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 134053896   23 AFAEAQKWIEQVTGRSFGDKDFRTGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNTILFLRGCKELGLKESQLFDP 102
Cdd:cd21278     1 AFTEAQKWIEQVTGRSFGDKDFRSGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNITLFLRGCKELGLKESQLFDP 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 134053896  103 SDLQDTSNRVTVKNLDYSRKLKNVLVTIYWLGKAANSC 140
Cdd:cd21278    81 GDLQDTSNRVTIKSSDCSRKLKNVLITIYWLGKAANSC 118

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 134053896    987 CSSCGLTLGkGAAMIIETLNLYFHIQCFRCGICKGQLgdavSGTDVRIRNGLLNCTDC 1044
Cdd:smart00132    2 CAGCGKPIY-GTERVLRALGKVWHPECFKCATCGKPL----SGDTFFEKDGKLYCKDC 54

Clathrin light chain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134053896   728 FPFLDKMPETNQlhlPNPSSQADSPSSEKSPGSTPFkfwawDPEEERRRQEKWQQEQERLLQERyQKEQDKLKEEW-EKA 806
Cdd:pfam01086   69 FPDVDTQNEAVG---PGGTITAIGPSDPYNPGYSSY-----EDEEEPEVIREWRERRDLEIEER-DEASAKKKEETiEKA 139

                   ..
gi 134053896   807 QK 808
Cdd:pfam01086  140 QK 141

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 134053896   23 AFAEAQKWIEQVTGRSFGDKDFRTGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNTILFLRGCKELGLKESQLFDP 102
Cdd:cd21278     1 AFTEAQKWIEQVTGRSFGDKDFRSGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNITLFLRGCKELGLKESQLFDP 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 134053896  103 SDLQDTSNRVTVKNLDYSRKLKNVLVTIYWLGKAANSC 140
Cdd:cd21278    81 GDLQDTSNRVTIKSSDCSRKLKNVLITIYWLGKAANSC 118

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 134053896     26 EAQKWIEQVTGRSFGDK--DFRTGLENGILLCELLNAIKPGLV--KKINRLPTPIAGLDNTILFLRGCKELGLKEsQLFD 101
Cdd:smart00033    2 TLLRWVNSLLAEYDKPPvtNFSSDLKDGVALCALLNSLSPGLVdkKKVAASLSRFKKIENINLALSFAEKLGGKV-VLFE 80

                    ....*.
gi 134053896    102 PSDLQD 107
Cdd:smart00033   81 PEDLVE 86

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 134053896    987 CSSCGLTLGkGAAMIIETLNLYFHIQCFRCGICKGQLgdavSGTDVRIRNGLLNCTDC 1044
Cdd:smart00132    2 CAGCGKPIY-GTERVLRALGKVWHPECFKCATCGKPL----SGDTFFEKDGKLYCKDC 54

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 134053896   987 CSSCGltlgKG--AAMIIETLNLYFHIQCFRCGICKGQLGDavsgTDVRIRNGLLNCTDCYMRSR 1049
Cdd:pfam00412    1 CAGCN----RPiyDRELVRALGKVWHPECFRCAVCGKPLTT----GDFYEKDGKLYCKHDYYKLF 57

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 134053896  771 EEERRRQEKWQQEQERLLQERYQKEQDKLKEEWEKAQK 808
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 134053896   23 AFAEAQKWIEQVTGRSFGDKDFRTGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNTILFLRGCKELGLKESQLFDP 102
Cdd:cd21278     1 AFTEAQKWIEQVTGRSFGDKDFRSGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNITLFLRGCKELGLKESQLFDP 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 134053896  103 SDLQDTSNRVTVKNLDYSRKLKNVLVTIYWLGKAANSC 140
Cdd:cd21278    81 GDLQDTSNRVTIKSSDCSRKLKNVLITIYWLGKAANSC 118

