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 568988041   242 MSYRRISAIEPKSALPFNRFLPNKSKQPSYVPAPLRKKRPDKHEDNRRSW-----ASPVYTETDGTFSRLFQKIYGENGS 316
Cdd:pfam15949    1 MLARRTSSSEPKSSVPFNQFLPNKSNQSAYVPAPLRKKRAEKEEDIRRSWstrtqPSKVAYPPRQFVQRLFQKVSDDLGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988041   317 KSMSDVSAEDV-QNLRQVRYEEMQKIKSQLKEQDQKWQDDLAKWKNRRKSYTSDLQKKKEEREEIEKQALEKS----DRS 391
Cdd:pfam15949   81 KSMSDIRCEEEaQPLSQVRYEELQKIRNQLKEEEDKWQDDLARWKSRRRSASQDLIKKEEERKKIEKLMSGEGgdsnRRK 160

                          170
                   ....*....|
gi 568988041   392 SKTFREMLQD 401
Cdd:pfam15949  161 SKTFKEMVEE 170

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 568988041    715 FGFTI---KWDISGIFVASVEQGSPAEFSQLQVDDEILAINNTKFSYKDTKkwEEVMANAQETGNLVMDVRR 783
Cdd:smart00228   14 LGFSLvggKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHL--EAVDLLKKAGGKVTLTVLR 83

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 568988041   242 MSYRRISAIEPKSALPFNRFLPNKSKQPSYVPAPLRKKRPDKHEDNRRSW-----ASPVYTETDGTFSRLFQKIYGENGS 316
Cdd:pfam15949    1 MLARRTSSSEPKSSVPFNQFLPNKSNQSAYVPAPLRKKRAEKEEDIRRSWstrtqPSKVAYPPRQFVQRLFQKVSDDLGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988041   317 KSMSDVSAEDV-QNLRQVRYEEMQKIKSQLKEQDQKWQDDLAKWKNRRKSYTSDLQKKKEEREEIEKQALEKS----DRS 391
Cdd:pfam15949   81 KSMSDIRCEEEaQPLSQVRYEELQKIRNQLKEEEDKWQDDLARWKSRRRSASQDLIKKEEERKKIEKLMSGEGgdsnRRK 160

                          170
                   ....*....|
gi 568988041   392 SKTFREMLQD 401
Cdd:pfam15949  161 SKTFKEMVEE 170

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 568988041    20 RWVEAVTEKNFET---TDFRASLENGVLLCDLINKLKPGVVKKINRLSTPIAGLDNINVFLRACEQ-IGLKEAQLfhpgD 95
Cdd:pfam00307    9 RWINSHLAEYGPGvrvTNFTTDLRDGLALCALLNKLAPGLVDKKKLNKSEFDKLENINLALDVAEKkLGVPKVLI----E 84

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 568988041    96 LQDLsnrvtvkqeeTDRRLKNVLITLYWLGRKAQS 130
Cdd:pfam00307   85 PEDL----------VEGDNKSVLTYLASLFRRFQA 109

Zinc-binding domain present in Lin-11, Isl-1, Mec-3; Zinc-binding domain family. Some LIM domains bind protein partners via tyrosine-containing motifs. LIM domains are found in many key regulators of developmental pathways.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 568988041   1322 VCSYCNNILGkGAAMIIETLGLSYHLHCFKCVSCGCDLGGSssgaEVRIRNHQLYCNDC 1380
Cdd:smart00132    1 KCAGCGKPIY-GTERVLRALGKVWHPECFKCATCGKPLSGD----TFFEKDGKLYCKDC 54

LIM domain; This family represents two copies of the LIM structural domain.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568988041  1323 CSYCNN-ILGKGAAMIietLGLSYHLHCFKCVSCGCDLGGSSSgaevRIRNHQLYCNDCYLRFK 1385
Cdd:pfam00412    1 CAGCNRpIYDRELVRA---LGKVWHPECFRCAVCGKPLTTGDF----YEKDGKLYCKHDYYKLF 57

