calponin homology (CH) domain superfamily; CH domains are actin filament (F-actin) binding motifs, which may be present as a single copy or in tandem repeats (which increase binding affinity). They either function as autonomous actin binding motifs or serve a regulatory function. CH domains are found in cytoskeletal and signal transduction proteins, including actin-binding proteins like spectrin, alpha-actinin, dystrophin, utrophin, and fimbrin, as well as proteins essential for regulation of cell shape (cortexillins), and signaling proteins (Vav).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319996634   14 AFQEAQRWIEEVTKKSFGSKSFRVALEDGVLLCDLINTLKPGIIKRLNRLSTPIAGLDNVNVFLKACKKLGLNEAQLFHP 93
Cdd:cd21277     1 AFSEAQRWIEAVTGKNFGNKDFRSALENGVLLCDLINKIKPGIIKKINRLSTPIAGLDNINVFLKACEKLGLKEAQLFHP 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 319996634   94 GDLQDVSTRVTVRREETNRRLKNVLITIYWLGRKAQ 129
Cdd:cd21277    81 GDLQDLSTRVTVKQEETDRRLKNVLITLYWLGRKAQ 116

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 319996634 1314 CSRCEQPLGkgAAMVIDSLELCFHIGCFKCVSCRTELGrgpesGAQVRVRHRQLFCNTCY 1373
Cdd:cd08368     1 CAGCGKPIE--GRELLRALGKKWHPECFKCAECGKPLG-----GDSFYEKDGKPYCEKCY 53

Coiled-coil domain-containing protein 66; This protein family, named Coiled-coil domain-containing protein 66 (CCDC) refers to a protein domain found in eukaryotes, and is approximately 160 amino acids in length. CCDC66 protein is detected mainly in the inner segments of photoreceptors in many vertebrates including mice and humans. It has been found in dogs, that a mutation in the CCDC66 gene causes generalized progressive retinal atrophy (gPRA). This shows that the protein encoded for by this gene is vital for healthy vision and guards against photoreceptor cell degeneration. The structure of CCDC66 proteins includes a heptad repeat pattern which contains at least one coiled-coil domain. There are at least two or more alpha-helices which form a cable-like structure.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 319996634  1019 EEERRRQEKwQMEQERLLQEKyRRDQEKLEEEWRRAQQEvygEEYCGLEEQKTLDVL 1075
Cdd:pfam15236   75 EEERRRQEE-QEEEERLRRER-EEEQKQFEEERRKQKEK---EEAMTRKTQALLQAM 126

calponin homology (CH) domain found in LIM domain only protein 7; LIM domain only protein 7 (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. It 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 319996634   14 AFQEAQRWIEEVTKKSFGSKSFRVALEDGVLLCDLINTLKPGIIKRLNRLSTPIAGLDNVNVFLKACKKLGLNEAQLFHP 93
Cdd:cd21277     1 AFSEAQRWIEAVTGKNFGNKDFRSALENGVLLCDLINKIKPGIIKKINRLSTPIAGLDNINVFLKACEKLGLKEAQLFHP 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 319996634   94 GDLQDVSTRVTVRREETNRRLKNVLITIYWLGRKAQ 129
Cdd:cd21277    81 GDLQDLSTRVTVKQEETDRRLKNVLITLYWLGRKAQ 116

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 319996634     17 EAQRWIEEVTKKSFGSK--SFRVALEDGVLLCDLINTLKPGII--KRLNRLSTPIAGLDNVNVFLKACKKLGlNEAQLFH 92
Cdd:smart00033    2 TLLRWVNSLLAEYDKPPvtNFSSDLKDGVALCALLNSLSPGLVdkKKVAASLSRFKKIENINLALSFAEKLG-GKVVLFE 80

                    ....*...
gi 319996634     93 PGDLQDVS 100
Cdd:smart00033   81 PEDLVEGP 88

Calponin [Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319996634   16 QEAQRWIEEVTKKSFGSK-SFRVALEDGVLLCDLINTLKPGIIkRLNRLSTPIAGLDNVNVFLKACKKLGLNEAQLFHPG 94
Cdd:COG5199    16 KEVTLWIETVLGEKFEPPgDLLSLLKDGVRLCRILNEASPLDI-KYKESKMPFVQMENISSFINGLKKLRVPEYELFQTN 94

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 319996634   95 DLQDvstrvtvrreetNRRLKNVLITIYWLGRKAQ-----SDPFyTGPQLNLK 142
Cdd:COG5199    95 DLFE------------AKDLRQVVICLYSLSRYAQkermfSGPF-LGPHLATK 134

