The third LIM domain of Ajuba-like proteins; The third 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 55741683 473 CAACGQPILPSEGCEDIVRVISMDRDYHFECYHCEDCRMQLSDEEGCCCFPLDGHLLCHGCH 534
Cdd:cd09438   1 CAACGQPILPAEGSEETIRVVSMDKDYHVECYHCEDCGLQLNDEEGHRCYPLDGHLLCHSCH 62

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 55741683 348 CIKCNKGIYGQSNACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCEEDY 401
Cdd:cd09352   1 CVKCGKGVYGASQACQAMGNLYHTNCFTCCSCGRTLRGKAFYNVNGKVYCEEDY 54

The third LIM domain of Ajuba-like proteins; The third 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 55741683 473 CAACGQPILPSEGCEDIVRVISMDRDYHFECYHCEDCRMQLSDEEGCCCFPLDGHLLCHGCH 534
Cdd:cd09438   1 CAACGQPILPAEGSEETIRVVSMDKDYHVECYHCEDCGLQLNDEEGHRCYPLDGHLLCHSCH 62

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 55741683 348 CIKCNKGIYGQSNACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCEEDY 401
Cdd:cd09352   1 CVKCGKGVYGASQACQAMGNLYHTNCFTCCSCGRTLRGKAFYNVNGKVYCEEDY 54

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 55741683   348 CIKCNKGIYGQSnACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCEEDY 401
Cdd:pfam00412   1 CAGCNRPIYDRE-LVRALGKVWHPECFRCAVCGKPLTTGDFYEKDGKLYCKHDY 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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 55741683    472 KCAACGQPILPSEgcediVRVISMDRDYHFECYHCEDCRMQLSDEEgccCFPLDGHLLCHGC 533
Cdd:smart00132   1 KCAGCGKPIYGTE-----RVLRALGKVWHPECFKCATCGKPLSGDT---FFEKDGKLYCKDC 54

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 55741683   473 CAACGQPILPSEgcedivRVISMDRDYHFECYHCEDCRMQLSDEegcCCFPLDGHLLCHGCHMQR 537
Cdd:pfam00412   1 CAGCNRPIYDRE------LVRALGKVWHPECFRCAVCGKPLTTG---DFYEKDGKLYCKHDYYKL 56

The third LIM domain of Ajuba-like proteins; The third 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 55741683 473 CAACGQPILPSEGCEDIVRVISMDRDYHFECYHCEDCRMQLSDEEGCCCFPLDGHLLCHGCH 534
Cdd:cd09438   1 CAACGQPILPAEGSEETIRVVSMDKDYHVECYHCEDCGLQLNDEEGHRCYPLDGHLLCHSCH 62

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 55741683 348 CIKCNKGIYGQSNACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCEEDY 401
Cdd:cd09352   1 CVKCGKGVYGASQACQAMGNLYHTNCFTCCSCGRTLRGKAFYNVNGKVYCEEDY 54

The second LIM domain of lipoma preferred partner (LPP); The second 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 55741683 413 CCVCGHLILEKILQAMGKSYHPGCFRCIVCNKCLDGVPFTVDFSNQVYCVTDYHKNYAPK 472
Cdd:cd09354   1 CSVCSKPILDRILRATGKPYHPQCFTCVVCGKSLDGIPFTVDATNQIHCIEDFHKKFAPR 60

The second LIM domain of Thyroid receptor-interacting protein 6 (TRIP6); The second 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 55741683 413 CCVCGHLILEKILQAMGKSYHPGCFRCIVCNKCLDGVPFTVDFSNQVYCVTDY 465
Cdd:cd09356   1 CSVCSKPIMERILRATGKAYHPHCFTCVVCHRSLDGIPFTVDATGQIHCIEDF 53

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 55741683 473 CAACGQPILPSEGCEDIVRVISMDRDYHFECYHCEDCRMQLSDE-EGCCCFPLDGHLLCHGCHMQRL 538
Cdd:cd09437   1 CCVCKLPIMPEPGQDETVRVVALDRSFHVQCYKCEDCGLLLSSEaEGRGCYPLDDHVLCKSCNAKRV 67

