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.

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767910779  14 CTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLMEDGRLVCKEDY 69
Cdd:cd09376    1 CAGCDEGIPPTQVVRRAQDNVYHLECFACFMCKRQLETGDEFYLMEDDRLVCKKDY 56

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.

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gi 767910779  14 CTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLMEDGRLVCKEDY 69
Cdd:cd09376    1 CAGCDEGIPPTQVVRRAQDNVYHLECFACFMCKRQLETGDEFYLMEDDRLVCKKDY 56

Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

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gi 767910779  83 KRPRTTITAKQLETLKNAYKNSPKPARHVREQLSSETGLDMRVVQVWFQNRRAKEKRLK 141
Cdd:cd00086    1 RRKRTRFTPEQLEELEKEFEKNPYPSREEREELAKELGLTERQVKIWFQNRRAKLKRSE 59

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

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gi 767910779   14 CTACQQGIPPTQVVRkAQDFVYHLHCFACIICNRQLATGDEFYLmeDGRLVCKEDYETAK 73
Cdd:pfam00412   1 CAGCNRPIYDRELVR-ALGKVWHPECFRCAVCGKPLTTGDFYEK--DGKLYCKHDYYKLF 57

Homeodomain-containing transcription factor [Transcription];

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767910779  75 NDDSEAGAKRPRTTITAKQLETLKNAYKNSPKPARHVREQLSSETGLDMRVVQVWFQNRRAKEKRLKK 142
Cdd:COG5576   44 KQDGSSPPKSKRRRTTDEQLMVLEREFEINPYPSSITRIKLSLLLNMPPKSVQIWFQNKRAKEKKKRS 111

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.

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gi 767910779  14 CTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLMEDGRLVCKEDY 69
Cdd:cd09376    1 CAGCDEGIPPTQVVRRAQDNVYHLECFACFMCKRQLETGDEFYLMEDDRLVCKKDY 56

The second LIM domain of Lhx3b; The second LIM domain of Lhx3b. Lhx3b is a member 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. Lhx3b is one of the two isoforms of Lhx3. The Lhx3 gene is expressed in the ventral spinal cord, the pons, the medulla oblongata, and the pineal gland of the developing nervous system during mouse embryogenesis, and transcripts are found in the emergent pituitary gland. Lhx3 functions in concert with other transcription factors to specify interneuron and motor neuron fates during development. Lhx3 proteins have been demonstrated to directly bind to the promoters of several pituitary hormone gene promoters. The Lhx3 gene encodes two isoforms, LHX3a and LHX3b that differ in their amino-terminal sequences, where Lhx3a has longer N-terminal. They show differential activation of pituitary hormone genes and distinct DNA binding properties. In human, Lhx3a trans-activated the alpha-glycoprotein subunit promoter and genes containing a high-affinity Lhx3 binding site more effectively than the hLhx3b isoform. In addition, hLhx3a induce transcription of the TSHbeta-subunit gene by acting on pituitary POU domain factor, Pit-1, while hLhx3b does not. 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 767910779  13 KCTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLMEDGRLVCKEDY 69
Cdd:cd09472    1 KCAACQQGIPPTQVVRRAQDFVYHLHCFACIVCKRQLATGDEFYLMEDSRLVCKADY 57

Homeodomain;

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gi 767910779   83 KRPRTTITAKQLETLKNAYKNSPKPARHVREQLSSETGLDMRVVQVWFQNRRAKEKR 139
Cdd:pfam00046   1 RRKRTTFTPEQLEELEKEFQENPYPSAEEREELAAQLGLTERQVKVWFQNRRAKWKR 57

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 767910779  14 CTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLMEDgRLVCKEDY 69
Cdd:cd09379    1 CAKCSRNISASDWVRRARDHVYHLACFACDACKRQLSTGEEFALIED-RVLCKAHY 55

