G2Cdb::Gene report

Gene id
G00001960
Gene symbol
EXOC5 (HGNC)
Species
Homo sapiens
Description
exocyst complex component 5
Orthologue
G00000711 (Mus musculus)

Databases (7)

Gene
ENSG00000180673 (Ensembl human gene)
10640 (Entrez Gene)
1120 (G2Cdb plasticity & disease)
EXOC5 (GeneCards)
Literature
604469 (OMIM)
Marker Symbol
HGNC:10696 (HGNC)
Protein Sequence
O00471 (UniProt)

Synonyms (2)

  • SEC10
  • SEC10P

Literature (15)

Pubmed - other

  • Exocyst Sec10 protects epithelial barrier integrity and enhances recovery following oxidative stress, by activation of the MAPK pathway.

    Park KM, Fogelgren B, Zuo X, Kim J, Chung DC and Lipschutz JH

    Department of Medicine, University of Pennsylvania, and the Veterans Administration Medical Center, Philadelphia, Pennsylvania, USA.

    Cell-cell contacts are essential for epithelial cell function, and disruption is associated with pathological conditions including ischemic kidney injury. We hypothesize that the exocyst, a highly-conserved eight-protein complex that targets secretory vesicles carrying membrane proteins, is involved in maintaining renal epithelial barrier integrity. Accordingly, increasing exocyst expression in renal tubule cells may protect barrier function from oxidative stress resulting from ischemia and reperfusion (I/R) injury. When cultured on plastic, Madin-Darby canine kidney (MDCK) cells overexpressing Sec10, a central exocyst component, formed domes showing increased resistance to hydrogen peroxide (H2O2). Transepithelial electric resistance (TER) of Sec10-overexpressing MDCK cells grown on Transwell filters was higher than in control MDCK cells, and the rate of TER decrease following H2O2 treatment was less in Sec10-overexpressing MDCK cells compared with control MDCK cells. After removal of H2O2, TER returned to normal more rapidly in Sec10-overexpressing compared with control MDCK cells. In collagen culture MDCK cells form cysts, and H2O2 treatment damaged Sec10-overexpressing MDCK cell cysts less than control MDCK cell cysts. The MAPK pathway has been shown to protect animals from I/R injury. Levels of active ERK, the final MAPK pathway step, were higher in Sec10-overexpressing compared with control MDCK cells. U0126 inhibited ERK activation, exacerbated the H2O2-induced decrease in TER and cyst disruption, and delayed recovery of TER following H2O2 removal. Finally, in mice with renal I/R injury, exocyst expression decreased early and returned to normal concomitant with functional recovery, suggesting that the exocyst may be involved in the recovery following I/R injury.

    Funded by: BLRD VA: I01 BX000820; NEI NIH HHS: EY017024; NIDDK NIH HHS: DK069909, P30 DK074038, P30 DK50306

    American journal of physiology. Renal physiology 2010;298;3;F818-26

  • The exocyst protein Sec10 is necessary for primary ciliogenesis and cystogenesis in vitro.

    Zuo X, Guo W and Lipschutz JH

    Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

    Primary cilia are found on many epithelial cell types, including renal tubular epithelial cells, in which they are felt to participate in flow sensing and have been linked to the pathogenesis of cystic renal disorders such as autosomal dominant polycystic kidney disease. We previously localized the exocyst, an eight-protein complex involved in membrane trafficking, to the primary cilium of Madin-Darby canine kidney cells and showed that it was involved in cystogenesis. Here, using short hairpin RNA (shRNA) to knockdown exocyst expression and stable transfection to induce exocyst overexpression, we show that the exocyst protein Sec10 regulates primary ciliogenesis. Using immunofluorescence, scanning, and transmission electron microscopy, primary cilia containing only basal bodies are seen in the Sec10 knockdown cells, and increased ciliogenesis is seen in Sec10-overexpressing cells. These phenotypes do not seem to be because of gross changes in cell polarity, as apical, basolateral, and tight junction proteins remain properly localized. Sec10 knockdown prevents normal cyst morphogenesis when the cells are grown in a collagen matrix, whereas Sec10 overexpression results in increased cystogenesis. Transfection with human Sec10 resistant to the canine shRNA rescues the phenotype, demonstrating specificity. Finally, Par3 was recently shown to regulate primary cilia biogenesis. Par3 and the exocyst colocalized by immunofluorescence and coimmunoprecipitation, consistent with a role for the exocyst in targeting and docking vesicles carrying proteins necessary for primary ciliogenesis.

