G2Cdb::Gene report

Gene id
G00001627
Gene symbol
DDOST (HGNC)
Species
Homo sapiens
Description
dolichyl-diphosphooligosaccharide--protein glycosyltransferase
Orthologue
G00000378 (Mus musculus)

Databases (7)

Gene
ENSG00000117242 (Ensembl human gene)
1650 (Entrez Gene)
733 (G2Cdb plasticity & disease)
DDOST (GeneCards)
Literature
602202 (OMIM)
Marker Symbol
HGNC:2728 (HGNC)
Protein Sequence
P39656 (UniProt)

Synonyms (4)

  • KIAA0115
  • OST
  • OST48
  • WBP1

Literature (13)

Pubmed - other

  • Defining the human deubiquitinating enzyme interaction landscape.

    Sowa ME, Bennett EJ, Gygi SP and Harper JW

    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.

    Deubiquitinating enzymes (Dubs) function to remove covalently attached ubiquitin from proteins, thereby controlling substrate activity and/or abundance. For most Dubs, their functions, targets, and regulation are poorly understood. To systematically investigate Dub function, we initiated a global proteomic analysis of Dubs and their associated protein complexes. This was accomplished through the development of a software platform called CompPASS, which uses unbiased metrics to assign confidence measurements to interactions from parallel nonreciprocal proteomic data sets. We identified 774 candidate interacting proteins associated with 75 Dubs. Using Gene Ontology, interactome topology classification, subcellular localization, and functional studies, we link Dubs to diverse processes, including protein turnover, transcription, RNA processing, DNA damage, and endoplasmic reticulum-associated degradation. This work provides the first glimpse into the Dub interaction landscape, places previously unstudied Dubs within putative biological pathways, and identifies previously unknown interactions and protein complexes involved in this increasingly important arm of the ubiquitin-proteasome pathway.

    Funded by: NIA NIH HHS: AG085011, R01 AG011085, R01 AG011085-16; NIGMS NIH HHS: GM054137, GM67945, R01 GM054137, R01 GM054137-14, R01 GM067945

    Cell 2009;138;2;389-403

  • Association study between single-nucleotide polymorphisms in 199 drug-related genes and commonly measured quantitative traits of 752 healthy Japanese subjects.

    Saito A, Kawamoto M and Kamatani N

    Division of Genomic Medicine, Department of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan. a-saito@horae.dti.ne.jp

    With dense single-nucleotide polymorphism (SNP) maps for 199 drug-related genes, we examined associations between 4190 SNPs and 38 commonly measured quantitative traits using data from 752 healthy Japanese subjects. On analysis, we observed a strong association between five SNPs within the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene and serum total bilirubin levels (minimum P-value in Mann-Whitney test=1.82 x 10(10)). UGT1A1 catalyzes the conjugation of bilirubin with glucuronic acid, thus enhancing bilirubin elimination. This enzyme is known to play an important role in the variation of serum bilirubin levels. The five SNPs, including a nonsynonymous SNP-rs4148323 (211G>A or G71R variant allele known as UGT1A1*6)-showed strong linkage disequilibrium with each other. No other genes were clearly associated with serum total bilirubin levels. Results of linear multiple regression analysis on serum total bilirubin levels followed by analysis of variance showed that at least 13% of the variance in serum total bilirubin levels could be explained by three haplotype-tagging SNPs in the UGT1A1 gene.

    Journal of human genetics 2009;54;6;317-23

  • Large-scale mapping of human protein-protein interactions by mass spectrometry.

    Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T and Figeys D

    Protana, Toronto, Ontario, Canada.

    Mapping protein-protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein-protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24,540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein-protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations.

    Molecular systems biology 2007;3;89

  • Proteomic analysis of mammalian oligosaccharyltransferase reveals multiple subcomplexes that contain Sec61, TRAP, and two potential new subunits.

    Shibatani T, David LL, McCormack AL, Frueh K and Skach WR

    Division of Molecular Medicine, Oregon Health and Sciences University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97201, USA.