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 134053896   23 AFAEAQKWIEQVTGRSFGDKDFRTGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNTILFLRGCKELGLKESQLFDP 102
Cdd:cd21208     1 ALKEARTWIEAVTGKKFPSDDFRESLEDGILLCELINAIKPGSIKKINRLPTPIAGLDNLNLFLKACEDLGLKDSQLFDP 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 134053896  103 SDLQDTSNRVT---VKNLDYSRKLKNVLVTIYWLGKAAN 138
Cdd:cd21208    81 TDLQDLSNRRIathVRKKEDERRLKNVAITLYWLGRAAR 119

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 134053896   25 AEAQKWIEQVTGRSFGD--KDFRTGLENGILLCELLNAIKPGLVKKINRLP-TPIAGLDNTILFLRGCKELGLKESQLFD 101
Cdd:cd00014     2 EELLKWINEVLGEELPVsiTDLFESLRDGVLLCKLINKLSPGSIPKINKKPkSPFKKRENINLFLNACKKLGLPELDLFE 81

                          90       100       110
                  ....*....|....*....|....*....|....
gi 134053896  102 PSDLQDTSNrvtvknldysrkLKNVLVTIYWLGK 135
Cdd:cd00014    82 PEDLYEKGN------------LKKVLGTLWALAL 103

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 134053896   25 AEAQKWIEQVTGRSFGDkDFRTGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNTILFLRGCKELGLKESQLFDPSD 104
Cdd:cd21283     6 AELRTWIEGLTGRSIGP-DFQKGLKDGVILCELMNKLQPGSVPKINRSMQNWHQLENLSNFIKAMVSYGMKPVDLFEAND 84

                          90
                  ....*....|.
gi 134053896  105 LQDTSNRVTVK 115
Cdd:cd21283    85 LFESGNMTQVQ 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 134053896   25 AEAQKWIEQVTGRSFGDkDFRTGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNTILFLRGCKELGLKESQLFDPSD 104
Cdd:cd21282     6 EELRVWIEGVTGRRIGD-NFMDGLKDGVILCELINKLQPGSVRKINESTQNWHKLENIGNFIKAIMHYGVKPHDIFEAND 84

                          90
                  ....*....|.
gi 134053896  105 LQDTSNRVTVK 115
Cdd:cd21282    85 LFENTNHTQVQ 95

calponin homology (CH) domain found in calponin-3; Calponin-3 (CNN3), also called acidic isoform calponin, is an F-actin-binding protein that is expressed in the brain and has been shown to control dendritic spine morphology, density, and plasticity by regulating actin cytoskeletal reorganization and dynamics. It contains a single copy of the CH domain. CH domains are actin filament (F-actin) binding motifs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134053896   26 EAQKWIEQVTGRSFGDkDFRTGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNTILFLRGCKELGLKESQLFDPSDL 105
Cdd:cd21284     9 ELRNWIEEVTGMSIGE-NFQKGLKDGVILCELINKLQPGSIRKINESKLNWHQLENIGNFIKAIQAYGMKPHDIFEANDL 87

                          90
                  ....*....|
gi 134053896  106 QDTSNRVTVK 115
Cdd:cd21284    88 FENGNMTQVQ 97

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 134053896    29 KWIEQVTGRSFGD---KDFRTGLENGILLCELLNAIKPGLVKKINRLPTPIAGLDNTILFLRGC-KELGLKEsQLFDPSD 104
Cdd:pfam00307    9 RWINSHLAEYGPGvrvTNFTTDLRDGLALCALLNKLAPGLVDKKKLNKSEFDKLENINLALDVAeKKLGVPK-VLIEPED 87

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 134053896   105 LqdtsnrvtvknldYSRKLKNVLVTIYWLGKAANS 139
Cdd:pfam00307   88 L-------------VEGDNKSVLTYLASLFRRFQA 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 134053896   25 AEAQKWIEQVTGRSFGD-KDFRTGLENGILLCELLNAIKPGLVKKINrlpTPIAGL-----DNTILFLRGCKELGLKESQ 98
Cdd:cd21206    11 EEAKQWIEACLNEELPPtTEFEEELRNGVVLAKLANKFAPKLVPLKK---IYDVGLqfrhtDNINHFLRALKKIGLPKIF 87