    Funded by: BLRD VA: I01 BX000820; NIDDK NIH HHS: DK-069909, DK-070980, P30 DK050306, P30 DK074038, P30 DK50306, R01 DK069909, R21 DK070980; NIGMS NIH HHS: GM-64690, R01 GM064690

    Molecular biology of the cell 2009;20;10;2522-9

  • A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.

    Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M and Zoghbi HY

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

    Many human inherited neurodegenerative disorders are characterized by loss of balance due to cerebellar Purkinje cell (PC) degeneration. Although the disease-causing mutations have been identified for a number of these disorders, the normal functions of the proteins involved remain, in many cases, unknown. To gain insight into the function of proteins involved in PC degeneration, we developed an interaction network for 54 proteins involved in 23 inherited ataxias and expanded the network by incorporating literature-curated and evolutionarily conserved interactions. We identified 770 mostly novel protein-protein interactions using a stringent yeast two-hybrid screen; of 75 pairs tested, 83% of the interactions were verified in mammalian cells. Many ataxia-causing proteins share interacting partners, a subset of which have been found to modify neurodegeneration in animal models. This interactome thus provides a tool for understanding pathogenic mechanisms common for this class of neurodegenerative disorders and for identifying candidate genes for inherited ataxias.

    Funded by: NICHD NIH HHS: HD24064; NINDS NIH HHS: NS27699

    Cell 2006;125;4;801-14

  • Association between single-nucleotide polymorphisms in the SEC8L1 gene, which encodes a subunit of the exocyst complex, and rheumatoid arthritis in a Japanese population.

    Hamada D, Takata Y, Osabe D, Nomura K, Shinohara S, Egawa H, Nakano S, Shinomiya F, Scafe CR, Reeve VM, Miyamoto T, Moritani M, Kunika K, Inoue H, Yasui N and Itakura M

    Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.

    Objective: To identify rheumatoid arthritis (RA) susceptibility genes in a Japanese population by conducting a large-scale case-control association analysis and linkage disequilibrium (LD) mapping on chromosome 7q31-34, a candidate susceptibility locus identified in a preliminary genome-wide scan in 53 Japanese families, using single-nucleotide polymorphisms (SNPs).

    Methods: We prepared 728 dense, evenly spaced SNPs with a minor allele frequency >0.15 in each gene locus on chromosome 7q31-34. Using these SNPs, a 2-stage case-control analysis was performed on 760 RA patients (157 men and 603 women) and 806 non-RA controls (189 men and 617 women). Haplotypes and LD mapping results were assessed based on SNP genotypes in 380 controls.

    Results: Forty-eight SNPs showed allele associations (P < 0.05) in the first set of DNA samples (380 RA cases and 380 non-RA controls; first-stage analysis). For 4 of the SNPs in the SEC8L1 gene, the association was replicated (P < 0.05) in the second, independent set of DNA samples (an additional 380 RA cases and 380 non-RA controls; second-stage analysis). When data from the 2 groups were combined, the most significant allele association was observed with SNP 441, an intronic SNP of the SEC8L1 gene (P = 0.000059). The SEC8L1 SNPs with significant allele associations were all located in a single conserved LD block (block 4). Haplotype analysis revealed the disease-risk (P = 0.0015) and disease-protective (P = 0.0000062) haplotypes. Resequencing of coding exons within block 4 did not identify any nonsynonymous SNPs. Real-time quantitative polymerase chain reaction revealed that SEC8L1 was expressed ubiquitously in human tissues, including fibroblast-like synoviocytes from RA patients.

