Alpha-internexin (INA) is a class-IV neuronal intermediate filament that is able to self-assemble. It is involved in the morphogenesis of neurons. INA is upregulated in some gliomas, particularly oligodendrogliomas [].
This entry includes the plant root meristem growth factors 1 /2/3 (RGF1/2/3, also known as GOLVEN 11/5/7) from Arabidopsis. They are signaling peptide that maintains the postembryonic root stem cell niche ina PIN2-traffic dependent manner [, , ]. RGF1 (At5g60810) acts as a peptide hormone recognized by receptors such as RGI1 and RGI2 to trigger signaling events including the regulation of RITF1 expression and leading to the production of reactive oxygen species (ROS) in roots to modulate meristem size [].
Na+/Ca2+exchange proteins are involved in maintaining Ca2+homeostasis ina wide variety of cell types. They are found in both the plasma membraneand intracellular organellar membranes, where they exchange Na+for Ca2+inan electrogenic manner. When located in the plasma membrane, they generallyutilise the transmembrane (TM) Na+concentration gradient in order toextrude Ca2+from cells. Three mammalian isoforms have been cloned to date(NCX1-3), which consist of 920-970 amino acid residues that are predictedto possess 11 or 12 TM domains. Interestingly, they possess a short motif(~30 residues) that is similar to the Na+/K+-ATPase, although its functionis unknown [, ].NCX1 has been found to be predominantly expressed in the heart, where itplays an important role in excitation-contraction coupling, but it is alsoabundant in a variety of other tissues []. NCX2 and NCX3 transcripts havebeen detected in the brain and skeletal muscle [, ]. Homologous Na+/Ca2+exchange proteins have also been found in Caenorhabditis elegans, Drosophila melanogaster andLoligo opalescens (California market squid).
Na+/Ca2+exchange proteins are involved in maintaining Ca2+homeostasis ina wide variety of cell types. They are found in both the plasma membraneand intracellular organellar membranes, where they exchange Na+for Ca2+inan electrogenic manner. When located in the plasma membrane, they generallyutilise the transmembrane (TM) Na+concentration gradient in order toextrude Ca2+from cells. Three mammalian isoforms have been cloned to date(NCX1-3), which consist of 920-970 amino acid residues that are predictedto possess 11 or 12 TM domains. Interestingly, they possess a short motif(~30 residues) that is similar to the Na+/K+-ATPase, although its functionis unknown [, ].NCX1 is the principal Na+/Ca2+exchanger of cardiac myocytes, where it isthought to play an important role in excitation-contraction coupling. It isalso found in a variety of other tissues, suggesting it serves as ahousekeeping protein, maintaining low cytosolic Ca2+concentration. Alternativelyspliced variants of NCX1 have been identified, expression of which is celltype-specific. Sequence analysis reveals two sets of tandem repeats arefound within the NCX1 protein sequence, which are usually referred to asalpha and beta. The alpha repeats are thought to be involved in the ionbinding and translocation reactions of the exchanger, and the first betarepeat may be part of a regulatory site that responds to Ca2+concentration.
Ribonuclease T2 (RNase T2) is a widespread family of secreted RNases found in every organism examined thus far. This family includes RNase Rh, RNase MC1, RNase LE, and self-incompatibility RNases (S-RNases) [, , , , ]. Plant T2 RNases are expressed during leaf senescence in order to scavenge phosphate from ribonucleotides. They are also expressed in response to wounding or pathogen invasion. S-RNases are thought to prevent self-fertilization by acting as selective cytotoxins of "self"pollen. Generally, RNases have two distinct binding sites: the primary site (B1 site) and the subsite (B2 site), for nucleotides located at the 5'- and 3'- terminal ends of the sissile bond, respectively.The fungal ribonucleases T2 from Aspergillus oryzae, M from Aspergillus saitoi and Rh from Rhizopus niveus are structurally and functionally related 30 Kd glycoproteins []that cleave the 3'-5' internucleotide linkage of RNA via a nucleotide 2',3'-cyclic phosphate intermediate (). Two histidines residues have been shown [, ]to be involved in the catalytic mechanism of RNase T2 and Rh. These residues and the region around them are highly conserved ina number of other RNAses that have been found to be evolutionary related to these fungal enzymes.The structure of ribonuclease T2 is composed of an alpha+beta fold.
