGVVKKI----NRLSTPIAGLDNINVFLRACE 81
Cdd:cd21204    13 EWLNDLLGDDLTPDNFLDELRNGVVLCQLAQKIqeaaekareagkknGPPPSYKLkcneNAKPGSFFARDNVANFLRWCR 92

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 568988027   82 QIGLKEAQLFHPGDLqdlsnrVTVKQEetdrrlKNVLITLYWLGRKAQS 130
Cdd:cd21204    93 KLGVDEVLLFESEDL------VLHKNP------RQVLLCLLELARIAAR 129

calponin homology (CH) domain found in Arabidopsis thaliana Kinesin-like KIN-14 protein family; Kinesins are microtubule-dependent molecular motors that play important roles in intracellular transport and in cell division. This family includes a group of kinesin-like proteins belonging to KIN-14 protein family. They all contain a single copy of the CH domain at the N-terminus. CH domains are actin filament (F-actin) binding motifs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568988027   34 DFRASLENGVLLCDLINKLKPGVVKKI--------NRLSTPIAGLDNINVFLRACEQIGLKeaqLFHPGDLQ 97
Cdd:cd21203    25 EFRLCLRDGVVLCKLLNKLQPGAVPKVvespddpdGAAGSAFQYFENVRNFLVAIEEMGLP---TFEASDLE 93

Calponin [Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   17 EAQRWVEAVTEKNFETT-DFRASLENGVLLCDLINKLKPGVVKkINRLSTPIAGLDNINVFLRACEQIGLKEAQLFHPGD 95
Cdd:COG5199    17 EVTLWIETVLGEKFEPPgDLLSLLKDGVRLCRILNEASPLDIK-YKESKMPFVQMENISSFINGLKKLRVPEYELFQTND 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 568988027   96 LQDLSNrvtvkqeetdrrLKNVLITLYWLGRKAQSNPYYNGPYL 139
Cdd:COG5199    96 LFEAKD------------LRQVVICLYSLSRYAQKERMFSGPFL 127

Predicted metalloprotease, contains C-terminal PDZ domain [General function prediction only];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568988027 1109 TPGNKPVFGFTIKWDISGIFVASVEQGSPAEFSQLQVDDEILAINNTKFSykdTKKWEEVMANAQETGNLVMDVRRYGK 1187
Cdd:COG3975   478 APSLKPSLGLRVSADGGGLVVTSVLWGSPAYKAGLSAGDELLAIDGLRVT---ADNLDDALAAYKPGDPIELLVFRRDE 553

calponin homology (CH) domain found in alpha-Pak Interactive eXchange factor; Alpha-Pak Interactive eXchange factor (alpha-PIX), also called PAK-interacting exchange factor alpha, Rho guanine nucleotide exchange factor 6 (ARHGEF6), Rac/Cdc42 guanine nucleotide exchange factor 6, or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Alpha-PIX contains a single copy of the CH domain at its N-terminus. CH domains are actin filament (F-actin) binding motifs.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568988027   36 RASLENGVLLCDLINKLKPGVVKKI-NRLSTPIAGLDNINVFLRACEQIGLkeaQLFHPGDL 96
Cdd:cd21265    32 KSSLKDGVVLCKLIERLLPGSVEKYcLEPKTEADCIGNIKEFLKGCAALKV---ETFEPDDL 90

calponin homology (CH) domain found in VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the CH domain, an actin-binding domain which is present as a single copy in VAV1 protein.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   25 VTEKNFETTDFRASLENGVLLCDLINKLKPGVV--KKIN---RLSTPIAgLDNINVFLRAC-EQIGLKEAQLFHPGDLQD 98
Cdd:cd21262    22 VTWDSAQVCDLAQALRDGVLLCQLLNNLLPHAVnlREINlrpQMSQFLC-LKNIRTFLSTCcEKFGLRKSELFEAFDLFD 100

                  .
gi 568988027   99 L 99
Cdd:cd21262   101 V 101

calponin homology (CH) domain found in Ras GTPase-activating-like protein IQGAP3; IQ motif containing GTPase activating protein 3 (IQGAP3) associates with Ras GTP-binding proteins. It regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton. It belongs to the IQGAP family, which consists of multi-domain proteins having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP3 contains a single copy of the CH domain at the N-terminus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   17 EAQRWVEAVTEKNFET-TDFRASLENGVLLCDLINKLKPGVV--KKI---NRLSTPIAGL-----DNINVFLRACEQIGL 85
Cdd:cd21276    12 EAKRWMEACLKEELPPpTELEESLRNGVYLAKLGHCFAPRVVplKKIydlEQMRYQATGLhfrhtDNINHWRNAMMHIGL 91