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 55741683 413 CCVCGHLILEKILQAMGKSYHPGCFRCIVCNKCLDGVPFTVDFSNQVYCVTDY 465
Cdd:cd09372   1 CAKCQGVITEHIIRALGKGYHPPCFTCVTCGRRIGDESFAVDEQNEVYCLDDY 53

LIM is a small protein-protein interaction domain, containing two zinc fingers; LIM domains are identified in a diverse group of proteins with wide variety of biological functions, including gene expression regulation, cell fate determination, cytoskeleton organization, tumor formation and development. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes. They perform their functions through interactions with other protein partners. LIM domains are 50-60 amino acids in size and share two characteristic highly conserved zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. The consensus sequence of LIM domain has been defined as C-x(2)-C-x(16,23)-H-x(2)-[CH]-x(2)-C-x(2)-C-x(16,21)-C-x(2,3)-[CHD] (where X denotes any amino acid).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 55741683 348 CIKCNKGIYGQSnACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCEEDY 401
Cdd:cd08368   1 CAGCGKPIEGRE-LLRALGKKWHPECFKCAECGKPLGGDSFYEKDGKPYCEKCY 53

LIM is a small protein-protein interaction domain, containing two zinc fingers; LIM domains are identified in a diverse group of proteins with wide variety of biological functions, including gene expression regulation, cell fate determination, cytoskeleton organization, tumor formation and development. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes. They perform their functions through interactions with other protein partners. LIM domains are 50-60 amino acids in size and share two characteristic highly conserved zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. The consensus sequence of LIM domain has been defined as C-x(2)-C-x(16,23)-H-x(2)-[CH]-x(2)-C-x(2)-C-x(16,21)-C-x(2,3)-[CHD] (where X denotes any amino acid).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 55741683 413 CCVCGHLILEK-ILQAMGKSYHPGCFRCIVCNKCLDGVPFTVDfSNQVYCVTDY 465
Cdd:cd08368   1 CAGCGKPIEGReLLRALGKKWHPECFKCAECGKPLGGDSFYEK-DGKPYCEKCY 53

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 55741683 348 CIKCNKGIYGQSNACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCEEDY 401
Cdd:cd09350   1 CGRCGENVVGEGTGCTAMDQVFHVDCFTCMTCNGKLRGQPFYAVEKKAYCEPCY 54

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 55741683 346 GTCIKCNKGIYGQsnACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCEEDY 401
Cdd:cd09406   1 GDCASCQKPIAGQ--VVTALGQTWHPEHFVCCQCGKELGSRPFFERNGQAYCEEDY 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 55741683    412 KCCVCGHLIL--EKILQAMGKSYHPGCFRCIVCNKCLDGVPFTVDfSNQVYCVTD 464
Cdd:smart00132   1 KCAGCGKPIYgtERVLRALGKVWHPECFKCATCGKPLSGDTFFEK-DGKLYCKDC 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 55741683    472 KCAACGQPILPSEgcediVRVISMDRDYHFECYHCEDCRMQLSDEEgccCFPLDGHLLCHGC 533
Cdd:smart00132   1 KCAGCGKPIYGTE-----RVLRALGKVWHPECFKCATCGKPLSGDT---FFEKDGKLYCKDC 54

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 55741683 348 CIKCNKGIYGQsnACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCE 398
Cdd:cd09360   1 CDKCGNGIVGV--VVKARDKNRHPECFVCADCGLNLKNKGYFFIEDELYCE 49

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 55741683   413 CCVCGHLILEK-ILQAMGKSYHPGCFRCIVCNKCLDGVPFTVdFSNQVYCVTDYHKNY 469
Cdd:pfam00412   1 CAGCNRPIYDReLVRALGKVWHPECFRCAVCGKPLTTGDFYE-KDGKLYCKHDYYKLF 57