                          90
                  ....*....|..
gi 134053896   99 LFDPSDLQDTSN 110
Cdd:cd21206    88 HFETTDLYEKKN 99

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 134053896   43 DFRTGLENGILLCELLNAIKPGLVKKINRLPTP----IAGLDNTILFLRGCKE-LGLKESQLFDPSDLQDTSN 110
Cdd:cd21201    31 DLAQALRDGVLLCQLLNRLSPGSVDDREINLRPqmsqFLCLKNIRTFLQACRTvFGLRSADLFEPEDLYDVTN 103

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 134053896    987 CSSCGLTLGkGAAMIIETLNLYFHIQCFRCGICKGQLgdavSGTDVRIRNGLLNCTDC 1044
Cdd:smart00132    2 CAGCGKPIY-GTERVLRALGKVWHPECFKCATCGKPL----SGDTFFEKDGKLYCKDC 54

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 134053896   987 CSSCGltlgKG--AAMIIETLNLYFHIQCFRCGICKGQLGDavsgTDVRIRNGLLNCTDCYMRSR 1049
Cdd:pfam00412    1 CAGCN----RPiyDRELVRALGKVWHPECFRCAVCGKPLTT----GDFYEKDGKLYCKHDYYKLF 57

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134053896   43 DFRTGLENGILLCELLNAIKPGLV--KKINRLP--TPIAGLDNTILFLRG-CKELGLKESQLFDPSDLQD 107
Cdd:cd21264    31 DLAQTLRDGVLLCQLLNNLRPHSInlKEINLRPqmSQFLCLKNIRTFLSAcCETFGMRKSELFEAFDLFD 100

Calponin [Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134053896   26 EAQKWIEQVTGRSFGDK-DFRTGLENGILLCELLNAIKPGLVK-KINRLPtpIAGLDNTILFLRGCKELGLKESQLFDPS 103
Cdd:COG5199    17 EVTLWIETVLGEKFEPPgDLLSLLKDGVRLCRILNEASPLDIKyKESKMP--FVQMENISSFINGLKKLRVPEYELFQTN 94

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 134053896  104 DLQDtsnrvtvknldySRKLKNVLVTIYWLGKAAN 138
Cdd:COG5199    95 DLFE------------AKDLRQVVICLYSLSRYAQ 117

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 134053896   26 EAQKWIEQVTGRSFGDKDFRTGLENGILLCELLNAIKPGLVKKI---NRLptPIAGLDNTILFLRGCKELGLKESQLFDP 102
Cdd:COG5261    48 EAKIWIEEVIEEALPELCFEDSLRNGVFLAKLTQRFNPDLTTVIfpaDKL--QFRHTDNINAFLDLIEHVGLPESFHFEL 125

                          90
                  ....*....|..
gi 134053896  103 SDLQDTSNRVTV 114
Cdd:COG5261   126 QDLYEKKNIPKV 137

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 134053896   44 FRTGLENGILLCELLNAIKPGLVKKINRLP-TPIAGLDNTILFLRGCKELGLkesQLFDPSDLQDTSN 110
Cdd:cd21266    29 LQASLKDGVVLCRLLERLLPGSIDKVYPEPrTESECLSNIREFLRGCGALRL---ETFDANDLYQGQN 93

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 134053896  987 CSSCGLTL----GKGAAMIIETLNLYFHIQCFRCGICKGQLGDAVSGTDVRIRNGLLNCTDC 1044
Cdd:cd09357     1 CSVCGEPImpepGQDETVRIVALDRSFHVNCYKCEDCGMLLSSEDEGQGCYPLDGHLLCKSC 62