The second LIM domain of Lmx1a and Lmx1b; The second LIM domain of Lmx1a and Lmx1b: Lmx1a and Lmx1b 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. Mouse Lmx1a is expressed in multiple tissues, including the roof plate of the neural tube, the developing brain, the otic vesicles, the notochord, and the pancreas. In mouse, mutations in Lmx1a result in failure of the roof plate to develop. Lmx1a may act upstream of other roof plate markers such as MafB, Gdf7, Bmp6, and Bmp7. Further characterization of these mice reveals numerous defects including disorganized cerebellum, hippocampus, and cortex; altered pigmentation; female sterility, skeletal defects, and behavioral abnormalities. In the mouse, Lmx1b functions in the developing limbs and eyes, the kidneys, the brain, and in cranial mesenchyme. The disruption of Lmx1b gene results kidney and limb defects. In the brain, Lmx1b is important for generation of mesencephalic dopamine neurons and the differentiation of serotonergic neurons. In the mouse eye, Lmx1b regulates anterior segment (cornea, iris, ciliary body, trabecular meshwork, and lens) development. 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 767910779  14 CTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLmEDGRLVCKEDY 69
Cdd:cd09378    1 CSGCLEKIAPSELVMRALENVYHLRCFCCCVCERQLQKGDEFVL-KEGQLLCKSDY 55

The second LIM domain of LMO4 (LIM domain only protein 4); The second LIM domain of LMO4 (LIM domain only protein 4): LMO4 is a nuclear protein that plays important roles in transcriptional regulation and development. LMO4 is involved in various functions in tumorigenesis and cellular differentiation. LMO4 proteins regulate gene expression by interacting with a wide variety of transcription factors and cofactors to form large transcription complexes. It can interact with Smad proteins, and associate with the promoter of the PAI-1 (plasminogen activator inhibitor-1) gene in a TGFbeta (transforming growth factor beta)-dependent manner. LMO4 can also form a complex with transcription regulator CREB (cAMP response element-binding protein) and interact with CLIM1 and CLIM2. In breast tissue, LMO4 interacts with multiple proteins, including the cofactor CtIP [CtBP (C-terminal binding protein)-interacting protein], the breast and ovarian tumor suppressor BRCA1 (breast-cancer susceptibility gene 1) and the LIM-domain-binding protein LDB1. Functionally, LMO4 is shown to repress BRCA1-mediated transcription activation, thus invoking a potential role for LMO4 as a negative regulator of BRCA1 in sporadic breast cancer. LMO4 also forms complex to both ERa (oestrogen receptor alpha), MTA1 (metastasis tumor antigen 1), and HDACs (histone deacetylases), implying that LMO4 is also a component of the MTA1 corepressor complex. Over-expressed LMO4 represses ERa transactivation functions in an HDAC-dependent manner, and contributes to the process of breast cancer progression by allowing the development of Era-negative phenotypes. All LIM domains are 50-60 amino acids in size and share two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes.

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gi 767910779  14 CTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLMeDGRLVCKED 68
Cdd:cd09387    1 CSACGQSIPASELVMRAQGNVYHLKCFTCSTCHNQLVPGDRFHYV-NGSLFCEHD 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.

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gi 767910779    13 KCTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLatGDEFYLMEDGRLVCKED 68
Cdd:smart00132   1 KCAGCGKPIYGTERVLRALGKVWHPECFKCATCGKPL--SGDTFFEKDGKLYCKDC 54

The second LIM domain of dLMO (Beaderx); The second LIM domain of dLMO (Beaderx): dLMO is a nuclear protein that plays important roles in transcriptional regulation and development. In Drosophila dLMO modulates the activity of LIM-homeodomain protein Apterous (Ap), which regulates the formation of the dorsal-ventral axis of the Drosophila wing. Biochemical analysis shows that dLMO protein influences the activity of Apterous by binding of its cofactor Chip. Further studies shown that dLMO proteins might function in an evolutionarily conserved mechanism involved in patterning the appendages. 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 767910779  14 CTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLMEDgRLVCKEDY 69
Cdd:cd09390    1 CAACSKTIPAFEMVMRARTNVYHLECFACQRCNHRFCVGDRFYLCEN-KILCEYDY 55

