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 1039750839 536 CSVCKEPIMPAPGQEETVRIVALDRDFHVHCYRCEDCGGLLSEGDNQGCYPLDGHILCKTCNSARI 601
Cdd:cd09436     1 CSVCKEPIMPAPGQEETVRIVALDRDFHVQCYRCEDCGSLLSEGDNQGCYPLDGHILCKACNSARI 66

The first LIM domain of Thyroid receptor-interacting protein 6 (TRIP6); The first LIM domain of Thyroid receptor-interacting protein 6 (TRIP6): TRIP6 is a member of the zyxin LIM protein family and contains three LIM zinc-binding domains at the C-terminal. TRIP6 protein localizes to focal adhesion sites and along actin stress fibers. Recruitment of this protein to the plasma membrane occurs in a lysophosphatidic acid (LPA)-dependent manner. TRIP6 recruits a number of molecules involved in actin assembly, cell motility, survival and transcriptional control. The function of TRIP6 in cell motility is regulated by Src-dependent phosphorylation at a Tyr residue. The phosphorylation activates the coupling to the Crk SH2 domain, which is required for the function of TRIP6 in promoting lysophosphatidic acid (LPA)-induced cell migration. TRIP6 can shuttle to the nucleus to serve as a coactivator of AP-1 and NF-kappaB transcriptional factors. Moreover, TRIP6 can form a ternary complex with the NHERF2 PDZ protein and LPA2 receptor to regulate LPA-induced activation of ERK and AKT, rendering cells resistant to chemotherapy. Recent evidence shows that TRIP6 antagonizes Fas-Induced apoptosis by enhancing the antiapoptotic effect of LPA in cells. 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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039750839 416 CARCGENVVGEGTGCTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCEPCY 469
Cdd:cd09350     1 CGRCGENVVGEGTGCTAMDQVFHVDCFTCMTCNGKLRGQPFYAVEKKAYCEPCY 54

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039750839 138 KPRPPQGSASSIASPPVSTPVTGHKrmVIP-QQPPLTATKKSATKPQPAPQAAPIPVTpIGTLKPQPQPVPASyTTASTS 216
Cdd:PRK14971  371 GGRGPKQHIKPVFTQPAAAPQPSAA--AAAsPSPSQSSAAAQPSAPQSATQPAGTPPT-VSVDPPAAVPVNPP-STAPQA 446

                          90       100
                  ....*....|....*....|...
gi 1039750839 217 SRPTFNVQVKSAQPSPHYMAGPS 239
Cdd:PRK14971  447 VRPAQFKEEKKIPVSKVSSLGPS 469

The third LIM domain of Thyroid receptor-interacting protein 6 (TRIP6); The third LIM domain of Thyroid receptor-interacting protein 6 (TRIP6): TRIP6 is a member of the zyxin LIM protein family and contains three LIM zinc-binding domains at the C-terminal. TRIP6 protein localizes to focal adhesion sites and along actin stress fibers. Recruitment of this protein to the plasma membrane occurs in a lysophosphatidic acid (LPA)-dependent manner. TRIP6 recruits a number of molecules involved in actin assembly, cell motility, survival and transcriptional control. The function of TRIP6 in cell motility is regulated by Src-dependent phosphorylation at a Tyr residue. The phosphorylation activates the coupling to the Crk SH2 domain, which is required for the function of TRIP6 in promoting lysophosphatidic acid (LPA)-induced cell migration. TRIP6 can shuttle to the nucleus to serve as a coactivator of AP-1 and NF-kappaB transcriptional factors. Moreover, TRIP6 can form a ternary complex with the NHERF2 PDZ protein and LPA2 receptor to regulate LPA-induced activation of ERK and AKT, rendering cells resistant to chemotherapy. Recent evidence shows that TRIP6 antagonizes Fas-Induced apoptosis by enhancing the antiapoptotic effect of LPA in cells. 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 1039750839 536 CSVCKEPIMPAPGQEETVRIVALDRDFHVHCYRCEDCGGLLSEGDNQGCYPLDGHILCKTCNSARI 601
Cdd:cd09436     1 CSVCKEPIMPAPGQEETVRIVALDRDFHVQCYRCEDCGSLLSEGDNQGCYPLDGHILCKACNSARI 66