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568988041  708 TPGNKPVFGFTIKWDISGIFVASVEQGSPAEFSQLQVDDEILAINNTKFSykdTKKWEEVMANAQETGNLVMDVRRYGK 786
Cdd:COG3975   478 APSLKPSLGLRVSADGGGLVVTSVLWGSPAYKAGLSAGDELLAIDGLRVT---ADNLDDALAAYKPGDPIELLVFRRDE 553

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains 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
                  ....*....|....*....|....*....|....*....|....
gi 568988041  715 FGFTI---KWDISGIFVASVEQGSPAEFS-QLQVDDEILAINNT 754
Cdd:cd00136    12 LGFSIrggKDGGGGIFVSRVEPGGPAARDgRLRVGDRILEVNGV 55

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 568988041   14 AFAEAQRWVEAVTEKNFETTDFRASLENGVLLCDLINKLKPGVVKKINRLSTPIAGLDNINVFLRACEQIGLKEAQLFHP 93
Cdd:cd21208     1 ALKEARTWIEAVTGKKFPSDDFRESLEDGILLCELINAIKPGSIKKINRLPTPIAGLDNLNLFLKACEDLGLKDSQLFDP 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 568988041   94 GDLQDLSNRVT---VKQEETDRRLKNVLITLYWLGRKAQ 129
Cdd:cd21208    81 TDLQDLSNRRIathVRKKEDERRLKNVAITLYWLGRAAR 119

calponin homology (CH) domain found in LIM and calponin homology domains-containing protein 1; LIM and calponin homology domains-containing protein 1 (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. LIMCH1 contains 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 568988041   14 AFAEAQRWVEAVTEKNFETTDFRASLENGVLLCDLINKLKPGVVKKINRLSTPIAGLDNINVFLRACEQIGLKEAQLFHP 93
Cdd:cd21278     1 AFTEAQKWIEQVTGRSFGDKDFRSGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNITLFLRGCKELGLKESQLFDP 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 568988041   94 GDLQDLSNRVTVKQEETDRRLKNVLITLYWLGRKAQS 130
Cdd:cd21278    81 GDLQDTSNRVTIKSSDCSRKLKNVLITIYWLGKAANS 117

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 568988041   16 AEAQRWVEAVTEKNFET-TDFRASLENGVLLCDLINKLKPGVVKKINRLSTPIAGLDNINVFLRACEQIGLKEAQLFHPG 94
Cdd:cd21207     8 AEALDWIEAVTGEKLDDgKDYEDVLKDGVILCKLINILKPGSVKKINTSKMAFKLMENIENFLTACKGYGVPKTDLFQTV 87

                          90       100       110
                  ....*....|....*....|....*....|..
gi 568988041   95 DLQDLSNrvtvkqeetdrrLKNVLITLYWLGR 126
Cdd:cd21207    88 DLYEKKN------------IPQVTNCLFALGR 107

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 568988041   16 AEAQRWVEAVTEKNFeTTDFRASLENGVLLCDLINKLKPGVVKKINRLSTPIAGLDNINVFLRACEQIGLKEAQLFHPGD 95
Cdd:cd21211     6 AELRTWIEGVTGLSI-GPNFQKGLKDGIILCELINKLQPGSVKKINESMQNWHQLENIGNFIKAIVSYGMKPHDIFEAND 84

                          90
                  ....*....|.
gi 568988041   96 LQDLSNRVTVK 106
Cdd:cd21211    85 LFENGNMTQVQ 95

calponin homology (CH) domain found in calponin-1 and similar proteins; Calponin-1 (CNN1), also called basic calponin, or smooth muscle calponin H1, is a thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin, troponin C, and tropomyosin. Calponin-1 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 568988041   16 AEAQRWVEAVTEKNFeTTDFRASLENGVLLCDLINKLKPGVVKKINRLSTPIAGLDNINVFLRACEQIGLKEAQLFHPGD 95
Cdd:cd21282     6 EELRVWIEGVTGRRI-GDNFMDGLKDGVILCELINKLQPGSVRKINESTQNWHKLENIGNFIKAIMHYGVKPHDIFEAND 84

                          90
                  ....*....|.
gi 568988041   96 LQDLSNRVTVK 106
Cdd:cd21282    85 LFENTNHTQVQ 95