Homeodomain-containing transcription factor [Transcription];

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gi 767910779  75 NDDSEAGAKRPRTTITAKQLETLKNAYKNSPKPARHVREQLSSETGLDMRVVQVWFQNRRAKEKRLKK 142
Cdd:COG5576   44 KQDGSSPPKSKRRRTTDEQLMVLEREFEINPYPSSITRIKLSLLLNMPPKSVQIWFQNKRAKEKKKRS 111

The second LIM domain of Isl2; The second LIM domain of Isl2: Isl is a member of LHX protein family, which features two tandem N-terminal LIM domains and a C-terminal DNA binding homeodomain. LHX proteins are critical for the development of specialized cells in multiple tissue types, including the nervous system, skeletal muscle, the heart, the kidneys, and endocrine organs, such as the pituitary gland and the pancreas. Isl proteins are found in the nucleus and act as transcription factors or cofactors. Isl1 and Isl2 are the two conserved members of this family. Mouse Isl2 is expressed in the retinal ganglion cells and the developing spinal cord where it plays a role in motor neuron development. Isl2 may be able to bind to the insulin gene enhancer to promote gene activation. All LIM domains are 50-60 amino acids in size and share two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes.

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gi 767910779  14 CTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLMEDgRLVCKEDY 69
Cdd:cd09471    1 CAQCRLGFSSSDLVMRARDSVYHIECFRCSVCSRQLLPGDEFCLREH-ELLCRADH 55

The second LIM domain of Lhx2; The second LIM domain of Lhx2: Lhx2 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. 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. The Lhx2 protein has been shown to bind to the mouse M71 olfactory receptor promoter. Similar to 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 767910779  13 KCTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYlMEDGRLVCK 66
Cdd:cd09474    4 RCARCHLGISASEMVMRARDLVYHLNCFTCTTCNKMLTTGDHFG-MKDNLVYCR 56

The second LIM domain of Lhx6; The second LIM domain of Lhx6. Lhx6 is a member 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. Lhx6 functions in brain and nervous system. It is expressed at high levels in several regions of the embryonic mouse CNS, including the telencephalon and hypothalamus, and the first branchial arch. Lhx6 is proposed to have a role in patterning of the mandible and maxilla, and in signaling during odontogenesis. In brain sections, knockdown of Lhx6 gene blocks the normal migration of neurons to the cortex. 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 complexes.

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gi 767910779  14 CTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLMEDgRLVCKEDY 69
Cdd:cd09382    1 CARCGRQIYASDWVRRARGNAYHLACFACFSCKRQLSTGEEFGLVEE-KVLCRIHY 55

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 767910779  14 CTACQQGIPPTQVVRKAQDfVYHLHCFACIICNRQLATgdeFYLMEDGRLVCKEDY 69
Cdd:cd09364    1 CAGCRGKILDSQYVQALNQ-DWHCDCFRCSVCSDSLSN---WYFEKDGKLYCRKDY 52

The first LIM domain of LIMK2 (LIM domain Kinase 2); The first LIM domain of LIMK2 (LIM domain Kinase 2): LIMK2 is a member of 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, altering the rate of actin depolymerization. LIMK activity is activated by phosphorylation of a threonine residue within the activation loop of the kinase by p21-activated kinases 1 and 4 and by Rho kinase. 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. LIMK2 is expressed in all tissues. While LIMK1 localizes mainly at focal adhesions, LIMK2 is found in cytoplasmic punctae, suggesting that they may have different cellular functions. The activity of LIM kinase 2 to regulate cofilin phosphorylation is inhibited by the direct binding of Par-3. LIMK2 activation promotes cell cycle progression. The phenotype of Limk2 knockout mice shows a defect in spermatogenesis. The LIM domains have been shown to play an important role in regulating kinase activity and likely also contribute to LIMK function by acting as sites of protein-to-protein interactions. All LIM domains are 50-60 amino acids in size and share two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes.