The first LIM domain of Thyroid receptor-interacting protein 6 (TRIP6); The first LIM domain of Thyroid receptor-interacting protein 6 (TRIP6): TRIP6 is a member of the zyxin LIM protein family and contains three LIM zinc-binding domains at the C-terminal. TRIP6 protein localizes to focal adhesion sites and along actin stress fibers. Recruitment of this protein to the plasma membrane occurs in a lysophosphatidic acid (LPA)-dependent manner. TRIP6 recruits a number of molecules involved in actin assembly, cell motility, survival and transcriptional control. The function of TRIP6 in cell motility is regulated by Src-dependent phosphorylation at a Tyr residue. The phosphorylation activates the coupling to the Crk SH2 domain, which is required for the function of TRIP6 in promoting lysophosphatidic acid (LPA)-induced cell migration. TRIP6 can shuttle to the nucleus to serve as a coactivator of AP-1 and NF-kappaB transcriptional factors. Moreover, TRIP6 can form a ternary complex with the NHERF2 PDZ protein and LPA2 receptor to regulate LPA-induced activation of ERK and AKT, rendering cells resistant to chemotherapy. Recent evidence shows that TRIP6 antagonizes Fas-Induced apoptosis by enhancing the antiapoptotic effect of LPA in cells. 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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039750839 416 CARCGENVVGEGTGCTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCEPCY 469
Cdd:cd09350     1 CGRCGENVVGEGTGCTAMDQVFHVDCFTCMTCNGKLRGQPFYAVEKKAYCEPCY 54

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 1039750839  535 RCSVCKEPIMPapgqeETVRIVALDRDFHVHCYRCEDCGGLLSegdNQGCYPLDGHILCKTC 596
Cdd:smart00132   1 KCAGCGKPIYG-----TERVLRALGKVWHPECFKCATCGKPLS---GDTFFEKDGKLYCKDC 54

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 1039750839  476 CSVCSKPIM--ERILRATGKAYHPHCFTCVMCHRSLDGIPFTVDAcGLIHCIED 527
Cdd:smart00132   2 CAGCGKPIYgtERVLRALGKVWHPECFKCATCGKPLSGDTFFEKD-GKLYCKDC 54

chromosomal replication initiator protein DnaA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039750839 191 IPVTPIGTLKPQPQPVPASYTTASTSSRPTFNVQVKSAQPSPHYMAGPSSGQIYGPGPRGY-NNQPVPVSGQCPPPPTCV 269
Cdd:PRK14086   86 ITVDPSAGEPAPPPPHARRTSEPELPRPGRRPYEGYGGPRADDRPPGLPRQDQLPTARPAYpAYQQRPEPGAWPRAADDY 165

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039750839 270 GTDYayiPPSGHPPESGYG----YTSNQGRYYEPYYAAGPSYG-GRSEGDTAYGQQVQPNTWKREAAYAPPASGNQNHPG 344
Cdd:PRK14086  166 GWQQ---QRLGFPPRAPYAspasYAPEQERDREPYDAGRPEYDqRRRDYDHPRPDWDRPRRDRTDRPEPPPGAGHVHRGG 242

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1039750839 345 MYPVSGPKKTYITDPVSAPCAPPLQPKGGYPGPMGPPSIPPSF 387
Cdd:PRK14086  243 PGPPERDDAPVVPIRPSAPGPLAAQPAPAPGPGEPTARLNPKY 285

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039750839 138 KPRPPQGSASSIASPPVSTPVTGHKrmVIP-QQPPLTATKKSATKPQPAPQAAPIPVTpIGTLKPQPQPVPASyTTASTS 216
Cdd:PRK14971  371 GGRGPKQHIKPVFTQPAAAPQPSAA--AAAsPSPSQSSAAAQPSAPQSATQPAGTPPT-VSVDPPAAVPVNPP-STAPQA 446

                          90       100
                  ....*....|....*....|...
gi 1039750839 217 SRPTFNVQVKSAQPSPHYMAGPS 239
Cdd:PRK14971  447 VRPAQFKEEKKIPVSKVSSLGPS 469

Uncharacterized conserved protein, contains PIN-related Mut7-C RNAse domain [General function prediction only];

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1039750839 535 RCSVCKEPIMPAPGQEETVRIVALDRDFHVHCYRCEDCG 573
Cdd:COG1656    92 RCLRCNGPLEPVDKEEVADRVPPYVRERYDEFWRCPKCG 130