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 568988041     17 EAQRWVEAVTEKNFE--TTDFRASLENGVLLCDLINKLKPGVV--KKINRLSTPIAGLDNINVFLRACEQIGLKEaQLFH 92
Cdd:smart00033    2 TLLRWVNSLLAEYDKppVTNFSSDLKDGVALCALLNSLSPGLVdkKKVAASLSRFKKIENINLALSFAEKLGGKV-VLFE 80

                    ....*.
gi 568988041     93 PGDLQD 98
Cdd:smart00033   81 PEDLVE 86

calponin homology (CH) domain found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as scaffold proteins, and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). 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 VAV proteins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568988041   34 DFRASLENGVLLCDLINKLKPGVVKKINRLSTP----IAGLDNINVFLRAC-EQIGLKEAQLFHPGDLQDLSN 101
Cdd:cd21201    31 DLAQALRDGVLLCQLLNRLSPGSVDDREINLRPqmsqFLCLKNIRTFLQACrTVFGLRSADLFEPEDLYDVTN 103

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 568988041 1323 CSYCNN-ILGKgaaMIIETLGLSYHLHCFKCVSCGCDLGGSSSGaevrIRNHQLYCNDCY 1381
Cdd:cd08368     1 CAGCGKpIEGR---ELLRALGKKWHPECFKCAECGKPLGGDSFY----EKDGKPYCEKCY 53

Zinc-binding domain present in Lin-11, Isl-1, Mec-3; Zinc-binding domain family. Some LIM domains bind protein partners via tyrosine-containing motifs. LIM domains are found in many key regulators of developmental pathways.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 568988041   1322 VCSYCNNILGkGAAMIIETLGLSYHLHCFKCVSCGCDLGGSssgaEVRIRNHQLYCNDC 1380
Cdd:smart00132    1 KCAGCGKPIY-GTERVLRALGKVWHPECFKCATCGKPLSGD----TFFEKDGKLYCKDC 54

LIM domain; This family represents two copies of the LIM structural domain.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568988041  1323 CSYCNN-ILGKGAAMIietLGLSYHLHCFKCVSCGCDLGGSSSgaevRIRNHQLYCNDCYLRFK 1385
Cdd:pfam00412    1 CAGCNRpIYDRELVRA---LGKVWHPECFRCAVCGKPLTTGDF----YEKDGKLYCKHDYYKLF 57

calponin homology (CH) domain found in the leucine-rich repeat and calponin homology domain-containing protein family; The leucine-rich repeat and calponin homology domain-containing protein (LRCH) family includes LRCH1-4. LRCH1, also called calponin homology domain-containing protein 1, or neuronal protein 81 (NP81), acts as a negative regulator of GTPase Cdc42 by sequestering Cdc42-guanine exchange factor DOCK8. LRCH2 may play a role in the organization of the cytoskeleton. LRCH3 is part of the DISP complex and may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. LRCH4, also called leucine-rich repeat neuronal protein 4, or leucine-rich neuronal protein, acts as a novel Toll-like receptor (TLR) accessory protein that regulates the innate immune response. Members of this family contain a single copy of the CH domain at the C-terminus. CH domains are actin filament (F-actin) binding motifs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988041   34 DFRASLENGVLLCDLINKLKPGVVKKINRLS------TPIAGLDNINVFLRACEQIGLKEAQLFHPGDLqdLSNRVTVKQ 107
Cdd:cd21205    21 DLGEALMDGVVLCHLANHVRPRSVPSIHVPSpavpklSMAKCRRNVENFLEACRKLGVPEERLCSPGDI--LEEKGLVRV 98

                  ....*..
gi 568988041  108 EETDRRL 114
Cdd:cd21205    99 AVTVQAL 105

calponin homology (CH) domain found in VAV3 protein and similar proteins; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. Its function has been implicated in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. 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. The model corresponds to CH domain, an actin-binding domain which is present as a single copy in VAV3 protein.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988041   25 VTEKNFETTDFRASLENGVLLCDLINKLKPGVV--KKIN---RLSTPIAgLDNINVFLRA-CEQIGLKEAQLFHPGDLQD 98
Cdd:cd21264    22 VTWDTAQVFDLAQTLRDGVLLCQLLNNLRPHSInlKEINlrpQMSQFLC-LKNIRTFLSAcCETFGMRKSELFEAFDLFD 100