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        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 319996634   1313 MCSRCEQPLGkGAAMVIDSLELCFHIGCFKCVSCRTELgrgpeSGAQVRVRHRQLFCNTC 1372
Cdd:smart00132    1 KCAGCGKPIY-GTERVLRALGKVWHPECFKCATCGKPL-----SGDTFFEKDGKLYCKDC 54

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. 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 NHERF-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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 319996634  828 RVCLNQKPNSGrdFGF--KAHWDSVGAYVKSVQAGSPAELYGLLMGDEIVALGGRRVDEMNYEQ 889
Cdd:cd06768     1 RLCHLVKGPEG--YGFnlHAEKGRPGHFIREVDPGSPAERAGLKDGDRLVEVNGENVEGESHEQ 62

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 319996634  1314 CSRCEQPLGkgAAMVIDSLELCFHIGCFKCVSCRTELGRGPEsgaqvRVRHRQLFCNTCYCR 1375
Cdd:pfam00412    1 CAGCNRPIY--DRELVRALGKVWHPECFRCAVCGKPLTTGDF-----YEKDGKLYCKHDYYK 55

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 319996634   848 DSVGAYVKSVQAGSPAELYGLLMGDEIVALGGRRVDemNYEQFKSSMETAQQNGTLLMDIRRHGQN 913
Cdd:TIGR02037  360 DVKGVVVTKVVSGSPAARAGLQPGDVILSVNQQPVS--SVAELRKVLARAKKGGRVALLILRGGAT 423

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 319996634 1019 EEERRRQEKWQMEQERLLQEKYRRDQEKLEEEWRRAQQE 1057
Cdd:cd16269   218 EEQQRELEQKLEDQERSYEEHLRQLKEKMEEERENLLKE 256

calponin homology (CH) domain found in LIM domain only protein 7; LIM domain only protein 7 (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. It 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 319996634   14 AFQEAQRWIEEVTKKSFGSKSFRVALEDGVLLCDLINTLKPGIIKRLNRLSTPIAGLDNVNVFLKACKKLGLNEAQLFHP 93
Cdd:cd21277     1 AFSEAQRWIEAVTGKNFGNKDFRSALENGVLLCDLINKIKPGIIKKINRLSTPIAGLDNINVFLKACEKLGLKEAQLFHP 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 319996634   94 GDLQDVSTRVTVRREETNRRLKNVLITIYWLGRKAQ 129
Cdd:cd21277    81 GDLQDLSTRVTVKQEETDRRLKNVLITLYWLGRKAQ 116

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 319996634   14 AFQEAQRWIEEVTKKSFGSKSFRVALEDGVLLCDLINTLKPGIIKRLNRLSTPIAGLDNVNVFLKACKKLGLNEAQLFHP 93
Cdd:cd21278     1 AFTEAQKWIEQVTGRSFGDKDFRSGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNITLFLRGCKELGLKESQLFDP 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 319996634   94 GDLQDVSTRVTVRREETNRRLKNVLITIYWLGRKAQS 130
Cdd:cd21278    81 GDLQDTSNRVTIKSSDCSRKLKNVLITIYWLGKAANS 117

calponin homology (CH) domain superfamily; CH domains are actin filament (F-actin) binding motifs, which may be present as a single copy or in tandem repeats (which increase binding affinity). They either function as autonomous actin binding motifs or serve a regulatory function. CH domains are found in cytoskeletal and signal transduction proteins, including actin-binding proteins like spectrin, alpha-actinin, dystrophin, utrophin, and fimbrin, as well as proteins essential for regulation of cell shape (cortexillins), and signaling proteins (Vav).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319996634   16 QEAQRWIEEVTKKSFG--SKSFRVALEDGVLLCDLINTLKPGIIKRLNRLS-TPIAGLDNVNVFLKACKKLGLNEAQLFH 92
Cdd:cd00014     2 EELLKWINEVLGEELPvsITDLFESLRDGVLLCKLINKLSPGSIPKINKKPkSPFKKRENINLFLNACKKLGLPELDLFE 81