The third LIM domain of Thyroid receptor-interacting protein 6 (TRIP6); The third LIM domain of Thyroid receptor-interacting protein 6 (TRIP6): TRIP6 is a member of the zyxin LIM protein family and contains three LIM zinc-binding domains at the C-terminal. TRIP6 protein localizes to focal adhesion sites and along actin stress fibers. Recruitment of this protein to the plasma membrane occurs in a lysophosphatidic acid (LPA)-dependent manner. TRIP6 recruits a number of molecules involved in actin assembly, cell motility, survival and transcriptional control. The function of TRIP6 in cell motility is regulated by Src-dependent phosphorylation at a Tyr residue. The phosphorylation activates the coupling to the Crk SH2 domain, which is required for the function of TRIP6 in promoting lysophosphatidic acid (LPA)-induced cell migration. TRIP6 can shuttle to the nucleus to serve as a coactivator of AP-1 and NF-kappaB transcriptional factors. Moreover, TRIP6 can form a ternary complex with the NHERF2 PDZ protein and LPA2 receptor to regulate LPA-induced activation of ERK and AKT, rendering cells resistant to chemotherapy. Recent evidence shows that TRIP6 antagonizes Fas-Induced apoptosis by enhancing the antiapoptotic effect of LPA in cells. 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 1039750839 536 CSVCKEPIMPAPGQEETVRIVALDRDFHVHCYRCEDCGGLLSEGDNQGCYPLDGHILCKTCNSARI 601
Cdd:cd09436     1 CSVCKEPIMPAPGQEETVRIVALDRDFHVQCYRCEDCGSLLSEGDNQGCYPLDGHILCKACNSARI 66

The third LIM domain of lipoma preferred partner (LPP); The third LIM domain of lipoma preferred partner (LPP): LPP is a member of the zyxin LIM protein family and contains three LIM zinc-binding domains at the C-terminal and proline-rich region at the N-terminal. LPP initially identified as the most frequent translocation partner of HMGA2 (High Mobility Group A2) in a subgroup of benign tumors of adipose tissue (lipomas). It was also shown to be rearranged in a number of other soft tissues, as well as in a case of acute monoblastic leukemia. In addition to its involvement in tumors, LPP was inedited as a smooth muscle restricted LIM protein that plays an important role in SMC migration. LPP is localized at sites of cell adhesion, cell-cell contacts and transiently in the nucleus. In nucleus, it acts as a coactivator for the ETS domain transcription factor PEA3. In addition to PEA3, it interacts with alpha-actinin,vasodilator stimulated phosphoprotein (VASP), Palladin, and Scrib. The LIM domains are the main focal adhesion targeting elements and that the proline- rich region, which harbors binding sites for alpha-actinin and vasodilator- stimulated phosphoprotein (VASP), has a weak targeting capacity. 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 1039750839 536 CSVCKEPIMPAPGQEETVRIVALDRDFHVHCYRCEDCGGLL-SEGDNQGCYPLDGHILCKTCNSARIR 602
Cdd:cd09437     1 CCVCKLPIMPEPGQDETVRVVALDRSFHVQCYKCEDCGLLLsSEAEGRGCYPLDDHVLCKSCNAKRVQ 68

The first LIM domain of Thyroid receptor-interacting protein 6 (TRIP6); The first LIM domain of Thyroid receptor-interacting protein 6 (TRIP6): TRIP6 is a member of the zyxin LIM protein family and contains three LIM zinc-binding domains at the C-terminal. TRIP6 protein localizes to focal adhesion sites and along actin stress fibers. Recruitment of this protein to the plasma membrane occurs in a lysophosphatidic acid (LPA)-dependent manner. TRIP6 recruits a number of molecules involved in actin assembly, cell motility, survival and transcriptional control. The function of TRIP6 in cell motility is regulated by Src-dependent phosphorylation at a Tyr residue. The phosphorylation activates the coupling to the Crk SH2 domain, which is required for the function of TRIP6 in promoting lysophosphatidic acid (LPA)-induced cell migration. TRIP6 can shuttle to the nucleus to serve as a coactivator of AP-1 and NF-kappaB transcriptional factors. Moreover, TRIP6 can form a ternary complex with the NHERF2 PDZ protein and LPA2 receptor to regulate LPA-induced activation of ERK and AKT, rendering cells resistant to chemotherapy. Recent evidence shows that TRIP6 antagonizes Fas-Induced apoptosis by enhancing the antiapoptotic effect of LPA in cells. 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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039750839 416 CARCGENVVGEGTGCTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCEPCY 469
Cdd:cd09350     1 CGRCGENVVGEGTGCTAMDQVFHVDCFTCMTCNGKLRGQPFYAVEKKAYCEPCY 54

The third LIM domain of Zyxin; The third LIM domain of Zyxin: Zyxin exhibits three copies of the LIM domain, an extensive proline-rich domain and a nuclear export signal. Localized at sites of cellsubstratum adhesion in fibroblasts, Zyxin interacts with alpha-actinin, members of the cysteine-rich protein (CRP) family, proteins that display Src homology 3 (SH3) domains and Ena/VASP family members. Zyxin and its partners have been implicated in the spatial control of actin filament assembly as well as in pathways important for cell differentiation. In addition to its functions at focal adhesion plaques, recent work has shown that zyxin moves from the sites of cell contacts to the nucleus, where it directly participates in the regulation of gene expression. 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 1039750839 536 CSVCKEPIMPAPGQEETVRIVALDRDFHVHCYRCEDCGGLLS-EGDNQGCYPLDGHILCKTCNSAR 600
Cdd:cd09435     1 CCVCSEPIMPEPGRDETVRVVALEKNFHMKCYKCEDCGRPLSiEADDNGCFPLDGHVLCMKCHTAR 66