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 55741683   473 CAACGQPILPSEgcedivRVISMDRDYHFECYHCEDCRMQLSDEegcCCFPLDGHLLCHGCHMQR 537
Cdd:pfam00412   1 CAGCNRPIYDRE------LVRALGKVWHPECFRCAVCGKPLTTG---DFYEKDGKLYCKHDYYKL 56

This family represents the LIM domain of ALP, actinin-associated LIM protein; This family represents the LIM domain of ALP, actinin-associated LIM protein. ALP contains an N-terminal PDZ domain, a C-terminal LIM domain and an ALP-subfamily-specific 34-amino-acid motif termed ALP-like motif (AM), which contains a putative consensus protein kinase C (PKC) phosphorylation site and two alpha-helices. ALP proteins are found in heart and in skeletal muscle. ALP may act as a signaling molecule which is regulated by PKC-dependent signaling. ALP plays an essential role in the development of RV (right ventricle) chamber. 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 55741683 348 CIKCNKGIYGqsNACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCE 398
Cdd:cd09450   1 CDKCGSGIVG--TVVKARDKYRHPECFVCSDCNLNLKQKGYFFVEGQLYCE 49

The first LIM domain of the paxillin like protein family; The first 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        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 55741683 348 CIKCNKGIYGQsnACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCEEDY 401
Cdd:cd09336   1 CAACNKPIVGQ--VVTALGKTWHPEHFVCVHCQTELGTSNFFERDGKPYCEKDY 52

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 55741683 348 CIKCNKGIYgQSNACQALDSLYHTQCFVCCSCGRTLRcKAFYSVNGSVYCEEDY 401
Cdd:cd09462  22 CASCGQSIY-DGQYLQALNSDWHADCFRCCECGASLS-HWYYEKDGRLFCKKDY 73

The first LIM domain of the paxillin like protein family; The first 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        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 55741683 413 CCVCGHLILEKILQAMGKSYHPGCFRCIVCNKCLDGVPFtVDFSNQVYCVTDYH 466
Cdd:cd09336   1 CAACNKPIVGQVVTALGKTWHPEHFVCVHCQTELGTSNF-FERDGKPYCEKDYH 53

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
                ....*....|....*....|....*....|...
gi 55741683 369 YHTQCFVCCSCGRTLRCKAFYSVNGSVYCEEDY 401
Cdd:cd09327  20 FHIKCFTCKVCGCDLAQGGFFVKEGEYYCTDDY 52

The third LIM domain of an Enigma subfamily with unknown function; The third LIM domain of an Enigma subfamily with unknown function: The Enigma LIM domain family is comprised of three characterized members: Enigma, ENH, and Cypher (mouse)/ZASP (human). These subfamily members contain a single PDZ domain at the N-terminus and three LIM domains at the C-terminus. They serve as adaptor proteins, where the PDZ domain tethers the protein to the cytoskeleton and the LIM domains, recruit signaling proteins to implement corresponding functions. The members of the enigma family have been implicated in regulating or organizing cytoskeletal structure, as well as involving multiple signaling pathways. LIM domains are 50-60 amino acids in size and share two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 55741683 348 CIKCNKGIYGQSNACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCE 398
Cdd:cd09461   1 CVSCGFPIEAGDRWVEALNNNYHSQCFNCTRCNVNLEGQSFYAKGGRPFCK 51

The second LIM domain on actin binding LIM (abLIM) proteins; The second 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
                ....*....|....*....|....*....|...
gi 55741683 412 KCCVCGHLILEKILQAMGKSYHPGCFRCIVCNK 444
Cdd:cd09328   3 KCDSCQDFVEGEVVSALGKTYHPKCFVCSVCRQ 35

The first LIM domain of ZASP/Cypher family; The first LIM domain of ZASP/Cypher family: ZASP was identified in human heart and skeletal muscle and Cypher is a mice ortholog of ZASP. ZASP/Cyppher contains three LIM domains at the C-terminus and a PDZ domain at N-terminus. 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 55741683 413 CCVCGHLILEKILQAMGKSYHPGCFRCIVCNKCLDGVPFtVDFSNQVYC 461
Cdd:cd09454   1 CGHCNNIIRGPFLVALGRSWHPEEFTCHYCHTSLADVSF-VEEQNNVYC 48