                  ...
gi 568988041   99 LSN 101
Cdd:cd21264   101 VRD 103

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568988041  708 TPGNKPVFGFTIKWDISGIFVASVEQGSPAEFSQLQVDDEILAINNTKFSykdTKKWEEVMANAQETGNLVMDVRRYGK 786
Cdd:COG3975   478 APSLKPSLGLRVSADGGGLVVTSVLWGSPAYKAGLSAGDELLAIDGLRVT---ADNLDDALAAYKPGDPIELLVFRRDE 553

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 568988041   715 FGFTIK----WDISGIFVASVEQGSPAEFSQLQVDDEILAINNTKFS 757
Cdd:pfam00595   12 LGFSLKggsdQGDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVE 58

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains 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
                  ....*....|....*....|....*....|....*....|....
gi 568988041  715 FGFTI---KWDISGIFVASVEQGSPAEFS-QLQVDDEILAINNT 754
Cdd:cd00136    12 LGFSIrggKDGGGGIFVSRVEPGGPAARDgRLRVGDRILEVNGV 55

first calponin homology (CH) domain found in the plastin/fimbrin family; This family includes plastin and fimbrin. Plastin has three isoforms, plastin-1, -2, and -3, which are all actin-bundling proteins. Plastin-1, also called intestine-specific plastin, or I-plastin, is an actin-bundling protein in the absence of calcium. Plastin-2, also called L-plastin, LC64P, or lymphocyte cytosolic protein 1 (LCP-1), plays a role in the activation of T-cells in response to costimulation through TCR/CD3 and CD2 or CD28. It modulates the cell surface expression of IL2RA/CD25 and CD69. Plastin-3, also called T-plastin, is found in intestinal microvilli, hair cell stereocilia, and fibroblast filopodia. It may play a role in the regulation of bone development. Fimbrin has been found in plants and fungi. Arabidopsis thaliana fimbrin (AtFIM) includes fimbrin-1, -2, -3, -4, and -5; they cross-link actin filaments (F-actin) in a calcium independent manner. They stabilize and prevent F-actin depolymerization mediated by profilin. They act as key regulators of actin cytoarchitecture, probably involved in cell cycle, cell division, cell elongation and cytoplasmic tractus. AtFIM5 is an actin bundling factor that is required for pollen germination and pollen tube growth. Fungal fimbrin binds to actin, and functionally associates with actin structures involved in the development and maintenance of cell polarity. Members of this family contain four copies of the CH domain. This model corresponds to the first CH domain. CH domains are actin filament (F-actin) binding motifs.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568988041   34 DFRASLENGVLLCDLINKLKPGVV--KKINRLS--TPIAGLDNINVFLRACEQIGLK 86
Cdd:cd21217    32 DLFEALRDGVLLCKLINKIVPGTIdeRKLNKKKpkNIFEATENLNLALNAAKKIGCK 88

PDZ domain 2 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. 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 whirlin 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988041  702 RVSINQTPGNKpvFGFTIKWDIS---GIFVASVEQGSPAEFSQLQVDDEILAINNTKF---SYKDTKKweeVMANAQEtg 775
Cdd:cd06741     3 KVNLVVEDGQS--LGLMIRGGAEyglGIYVTGVDPGSVAENAGLKVGDQILEVNGRSFldiTHDEAVK---ILKSSKH-- 75

                          90
                  ....*....|
gi 568988041  776 nLVMDVRRYG 785
Cdd:cd06741    76 -LIMTVKDVG 84

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. 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 Par6-like family 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988041  702 RVSINQTPGnKPvFGFTIK----WD-ISGIFVASVEQGSPAEFSQ-LQVDDEILAINNTKFSYKDTkkwEEVMANAQETG 775
Cdd:cd06718     2 RVELIKPPG-KP-LGFYIRdgngVErVPGIFISRLVLGSLADSTGlLAVGDEILEVNGVEVTGKSL---DDVTDMMVAPT 76

                  ....*...
gi 568988041  776 NLVMDVRR 783
Cdd:cd06718    77 RLIITVKP 84

calponin homology (CH) domain found in VAV2 protein and similar proteins; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. 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. The model corresponds to CH domain, an actin-binding domain which is present as a single copy in VAV2 protein.