The second LIM domain of Zyxin; The second LIM domain of Zyxin: Zyxin exhibits three copies of the LIM domain, an extensive proline-rich domain and a nuclear export signal. Localized at sites of cellsubstratum adhesion in fibroblasts, Zyxin interacts with alpha-actinin, members of the cysteine-rich protein (CRP) family, proteins that display Src homology 3 (SH3) domains and Ena/VASP family members. Zyxin and its partners have been implicated in the spatial control of actin filament assembly as well as in pathways important for cell differentiation. In addition to its functions at focal adhesion plaques, recent work has shown that zyxin moves from the sites of cell contacts to the nucleus, where it directly participates in the regulation of gene expression. 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 o r scaffolds to support the assembly of multimeric protein.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039750839 476 CSVCSKPIMERILRATGKAYHPHCFTCVMCHRSLDGIPFTVDACGLIHCIEDFHKKFAPR 535
Cdd:cd09353     1 CAVCDQKITDRMLKATGKSYHPQCFTCVVCKCPLEGESFIVDQANQPHCVNDYHRRYAPR 60

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1039750839 476 CSVCSKPIMERILRATGKAYHPHCFTCVMCHRSLDGIPFTVDACGLIHCIEDF 528
Cdd:cd09355     1 CAVCGHLIMEMILQALGKSYHPGCFRCCVCNECLDGVPFTVDVENNIYCVKDY 53

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1039750839  415 RCARCGENVVGEGTGCTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCEPC 468
Cdd:smart00132   1 KCAGCGKPIYGTERVLRALGKVWHPECFKCATCGKPLSGDTFFEKDGKLYCKDC 54

The first LIM domain of Ajuba-like proteins; The first 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1039750839 416 CARCGENVVGEGTGCTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCE 466
Cdd:cd09352     1 CVKCGKGVYGASQACQAMGNLYHTNCFTCCSCGRTLRGKAFYNVNGKVYCE 51

The second LIM domain of the filamin-binding LIM protein-1 (FBLP-1); The second LIM domain of the filamin-binding LIM protein-1 (FBLP-1): Fblp-1 contains a proline-rich domain near its N terminus and two LIM domains at its C terminus. FBLP-1 mRNA was detected in a variety of tissues and cells including platelets and endothelial cells. FBLP-1 binds to Filamins. The association between filamin B and FBLP-1 may play an unknown role in cytoskeletal function, cell adhesion, and cell motility. As in other LIM domains, this domain family is 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1039750839 476 CSVCSKPIMERILRATGKAYHPHCFTCVMCHRSLDGIPFTVDACGLIHCIEDF 528
Cdd:cd09372     1 CAKCQGVITEHIIRALGKGYHPPCFTCVTCGRRIGDESFAVDEQNEVYCLDDY 53

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039750839 416 CARCGENVVGEGTgCTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCEPCYIN 471
Cdd:pfam00412   1 CAGCNRPIYDREL-VRALGKVWHPECFRCAVCGKPLTTGDFYEKDGKLYCKHDYYK 55

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1039750839 476 CSVCSKPIMER-ILRATGKAYHPHCFTCVMCHRSL-DGIPFTVDacGLIHCIEDFHKKF 532
Cdd:pfam00412   1 CAGCNRPIYDReLVRALGKVWHPECFRCAVCGKPLtTGDFYEKD--GKLYCKHDYYKLF 57

chromosomal replication initiator protein DnaA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039750839 191 IPVTPIGTLKPQPQPVPASYTTASTSSRPTFNVQVKSAQPSPHYMAGPSSGQIYGPGPRGY-NNQPVPVSGQCPPPPTCV 269
Cdd:PRK14086   86 ITVDPSAGEPAPPPPHARRTSEPELPRPGRRPYEGYGGPRADDRPPGLPRQDQLPTARPAYpAYQQRPEPGAWPRAADDY 165

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039750839 270 GTDYayiPPSGHPPESGYG----YTSNQGRYYEPYYAAGPSYG-GRSEGDTAYGQQVQPNTWKREAAYAPPASGNQNHPG 344
Cdd:PRK14086  166 GWQQ---QRLGFPPRAPYAspasYAPEQERDREPYDAGRPEYDqRRRDYDHPRPDWDRPRRDRTDRPEPPPGAGHVHRGG 242