                          90       100       110
                  ....*....|....*....|....*....|....
gi 319996634   93 PGDLQDvstrvtvrreetNRRLKNVLITIYWLGR 126
Cdd:cd00014    82 PEDLYE------------KGNLKKVLGTLWALAL 103

calponin homology (CH) domain found in Saccharomyces cerevisiae transgelin (SCP1) and similar proteins; The family includes transgelins from Saccharomyces cerevisiae and Schizosaccharomyces pombe, which are also called SCP1 and STG1, respectively. Transgelin, also called calponin homolog 1, has actin-binding and actin-bundling activity. It stabilizes actin filaments against disassembly. Transgelin 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 319996634   16 QEAQRWIEEVTKKSFGSKSFRVALEDGVLLCDLINTLKPGIIKRLNRLSTPIAGLDNVNVFLKACKKLGLNEAQLFHPGD 95
Cdd:cd21210     3 QEAREWIEEVLGEKLAQGDLLDALKDGVVLCKLANRILPADIRKYKESKMPFVQMENISAFLNAARKLGVPENDLFQTVD 82

                          90       100       110
                  ....*....|....*....|....*....|.
gi 319996634   96 LQDvstrvtvrreetNRRLKNVLITIYWLGR 126
Cdd:cd21210    83 LFE------------RKNPAQVLQCLHALSR 101

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 319996634   16 QEAQRWIEEVTKKSFGsKSFRVALEDGVLLCDLINTLKPGIIKRLNRLSTPIAGLDNVNVFLKACKKLGLNEAQLFHPGD 95
Cdd:cd21284     8 EELRNWIEEVTGMSIG-ENFQKGLKDGVILCELINKLQPGSIRKINESKLNWHQLENIGNFIKAIQAYGMKPHDIFEAND 86

                  .
gi 319996634   96 L 96
Cdd:cd21284    87 L 87

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 319996634   16 QEAQRWIEEVTKKSFGSkSFRVALEDGVLLCDLINTLKPGIIKRLNRLSTPIAGLDNVNVFLKACKKLGLNEAQLFHPGD 95
Cdd:cd21282     6 EELRVWIEGVTGRRIGD-NFMDGLKDGVILCELINKLQPGSVRKINESTQNWHKLENIGNFIKAIMHYGVKPHDIFEAND 84

                  .
gi 319996634   96 L 96
Cdd:cd21282    85 L 85

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 319996634   35 FRVALEDGVLLCDLINTLKPGII----KRLNRLSTPIAGLDNVNVFLKACK-KLGLNEAQLFHPGDLQDVS 100
Cdd:cd21201    32 LAQALRDGVLLCQLLNRLSPGSVddreINLRPQMSQFLCLKNIRTFLQACRtVFGLRSADLFEPEDLYDVT 102

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 319996634    16 QEAQRWIEEVTKKSFGS---KSFRVALEDGVLLCDLINTLKPGIIKRLNRLSTPIAGLDNVNVFLK-ACKKLGLNEaQLF 91
Cdd:pfam00307    5 KELLRWINSHLAEYGPGvrvTNFTTDLRDGLALCALLNKLAPGLVDKKKLNKSEFDKLENINLALDvAEKKLGVPK-VLI 83

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 319996634    92 HPGDLQDVstrvtvrreetnrRLKNVLITIYWLGRKAQS 130
Cdd:pfam00307   84 EPEDLVEG-------------DNKSVLTYLASLFRRFQA 109

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 319996634   11 CELAfqEAQRWIEEVTKKSFGSKS-FRVALEDGVLLCDLINTLKPGIIKRLNrlsTPIAGL-----DNVNVFLKACKKLG 84
Cdd:cd21206     8 CRLE--EAKQWIEACLNEELPPTTeFEEELRNGVVLAKLANKFAPKLVPLKK---IYDVGLqfrhtDNINHFLRALKKIG 82

                          90
                  ....*....|....
gi 319996634   85 LNEAQLFHPGDLQD 98
Cdd:cd21206    83 LPKIFHFETTDLYE 96

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319996634   16 QEAQRWIEEVTKKSFGSKS----FRVALEDGVLLCDLINTLKPGIIKRL--------NRLSTPIAGLDNVNVFLKACKKL 83
Cdd:cd21203     3 YEAAEWIQNVLGVLVLPDPseeeFRLCLRDGVVLCKLLNKLQPGAVPKVvespddpdGAAGSAFQYFENVRNFLVAIEEM 82

                          90
                  ....*....|....
gi 319996634   84 GLneaQLFHPGDLQ 97
Cdd:cd21203    83 GL---PTFEASDLE 93

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        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 319996634   1313 MCSRCEQPLGkGAAMVIDSLELCFHIGCFKCVSCRTELgrgpeSGAQVRVRHRQLFCNTC 1372
Cdd:smart00132    1 KCAGCGKPIY-GTERVLRALGKVWHPECFKCATCGKPL-----SGDTFFEKDGKLYCKDC 54