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gi 568988041   34 DFRASLENGVLLCDLINKLKPGVV--KKIN---RLSTPIAgLDNINVFLRAC-EQIGLKEAQLFHPGDLQDLSN 101
Cdd:cd21263    31 DLAQALRDGVLLCQLLHNLSPGSIdlKDINfrpQMSQFLC-LKNIRTFLKVChDKFGLRNSELFDPFDLFDVRD 103

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.

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                  ....*....|....*....|....*....|..
gi 568988041  725 GIFVASVEQGSPAEFSQLQVDDEILAINNTKF 756
Cdd:cd06729    24 GIFVAGVQEGSPAEKQGLQEGDQILKVNGVDF 55

calponin homology (CH) domain found in leucine-rich repeat and calponin homology domain-containing protein 3; Leucine-rich repeat and calponin homology domain-containing protein 3 (LRCH3) is part of the DISP (DOCK7-Induced Septin disPlacement) complex. It may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. LRCH3 contains a single copy of the CH domain at the C-terminus. CH domains are actin filament (F-actin) binding motifs.

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gi 568988041   27 EKNFET-------TDFRASLENGVLLCDLINKLKPGVVKKINRLSTPIAGLD------NINVFLRACEQIGLKEAQLFHP 93
Cdd:cd21272     7 RKNIESrlkvslpSDLGAALTDGVVLCHLANHVRPRSVPSIHVPSPAVPKLTmakcrrNVENFLEACRRIGVPQEQLCLP 86

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988041  703 VSINQTPGNKpvFGFTIKWDIS---GIFVASVEQGSPAEFSQLQVDDEILAINNTKFSYKDTKKWEEVManaqeTGN--L 777
Cdd:cd10833     4 VTVEKSPDGS--LGFSVRGGSEhglGIFVSKVEEGSAAERAGLCVGDKITEVNGVSLENITMSSAVKVL-----TGSnrL 76

                  ....*...
gi 568988041  778 VMDVRRYG 785
Cdd:cd10833    77 RMVVRRMG 84

PDZ domain of tax1-binding protein 3 (TAX1BP3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of TAX1BP3, and related domains. TAX1BP3 (also known as glutaminase-interacting protein 3, tax interaction protein 1, TIP-1, tax-interacting protein 1) may regulate a number of protein-protein interactions by competing for PDZ domain binding sites. TAX1BP3 binds beta-catenin and may act as an inhibitor of the Wnt signaling pathway. It competes with LIN7A (also known as Lin-7A or LIN-7A) for inward rectifier potassium channel 4 (KCNJ4) binding, and thereby promotes KCNJ4 internalization. It may play a role in the Rho signaling pathway, and in the activation of CDC42 by the viral protein HPV16 E6. Binding partners of the TAX1BP3 PDZ domain include beta-catenin, KCNJ4, glutaminase liver isoform (GLS2), rho guanine nucleotide exchange factor 16 (ARHGEF16), rhotekin, and CDK5 regulatory subunit-associated protein 3 (also known as LAPZ). 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 TAX1BP3-like family 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.

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                  ....*....|....*....|....*....|....*....|....*...
gi 568988041  705 INQTPGNKPvFGFTIKwdisGIFVASVEQGSPAEFSQLQVDDEILAIN 752
Cdd:cd10822    23 IDQDPSKNP-FSYTDK----GIYVTRVSEGGPAEKAGLQVGDKILQVN 65

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]

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gi 568988041   684 RGSPLREVSRSLDQFSDmrvsiNQTPGNKPVFGFT-------------IKWDISGIFVASVEQGSPAEFSQLQVDDEILA 750
Cdd:TIGR02037  314 RKGKEKTITVTLGASPE-----EQASSSNPFLGLTvanlspeirkelrLKGDVKGVVVTKVVSGSPAARAGLQPGDVILS 388

                           90       100       110
                   ....*....|....*....|....*....|...
gi 568988041   751 INNTkfSYKDTKKWEEVMANAQETGNLVMDVRR 783
Cdd:TIGR02037  389 VNQQ--PVSSVAELRKVLARAKKGGRVALLILR 419