                          90
                  ....*....|....*...
gi 568988027   86 keAQLFHP--GDLQDLSN 101
Cdd:cd21276    92 --PSIFHPetTDIYDKKN 107

calponin homology (CH) domain found in the transgelin family; The transgelin (TAGLN) family includes transgelin, transgelin-2 and transgelin-3. Transgelin, also called 22 kDa actin-binding protein, protein WS3-10, or smooth muscle protein 22-alpha (SM22-alpha), acts as an actin cross-linking/gelling protein that may be involved in calcium interactions and in regulating contractile properties of the cell. Transgelin-2, also called epididymis tissue protein Li 7e, or SM22-alpha homolog, acts as an actin-binding protein that induces actin gelation and regulates actin cytoskeleton. It may participate in the development and progression of multiple cancers. Transgelin-3, also called neuronal protein 22 (NP22), or neuronal protein NP25, may have a role in alcohol-related adaptations and may mediate regulatory signal transduction pathways in neurons. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568988027   33 TDFRASLENGVLLCDLINKLKP---GVVKKINRLSTPIAGLDNINVFLRACEQIGLKEAQLFHPGDLQDLSNRVTVKQ 107
Cdd:cd21209    28 LGFQKWLKDGTVLCKLINSLYPegsKPVKKIQSSKMAFKQMEQISQFLKAAEDYGVRTTDIFQTVDLWEGKDMAAVQR 105

The third LIM domain of actin binding LIM (abLIM) proteins; The third LIM domain of actin binding LIM (abLIM) proteins: Three homologous members of the abLIM protein family have been identified; abLIM-1, abLIM-2 and abLIM-3. The N-terminal of abLIM consists of four tandem repeats of LIM domains and the C-terminal of acting binding LIM protein is a villin headpiece domain, which has strong actin binding activity. The abLIM-1, which is expressed in retina, brain, and muscle tissue, has been indicated to function as a tumor suppressor. AbLIM-2 and -3, mainly expressed in muscle and neuronal tissue, bind to F-actin strongly. They may serve as a scaffold for signaling modules of the actin cytoskeleton and thereby modulate transcription. It has shown that LIM domains of abLIMs interact with STARS (striated muscle activator of Rho signaling), which directly binds actin and stimulates serum-response factor (SRF)-dependent transcription. All LIM domains are 50-60 amino acids in size and share two characteristic highly conserved zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes.

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568988027 1678 CSYCNNILGKGAAMIieTLGLSYHLHCFKCVSCGCDLGGSSSGaevriRNHQLYCNDCY 1736
Cdd:cd09329     1 CAGCGQEIKNGQALL--ALDKQWHVWCFKCKECGKVLTGEYMG-----KDGKPYCERDY 52

PDZ domain 3 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 568988027 1126 GIFVASVEQGSPAEFSQLQVDDEILAINNTKF 1157
Cdd:cd06729    24 GIFVAGVQEGSPAEKQGLQEGDQILKVNGVDF 55

The third LIM domain of Zyxin-like family; The third LIM domain of Zyxin like family: This family includes Ajuba, Limd1, WTIP, Zyxin, LPP, and Trip6 LIM proteins. Members of Zyxin family contain three tandem C-terminal LIM domains, and a proline-rich N-terminal region. Zyxin proteins are detected primarily in focal adhesion plaques. They function as scaffolds, participating in the assembly of multiple interactions and signal transduction networks, which regulate cell adhesion, spreading, and motility. They can also shuffle into nucleus. In nucleus, zyxin proteins affect gene transcription by interaction with a variety of nuclear proteins, including several transcription factors, playing regulating roles in cell proliferation, differentiation and apoptosis. As in other LIM domains, this domain family is 50-60 amino acids in size and shares two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568988027 1678 CSYCNN-IL---GKGAAMIIETLGLSYHLHCFKCVSCGCDLggsSSGAEVR----IRNHqLYCNDC 1735
Cdd:cd09357     1 CSVCGEpIMpepGQDETVRIVALDRSFHVNCYKCEDCGMLL---SSEDEGQgcypLDGH-LLCKSC 62

PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the first PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027 1104 VSINQTPGNKpvFGFTIKWDIS---GIFVASVEQGSPAEFSQLQVDDEILAINNTKFSYKDTKKWEEVManaqeTGN--L 1178
Cdd:cd10833     4 VTVEKSPDGS--LGFSVRGGSEhglGIFVSKVEEGSAAERAGLCVGDKITEVNGVSLENITMSSAVKVL-----TGSnrL 76

                  ....*...
gi 568988027 1179 VMDVRRYG 1186
Cdd:cd10833    77 RMVVRRMG 84

PDZ domain 2 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568988027 1105 SINQTPGNKPvfgftikwdisGIFVASVEQGSPAEFSQLQVDDEILAINNTKFSYKDTKkwEEVMA 1170
Cdd:cd06738    18 SISSGPTQKP-----------GIFISNVKPGSLAEEVGLEVGDQIVEVNGTSFTNVDHK--EAVMA 70

calponin homology (CH) domain found in Ras GTPase-activating-like protein IQGAP2; IQ motif containing GTPase activating protein 2 (IQGAP2) is a member of the IQGAP family, which consists of multi-domain proteins having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP2 binds to activated Cdc42 and Rac1 but does not seem to stimulate their GTPase activity. It associates with calmodulin. IQGAP2 contains a single copy of the CH domain at the N-terminus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988027   17 EAQRWVEAVTEKNFE-TTDFRASLENGVLLCDLINKLKPGVV--KKI---NRLSTPIAGL-----DNINVFLRACEQIGL 85
Cdd:cd21275    36 EAKQWIEACLNEELPpTTELEEGLRNGVYLVKLAKFFAPKLVseKKIydvDQVRYKRSGLhfrhtDNTVQWLRAMESIGL 115