LOCATE: a mouse protein subcellular localization database

Fink, J.; Aturaliya, Rajith; Davis, Melissa B.; Zhang, Fasheng; Hanson, Kelly; Teasdale, Melvena; Cui, Kai; Kawai, Jun; Carninci, Piero; Hayashizaki, Yoshihide; Teasdale, Rohan D.

doi:10.4016/1413.01

Cited by 28 publications

(46 citation statements)

References 5 publications

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“…For the FPP assay, transfected HeLa cells on 35-mm poly-D-lysinecoated glass-bottomed plates (MatTek) were used for visualization of all GFP-LMF1 fusion constructs and of eCFP-CD3␦ and CD3␦-YFP in live cells. The FPP assay was performed as described (23) LMF1 Topology Prediction Methods-LOCATE, a mammalian protein localization data base, used the Membrane Organization Prediction Data (MemO) automated pipeline to assign a total of seven ␣-helical TM domains for mouse and human LMF1 derived from data supplied by five individual predicators: HMMTOP, TMHMM v2.0, SVMTM v3.0, MEMSAT, and DAS (24). Predicted ␣-helical TM sequences for mouse and human LMF1 were also obtained with three additional prediction methods: TMpred, SOUSUI, and PSORTII.…”

Section: Methodsmentioning

confidence: 99%

Lipase Maturation Factor LMF1, Membrane Topology and Interaction with Lipase Proteins in the Endoplasmic Reticulum

Doolittle

Neher

Ben-Zeev

et al. 2009

Journal of Biological Chemistry

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Lipase maturation factor 1 (LMF1) is predicted to be a polytopic protein localized to the endoplasmic reticulum (ER) membrane. It functions in the post-translational attainment of enzyme activity for both lipoprotein lipase and hepatic lipase. By using transmembrane prediction methods in mouse and human orthologs, models of LMF1 topology were constructed and tested experimentally. Employing a tagging strategy that used insertion of ectopic glycan attachment sites and terminal fusions of green fluorescent protein, we established a five-transmembrane model, thus dividing LMF1 into six domains. Three domains were found to face the cytoplasm (the amino-terminal domain and loops B and D), and the other half was oriented to the ER lumen (loops A and C and the carboxyl-terminal domain). This representative model shows the arrangement of an evolutionarily conserved domain within LMF1 (DUF1222) that is essential to lipase maturation. DUF1222 comprises four of the six domains, with the two largest ones facing the ER lumen. We showed for the first time, using several naturally occurring variants featuring DUF1222 truncations, that Lmf1 interacts physically with lipoprotein lipase and hepatic lipase and localizes the lipase interaction site to loop C within DUF1222. We discuss the implication of our results with regard to lipase maturation and DUF1222 domain structure. Lipoprotein lipase (LPL)6 and hepatic lipase (HL) are secreted glycoproteins that hydrolyze triglycerides sequestered in the core of circulating lipoproteins. As such, they play important roles in lipoprotein remodeling and uptake. LPL also mediates tissue influx of fatty acids derived from triglyceride-rich lipoproteins, and both lipases have been implicated in atherosclerosis and inflammation (1-4). These functions require nascent lipase polypeptides to fold and assemble into native structures, a necessary prerequisite for enzyme activity and secretion. However, both lipases require a trans-acting factor to attain a functional state, as exemplified by a naturally occurring mutation in the mouse called combined lipase deficiency (cld). In tissues and cells homozygous for the cld mutation, intracellular levels of LPL mRNA and protein are normal; however, the vast majority of LPL protein (ϳ95%) remains within the endoplasmic reticulum (ER) as misfolded (inactive) mass that is eventually degraded (5-8). HL activity is also diminished in cld/cld cells but to a lesser extent than LPL (9). In affected newborn mice, the resulting combined lipase deficiency causes massive chylomicronemia and neonatal death because of tissue ischemia and the absence of triglyceride-derived fatty acid influx (10). Indeed, this phenotype mirrors an LPL knock-out model (11), indicating that cld causes virtual abolishment of LPL function. The identity of this critical lipase maturation factor was made clear when a gene encoding a predicted transmembrane protein on mouse chromosome 17 (Tmem112) was found to harbor the cld mutation (9). The gene was renamed lipase maturation factor 1 (Lmf1...