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1039750839 345 MYPVSGPKKTYITDPVSAPCAPPLQPKGGYPGPMGPPSIPPSF 387
Cdd:PRK14086  243 PGPPERDDAPVVPIRPSAPGPLAAQPAPAPGPGEPTARLNPKY 285

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039750839 536 CSVCKEPImpapgqEETVRIVALDRDFHVHCYRCEDCGGLLSEGDNqgcYPLDGHILCKTC 596
Cdd:pfam00412   1 CAGCNRPI------YDRELVRALGKVWHPECFRCAVCGKPLTTGDF---YEKDGKLYCKHD 52

The third LIM domain of Four and a half LIM domains protein (FHL); The third 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039750839 416 CARCGENVVGEGTgcTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCEPCY 469
Cdd:cd09346     1 CAKCKKAITSGGV--TYRDQPWHKECFVCTGCKKQLAGQRFTSRDEYPYCVDCF 52

The first LIM domain of Leupaxin; The first LIM domain of Leupaxin: Leupaxin is a cytoskeleton adaptor protein, which is preferentially expressed in hematopoietic cells. Leupaxin belongs to the paxillin focal adhesion protein family. Same as other members of the family, it has four leucine-rich LD-motifs in the N-terminus and four LIM domains in the C-terminus. It may function in cell type-specific signaling by associating with interaction partners PYK2, FAK, PEP and p95PKL. When expressed in human leukocytic cells, leupaxin significantly suppressed integrin-mediated cell adhesion to fibronectin and the tyrosine phosphorylation of paxillin. These findings indicate that leupaxin may negatively regulate the functions of paxillin during integrin signaling. 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 1039750839 476 CSVCSKPIMERILRATGKAYHPHCFTCVMCHRSLDGIPFtVDACGLIHCIEDFH 529
Cdd:cd09406     3 CASCQKPIAGQVVTALGQTWHPEHFVCCQCGKELGSRPF-FERNGQAYCEEDYH 55

The LIM domain of ALP (actinin-associated LIM protein) family; This family represents the LIM domain of ALP (actinin-associated LIM protein) family. Four proteins: ALP, CLP36, RIL, and Mystique have been classified into the ALP subfamily of LIM domain proteins. Each member of the subfamily contains an N-terminal PDZ domain and a C-terminal LIM domain. Functionally, these proteins bind to alpha-actinin through their PDZ domains and bind or other signaling molecules through their LIM domains. ALP proteins have been implicated in cardiac and skeletal muscle structure, function and disease, platelet, and epithelial cell motility. 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 1039750839 416 CARCGENVVGegTGCTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCE 466
Cdd:cd09360     1 CDKCGNGIVG--VVVKARDKNRHPECFVCADCGLNLKNKGYFFIEDELYCE 49

The LIM domain of RIL; The LIM domain of RIL: RIL contains an N-terminal PDZ domain, a LIM domain, and a short consensus C-terminal region. It is the smallest molecule in the ALP LIM domain containing protein family. RIL was identified in rat fibroblasts and in human lymphocytes. The LIM domain interacts with the AMPA glutamate receptor in dendritic spines. The consensus C-terminus interacts with PTP-BL, a submembranous protein tyrosine phosphatase and the PDZ domain is responsible to interact with alpha-actinin molecules. 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 1039750839 416 CARCGENVVGegTGCTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCE 466
Cdd:cd09451     1 CTRCGNGIVG--TIVKARDKLYHPECFMCDDCGLNLKQRGYFFIDEQLYCE 49

The first LIM domain of protein PINCH; The first LIM domain of paxillin: Paxillin is an adaptor protein, which recruits key components of the signal-transduction machinery to specific sub-cellular locations to respond to environmental changes rapidly. The C-terminal region of paxillin contains four LIM domains which target paxillin to focal adhesions, presumably through a direct association with the cytoplasmic tail of beta-integrin. The N-terminal of paxillin is leucine-rich LD-motifs. Paxillin is found at the interface between the plasma membrane and the actin cytoskeleton. The binding partners of paxillin are diverse and include protein tyrosine kinases, such as Src and FAK, structural proteins, such as vinculin and actopaxin, and regulators of actin organization. Paxillin recruits these proteins to their function sites to control the dynamic changes in cell adhesion, cytoskeletal reorganization and gene expression. 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039750839 476 CSVCSKPIM--ERILRATGKAYHPHCFTCVMCHRSL-DGIPFTVDacGLIHCIEDFHKKFA 533
Cdd:cd09331     1 CERCREGFEpdEKIVNSNGELYHEQCFVCAQCFQPFpDGLFYEFE--GRKYCEHDFQVLFA 59