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319996634  827 MRVCLNQKPNSGRDFGFKAHWDSVGAYVKSVQAGSPAELYGLLMGDEIVALGGRRVDEmnyEQFKSSMETAQQNGTLLMD 906
Cdd:COG3975   471 LKLVYEDAPSLKPSLGLRVSADGGGLVVTSVLWGSPAYKAGLSAGDELLAIDGLRVTA---DNLDDALAAYKPGDPIELL 547

                  ....*.
gi 319996634  907 IRRHGQ 912
Cdd:COG3975   548 VFRRDE 553

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. 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 NHERF-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 319996634  828 RVCLNQKPNSGrdFGF--KAHWDSVGAYVKSVQAGSPAELYGLLMGDEIVALGGRRVDEMNYEQ 889
Cdd:cd06768     1 RLCHLVKGPEG--YGFnlHAEKGRPGHFIREVDPGSPAERAGLKDGDRLVEVNGENVEGESHEQ 62

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.

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gi 319996634    848 DSVGAYVKSVQAGSPAELYGLLMGDEIVALGGRRVDEMNYEQ 889
Cdd:smart00228   24 EGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLE 65

The first LIM domain of Four and a half LIM domains protein (FHL); The first LIM domain of Four and a half LIM domains protein (FHL): LIM-only protein family consists of five members, designated FHL1, FHL2, FHL3, FHL5 and LIMPETin. The first four members are composed of four complete LIM domains arranged in tandem and an N-terminal single zinc finger domain with a consensus sequence equivalent to the C-terminal half of a LIM domain. LIMPETin is an exception, containing six LIM domains. FHL1, 2 and 3 are predominantly expressed in muscle tissues, and FHL5 is highly expressed in male germ cells. FHL proteins exert their roles as transcription co-activators or co-repressors through a wide array of interaction partners. For example, FHL1 binds to Myosin-binding protein C, regulating myosin filament formation and sarcomere assembly. FHL2 has shown to interact with more than 50 different proteins, including receptors, structural proteins, transcription factors and cofactors, signal transducers, splicing factors, DNA replication and repair enzymes, and metabolic enzymes. FHL3 int eracts with many transcription factors, such as CREB, BKLF/KLF3, CtBP2, MyoD, and MZF_1. FHL5 is a tissue-specific coactivator of CREB/CREM family transcription factors. LIM domains are 50-60 amino acids in size and share 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 complexes.

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gi 319996634 1314 CSRCEQPLGkgaamvIDSLELCF-----HIGCFKCVSCRTELGRGPESgaqvrVRHRQLFCNTCYC 1374
Cdd:cd09343     5 CEECKKKIG------CDSKDLSYkdrhwHEGCFKCFKCQRSLVDKPFA-----AKDEDLLCTECYS 59

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.

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gi 319996634   31 GSKSFRVALEDGVLLCDLINTLKP---GIIKRLNRLSTPIAGLDNVNVFLKACKKLGLNEAQLFHPGDLQDVSTRVTVRR 107
Cdd:cd21209    26 GRLGFQKWLKDGTVLCKLINSLYPegsKPVKKIQSSKMAFKQMEQISQFLKAAEDYGVRTTDIFQTVDLWEGKDMAAVQR 105

The second LIM domain of LIMK1 (LIM domain Kinase 1); The second LIM domain of LIMK1 (LIM domain Kinase 1): LIMK1 belongs to the LIMK protein family, which comprises LIMK1 and LIMK2. LIMK contains two LIM domains, a PDZ domain, and a kinase domain. LIMK is involved in the regulation of actin polymerization and microtubule disassembly. LIMK influences architecture of the actin cytoskeleton by regulating the activity of the cofilin family proteins cofilin1, cofilin2, and destrin. The mechanism of the activation is to phosphorylates cofilin on serine 3 and inactivates its actin-severing activity, and altering the rate of actin depolymerization. LIMKs can function in both cytoplasm and nucleus. Both LIMK1 and LIMK2 can act in the nucleus to suppress Rac/Cdc42-dependent cyclin D1 expression. LIMK1 is expressed in all tissues and is localized to focal adhesions in the cell. LIMK1 can form homodimers upon binding of HSP90 and is activated by Rho effector Rho kinase and MAPKAPK2. LIMK1 is important for normal central nervous system development, and its deletion has been implicated in the development of the human genetic disorder Williams syndrome. Moreover, LIMK1 up-regulates the promoter activity of urokinase type plasminogen activator and induces its mRNA and protein expression in breast cancer cells. The LIM domains have been shown to play an important role in regulating kinase activity and likely also contribute to LIMK function by acting as sites of protein-to-protein interactions. All LIM domains are 50-60 amino acids in size and share 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 complexes.