Sphingolipids are bioactive compounds found in lower and higher eukaryotes.They are involved in the regulation of various cellular functions, such asgrowth, differentiation and apoptosis, and are believed to be essential ina healthy diet. Sphigolipids are degraded in the lysosome, and theproducts from their hydrolysis are used in other biosynthetic and regulatorypathways in the host.There are a number of lysosomal enzymes involved in the breakdown ofsphinogolipids, and these act in sequence to degrade the moieties []. These enzymes require co-proteins called sphingolipid activator proteins, (SAPs or saposins), to stabilise and activate them as necessary. SAPs are non-enzymatic and usually have a low molecular weight. They are conserved across a wide range of eukaryotes and contain specific saposin domains that aid in the activation of hydrolase enzymes. There have been four human saposins described so far, sharing significant similarity with each otherand with other eukaryotic SAP proteins.Mutations in SAP genes have been linked to a number of conditions. A defectin the saposin B region leads to metachromatic leucodystrophy (MLD), whilea single nucleotide polymorphism in the SAP-C region may give rise toGaucher disease []. More recently, an opportunistic protozoan parasite protein has shown similarity both to the higher and lower eukaryotic saposins. The pore-forming protein isolated from virulent Naegleria fowleri (Brain eating amoeba) has been dubbed Naegleriapore A. It also shares structural similarity with cytolytic bacterial peptides, although this similarity does not extend to the sequence level.This entry represents a group of saposins found specifically in chordates.
Sphingolipids are bioactive compounds found in lower and higher eukaryotes.They are involved in the regulation of various cellular functions, such asgrowth, differentiation and apoptosis, and are believed to be essential ina healthy diet. Sphigolipids are degraded in the lysosome, and theproducts from their hydrolysis are used in other biosynthetic and regulatorypathways in the host.There are a number of lysosomal enzymes involved in the breakdown ofsphinogolipids, and these act in sequence to degrade the moieties []. These enzymes require co-proteins called sphingolipid activator proteins, (SAPs or saposins), to stabilise and activate them as necessary. SAPs are non-enzymatic and usually have a low molecular weight. They are conserved across a wide range of eukaryotes and contain specific saposin domains that aid in the activation of hydrolase enzymes. There have been four human saposins described so far, sharing significant similarity with each otherand with other eukaryotic SAP proteins.Mutations in SAP genes have been linked to a number of conditions. A defectin the saposin B region leads to metachromatic leucodystrophy (MLD), whilea single nucleotide polymorphism in the SAP-C region may give rise toGaucher disease []. More recently, an opportunistic protozoan parasite protein has shown similarity both to the higher and lower eukaryotic saposins. The pore-forming protein isolated from virulent Naegleria fowleri (Brain eating amoeba) has been dubbed Naegleriapore A. It also shares structural similarity with cytolytic bacterial peptides, although this similarity does not extend to the sequence level.
The SAP motif is a 35-residue motif, which has been named after SAF-A/B,Acinus and PIAS, three proteins known to contain it. The SAP motif is found ina variety of nuclear proteins involved in transcription, DNA repair, RNAprocessing or apoptotic chromatin degradation. As the sap motif of SAF-A hasbeen shown to be essential for specific DNA binding activity, it has beenproposed that it could be a DNA-binding motif [].A multiple alignment of the SAP motif reveals a bipartite distribution ofstrongly conserved hydrophobic, polar and bulky amino acids separated by aregion that contains a glycine. Secondary structure predictions suggest thatthe SAP motif could form two alpha helices separated by a turn [].Some proteins known to contain a SAP motif are listed below:Vertebrate scaffold attachment factors A and B (SAF-A/B). These twoproteins are heterogeneous nuclear ribonucleoproteins (hnRNPs) that bind toAT-rich chromosomal region. It has been proposed that they couple RNAmetabolism to nuclear organisation [, ]. The SAF-A protein is cleaved bycaspase-3 during apoptosis [].Mammalian Acinus, a protein which induces apoptotic chromatin condensationafter cleavage by caspase-3 []. Acinus also contains a RNA-recognitionmotif.Eukaryotic proteins of the PIAS (protein inhibitor of activated STAT)family. These proteins interact with phosphorylated STAT dimers and inhibitSTAT mediated gene activation. Deletion of the first 50 amino acid residuescontaining the SAP domain allows the interaction of PIAS1 with STAT1monomer [].Plant poly(ADP-ribose) polymerase (PARP). PARP is a nuclear protein thatcatalyzes the poly(ADP-ribosyl)ation of proteins. It is involved inresponses to mild and severe oxidative stresses, by mediating DNA repairand programmed cell death processes, respectively []. PARP is tightlybound to chromatin or nuclear matrix.Arabidopsis thaliana Arp, an apurinic endonuclease-redox protein.Yeast THO1 protein. It could be involved in the regulation oftranscriptional elongation by RNA polymerase II [].Animal Ku70. Together with Ku86, it forms a DNA ends binding complex thatis involved in repairing DNA double-strand breaks.Yeast RAD18, a protein involved in DNA repair.Neurospora crassa UVS-2, the homologue of RAD18.
