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 688584924   39 AVREAQRWIEAVTGRSFADRDFRTGLDNGILLCELLSSIRPGLVKKINRLPTPVAAQDNVVLFLKGCEELGLKGSQLFDP 118
Cdd:cd21278     1 AFTEAQKWIEQVTGRSFGDKDFRSGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNITLFLRGCKELGLKESQLFDP 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 688584924  119 GDLQDTSTRTN-KSPDNNKKLKNVLITIYWLGRAANS 154
Cdd:cd21278    81 GDLQDTSNRVTiKSSDCSRKLKNVLITIYWLGKAANS 117

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 688584924  794 EEERNRQERWQKEQERMLQEKYRREQEKLKQEWEQAQK 831
Cdd:cd16269   218 EEQQRELEQKLEDQERSYEEHLRQLKEKMEEERENLLK 255

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 688584924   39 AVREAQRWIEAVTGRSFADRDFRTGLDNGILLCELLSSIRPGLVKKINRLPTPVAAQDNVVLFLKGCEELGLKGSQLFDP 118
Cdd:cd21278     1 AFTEAQKWIEQVTGRSFGDKDFRSGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNITLFLRGCKELGLKESQLFDP 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 688584924  119 GDLQDTSTRTN-KSPDNNKKLKNVLITIYWLGRAANS 154
Cdd:cd21278    81 GDLQDTSNRVTiKSSDCSRKLKNVLITIYWLGKAANS 117

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 688584924    37 EPAVREAQRWIEAVTGRSFAD---RDFRTGLDNGILLCELLSSIRPGLVKKINRLPTPVAAQDNVVLFLKGCE-ELGLKg 112
Cdd:pfam00307    1 LELEKELLRWINSHLAEYGPGvrvTNFTTDLRDGLALCALLNKLAPGLVDKKKLNKSEFDKLENINLALDVAEkKLGVP- 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 688584924   113 SQLFDPGDLqdtstrtnkspdNNKKLKNVLITIYWLGRAANS 154
Cdd:pfam00307   80 KVLIEPEDL------------VEGDNKSVLTYLASLFRRFQA 109

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 688584924 1013 CSSCGHPLGkgAAMIIETLSLYFHIQCFKCGICKGQLGDTStgtdVRIRNGLLNCHQCY 1071
Cdd:cd08368     1 CAGCGKPIE--GRELLRALGKKWHPECFKCAECGKPLGGDS----FYEKDGKPYCEKCY 53

Calponin [Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688584924   34 PAPEPAVREAQRWIEAVTGRSFADR-DFRTGLDNGILLCELLSSIRPGLVK-KINRLPtpVAAQDNVVLFLKGCEELGLK 111
Cdd:COG5199     9 PGMDKQQKEVTLWIETVLGEKFEPPgDLLSLLKDGVRLCRILNEASPLDIKyKESKMP--FVQMENISSFINGLKKLRVP 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 688584924  112 GSQLFDPGDLQDTstrtnkspdnnKKLKNVLITIYWLGRAANSSATYNGPTLDLH 166
Cdd:COG5199    87 EYELFQTNDLFEA-----------KDLRQVVICLYSLSRYAQKERMFSGPFLGPH 130

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 688584924   39 AVREAQRWIEAVTGRSFADRDFRTGLDNGILLCELLSSIRPGLVKKINRLPTPVAAQDNVVLFLKGCEELGLKGSQLFDP 118
Cdd:cd21278     1 AFTEAQKWIEQVTGRSFGDKDFRSGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNITLFLRGCKELGLKESQLFDP 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 688584924  119 GDLQDTSTRTN-KSPDNNKKLKNVLITIYWLGRAANS 154
Cdd:cd21278    81 GDLQDTSNRVTiKSSDCSRKLKNVLITIYWLGKAANS 117

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 688584924   39 AVREAQRWIEAVTGRSFADRDFRTGLDNGILLCELLSSIRPGLVKKINRLPTPVAAQDNVVLFLKGCEELGLKGSQLFDP 118
Cdd:cd21277     1 AFSEAQRWIEAVTGKNFGNKDFRSALENGVLLCDLINKIKPGIIKKINRLSTPIAGLDNINVFLKACEKLGLKEAQLFHP 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 688584924  119 GDLQDTSTR-TNKSPDNNKKLKNVLITIYWLGRAA 152
Cdd:cd21277    81 GDLQDLSTRvTVKQEETDRRLKNVLITLYWLGRKA 115