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gi 767910779  14 CTACQQGIPPTQVVRKAQDfVYHLHCFACIICNRQLATgdeFYLMEDGRLVCKEDY 69
Cdd:cd09463    1 CTGCGGRIQDSFHYRVVQE-AWHNSCFQCSVCQDLLTN---WYYEKDGKLYCHKHY 52

The first LIM domain of Zyxin; The first 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 cell substratum 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.

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gi 767910779  14 CTACQQGIPPTQVVRKAQDFVYHLHCFACIICNRQLaTGDEFYLMEdGRLVCKEDY 69
Cdd:cd09349   34 CGICGQPLSRTQPAVRALGHLFHVTCFTCHQCEQQL-QGQQFYSLE-GKPYCEECY 87

The second LIM domain of Enigma; The second LIM domain of Enigma: Enigma was initially characterized in humans as a protein containing three LIM domains at the C-terminus and a PDZ domain at N-terminus. 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. Enigma 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.

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gi 767910779  14 CTACQQGIppTQVVRKAQDFVYHLHCFACIICnrQLATGDEFYLMEDGRLVCKEDY 69
Cdd:cd09456    1 CAKCKKKI--TGEIMHALKMTWHVHCFTCAAC--KTPIRNRAFYMEEGAPYCERDY 52

The first LIM domain of lipoma preferred partner (LPP); The first 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.

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                 ....*....|....*....|....*....|....*....|
gi 767910779  30 AQDFVYHLHCFACIICNRQLaTGDEFYLMeDGRLVCKEDY 69
Cdd:cd09351   17 AMDQVYHISCFTCHQCQINL-QGKPFYAL-DGKPYCEEDY 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        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767910779  14 CTACQQGIPPTQVvrKAQDFVYHLHCFACIICNRQLATgdEFYLMEDGR-----LVCKEDY 69
Cdd:cd09391    1 CAKCGKPITGQFV--RALGDVYHLDCFTCHDCGKPVAS--KFFPVDDPDtseqvPLCETDY 57

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 767910779  14 CTACQQgiPPTQVVRKAQDFVYHLHCFACIICNRQLaTGDEFYLMEDGRLVCKEDY 69
Cdd:cd09356    1 CSVCSK--PIMERILRATGKAYHPHCFTCVVCHRSL-DGIPFTVDATGQIHCIEDF 53

The fifth LIM domain of protein PINCH; The fifth LIM domain of protein PINCH: PINCH plays pivotal roles 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. 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 767910779  14 CTACQQgiPPTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLMeDGRLVCKEDYE 70
Cdd:cd09335    1 CYHCNQ--VIEGDVVSALNKTWCVDHFSCSFCDTKLTLKSKFYEF-DMKPVCKKCYD 54

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 767910779  14 CTACQQGIppTQVVRKAQDFVYHLHCFACIICNRqlATGDE-FYLMEDGRLVCKEDY 69
Cdd:cd09372    1 CAKCQGVI--TEHIIRALGKGYHPPCFTCVTCGR--RIGDEsFAVDEQNEVYCLDDY 53

LIM domain in proteins of unknown function; LIM domain in proteins of unknown function: 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. The 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).