    Oligosaccharyltransferase (OST) catalyzes the cotranslational transfer of high-mannose sugars to nascent polypeptides during N-linked glycosylation in the rough endoplasmic reticulum lumen. Nine OST subunits have been identified in yeast. However, the composition and organization of mammalian OST remain unclear. Using two-dimensional Blue Native polyacrylamide gel electrophoresis/sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry, we now demonstrate that mammalian OST can be isolated from solubilized, actively engaged ribosomes as multiple distinct protein complexes that range in size from approximately 500 to 700 kDa. These complexes exhibit different ribosome affinities and subunit compositions. The major complex, OSTC(I), had an apparent size of approximately 500 kDa and was readily released from ribosome translocon complexes after puromycin treatment under physiological salt conditions. Two additional complexes were released only after treatment with high salt: OSTC(II) ( approximately 600 kDa) and OSTC(III) ( approximately 700 kDa). Both remained stably associated with heterotrimeric Sec61alphabetagamma, while OSTC(III) also contained the tetrameric TRAP complex. All known mammalian OST subunits (STT3-A, ribophorin I, ribophorin II, OST48, and DAD1) were present in all complexes. In addition, two previously uncharacterized proteins were also copurified with OST. Mass spectrometry identified a 17 kDa protein as DC2 which is weakly homologous to the C-terminal half of yeast Ost3p and Ost6p. The second protein (14 kDa) was tentatively identified as keratinocyte-associated protein 2 (KCP2) and has no previously known function. Our results identify two potential new subunits of mammalian OST and demonstrate a remarkable heterogeneity in OST composition that may reflect a means for controlling nascent chain glycosylation.

    Funded by: NEI NIH HHS: EY10572; NHLBI NIH HHS: T32HL07781; NIDDK NIH HHS: DK51818; NIGMS NIH HHS: GM53457

    Biochemistry 2005;44;16;5982-92

  • The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

    Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J and MGC Project Team

    The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

    Funded by: PHS HHS: N01-C0-12400

    Genome research 2004;14;10B;2121-7

  • Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.

    Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K and Sugano S

    Human Genome Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan. ysuzuki@ims.u-tokyo.ac.jp

    Comparative sequence analysis was carried out for the regions adjacent to experimentally validated transcriptional start sites (TSSs), using 3324 pairs of human and mouse genes. We aligned the upstream putative promoter sequences over the 1-kb proximal regions and found that the sequence conservation could not be further extended at, on average, 510 bp upstream positions of the TSSs. This discontinuous manner of the sequence conservation revealed a "block" structure in about one-third of the putative promoter regions. Consistently, we also observed that G+C content and CpG frequency were significantly different inside and outside the blocks. Within the blocks, the sequence identity was uniformly 65% regardless of their length. About 90% of the previously characterized transcription factor binding sites were located within those blocks. In 46% of the blocks, the 5' ends were bounded by interspersed repetitive elements, some of which may have nucleated the genomic rearrangements. The length of the blocks was shortest in the promoters of genes encoding transcription factors and of genes whose expression patterns are brain specific, which suggests that the evolutional diversifications in the transcriptional modulations should be the most marked in these populations of genes.

    Genome research 2004;14;9;1711-8

  • Advanced glycation endproduct (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells.

    Lu C, He JC, Cai W, Liu H, Zhu L and Vlassara H

    Department of Geriatrics and Adult Development, Division of Experimental Diabetes and Aging, Mount Sinai School of Medicine, New York, NY 10029, USA.

    Advanced glycation endproducts (AGE) contribute to kidney disease due to diabetes or aging by means of mesangial cell (MC) receptors, such as the receptor for AGE (RAGE), which promote oxidant-stress-dependent NF-kappaB activation and inflammatory gene expression. MC also express scavenger receptors SR-I and SR-II and AGE receptors 1, 2, and 3 (AGE-R1, -R2, and -R3), some of which are linked to AGE turnover. Because AGE-R1 expression is found suppressed in severe diabetic kidney disease, as other receptors increase, we investigated whether his molecule has a protective role against AGE-induced MC injury. A stable murine MC line overexpressing AGE-R1 (R1-MC) was generated, exhibiting a 1.8- to 2.7-fold increase in (125)I-AGE-specific binding, uptake, and degradation, compared with mock-MC. However, AGE-stimulated NF-kappaB activity and mitogen-activated protein kinase (MAPK) (p44/42) phosphorylation were found markedly suppressed in R1-MC. Additionally, AGE-stimulated macrophage chemotaxis protein 1 and RAGE overexpression were abolished in R1-MC. The effect of R1 on RAGE signaling was investigated after overexpressing RAGE in Chinese hamster ovary cells, which lack RAGE. AGE stimulation elicited NF-kappaB and MAPK activities in RAGE-Chinese hamster ovary cells; however, after cotransfection with R1, these responses were suppressed. Also, after silencing endogenous R1 in wild-type MC by R1 small interfering RNA, AGE-mediated MAPK/p44/42 activation exceeded by >2-fold that of mock-MC, consistent with loss of the activation-inhibitory properties of native AGE-R1. AGE-R1, although enhancing AGE removal, is also a distinct receptor in that it suppresses AGE-mediated MC inflammatory injury through negative regulation of RAGE, a previously uncharacterized pathway that may protect renal and other tissue injury due to diabetes and aging.