The first LIM domain of Lhx3 and Lhx4 family; The first 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
                ....*....|....*....|....*....|....*....
gi 55741683 363 QALDSLYHTQCFVCCSCGRTLRCKAFYSvNGSVYCEEDY 401
Cdd:cd09368  15 KVLDRTWHAKCLKCNDCGAQLTDKCFAR-NGHVYCKDDF 52

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 55741683 348 CIKCNKGIYGQSNACQALDSLYHTQCFVCCSCGRTLRCKAFYSV-NGSVYCEEDY 401
Cdd:cd09377   5 CARCHLGISASELVMRARDLVFHLNCFTCATCNKPLTKGDHFGMrDGLVYCRLHY 59

This family represents the LIM domain of CLP36; This family represents the LIM domain of CLP36. CLP36 has also been named as CLIM1, Elfin, or PDLIM1. CLP36 contains a C-terminal LIM domain and an N-terminal PDZ domain. CLP36 is highly expressed in heart and is present in many other tissues including lung, liver, spleen, and blood. CLP36 has been implicated in many processes including hypoxia and regulation of actin stress fibers. CLP36 co-localizes with alpha-actinin-2 at the Z-lines in myocardium. In addition, CLP36 binds to alpha-actinin-1 and alpha-actinin-4, and associates with F-actin filaments and stress fibers. CLP36 might be involved in not only the function of sarcomeres in muscle cells, but also in actin stress fiber-mediated cellular processes, such as cell shape, migration, polarit, and cytokinesis in non-muscle cells. 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 55741683 348 CIKCNKGIYGQsnACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCEE 399
Cdd:cd09448   1 CDKCGSGIVGV--FVKIRDKPRHPECYVCTDCGTNLKQKGHFFVEDQIYCEK 50

The first LIM domain of Lhx1 (also known as Lim1) and Lhx5; The first 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 55741683 473 CAACGQPILpsegceDIVRVISMDRDYHFECYHCEDCRMQLSDEegccCFPLDGHLLC 530
Cdd:cd09367   1 CAGCDRPIL------DKFLLNVLDRAWHAKCVQCCDCKCPLTEK----CFSREGKLYC 48

The first LIM domain of Cysteine Rich Protein 1 (CRP1); The first LIM domain of Cysteine Rich Protein 1 (CRP1): Cysteine-rich proteins (CRPs) are characterized by the presence of two LIM domains linked to a short glycine-rich repeats (GRRs). The CRP family members include CRP1, CRP2, CRP3/MLP and TLP. CRP1, CRP2 and CRP3 share a conserved nuclear targeting signal (K/R-K/R-Y-G-P-K), which supports the fact that these proteins function not only in the cytoplasm but also in the nucleus. CRPs control regulatory pathways during cellular differentiation, and involve in complex transcription circuits, and the organization as well as the arrangement of the myofibrillar/cytoskeletal network. CRP1 can associate with the actin cytoskeleton and are capable of interacting with alpha-actinin and zyxin. CRP1 was shown to regulate actin filament bundling by interaction with alpha-actinin and direct binding to actin filaments. 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 55741683 411 EKCCVCGHLI-LEKILQAMGKSYHPGCFRCIVCNKCLDGVPFTVDfSNQVYCVTDY 465
Cdd:cd09479   1 KKCGVCQKTVyFAEEVQCEGRSFHKSCFLCMVCKKNLDSTTVAVH-GEEIYCKSCY 55