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gi 319996634 1314 CSRCEQPLGKGAAMVidSLELCFHIGCFKCVSCRTELGRGpesGAQVRVRHRQLFCNTCY 1373
Cdd:cd09464     1 CHGCSETITTGLVMV--AGEQKYHPECFSCLRCGAFIGDG---DTYALVEHSKLYCGHCY 55

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.

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gi 319996634   20 RWIEEVTKKSFGSKSFRVALEDGVLLCDLINTL-----------KPGIIKRLNRL-------STPIAGLDNVNVFLKACK 81
Cdd:cd21204    13 EWLNDLLGDDLTPDNFLDELRNGVVLCQLAQKIqeaaekareagKKNGPPPSYKLkcnenakPGSFFARDNVANFLRWCR 92

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 319996634   82 KLGLNEAQLFHPGDLqdvstrVTVRREetnrrlKNVLITIYWLGRKAQS 130
Cdd:cd21204    93 KLGVDEVLLFESEDL------VLHKNP------RQVLLCLLELARIAAR 129

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.

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gi 319996634   39 LEDGVLLCDLINTLKPGII--KRLN---RLSTPIAgLDNVNVFLKA-CKKLGLNEAQLFHPGDLQDV 99
Cdd:cd21264    36 LRDGVLLCQLLNNLRPHSInlKEINlrpQMSQFLC-LKNIRTFLSAcCETFGMRKSELFEAFDLFDV 101

calponin homology (CH) domain found in leucine-rich repeat and calponin homology domain-containing protein 1; Leucine-rich repeat and calponin homology domain-containing protein 1 (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. LRCH1 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 319996634   38 ALEDGVLLCDLINTLKPGIIKRLNRLSTPIAGLD------NVNVFLKACKKLGLNEAQLFHPGDL 96
Cdd:cd21270    28 ALMDGVVLCHLVNHVRPRSVASIHVPSPAVPKLSmakcrrNVENFLEACRKIGVPEADLCSPYDI 92

Membrane-associated protease RseP, regulator of RpoE activity [Posttranslational modification, protein turnover, chaperones, Transcription];

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gi 319996634  854 VKSVQAGSPAELYGLLMGDEIVALGGRRVDemNYEQFKSSMETAqQNGTLLMDIRRHGQ 912
Cdd:COG0750   132 VGEVVPGSPAAKAGLQPGDRIVAINGQPVT--SWDDLVDIIRAS-PGKPLTLTVERDGE 187

PDZ domain 1 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 1 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 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 319996634  838 GRDFGfkahwdsVGAYVKSVQAGSPAELYGLLMGDEIVALGGRRVDEMNYEQFKSSMETAQqngTLLMDIRRHG 911
Cdd:cd06737    22 GLEHG-------CGLFVSHVSPGSQADNKGLRVGDEIVRINGYSISQCTHEEVINLIKTKK---TVSLKVRHVG 85

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.

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gi 319996634   36 RVALEDGVLLCDLINTLKPG-IIKRLNRLSTPIAGLDNVNVFLKACKKLGLneaQLFHPGDL 96
Cdd:cd21265    32 KSSLKDGVVLCKLIERLLPGsVEKYCLEPKTEADCIGNIKEFLKGCAALKV---ETFEPDDL 90

calponin homology (CH) domain found in leucine-rich repeat and calponin homology domain-containing protein 2; Leucine-rich repeat and calponin homology domain-containing protein 2 (LRCH2) may play a role in the organization of the cytoskeleton. It 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 319996634   38 ALEDGVLLCDLINTLKPGIIKRLNRLSTPIAGLD------NVNVFLKACKKLGLNEAQLFHP 93
Cdd:cd21271    29 ALMDGVVLCHLANHIRPRSVGSIHVPSPAVPKLSmakcrrNVENFLDACRKLGVPEDKLCLP 90

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 319996634   38 ALEDGVLLCDLINTLKPGIIKRLNRLSTPIAGLD------NVNVFLKACKKLGLNEAQLFHP 93
Cdd:cd21272    25 ALTDGVVLCHLANHVRPRSVPSIHVPSPAVPKLTmakcrrNVENFLEACRRIGVPQEQLCLP 86