    Funded by: NIDDK NIH HHS: DK54788, R01 DK054788

    Proceedings of the National Academy of Sciences of the United States of America 2004;101;32;11767-72

  • Characterization of the advanced glycation end-product receptor complex in human vascular endothelial cells.

    Stitt AW, He C and Vlassara H

    Department of Opthalmology, Queen's University of Belfast, Royal Victoria Hospital, Belfast, BT12 6BA, Northern Ireland, United Kingdom. a.stitt@qub.ac.uk

    Advanced glycation end products (AGEs) have been implicated as causal factors in the vascular complications of diabetes and it is known that these products interact with cells through specific receptors. The AGE-receptor complex, originally described as p60 and p90, has been characterised in hemopoietic cells and the component proteins identified and designated AGE-R1, -R2 and -R3. In the current study we have characterised this receptor in human umbilical vein endothelial cells (HUVECs) and elucidated several important biological properties which may impact on AGE mediated vascular disease. 125I-AGE-BSA binding to HUVEC monolayers was determined with and without various cold competitors. The synthetic AGE, 2-(2-furoyl)-4(5)-furanyl-1H-imidazole (FFI)-BSA, failed to compete with AGE-BSA binding unlike observations already reported in hemopoietic cells. The ability of 125I-AGE-BSA to bind to separated HUVEC plasma membrane (PM) proteins was also examined and the binding at specific bands inhibited by antibodies to each component of the AGE-receptor complex. Western blotting of whole cell and PM fractions, before and after exposure to AGE-BSA, revealed that AGE-R1, -R2 and -R3 are subject to upregulation upon exposure to their ligand, a phenomenon which was also demonstrated by immunofluorescence of non-permeabilised cells. mRNA expression of each AGE-receptor component was apparent in HUVECs, with the AGE-R2 and -R3 gene expression being upregulated upon exposure to AGEs in a time-dependent manner. A phosporylation assay in combination with AGE-R2 immunoprecipitation demonstrated that this component of the receptor complex is phosphorylated by acute exposure to AGE-BSA. These results indicate the presence of a conserved AGE-receptor complex in vascular endothelium which demonstrates subtle differences to other cell-types. In response to AGE-modified molecules, this complex is subject to upregulation, while the AGE-R2 component also displays increased phosphorylation possibly leading to enhanced signal transduction.

    Biochemical and biophysical research communications 1999;256;3;549-56

  • Interleukin-2 induces N-glycosylation in T-cells: characterization of human lymphocyte oligosaccharyltransferase.

    Kumar V, Heinemann FS and Ozols J

    Department of Biochemistry, University of Connecticut Health Center, Farmington, Connecticut, 06030, USA. Vijay_Kumar@dfci.harvard.edu

    We have investigated the enzyme mediating N-glycosylation in "resting" and activated lymphocytes. Normal peripheral blood lymphocytes (PBLs) were found to have low activity for glycosylation of a synthetic glycan acceptor peptide. N-glycosylation activity increased 10-fold after mitogen activation of PBLs. N-glycosylation activity remained elevated during long-term culture and expansion of human lymphocytes when growth was supported by interleukin-2. To our knowledge, this is the first biochemical evidence for induction of endoplasmic reticulum functions during T-cell activation. The enzyme mediating N-glycosylation in lymphocytes was localized predominantly but not entirely to a microsomal organelle by subcellular fractionation. After solubilization and 85-fold purification from salt-washed microsomes, the enzyme preparation contained four predominant proteins. N-terminal sequence analysis identified the proteins as ribophorin I, ribophorin II (doublet), and a 50-kDa homologue of Wbp1, a yeast protein essential for N-glycosylation.

    Funded by: NIGMS NIH HHS: R01-GM-26351

    Biochemical and biophysical research communications 1998;247;2;524-9

  • Genome organization of human 48-kDa oligosaccharyltransferase (DDOST).