The first LIM domain of Enigma-like family; The first LIM domain of Enigma-like family: The Enigma LIM domain family is comprised of three 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. Enigma was initially characterized in humans and is expressed in multiple tissues, such as skeletal muscle, heart, bone, and brain. The third LIM domain specifically interacts with the insulin receptor and the second LIM domain interacts with the receptor tyrosine kinase Ret and the adaptor protein APS. Thus Enigma is implicated in signal transduction processes, such as mitogenic activity, insulin related actin organization, and glucose metabolism. The second member, ENH protein, was first identified in rat brain. It has been shown that ENH interacts with protein kinase D1 (PKD1) via its LIM domains and forms a complex with PKD1 and the alpha1C subunit of cardiac L-type voltage-gated calcium channel in rat neonatal cardiomyocytes. The N-terminal PDZ domain interacts with alpha-actinin at the Z-line. ZASP/Cypher is required for maintenance of Z-line structure during muscle contraction, but not required for Z-line assembly. In heart, Cypher/ZASP plays a structural role through its interaction with cytoskeletal Z-line proteins. In addition, there is increasing evidence that Cypher/ZASP also performs signaling functions. Studies reveal that Cypher/ZASP interacts with and directs PKC to the Z-line, where PKC phosphorylates downstream signaling targets. 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
                  ....*....|....*....|....*....|....*....|....*....
gi 1039750839 476 CSVCSKPIMERILRATGKAYHPHCFTCVMCHRSLDGIPFtVDACGLIHC 524
Cdd:cd09361     1 CAHCNQVIRGPFLVALGRSWHPEEFTCSHCHCSLAEIGF-VEEKGSLYC 48

The second LIM domain of the Enigma Homolog (ENH) family; The second LIM domain of the Enigma Homolog (ENH) family: ENH was initially identified in rat brain. Same as enigma, it contains three LIM domains at the C-terminus and a PDZ domain at N-terminus. ENH is implicated in signal transduction processes involving protein kinases. It has also been shown that ENH interacts with protein kinase D1 (PKD1) via its LIM domains and forms a complex with PKD1 and the alpha1C subunit of cardiac L-type voltage-gated calcium channel in rat neonatal cardiomyocytes. The N-terminal PDZ domain interacts with alpha-actinin at the Z-line. ENH is expressed in multiple tissues, such as skeletal muscle, heart, bone, and brain. 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 1039750839 416 CARCGENVVGEGTgcTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCEPCY 469
Cdd:cd09457     1 CGRCQRKILGEVI--NALKQTWHVSCFVCVACHNPIRNNVFHLEDGEPYCETDY 52

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039750839  129 ADLECSSPYKPRPPQGSASSIASPPVSTPVTGHKRMVIPQQPPLTATKKSATKPqPAPQAAPIP----VTPIGTLKPQPQ 204
Cdd:PHA03247  2789 ASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPP-PGPPPPSLPlggsVAPGGDVRRRPP 2867

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039750839  205 PVPASYTTASTSSRPTFNVQVKSAQPSPHYMAGPSSGQIYGPGPrgynnqPVPVSGQCPPPPTCVGTDYAYIPPSGHPPE 284
Cdd:PHA03247  2868 SRSPAAKPAAPARPPVRRLARPAVSRSTESFALPPDQPERPPQP------QAPPPPQPQPQPPPPPQPQPPPPPPPRPQP 2941

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1039750839  285 SGYGYTSNQGRYYEPYYAAGPSYGGRSEGDTAYGQQVQPNTWKREAAYAPPASGNQNHP 343
Cdd:PHA03247  2942 PLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPASSTPPLTGHS 3000

The fourth LIM domain of protein PINCH; The fourth LIM domain of protein PINCH: PINCH plays a pivotal role in the assembly of focal adhesions (FAs), regulating diverse functions in cell adhesion, growth, and differentiation through LIM-mediated protein-protein interactions. PINCH comprises an array of five LIM domains that interact with integrin-linked kinase (ILK), Nck2 (also called Nckbeta or Grb4) and other interaction partners. These interactions are essential for triggering the FA assembly and for relaying diverse mechanical and biochemical signals between Cell-extracellular matrix and the actin cytoskeleton. The PINCH LIM4 domain recognizes the third SH3 domain of another adaptor protein, Nck2. This step is an important component of integrin signaling event. 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 assem bly of multimeric protein complexes.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039750839 416 CARCGENVvgEGTGCTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCEPCY 469
Cdd:cd09334     3 CGACRRPI--EGRVVTALGKHWHVEHFVCAKCEKPFLGHRHYEKKGLAYCETHY 54