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 767910779  13 KCTACQQGIPPTQVVRKAQDfVYHLHCFACIICNRQLATGdEFYLMEDGRLVC 65
Cdd:cd09400    4 PCASCGLPVFLAERLLIEGK-VYHRTCFKCARCGVQLTPG-SFYETEYGSYCC 54

The second LIM domain of LIMK (LIM domain Kinase ); The second 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 depolymerization. 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767910779  14 CTACQQGIppTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLMEDGRLVC 65
Cdd:cd09365    1 CHGCSQII--TGPVMVAGDHKFHPECFSCSSCKAFIGDGDSYALVERSKLYC 50

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
                 ....*....|....*....|....*....|....*....|
gi 767910779  30 AQDFVYHLHCFACIICNRQLaTGDEFYLMEdGRLVCKEDY 69
Cdd:cd09350   17 AMDQVFHVDCFTCMTCNGKL-RGQPFYAVE-KKAYCEPCY 54

The Lim domain of Epithelial Protein Lost in Neoplasm (Eplin) like proteins; The Lim domain of Epithelial Protein Lost in Neoplasm (Eplin) like proteins: This family contains Epithelial Protein Lost in Neoplasm in Neoplasm (Eplin), xin actin-binding repeat-containing protein 2 (XIRP2) and a group of protein with unknown function. The members of this family all contain a single LIM domain. 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. Xirp2 contains a LIM domain and Xin re peats for binding to and stabilising F-actin. Xirp2 is expressed in muscles and is significantly induced in the heart in response to systemic administration of angiotensin II. Xirp2 is an important effector of the Ang II signaling pathway in the heart. The expression of Xirp2 is activated by myocyte enhancer factor (MEF)2A, whose transcriptional activity is stimulated by angiotersin II. Thus, Xirp2 plays important pathological roles in the angiotensin II induced hypertension. 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 767910779  14 CTACQQGIPPTQVVrKAQDFVYHLHCFACIICNRQLATGDefYLMEDGRLVCKEDY 69
Cdd:cd09442    1 CTVCQKRVYPMERL-IADKQNFHKSCFRCEHCNSKLSLGN--YASLHGRIYCKPHF 53

Homeobox KN domain; This is a homeobox transcription factor KN domain conserved from fungi to human and plants. They were first identified as TALE homeobox genes in eukaryotes, (including KNOX and MEIS genes). They have been recently classified.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 767910779   94 LETLKNAYknspkPARHVREQLSSETGLDMRVVQVWFQNRR 134
Cdd:pfam05920   2 YEHLHNPY-----PSEEEKAELAKETGLSRKQISNWFINAR 37

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        40
                 ....*....|....*....|....*....|....*....|...
gi 767910779  11 GTKCTACQQGIPpTQVVrKAQDFVYHLHCFACIICNRQLATGD 53
Cdd:cd09328    1 GTKCDSCQDFVE-GEVV-SALGKTYHPKCFVCSVCRQPFPPGD 41

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

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767910779  14 CTACQQGIPpTQVVRKAQDFVYHLHCFACIICNRQLATGDEFYLMEDGRLVCKEDY 69
Cdd:cd09464    1 CHGCSETIT-TGLVMVAGEQKYHPECFSCLRCGAFIGDGDTYALVEHSKLYCGHCY 55

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 767910779  14 CTACQQGIPPTQVvrKAQDFVYHLHCFACIICNRQLATGDEFYLmeDGRLVCK 66
Cdd:cd09451    1 CTRCGNGIVGTIV--KARDKLYHPECFMCDDCGLNLKQRGYFFI--DEQLYCE 49

The second LIM domain of protein PINCH; The second 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. 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 767910779  27 VRKAQDFVYHLHCFACIICNRQLAtgDEFYLMEDGRLVCKE 67
Cdd:cd09332   12 VIKAMNNNWHPDCFRCEICNKELA--DIGFVKNAGRALCHP 50

The first LIM domain of Lmx1b; The first LIM domain of Lmx1b: Lmx1b 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. In mouse, Lmx1b functions in the developing limbs and eyes, the kidneys, the brain, and in cranial mesenchyme. The disruption of Lmx1b gene results kidney and limb defects. In the brain, Lmx1b is important for generation of mesencephalic dopamine neurons and the differentiation of serotonergic neurons. In the mouse eye, Lmx1b regulates anterior segment (cornea, iris, ciliary body, trabecular meshwork, and lens) development. 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 767910779  14 CTACQQGIPPTQVVRkAQDFVYHLHCFACIICnRQLATGDEFYlmEDGRLVCKEDYE 70
Cdd:cd09371    1 CAGCQRPISDRYLLR-VNERSWHEECLQCSVC-QQPLTTSCYF--RDRKLYCKQDYQ 53