    Yamagata T, Tsuru T, Momoi MY, Suwa K, Nozaki Y, Mukasa T, Ohashi H, Fukushima Y and Momoi T

    Department of Pediatrics, Jichi Medical School, Minamikawachi-machi, Kawachi-gun, Tochigi, 329-04, Japan.

    The enzyme oligosaccharyltransferase (dolichyl-diphosphooligosaccharide-protein glycosyltransferase; EC 2. 4.1.119) (DDOST) catalyzes the transfer of a high-mannose oligosaccharide (GlcNac2Man9Glc3) from a dolichol-linked oligosaccharide donor (dolichol-P-GlcNac2Man9Glc3) onto the asparagine acceptor site within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains across the membrane of the endoplasmic reticulum. We isolated mouse and human DDOST cDNAs from retinoic acid-treated mouse P19 EC cells and human NT-2 cells, respectively. DDOST mRNA is expressed intensely in heart and pancreas, but at lower levels in brain. Here we show that the human DDOST 48-kDa subunit gene (HGMW-approved symbol DDOST) is organized into 11 exons expanding about 9 kb. This DDOST subunit gene is localized on chromosome 1p36.1 by fluorescence in situ hybridization analysis.

    Genomics 1997;45;3;535-40

  • Human oligosaccharyltransferase: isolation, characterization, and the complete amino acid sequence of 50-kDa subunit.

    Kumar V, Korza G, Heinemann FS and Ozols J

    Department of Biochemistry, University of Connecticut Health Center, Farmington 06030, USA.

    Oligosaccharyltransferase (OT) catalyzes the glycosylation of asparagine residues in nascent polypeptides in the endoplasmic reticulum. In a previous communication we reported the purification and characterization of this enzyme from chicken oviduct. Here we describe the purification and sequence analysis of OT from human liver microsomes. Oligosaccharyltransferase copurified with three proteins designated 50-kDa, 65-I and 65-II based on their molecular weights by gel electrophoresis. The N-terminal sequence of the 50-kDa component was homologous to the 50-kDa subunit of avian OT. The N-terminal sequences of 65-I and 65-II were identical to the primary structures of human ribophorins I and II, respectively, predicted by cDNA sequencing. The complete amino acid sequence of the 50-kDa subunit of human OT was determined by chemical sequencing of peptides isolated from chemical and enzymatic digests. The 50-kDa subunit of human OT is 98% identical to its canine homolog, 93% identical to its avian homolog, and 25% identical to the beta subunit of yeast OT. These data indicate that structural features of oligosaccharyltransferase are conserved in all eukaryotes.

    Funded by: NIGMS NIH HHS: GM26351

    Archives of biochemistry and biophysics 1995;320;2;217-23

  • Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1.

    Nagase T, Miyajima N, Tanaka A, Sazuka T, Seki N, Sato S, Tabata S, Ishikawa K, Kawarabayasi Y, Kotani H et al.

    Kazusa DNA Research Institute, Chiba, Japan.

    We isolated full-length cDNA clones from size-fractionated cDNA libraries of human immature myeloid cell line KG-1, and the coding sequences of 40 genes were newly predicted. A computer search of the GenBank/EMBL databases indicated that the sequences of 14 genes were unrelated to any reported genes, while the remaining 26 genes carried some sequences with similarities to known genes. Significant transmembrane domains were identified in 17 genes, and protein motifs that matched those in the PROSITE motif database were identified in 11 genes. Northern hybridization analysis with 18 different cells and tissues demonstrated that 10 genes were apparently expressed in a cell-specific or tissue-specific manner. Among the genes predicted, half were isolated from the medium-sized cDNA library and the other half from the small-sized cDNA library, and their average sizes were 4 kb and 1.4 kb, respectively. As judged by Northern hybridization profiles, small-sized cDNAs appeared to be expressed more ubiquitously and abundantly in various tissues, compared with that of medium-sized cDNAs.

    DNA research : an international journal for rapid publication of reports on genes and genomes 1995;2;1;37-43

Gene lists (5)

Gene List Source Species Name Description Gene count
L00000009 G2C Homo sapiens Human PSD Human orthologues of mouse PSD adapted from Collins et al (2006) 1080
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
L00000061 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-CONSENSUS Mouse cortex PSD consensus (ortho) 984
L00000069 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list 1461
L00000071 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-FULL Mouse cortex PSD full list (ortho) 1556
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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