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 688584924   41 REAQRWIEAVTGRSFAD-RDFRTGLDNGILLCELLSSIRPGLVKKINRLPTPVAAQDNVVLFLKGCEELGLKGSQLFDPG 119
Cdd:cd21207     8 AEALDWIEAVTGEKLDDgKDYEDVLKDGVILCKLINILKPGSVKKINTSKMAFKLMENIENFLTACKGYGVPKTDLFQTV 87

                          90       100       110
                  ....*....|....*....|....*....|.
gi 688584924  120 DLQDtstrtnkspdnNKKLKNVLITIYWLGR 150
Cdd:cd21207    88 DLYE-----------KKNIPQVTNCLFALGR 107

calponin homology (CH) domain found in calponin-2; Calponin-2 (CNN2), also called neutral calponin, or smooth muscle calponin H2, is an actin cytoskeleton-associated regulatory protein that inhibits the activity of myosin-ATPase and cytoskeleton 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 688584924   42 EAQRWIEAVTGRSFADrDFRTGLDNGILLCELLSSIRPGLVKKINRLPTPVAAQDNVVLFLKGCEELGLKGSQLFDPGDL 121
Cdd:cd21283     7 ELRTWIEGLTGRSIGP-DFQKGLKDGVILCELMNKLQPGSVPKINRSMQNWHQLENLSNFIKAMVSYGMKPVDLFEANDL 85

                  ....*..
gi 688584924  122 QDTSTRT 128
Cdd:cd21283    86 FESGNMT 92

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 688584924   41 REAQRWIEAVTGRSFADrDFRTGLDNGILLCELLSSIRPGLVKKINRLPTPVAAQDNVVLFLKGCEELGLKGSQLFDPGD 120
Cdd:cd21282     6 EELRVWIEGVTGRRIGD-NFMDGLKDGVILCELINKLQPGSVRKINESTQNWHKLENIGNFIKAIMHYGVKPHDIFEAND 84

                  ....*...
gi 688584924  121 LQDTSTRT 128
Cdd:cd21282    85 LFENTNHT 92

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 688584924   37 EPAVREAQR-WIEAVTGRSFADrDFRTGLDNGILLCELLSSIRPGLVKKINRLPTPVAAQDNVVLFLKGCEELGLKGSQL 115
Cdd:cd21284     3 DPQKEEELRnWIEEVTGMSIGE-NFQKGLKDGVILCELINKLQPGSIRKINESKLNWHQLENIGNFIKAIQAYGMKPHDI 81

                  ....*.
gi 688584924  116 FDPGDL 121
Cdd:cd21284    82 FEANDL 87

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688584924   56 ADRDFRTGLDNGILLCELLSSIRPGLVKKInrLPTPVAAQD---NVVLFLKGCEELGLKGSQLFDPGDLQdtstrtnkSP 132
Cdd:cd21202    26 PERFLSESLKNGVVLCRLVNRLKPGTVEKI--YDEPTTEEEclyNFESFLKACQELGILAEEIFDPNDLY--------SG 95

                          90       100
                  ....*....|....*....|..
gi 688584924  133 DNNKKlknVLITIYWLGRAANS 154
Cdd:cd21202    96 GNFQK---VLSTLERLEKVAGG 114

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 688584924  1013 CSSCGHPlgkgaamIIET-----LSLYFHIQCFKCGICKGQLGDtstgTDVRIRNGLLNCHQCYIRSR 1075
Cdd:pfam00412    1 CAGCNRP-------IYDRelvraLGKVWHPECFRCAVCGKPLTT----GDFYEKDGKLYCKHDYYKLF 57

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 688584924   1013 CSSCGHPLGkGAAMIIETLSLYFHIQCFKCGICKGQLGDTStgtdVRIRNGLLNCHQC 1070
Cdd:smart00132    2 CAGCGKPIY-GTERVLRALGKVWHPECFKCATCGKPLSGDT----FFEKDGKLYCKDC 54

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 688584924   42 EAQRWIEAVTGRSFAD-RDFRTGLDNGILLCELLSSIRPGLVKKInRLPTPVAA---QDNVVLFLKGCEELGLKGSQLFD 117
Cdd:cd21206    12 EAKQWIEACLNEELPPtTEFEEELRNGVVLAKLANKFAPKLVPLK-KIYDVGLQfrhTDNINHFLRALKKIGLPKIFHFE 90