The LIM domain of LIM and SH3 Protein (LASP)-like proteins; The LIM domain of LIM and SH3 Protein (LASP) like proteins: This family contains two types of LIM containing proteins; LASP and N-RAP. LASP family contains two highly homologous members, LASP-1 and LASP-2. LASP contains a LIM motif at its amino terminus, a src homology 3 (SH3) domains at its C-terminal part, and a nebulin-like region in the middle. LASP-1 and -2 are highly conserved in their LIM, nebulin-like, and SH3 domains, but differ significantly at their linker regions. Both proteins are ubiquitously expressed and involved in cytoskeletal architecture, especially in the organization of focal adhesions. LASP-1 and LASP-2, are important during early embryo- and fetogenesis and are highly expressed in the central nervous system of the adult. However, only LASP-1 seems to participate significantly in neuronal differentiation and plays an important functional role in migration and proliferation of certain cancer cells while the role of LASP-2 is more structural. The expression of LASP-1 in breast tumors is increased significantly. N-RAP is a muscle-specific protein concentrated at myotendinous junctions in skeletal muscle and intercalated disks in cardiac muscle. LIM domain is found at the N-terminus of N-RAP and the C-terminal of N-RAP contains a region with multiple of nebulin repeats. N-RAP functions as a scaffolding protein that organizes alpha-actinin and actin into symmetrical I-Z-I structures in developing myofibrils. Nebulin repeat is known as actin binding domain. The N-RAP is hypothesized to form antiparallel dimerization via its LIM domain. 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
                ....*....|....*....|....*....|....*....|..
gi 55741683 473 CAACGQPILPSEgcedivRVISMDRDYHFECYHCEDCRMQLS 514
Cdd:cd09359   1 CARCGKIVYPTE------KVNCLDKTWHKACFHCEVCKMTLN 36

The fourth LIM domain of actin binding LIM (abLIM) proteins; The fourth 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
                ....*....|....*....|....*....|..
gi 55741683 413 CCVCGHLILEKILQAMGKSYHPGCFRCIVCNK 444
Cdd:cd09330   1 CEACDKFITGKVLEAGGKHYHPTCARCSRCGQ 32

The second LIM domain of the paxillin like protein family; The second 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        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 55741683 413 CCVCGHLILEKILQAMGKSYHPGCFRCIVCNKCLDGVPFTvDFSNQVYCVTDY 465
Cdd:cd09337   1 CAYCNGPILDKCVTALDKTWHPEHFFCAQCGKPFGDEGFH-EKDGKPYCREDY 52

The first LIM domain of LIMK (LIM domain Kinase ); The first LIM domain of LIMK (LIM domain Kinase ): LIMK protein family is comprised of two members LIMK1 and LIMK2. LIMK contains two LIM domains, a PDZ domain and a kinase domain. LIMK is involved in the regulation of actin polymerization and microtubule disassembly. LIMK influences architecture of the actin cytoskeleton by regulating the activity of the cofilin family proteins cofilin1, cofilin2, and destrin. The mechanism of the activation is to phosphorylates cofilin on serine 3 and inactivates its actin-severing activity, and altering the rate of actin depolymerisation. LIMKs can function in both cytoplasm and nucleus and are expressed in all tissues. Both LIMK1 and LIMK2 can act in the nucleus to suppress Rac/Cdc42-dependent cyclin D1 expression. However, LIMK1 and LIMk2 have different cellular locations. While LIMK1 localizes mainly at focal adhesions, LIMK2 is found in cytoplasmic punctae, suggesting that they may have different cellular functions. The LIM domains of LIMK have been shown to play an important role in regulating kinase activity and likely also contribute to LIMK function by acting as sites of protein-to-protein interactions. All LIM domains are 50-60 amino acids in size and share two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes.

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gi 55741683 416 CGHLILEKILQAMGKSYHPGCFRCIVCNKCLDGVPFTVDfsNQVYCVTDY 465
Cdd:cd09364   5 RGKILDSQYVQALNQDWHCDCFRCSVCSDSLSNWYFEKD--GKLYCRKDY 52

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.

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gi 55741683 422 EKILQAMGKSYHPGCFrciVCNKCLDGVPFTV--DFSNQVYCVTDYHKNYA 470
Cdd:cd09331  12 EKIVNSNGELYHEQCF---VCAQCFQPFPDGLfyEFEGRKYCEHDFQVLFA 59

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.