The first LIM domain of Lrg1p, a LIM and RhoGap domain containing protein; The first LIM domain of Lrg1p, a LIM and RhoGap domain containing protein: The members of this family contain three tandem repeats of LIM domains and a Rho-type GTPase activating protein (RhoGap) domain. Lrg1p is a Rho1 GTPase-activating protein required for efficient cell fusion in yeast. Lrg1p-GAP domain strongly and specifically stimulates the GTPase activity of Rho1p, a regulator of beta (1-3)-glucan synthase in vitro. The LIM domain 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
                  ....*....|....*....|....*....|..
gi 1039750839 476 CSVCSKPIMERILRATGKAYHPHCFTCVMCHR 507
Cdd:cd09391     1 CAKCGKPITGQFVRALGDVYHLDCFTCHDCGK 32

The second LIM domain of Lhx2 and Lhx9 family; The second LIM domain of Lhx2 and Lhx9 family: Lhx2 and Lhx9 are highly homologous LHX regulatory proteins. They belong 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. Although Lhx2 and Lhx9 are highly homologous, they seems to play regulatory roles in different organs. In animals, Lhx2 plays important roles in eye, cerebral cortex, limb, the olfactory organs, and erythrocyte development. Lhx2 gene knockout mice exhibit impaired patterning of the cortical hem and the telencephalon of the developing brain, and a lack of development in olfactory structures. Lhx9 is expressed in several regions of the developing mouse brain, the spinal cord, the pancreas, in limb mesenchyme, and in the urogenital region. Lhx9 plays critical roles in gonad development. Homozygous mice lacking functional Lhx9 alleles exhibit numerous urogenital defects, such as gonadal agenesis, infertility, and undetectable levels of testosterone and estradiol coupled with high FSH levels. Lhx9 null mice are phenotypically female, even those that are genotypically male. 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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039750839 415 RCARCGENVVGEGTGCTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKA-YCEPCY 469
Cdd:cd09377     4 RCARCHLGISASELVMRARDLVFHLNCFTCATCNKPLTKGDHFGMRDGLvYCRLHY 59

The first LIM domain of Leupaxin; The first LIM domain of Leupaxin: Leupaxin is a cytoskeleton adaptor protein, which is preferentially expressed in hematopoietic cells. Leupaxin belongs to the paxillin focal adhesion protein family. Same as other members of the family, it has four leucine-rich LD-motifs in the N-terminus and four LIM domains in the C-terminus. It may function in cell type-specific signaling by associating with interaction partners PYK2, FAK, PEP and p95PKL. When expressed in human leukocytic cells, leupaxin significantly suppressed integrin-mediated cell adhesion to fibronectin and the tyrosine phosphorylation of paxillin. These findings indicate that leupaxin may negatively regulate the functions of paxillin during integrin signaling. 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 1039750839 414 GRCARCGENVVGEGTgcTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCEPCY 469
Cdd:cd09406     1 GDCASCQKPIAGQVV--TALGQTWHPEHFVCCQCGKELGSRPFFERNGQAYCEEDY 54

The third LIM domain of Four and a half LIM domains protein 2 (FHL2); The third LIM domain of Four and a half LIM domains protein 2 (FHL2): FHL2 is one of the best studied FHL proteins. FHL2 expression is most abundant in the heart, and in brain, liver and lung to a lesser extent. FHL2 participates in a wide range of cellular processes, such as transcriptional regulation, signal transduction, and cell survival by binding to various protein partners. 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. Although FHL2 is abundantly expressed in heart, the fhl2 null mice are viable and had no detectable abnormal cardiac phenotype. 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 s upport the assembly of multimeric protein complexes.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039750839 416 CARCGENVVGEGTgcTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCEPCYIN 471
Cdd:cd09431     1 CVQCKKPITTGGV--TYRDQPWHKECFVCTGCKKQLSGQRFTSRDDFAYCLNCFCN 54

The second LIM domain of Lhx3-Lhx4 family; The second LIM domain of Lhx3-Lhx4 family: Lhx3 and Lhx4 belong 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. The LHX3 and LHX4 LIM-homeodomain transcription factors play essential roles in pituitary gland and nervous system development. Although LHX3 and LHX4 share marked sequence homology, the genes have different expression patterns. They play overlapping, but distinct functions during the establishment of the specialized cells of the mammalian pituitary gland and the nervous system. Lhx3 proteins have been demonstrated the ability to directly bind to the promoters/enhancers of several pituitary hormone gene promoters to cause increased transcription.Lhx3a and Lhx3b, whose mRNAs have distinct temporal expression profiles during development, are two isoforms of Lhx3. LHX4 plays essential roles in pituitary gland and nervous system development. In mice, the lhx4 gene is expressed in the developing hindbrain, cerebral cortex, pituitary gland, and spinal cord. LHX4 shows significant sequence similarity to LHX3, particularly to isoforms Lhx3a. In gene regulation experiments, the LHX4 protein exhibits regulation roles towards pituitary genes, acting on their promoters/enhancers. 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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039750839 416 CARCGENVVGEGTGCTAMDQVFHVDCFTCIVCDVKLR-GQPFYAVE-KKAYCEPCY 469
Cdd:cd09376     1 CAGCDEGIPPTQVVRRAQDNVYHLECFACFMCKRQLEtGDEFYLMEdDRLVCKKDY 56