                  ....*.
gi 688584924  118 PGDLQD 123
Cdd:cd21206    91 TTDLYE 96

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688584924   59 DFRTGLDNGILLCELLSSIRPGLV--KKINRLP--TPVAAQDNVVLFLKGC-EELGLKGSQLFDPGDLQD 123
Cdd:cd21263    31 DLAQALRDGVLLCQLLHNLSPGSIdlKDINFRPqmSQFLCLKNIRTFLKVChDKFGLRNSELFDPFDLFD 100

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 688584924 1013 CSSCGHPL----GKGAAMIIETLSLYFHIQCFKCGICKGQLGDTSTGTDVRIRNGLLNCHQC 1070
Cdd:cd09357     1 CSVCGEPImpepGQDETVRIVALDRSFHVNCYKCEDCGMLLSSEDEGQGCYPLDGHLLCKSC 62

calponin homology (CH) domain found in beta-Pak Interactive eXchange factor; Beta-Pak Interactive eXchange factor (beta-PIX), also called PAK-interacting exchange factor beta, Rho guanine nucleotide exchange factor 7 (ARHGEF7), p85, or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. Beta-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 688584924   60 FRTGLDNGILLCELLSSIRPGLVKKINRLP-TPVAAQDNVVLFLKGCEELGLkgsQLFDPGDL 121
Cdd:cd21266    29 LQASLKDGVVLCRLLERLLPGSIDKVYPEPrTESECLSNIREFLRGCGALRL---ETFDANDL 88

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 688584924   47 IEAVTGRSFADrDFRTGLDNGILLCELLSSIRPGLVKKINRLP------TPVAAQDNVVLFLKGCEELGLKGSQLFDPGD 120
Cdd:cd21205    10 IESRLKVTLPD-DLGEALMDGVVLCHLANHVRPRSVPSIHVPSpavpklSMAKCRRNVENFLEACRKLGVPEERLCSPGD 88

                  .
gi 688584924  121 L 121
Cdd:cd21205    89 I 89

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 688584924  794 EEERNRQERWQKEQERMLQEKYRREQEKLKQEWEQAQK 831
Cdd:cd16269   218 EEQQRELEQKLEDQERSYEEHLRQLKEKMEEERENLLK 255

Protein involved in regulation of cellular morphogenesis/cytokinesis [Cell division and chromosome partitioning / Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688584924   40 VREAQRWIEAVTGRSFADRDFRTGLDNGILLCELLSSIRPGLVKKI---NRLptPVAAQDNVVLFLKGCEELGLKGSQLF 116
Cdd:COG5261    46 VSEAKIWIEEVIEEALPELCFEDSLRNGVFLAKLTQRFNPDLTTVIfpaDKL--QFRHTDNINAFLDLIEHVGLPESFHF 123

                  ....*
gi 688584924  117 DPGDL 121
Cdd:COG5261   124 ELQDL 128

The third LIM domain of an Enigma subfamily with unknown function; The third LIM domain of an Enigma subfamily with unknown function: The Enigma LIM domain family is comprised of three characterized members: Enigma, ENH, and Cypher (mouse)/ZASP (human). These subfamily members contain a single PDZ domain at the N-terminus and three LIM domains at the C-terminus. They serve as adaptor proteins, where the PDZ domain tethers the protein to the cytoskeleton and the LIM domains, recruit signaling proteins to implement corresponding functions. The members of the enigma family have been implicated in regulating or organizing cytoskeletal structure, as well as involving multiple signaling pathways. 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.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 688584924 1013 CSSCGHPLGKGAAMIiETLSLYFHIQCFKCGICKGQL 1049
Cdd:cd09461     1 CVSCGFPIEAGDRWV-EALNNNYHSQCFNCTRCNVNL 36