The G-patch domain is an approximately 48 amino acid domain, which is found ina single copy in several RNA-associated proteins and in type D retroviralpolyproteins. It is widespread among eukaryotes but is absent in archaea andbacteria. The G-patch domain has been called after its most notable feature,the presence of six highly conserved glycine residues. The position followingthe first conserved glycine is occupied almost invariably by an aromaticresidue, and several other positions are occupied predominantly by eitherhydrophobic or small residues. Several groups of G-patch containing proteinsare conserved in animals, plants and fungi. In some of these proteins the G-patch is the only recognisable domain but in most of them it is combined withother domains, which include well-defined RNA-binding domains, such as theRRM, dsRBD, SURP and R3H. It has been suggested that the G-patch domain has a specific function in RNA processing and, in particular, that it might be a previously undetected RNA-binding domain mediating a distinct type of RNA-protein interaction.Secondary structure prediction indicates that the G-patch domain probablycontains two α-helices, with four out of the six glycines located withinan intervening loop.Proteins known to contain a G-patch domain include:Eukaryotic 45kDa splicing factor (SPF-45).Mammmalian SON protein, a DNA-binding protein.Human LUCA15, a multidomain RNA-binding protein that is the product of a gene deleted in certain lung tumors.Human DAN26/EPROT, a multidomain protein, which, in addition to the G-patch domain, contains an RNA polymerase II C-terminal repeat-binding domain seen in many proteins of the polyA-addition machinery.Arabidopsis thaliana DRT111, a protein which has been shown to partially restore recombination proficiency and DNA-damage resistance to E. coli mutants.Type D retroviral polyprotein, where the G-patch domain is found directly downstream of the protease domain.
The SAP motif is a 35-residue motif, which has been named after SAF-A/B,Acinus and PIAS, three proteins known to contain it. The SAP motif is found ina variety of nuclear proteins involved in transcription, DNA repair, RNAprocessing or apoptotic chromatin degradation. As the sap motif of SAF-A hasbeen shown to be essential for specific DNA binding activity, it has beenproposed that it could be a DNA-binding motif [].A multiple alignment of the SAP motif reveals a bipartite distribution ofstrongly conserved hydrophobic, polar and bulky amino acids separated by aregion that contains a glycine. Secondary structure predictions suggest thatthe SAP motif could form two alpha helices separated by a turn [].Some proteins known to contain a SAP motif are listed below:Vertebrate scaffold attachment factors A and B (SAF-A/B). These twoproteins are heterogeneous nuclear ribonucleoproteins (hnRNPs) that bind toAT-rich chromosomal region. It has been proposed that they couple RNAmetabolism to nuclear organisation [, ]. The SAF-A protein is cleaved bycaspase-3 during apoptosis [].Mammalian Acinus, a protein which induces apoptotic chromatin condensationafter cleavage by caspase-3 []. Acinus also contains a RNA-recognitionmotif.Eukaryotic proteins of the PIAS (protein inhibitor of activated STAT)family. These proteins interact with phosphorylated STAT dimers and inhibitSTAT mediated gene activation. Deletion of the first 50 amino acid residuescontaining the SAP domain allows the interaction of PIAS1 with STAT1monomer [].Plant poly(ADP-ribose) polymerase (PARP). PARP is a nuclear protein thatcatalyzes the poly(ADP-ribosyl)ation of proteins. It is involved inresponses to mild and severe oxidative stresses, by mediating DNA repairand programmed cell death processes, respectively []. PARP is tightlybound to chromatin or nuclear matrix.Arabidopsis thaliana Arp, an apurinic endonuclease-redox protein.Yeast THO1 protein. It could be involved in the regulation oftranscriptional elongation by RNA polymerase II [].Animal Ku70. Together with Ku86, it forms a DNA ends binding complex thatis involved in repairing DNA double-strand breaks.Yeast RAD18, a protein involved in DNA repair.Neurospora crassa UVS-2, the homologue of RAD18.