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039750839 138 KPRPPQGSASSIASPPVSTPVTGHKrmVIP-QQPPLTATKKSATKPQPAPQAAPIPVTpIGTLKPQPQPVPASyTTASTS 216
Cdd:PRK14971  371 GGRGPKQHIKPVFTQPAAAPQPSAA--AAAsPSPSQSSAAAQPSAPQSATQPAGTPPT-VSVDPPAAVPVNPP-STAPQA 446

                          90       100
                  ....*....|....*....|...
gi 1039750839 217 SRPTFNVQVKSAQPSPHYMAGPS 239
Cdd:PRK14971  447 VRPAQFKEEKKIPVSKVSSLGPS 469

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039750839 416 CARCGENVVGEGTgcTAMDQVFHVDCFTCIVCDVKLRGQPFYAVEKKAYCEPCY 469
Cdd:cd09327     1 CYKCGKKCKGEVL--RVQDKYFHIKCFTCKVCGCDLAQGGFFVKEGEYYCTDDY 52

The second LIM domain of Lhx1 (also known as Lim1) and Lhx5; The second LIM domain of Lhx1 (also known as Lim1) and Lhx5. Lhx1 and Lhx5 are closely related members of 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. Lhx1 is required for regulating the vertebrate head organizer, the nervous system, and female reproductive tract development. During embryogenesis in the mouse, Lhx1 is expressed early in mesodermal tissue, then later during urogenital, kidney, liver, and nervous system development. In the adult, expression is restricted to the kidney and brain. A mouse embryos with Lhx1 gene knockout cannot grow normal anterior head structures, kidneys, and gonads, but with normally developed trunk and tail morphology. In the developing nervous system, Lhx1 is required to direct the trajectories of motor axons in the limb. Lhx1 null female mice lack the oviducts and uterus. Lhx5 protein may play complementary or overlapping roles with Lhx1. The expression of Lhx5 in the anterior portion of the mouse neural tube suggests a role in patterning of the forebrain. 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 1039750839 416 CARCGENVVGEGTGCTAMDQVFHVDCFTCIVCDVKLR-GQPFYAVEKKAY-CEPCY 469
Cdd:cd09375     1 CAGCDQGISPNDLVRRARDKVFHLNCFTCMVCRKQLStGEELYILDENKFiCKEDY 56

The third LIM domain of the paxillin like protein family; The third LIM domain of the paxillin like protein family: This family consists of paxillin, leupaxin, Hic-5 (ARA55), and other related proteins. There are four LIM domains in the C-terminal of the proteins and leucine-rich LD-motifs in the N-terminal region. Members of this family are adaptor proteins to recruit key components of signal-transduction machinery to specific sub-cellular locations. Paxillin is found at the interface between the plasma membrane and the actin cytoskeleton. Paxillin serves as a platform for the recruitment of numerous regulatory and structural proteins that together control the dynamic changes in cell adhesion, cytoskeletal reorganization and gene expression that are necessary for cell migration and survival. Leupaxin is a cytoskeleton adaptor protein, which is preferentially expressed in hematopoietic cells. It associates with focal adhesion kinases PYK2 and pp125FAK and identified to be a component of the osteoclast pososomal signaling complex. Hic-5 controls cell proliferation, migration and senescence by functioning as coactivator for steroid receptors such as androgen receptor, glucocorticoid receptor and progesterone receptor. 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
                  ....*....|....*....|....*....|....*....|....*..
gi 1039750839 476 CSVCSKPIMERILRATGKAYHPHCFTCVMCHRS--------LDGIPF 514
Cdd:cd09338     1 CGGCNKPILENYISALNTQWHPECFVCRECHKPfingsffeHEGLPY 47

The first LIM domain of Ajuba-like proteins; The first 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039750839 476 CSVCSKPI--MERILRATGKAYHPHCFTCVMCHRSLDGIPFtVDACGLIHCIEDF 528
Cdd:cd09352     1 CVKCGKGVygASQACQAMGNLYHTNCFTCCSCGRTLRGKAF-YNVNGKVYCEEDY 54