The second LIM domain of Ajuba-like proteins; The second LIM domain of Ajuba-like proteins: Ajuba like LIM protein family includes three highly homologous proteins Ajuba, Limd1, and WTIP. Members of the family contain three tandem C-terminal LIM domains and a proline-rich N-terminal region. This family of proteins functions as scaffolds, participating in the assembly of numerous protein complexes. In the cytoplasm, Ajuba binds Grb2 to modulate serum-stimulated ERK activation. Ajuba also recruits the TNF receptor-associated factor 6 (TRAF6) to p62 and activates PKCKappa activity. Ajuba interacts with alpha-catenin and F-actin to contribute to the formation or stabilization of adheren junctions by linking adhesive receptors to the actin cytoskeleton. Although Ajuba is a cytoplasmic protein, it can shuttle into the nucleus. In nucleus, Ajuba functions as a corepressor for the zinc finger-protein Snail. It binds to the SNAG repression domain of Snail through its LIM region. Arginine methyltransferase-5 (Prmt5), a protein in the complex, is recruited to Snai l through an interaction with Ajuba. This ternary complex functions to repress E-cadherin, a Snail target gene. In addition, Ajuba contains functional nuclear-receptor interacting motifs and selectively interacts with retinoic acid receptors (RARs) and rexinoid receptor (RXRs) to negatively regulate retinoic acid signaling. Wtip, the Wt1-interacting protein, was originally identified as an interaction partner of the Wilms tumour protein 1 (WT1). Wtip is involved in kidney and neural crest development. Wtip interacts with the receptor tyrosine kinase Ror2 and inhibits canonical Wnt signaling. LIMD1 was reported to inhibit cell growth and metastases. The inhibition may be mediated through an interaction with the protein barrier-to-autointegration (BAF), a component of SWI/SNF chromatin-remodeling protein; or through the interaction with retinoblastoma protein (pRB), resulting in inhibition of E2F-mediated transcription, and expression of the majority of genes with E2F1- responsive elements. Recently, Limd1 was shown to interact with the p62/sequestosome protein and influence IL-1 and RANKL signaling by facilitating the assembly of a p62/TRAF6/a-PKC multi-protein complex. The Limd1-p62 interaction affects both NF-kappaB and AP-1 activity in epithelial cells and osteoclasts. Moreover, LIMD1 functions as tumor repressor to block lung tumor cell line in vitro and in vivo. Recent studies revealed that LIM proteins Wtip, LIMD1 and Ajuba interact with components of RNA induced silencing complexes (RISC) as well as eIF4E and the mRNA m7GTP cap-protein complex and are required for microRNA-mediated gene silencing. 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.

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gi 688584924 1013 CSSCGHPLGKgaaMIIETLSLYFHIQCFKCGICKGQL 1049
Cdd:cd09355     1 CAVCGHLIME---MILQALGKSYHPGCFRCCVCNECL 34

calponin homology (CH) domain found in growth arrest-specific protein 2; Growth arrest-specific protein 2 (GAS-2) may play a role in apoptosis by acting as a cell death substrate for caspases. It contains 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 688584924   46 WIEAVTGRSFADRDFRTGLDNGILLCELLSSI------------RPGLVKKINRLPTPVA-------AQDNVVLFLKGCE 106
Cdd:cd21267    15 WLTNLLGKEITAESFMEKLDNGALLCQLAETLqekfkensadanKPGKSLPVRKIPCRANapsgsffARDNTANFLSWCR 94

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gi 688584924  107 ELGLKGSQLFD 117
Cdd:cd21267    95 DVGVGDTCLFE 105

The second LIM domain of Arrowhead (AWH); The second LIM domain of Arrowhead (AWH): Arrowhead belongs to the LHX protein family, which features two tandem N-terminal LIM domains and a C-terminal DNA binding homeodomain. Members of LHX family are found in the nucleus and act as transcription factors or cofactors. LHX proteins are critical for the development of specialized cells in multiple tissue types, including the nervous system, skeletal muscle, the heart, the kidneys, and endocrine organs such as the pituitary gland and the pancreas. During embryogenesis of Drosophila, Arrowhead is expressed in each abdominal segment and in the labial segment. Late in embryonic development, expression of arrowhead is refined to the abdominal histoblasts and salivary gland imaginal ring cells themselves. The Arrowhead gene required for establishment of a subset of imaginal tissues: the abdominal histoblasts and the salivary gland imaginal rings. 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.

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gi 688584924 1013 CSSCGHPLGkGAAMIIETLSLYFHIQCFKCGICKGQLgdtSTGTDVRIRNGLLNCHQCY 1071
Cdd:cd09379     1 CAKCSRNIS-ASDWVRRARDHVYHLACFACDACKRQL---STGEEFALIEDRVLCKAHY 55