Poly(ADP-ribose) polymerases (PARP) are a family of enzymespresent in eukaryotes, which catalyze the poly(ADP-ribosyl)ation of a limitednumber of proteins involved in chromatin architecture, DNA repair, or in DNAmetabolism, including PARP itself. PARP, also known as poly(ADP-ribose)synthetase and poly(ADP-ribose) transferase, transfers the ADP-ribose moietyfrom its substrate, nicotinamide adenine dinucleotide (NAD), to carboxylategroups of aspartic and glutamic residues. Whereas some PARPs might function ingenome protection, others appear to play different roles in the cell,including telomere replication and cellular transport. PARP-1 is amultifunctional enzyme. The polypeptide has a highly conserved modularorganisation consisting of an N-terminal DNA-binding domain, a centralregulating segment, and a C-terminal or F region accommodating the catalyticcentre. The F region is composed of two parts: a purely α-helical N-terminal domain (alpha-hd), and the mixed alpha/beta C-terminal catalyticdomain bearing the putative NAD binding site. Although proteins of the PARPfamily are related through their PARP catalytic domain, they do not resembleeach other outside of that region, but rather, they contain unique domainsthat distinguish them from each other and hint at their discrete functions.Domains with which the PARP catalytic domain is found associated includezinc fingers, SAP, ankyrin, BRCT, Macro, SAM, WWE and UIM domains [, , ].The alpha-hd domain is about 130 amino acids in length and consists of an up-up-down-up-down-down motif of helices. It isthought to relay the activation signal issued on binding to damaged DNA [, ].The PARP catalytic domain is about 230 residues in length. Its core consists of a five-stranded antiparallel β-sheet andfour-stranded mixed β-sheet. The two sheets are consecutive and areconnected via a single pair of hydrogen bonds between two strands that run atan angle of 90 degrees. These central β-sheets are surrounded by five α-helices, three 3(10)-helices, and by a three- and a two-stranded β-sheet ina 37-residue excursion between two central β-strands [, ]. The activesite, known as the 'PARP signature' is formed by a block of 50 amino acids that is strictly conserved among the vertebrates andhighly conserved among all species. The 'PARP signature' is characteristic ofall PARP protein family members. It is formed by a segment of conserved aminoacid residues formed by a β-sheet, an α-helix, a 3(10)-helix, a β-sheet, and an α-helix [].
The CD34 group of monoclonal antibodies recognises CD34 (also termed CD34antigen), a 105-120kDa cell surface glycoprotein, which is selectively expressed by human myeloid and lymphoid progenitor cells, including the haemopoietic stem cell. The protein is also expressed on vascularendothelial cells. Here, it is concentrated on the surface of the inter-digitating processes, suggesting a possible involvement in cell interactionsor adhesion, by mediating the attachment of stem cells to the bone marrow extracellular matrix, or directly to stromal cells. The restricted patternof expression of CD34 in haemopoiesis suggests that it may have a significant function in the earliest stages of blood cell differentiation in the bone marrow [, ].CD34 is a phosphoprotein shown to be activated by protein kinase C (PKC) ina developmental stage-specific manner. Analysis of the human CD34 sequencereveals that the protein appears to be a type I transmembrane (TM) molecule.The predicted internal portion of the protein appears to retain basic amino acid residues adjacent to Ser residues, presenting at least two potentialtarget sites for PKC phosphorylation. In addition, there are two other consensus motifs that correspond to potential target sites for Ca+/calmodulin-dependent kinase and/or protease activated kinase I [].The protein is not strongly similar to other known proteins, but some weaksimilarities do exist: e.g., to the S+T region (a region rich in potentialO-linked carbohydrate attachment sites), the TM domain and cytoplasmic domain of cell surface proteins such as leukosialin, a major sialoglyco-protein of rat and human leukocytes; to the N-terminal glycosylated regionof CD45 (the leukocyte common antigen); and to groups of interrelatedproteins involved in cell adhesion or the regulation of complement.A homologue of human CD34 is expressed in mouse. The amino acid sequencesonly diverge significantly at their N-termini, which are predicted to be highly glycosylated and whose functions are probably modulated by carbohydrate. The observed pattern of expression of the murine CD34 geneis consistent with that of the human antigen. That CD34 is also highlyexpressed outside haematopoiesis, by vascular endothelial cells and by fibroblasts in differentiated tissue, suggests a role common to a varietyof cell types. Concentration of CD34 on the interdigitating membraneprojections of adjacent capillary endothelial cells has strengthened theidea that it functions in the control of events leading to cell-cell orcell-matrix adhesion, which role could be modulated by variation in itslevels of glycosylation. The conservation between the human and mousecysteine-rich domain in the extracellular part of the protein, and theexceptionally high conservation of the cytoplasmic domain, imply that theprotein is more than a carrier for either carbohydrate or negatively chargedterminal sialic acid residues (a role postulated for leukosialin/sialophorin).The highly conserved domain may serve to provide an internal signal of external contact with a ligand.