The second LIM domain of LMO4 (LIM domain only protein 4); The second LIM domain of LMO4 (LIM domain only protein 4): LMO4 is a nuclear protein that plays important roles in transcriptional regulation and development. LMO4 is involved in various functions in tumorigenesis and cellular differentiation. LMO4 proteins regulate gene expression by interacting with a wide variety of transcription factors and cofactors to form large transcription complexes. It can interact with Smad proteins, and associate with the promoter of the PAI-1 (plasminogen activator inhibitor-1) gene in a TGFbeta (transforming growth factor beta)-dependent manner. LMO4 can also form a complex with transcription regulator CREB (cAMP response element-binding protein) and interact with CLIM1 and CLIM2. In breast tissue, LMO4 interacts with multiple proteins, including the cofactor CtIP [CtBP (C-terminal binding protein)-interacting protein], the breast and ovarian tumor suppressor BRCA1 (breast-cancer susceptibility gene 1) and the LIM-domain-binding protein LDB1. Functionally, LMO4 is shown to repress BRCA1-mediated transcription activation, thus invoking a potential role for LMO4 as a negative regulator of BRCA1 in sporadic breast cancer. LMO4 also forms complex to both ERa (oestrogen receptor alpha), MTA1 (metastasis tumor antigen 1), and HDACs (histone deacetylases), implying that LMO4 is also a component of the MTA1 corepressor complex. Over-expressed LMO4 represses ERa transactivation functions in an HDAC-dependent manner, and contributes to the process of breast cancer progression by allowing the development of Era-negative phenotypes. 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 134053896  987 CSSCGLTLgKGAAMIIETLNLYFHIQCFRCGICKGQLgdaVSGTDVRIRNGLLNC-TDC 1044
Cdd:cd09387     1 CSACGQSI-PASELVMRAQGNVYHLKCFTCSTCHNQL---VPGDRFHYVNGSLFCeHDR 55

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 134053896  771 EEERRRQEKWQQEQERLLQERYQKEQDKLKEEWEKAQK 808
Cdd:cd16269   218 EEQQRELEQKLEDQERSYEEHLRQLKEKMEEERENLLK 255

The second LIM domain of Isl, a member of LHX protein family; The second LIM domain of Isl: Isl is a member of LHX protein family, which features two tandem N-terminal LIM domains and a C-terminal DNA binding homeodomain. Isl1 and Isl2 are the two conserved members of this family. Proteins in this group 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. Isl-1 is one of the LHX proteins isolated originally by virtue of its ability to bind DNA sequences from the 5'-flanking region of the rat insulin gene in pancreatic insulin-producing cells. Mice deficient in Isl-1 fail to form the dorsal exocrine pancreas and islet cells fail to differentiate. On the other hand, Isl-1 takes part in the pituitary development by activating the gonadotropin-releasing hormone receptor gene together with LHX3 and steroidogenic factor 1. Mouse Isl2 is expressed in the retinal ganglion cells and the developing spinal cord where it plays a role in motor neuron development. Same as Isl1, Isl2 may also be able to bind to the insulin gene enhancer to promote gene activation. 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 134053896  987 CSSCGLTLGKgAAMIIETLNLYFHIQCFRCGICKGQLgdaVSGTDVRIRNGLLNC 1041
Cdd:cd09374     1 CAKCQQSFSK-NDFVMRARTKIYHIECFRCSACSRQL---IPGDEFALRDDGLFC 51

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 134053896   30 WIEQVTGRSFGDKDFRTGLENGILLCELLNAI------------KPGL---VKKINRLPTPIAG----LDNTILFLRGCK 90
Cdd:cd21267    15 WLTNLLGKEITAESFMEKLDNGALLCQLAETLqekfkensadanKPGKslpVRKIPCRANAPSGsffaRDNTANFLSWCR 94

                          90
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gi 134053896   91 ELGLKESQLFDPSDL 105
Cdd:cd21267    95 DVGVGDTCLFESEGL 109

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 134053896  987 CSSCGLTLGKgaaMIIETLNLYFHIQCFRCGICKGQL 1023
Cdd:cd09355     1 CAVCGHLIME---MILQALGKSYHPGCFRCCVCNECL 34