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 767910779  30 AQDFVYHLHCFACIICNRQLATGDEFYLmEDGRLVCKEDY 69
Cdd:cd09369   16 AVDRQWHASCLKCCECRLPLDSELSCFS-RDGNIYCKEDY 54

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767910779  14 CTACQQGIPPTQVVrkAQDFVYHLHCFACIICNRQLatGDEFYLMEDGRLVCKEDY 69
Cdd:cd09337    1 CAYCNGPILDKCVT--ALDKTWHPEHFFCAQCGKPF--GDEGFHEKDGKPYCREDY 52

The LIM domain of Mical (molecule interacting with CasL); The LIM domain of Mical (molecule interacting with CasL): MICAL is a large, multidomain, cytosolic protein with a single LIM domain, a calponin homology (CH) domain and a flavoprotein monooxygenase domain. In Drosophila, MICAL is expressed in axons, interacts with the neuronal A (PlexA) receptor and is required for Semapho-rin 1a (Sema-1a)-PlexA-mediated repulsive axon guidance. The LIM domain and calporin homology domain are known for interactions with the cytoskeleton, cytoskeletal adaptor proteins, and other signaling proteins. The flavoprotein monooxygenase (MO) is required for semaphorin-plexin repulsive axon guidance during axonal pathfinding in the Drosophila neuromuscular system. In addition, MICAL was characterized to interact with Rab13 and Rab8 to coordinate the assembly of tight junctions and adherens junctions in epithelial cells. Thus, MICAL was also named junctional Rab13-binding protein (JRAB). 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 767910779  30 AQDFVYHLHCFACIICNRQLATGDEFYLMEDGRLVCKEDY 69
Cdd:cd09439   16 AEGLFFHRSCFKCSYCGTTLRLGAYAFDRDDGKFYCKPHF 55

The third LIM domain of Zyxin-like family; The third LIM domain of Zyxin like family: This family includes Ajuba, Limd1, WTIP, Zyxin, LPP, and Trip6 LIM proteins. Members of Zyxin family contain three tandem C-terminal LIM domains, and a proline-rich N-terminal region. Zyxin proteins are detected primarily in focal adhesion plaques. They function as scaffolds, participating in the assembly of multiple interactions and signal transduction networks, which regulate cell adhesion, spreading, and motility. They can also shuffle into nucleus. In nucleus, zyxin proteins affect gene transcription by interaction with a variety of nuclear proteins, including several transcription factors, playing regulating roles in cell proliferation, differentiation and apoptosis. As in other LIM domains, this domain family is 50-60 amino acids in size and shares two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767910779  14 CTACQQGIPPTQ----VVR-KAQDFVYHLHCFACIICNRQLATGDE----FYLmeDGRLVCK 66
Cdd:cd09357    1 CSVCGEPIMPEPgqdeTVRiVALDRSFHVNCYKCEDCGMLLSSEDEgqgcYPL--DGHLLCK 60

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.

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gi 767910779  14 CTACQQGIPPTQ-------VVRKAQDfvYHLHCFACIICNRQLATGDE---FYLmeDGRLVCK 66
Cdd:cd09438    1 CAACGQPILPAEgseetirVVSMDKD--YHVECYHCEDCGLQLNDEEGhrcYPL--DGHLLCH 59

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.

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 767910779  14 CTACQQGIPPTQVvrKAQDFVYHLHCFACIICNRQLATGDEFYLmeDGRLVCK 66
Cdd:cd09450    1 CDKCGSGIVGTVV--KARDKYRHPECFVCSDCNLNLKQKGYFFV--EGQLYCE 49