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gi 55741683 413 CCVCGHLILEKILQAMGKSYHPGCFRCIVCNKCLDG--VPFTVDFSNQVY--CVTDY 465
Cdd:cd09391   1 CAKCGKPITGQFVRALGDVYHLDCFTCHDCGKPVASkfFPVDDPDTSEQVplCETDY 57

The LIM domain of Mical (molecule interacting with CasL) like family; The LIM domain of Mical (molecule interacting with CasL) like family: Known members of this family includes LIM domain containing proteins; Mical (molecule interacting with CasL), pollen specific protein SF3, Eplin, xin actin-binding repeat-containing protein 2 (XIRP2) and Ltd-1. The members of this family function mainly at the cytoskeleton and focal adhesions. They interact with transcription factors or other signaling molecules to play roles in muscle development, neuronal differentiation, cell growth and mobility. Eplin has also found to be tumor suppressor. 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 55741683 348 CIKCNKGIYgQSNACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYC 397
Cdd:cd09358   1 CAVCGKTVY-PMERLVADGKLFHKSCFRCSHCNKTLRLGNYASLEGKLYC 49

The Lim domain of Epithelial Protein Lost in Neoplasm (Eplin); The Lim domain of Epithelial Protein Lost in Neoplasm (Eplin): Epithelial Protein Lost in Neoplasm is a cytoskeleton-associated tumor suppressor whose expression inversely correlates with cell growth, motility, invasion and cancer mortality. Eplin interacts and stabilizes F-actin filaments and stress fibers, which correlates with its ability to suppress anchorage independent growth. In epithelial cells, Eplin is required for formation of the F-actin adhesion belt by binding to the E-cadherin-catenin complex through alpha-catenin. Eplin is expressed in two isoforms, a longer Eplin-beta and a shorter Eplin-alpha. Eplin-alpha mRNA is detected in various tissues and cell lines, but is absent or down regulated in cancer 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.

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gi 55741683 348 CIKCNKGIYgQSNACQALDSLYHTQCFVCCSCGRTLRCKAFYSVNGSVYCEEDY 401
Cdd:cd09485   1 CVSCQKTVY-PLERLVANQQIYHNSCFRCSYCNTKLSLGTYASLHGNIYCKPHF 53

The second LIM domain of Arrowhead (AWH); The second LIM domain of Arrowhead (AWH): Arrowhead belongs to the LHX protein family, which features two tandem N-terminal LIM domains and a C-terminal DNA binding homeodomain. Members of LHX family are found in the nucleus and act as transcription factors or cofactors. LHX proteins are critical for the development of specialized cells in multiple tissue types, including the nervous system, skeletal muscle, the heart, the kidneys, and endocrine organs such as the pituitary gland and the pancreas. During embryogenesis of Drosophila, Arrowhead is expressed in each abdominal segment and in the labial segment. Late in embryonic development, expression of arrowhead is refined to the abdominal histoblasts and salivary gland imaginal ring cells themselves. The Arrowhead gene required for establishment of a subset of imaginal tissues: the abdominal histoblasts and the salivary gland imaginal rings. As in other LIM domains, this domain family is 50-60 amino acids in size and shares two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein.

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gi 55741683 473 CAACGQPILPSegceDIVRViSMDRDYHFECYHCEDCRMQLSDEEGcccFPL-DGHLLC 530
Cdd:cd09379   1 CAKCSRNISAS----DWVRR-ARDHVYHLACFACDACKRQLSTGEE---FALiEDRVLC 51

The first LIM domain of Lhx2 and Lhx9 family; The first 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.

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gi 55741683 363 QALDSLYHTQCFVCCSCGRTLRCK-AFYSVNGSVYCEEDY 401
Cdd:cd09369  15 LAVDRQWHASCLKCCECRLPLDSElSCFSRDGNIYCKEDY 54