Disease relevance of LSM4

• A gene induced by the plant hormone abscisic acid in response to water stress encodes a glycine-rich protein [1].
• Granuloma-specific expression of Mycobacterium virulence proteins from the glycine-rich PE-PGRS family [2].
• During infectious mononucleosis, IgM autoantibodies are generated to a protein, p542, which contains a glycine-rich 28-mer epitope cross-reactive with the Epstein-Barr nuclear antigen-1 through Epstein-Barr nuclear antigen-1's glycine/alanine repeat [3].
• Different effects of point mutations within the B-Raf glycine-rich loop in colorectal tumors on mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase and nuclear factor kappaB pathway and cellular transformation [4].
• Recent studies indicate that the protein affected in spinal muscular atrophy, SMN, plays a role in the assembly of a number of macromolecular complexes that function in the nucleus, interacting with its partner proteins via their arginine- and glycine-rich domains [5].

High impact information on LSM4

• However, they contain unusual glycine-rich tandem repeats similar to the amino terminus of the Type I keratin [6].
• M. tuberculosis differs radically from other bacteria in that a very large portion of its coding capacity is devoted to the production of enzymes involved in lipogenesis and lipolysis, and to two new families of glycine-rich proteins with a repetitive structure that may represent a source of antigenic variation [7].
• The elastic domains have sequence motifs that strongly resemble those of elastin and the amorphous glycine-rich regions of spider silk fibroins [8].
• The HOX11 homeodomain is most similar to that of the murine gene Hlx and possesses a markedly glycine-rich variable region and an acidic carboxyl terminus [9].
• All nuclear transport factors can bidirectionally traverse the nuclear pore complex through specific interactions with phenylalanine/glycine-rich nuclear pore complex components [10].

Chemical compound and disease context of LSM4

• We investigated the functional role of the glycine-rich segment, Met-326 to Ser-337, of the human T-cell leukemia virus type 1 (HTLV-1) TM, gp21, by alanine and proline scanning mutagenesis [11].
• This disordered region contains a glycine-rich sequence 353-GVGGP-357 (numbering refers to the initiation methionine of Gag) that is highly conserved within the Gag proteins of HIV-1, HIV-2, and simian immunodeficiency virus, which suggests the importance of this sequence in virus replication [12].
• The adenylate cyclase-hemolysin of Bordetella pertussis consists of a cell-invasive N-terminal adenylate cyclase domain linked to a C-terminal RTX hemolysin containing extensive glycine-rich repeats [13].
• Flexible glycine rich motif of Escherichia coli deoxyuridine triphosphate nucleotidohydrolase is important for functional but not for structural integrity of the enzyme [14].
• CONCLUSIONS: The inhibitory effects of GHRH antagonists on PC-3 human androgen-independent prostate cancer can be potentiated by concomitant use of BN/GRP antagonists [15].

Biological context of LSM4

• Furthermore, adding a fourth sample (e.g., LSM 4) did not substantially decrease the bias or increase the accuracy for temozolomide clearance or MTIC AUC [16].
• The reactive epitopes on p542 were mapped with deletion mutants, which indicated that the glycine-rich 28-mer was the major antigenic determinant, with lesser antibody responses to other epitopes [3].
• However, we observed many variations in the V2 subdomain near the C terminus in glycine-rich sequences with a variation of as much as 114 base pairs (38 amino acids), but all individuals had either one or two variants [17].
• These mRNA changes include differential regulation of transcripts derived from the GRP and HRGP multigene families [18].
• The GRP promoters contain multiple copies of the ER stress response element (ERSE), consisting of a unique tripartite structure, CCAAT(N(9))CCACG [19].

Anatomical context of LSM4

• The methylosome functions to modify specific arginines to dimethylarginines in the arginine- and glycine-rich domains of several spliceosomal Sm proteins, and this modification targets these proteins to the survival of motor neurons (SMN) complex for assembly into small nuclear ribonucleoprotein (snRNP) core particles [20].
• Antibodies raised against regions of the glycine-rich protein 1.8, expressed as a lacZ fusion protein in bacteria, react with a protein of 53 kd in a protein fraction extracted from cell walls of bean ovaries [21].
• This mutation in the conserved cytoskeleton-associated protein, glycine-rich (CAP-Gly) domain lowers the affinity of p150Glued for microtubules and EB1 [22].
• This was tested by subjecting L8 myocytes and NIH 3T3 fibroblasts to glucose starvation or exposure to the calcium ionophore A23187, 2-mercaptoethanol, or tunicamycin, all known to increase GRP levels [23].
• When mammalian cells are subjected to stress targeted to the endoplasmic reticulum (ER), such as depletion of the ER Ca(2+) store, the transcription of a family of glucose-regulated protein (GRP) genes encoding ER chaperones is induced [19].