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Section: Methodsmentioning

confidence: 99%

Lipase Maturation Factor LMF1, Membrane Topology and Interaction with Lipase Proteins in the Endoplasmic Reticulum

Doolittle

Neher

Ben-Zeev

et al. 2009

Journal of Biological Chemistry

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“…Of these 153 genes, 83 that encode 107 RefSeq transcripts were mapped to the X chromosome (CT-X genes) whereas 70 genes were on autosomes (non-X CT genes). Subcellular localization was based on predictions in the human version of the LOCATE system (40). SEREX information was obtained from the Cancer Immunome Database website (http://ludwig-sun5.unil.ch/CancerImmunomeDB).…”

Section: Methodsmentioning

confidence: 99%

Genome-wide analysis of cancer/testis gene expression

Hofmann

Caballero

Stevenson

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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300

309

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Cancer/Testis (CT) genes, normally expressed in germ line cells but also activated in a wide range of cancer types, often encode antigens that are immunogenic in cancer patients, and present potential for use as biomarkers and targets for immunotherapy. Using multiple in silico gene expression analysis technologies, including twice the number of expressed sequence tags used in previous studies, we have performed a comprehensive genomewide survey of expression for a set of 153 previously described CT genes in normal and cancer expression libraries. We find that although they are generally highly expressed in testis, these genes exhibit heterogeneous gene expression profiles, allowing their classification into testis-restricted (39), testis/brain-restricted (14), and a testis-selective (85) group of genes that show additional expression in somatic tissues. The chromosomal distribution of these genes confirmed the previously observed dominance of X chromosome location, with CT-X genes being significantly more testis-restricted than non-X CT. Applying this core classification in a genome-wide survey we identified >30 CT candidate genes; 3 of them, PEPP-2, OTOA, and AKAP4, were confirmed as testisrestricted or testis-selective using RT-PCR, with variable expression frequencies observed in a panel of cancer cell lines. Our classification provides an objective ranking for potential CT genes, which is useful in guiding further identification and characterization of these potentially important diagnostic and therapeutic targets.gene index ͉ prediction

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“…Translational inhibition by miRNAs, mRNA localization 61 and regulated local translation have been demonstrated to be of considerable importance in the differentiation of dendrites 49,13 . More attention has been payed to subcellular localization of proteins as reflected by the LOCATE Database 19 . The mechanism of intra-and inter-cellular trafficking by protein targeting via signal peptides, direct protein synthesis into the target compartment and usage of the secretory pathway have been described decades ago.…”

Section: Space Mattersmentioning

confidence: 99%

A Story of Growing Confusion: Genes and Their Regulation

Prohaska

Stadler

2008

Biophys. Rev. Lett.

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High-throughput experiments have produced convicing evidence for an extensive contribution of diverse classes of RNAs in the expression of genetic information. Instead of a simple arrangement of mostly protein-coding genes, the human transcriptome features a complex arrangement of overlapping transcripts, many of which do not code for proteins at all, while others "sample" exons from several different "genes". The complexity of the transcriptome and the prevalence of noncoding transcripts forces us to reconsider both the concept of the "gene" itself and our understanding of the mechanisms that regulate "gene expression".

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LOCATE: a mouse protein subcellular localization database

Cited by 28 publications

References 5 publications

Lipase Maturation Factor LMF1, Membrane Topology and Interaction with Lipase Proteins in the Endoplasmic Reticulum

Lipase Maturation Factor LMF1, Membrane Topology and Interaction with Lipase Proteins in the Endoplasmic Reticulum

Genome-wide analysis of cancer/testis gene expression

A Story of Growing Confusion: Genes and Their Regulation

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