Associations of LSM4 with chemical compounds

• Furthermore, the carboxyl-terminal arginine- and glycine-rich domain of Lsm4 directly interacts with SMN [24].
• All three putative gene products contain a single RNA Recognition Motif (RRM) that includes the highly conserved RNP1 and RNP2 regions and all three have an auxiliary motif consisting either of a short glycine-rich carboxy-terminal tail or a carboxy-terminal tail rich in both asparagine and glycine [25].
• Many ATP- and GTP-binding proteins have a phosphate-binding loop (P-loop), the primary structure of which typically consists of a glycine-rich sequence followed by a conserved lysine and a serine or threonine [26].
• The NH2-terminal half of the antigen contains two conserved RNA binding domains whereas its COOH-terminal part is extremely glycine-rich [27].
• O126 encodes a glycine-rich protein that is expressed in mature ovules, and O141 encodes a cysteine proteinase that is expressed in the outer integument of ovules during seed formation [28].

Physical interactions of LSM4

• The verprolin-homology region in N-WASP was required for binding to the glycine-rich repeats domain of VirG, an essential domain for recruitment of F-actin on intracellular S.flexneri [29].
• By deletion analysis, we mapped the apobec-1-binding region to the glycine-rich domain [30].
• Cdc37 interacts with the glycine-rich loop of Hsp90 client kinases [31].
• The purified reductase cross-reacted with polyclonal antibodies against both hepatic NADPH-cytochrome P-450 reductase and a synthetic peptide, ILVGPGTGIAPFRSF, which indicates residues 529-543 located in the glycine-rich NADPH-binding domain of the P-450 reductase, but cytochrome b558 did not produce any immunoreactive bands to these antibodies [32].
• JKTBP proteins consisting of two canonical RNA binding domains (RBDs) and a glycine-rich carboxyl domain are nucleocytoplasmic shuttling proteins [33].

Enzymatic interactions of LSM4

• Arginine methylation in RNA-binding proteins containing arginine- and glycine-rich RGG motifs is catalyzed by specific protein arginine N-methyltransferase in cells [34].

Other interactions of LSM4

• These findings demonstrate that arginine- and glycine-rich domains are necessary and sufficient for SMN interaction, and they expand further the range of targets of the SMN protein [24].
• SMN binds preferentially and directly to the symmetrical dimethylarginine (sDMA)-modified arginine- and glycine-rich (RG-rich) domains of SmD1 and SmD3 [35].
• SMN interaction requires the arginine- and glycine-rich domains of both fibrillarin and GAR1 and is defective in SMN mutants found in some SMA patients [36].
• Our results argue against post-translational arginine dimethylation as a general requirement for SMN recognition of proteins bearing arginine/glycine-rich domains [37].
• Furthermore, we find that either of the two arginine/glycine-rich domains of GAR1 can provide for interaction with SMN, but removal of both results in loss of the interaction [37].

Analytical, diagnostic and therapeutic context of LSM4

• Female nude mice bearing orthotopic xenografts of MDA-MB-435 human estrogen-independent breast cancers were treated daily with BN/GRP antagonists RC-3095 (20 microg) or RC-3940-II (10 microg) for 6 weeks [38].
• A new, clearly distinct structural element containing glycine-rich proteins is now visualized for the first time, using confocal laser scanning microscopy in the mature protoxylem of elongating organs of seed plants [39].
• Sequence analysis of the cDNA indicated that the plastid Protox of spinach is composed of 562 amino acids containing the glycine-rich motif GxGxxG previously proposed to be a dinucleotide binding site of many flavin-containing proteins [40].
• Comparative sequence alignment of Pa-RRM-GRP1 reveals extensive homology to known and presumed glycine-rich RNA binding proteins from angiosperms and gymnosperms [41].
• The marked species charge heterogeneity of the 2-D pattern was used as a criterion to assign the majority of GRP components to "series'. Series are composed of families of related proteins or glycoproteins distributed in a line of evenly spaced members in the isoelectric focusing dimension [42].

References