    Conclusion: Our locus-wide association and LD analyses identified intronic SNPs and haplotypes in the SEC8L1 gene that are strongly associated with RA. We propose that SEC8L1, which encodes a component of the exocyst complex, is a candidate susceptibility gene for RA in the Japanese population.

    Arthritis and rheumatism 2005;52;5;1371-80

  • Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.

    Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J and Stanton LW

    Geron Corporation, Menlo Park, California 94025, USA. rbrandenberger@geron.com

    Human embryonic stem (hES) cells hold promise for generating an unlimited supply of cells for replacement therapies. To characterize hES cells at the molecular level, we obtained 148,453 expressed sequence tags (ESTs) from undifferentiated hES cells and three differentiated derivative subpopulations. Over 32,000 different transcripts expressed in hES cells were identified, of which more than 16,000 do not match closely any gene in the UniGene public database. Queries to this EST database revealed 532 significantly upregulated and 140 significantly downregulated genes in undifferentiated hES cells. These data highlight changes in the transcriptional network that occur when hES cells differentiate. Among the differentially regulated genes are several components of signaling pathways and transcriptional regulators that likely play key roles in hES cell growth and differentiation. The genomic data presented here may facilitate the derivation of clinically useful cell types from hES cells.

    Nature biotechnology 2004;22;6;707-16

  • The exocyst complex in polarized exocytosis.

    Hsu SC, TerBush D, Abraham M and Guo W

    Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA.

    Exocytosis is an essential membrane traffic event mediating the secretion of intracellular protein contents such as hormones and neurotransmitters as well as the incorporation of membrane proteins and lipids to specific domains of the plasma membrane. As a fundamental cell biological process, exocytosis is crucial for cell growth, cell-cell communication, and cell polarity establishment. For most eukaryotic cells exocytosis is polarized. A multiprotein complex, named the exocyst, is required for polarized exocytosis from yeast to mammals. The exocyst consists of eight components: Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84. They are localized to sites of active exocytosis, where they mediate the targeting and tethering of post-Golgi secretory vesicles for subsequent membrane fusion. Here we review the progress made in the understanding of the exocyst and its role in polarized exocytosis.

    International review of cytology 2004;233;243-65

  • Ral GTPases regulate exocyst assembly through dual subunit interactions.

    Moskalenko S, Tong C, Rosse C, Mirey G, Formstecher E, Daviet L, Camonis J and White MA

    Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9039, USA.

    Ral GTPases have been implicated in the regulation of a variety of dynamic cellular processes including proliferation, oncogenic transformation, actin-cytoskeletal dynamics, endocytosis, and exocytosis. Recently the Sec6/8 complex, or exocyst, a multisubunit complex facilitating post-Golgi targeting of distinct subclasses of secretory vesicles, has been identified as a bona fide Ral effector complex. Ral GTPases regulate exocyst-dependent vesicle trafficking and are required for exocyst complex assembly. Sec5, a membrane-associated exocyst subunit, has been identified as a direct target of activated Ral; however, the mechanism by which Ral can modulate exocyst assembly is unknown. Here we report that an additional component of the exocyst, Exo84, is a direct target of activated Ral. We provide evidence that mammalian exocyst components are present as distinct subcomplexes on vesicles and the plasma membrane and that Ral GTPases regulate the assembly interface of a full octameric exocyst complex through interaction with Sec5 and Exo84.

    Funded by: NCI NIH HHS: CA71443

    The Journal of biological chemistry 2003;278;51;51743-8

  • ARF6 controls post-endocytic recycling through its downstream exocyst complex effector.

    Prigent M, Dubois T, Raposo G, Derrien V, Tenza D, Rossé C, Camonis J and Chavrier P

    Membrane and Cytoskeleton Dynamics Group, UMR144 Centre National de la Recherche Scientifique, Institut Curie, 26 rue d'Ulm, F-75248 Paris cedex 05, France.

    The small guanosine triphosphate (GTP)-binding protein ADP-ribosylation factor (ARF) 6 regulates membrane recycling to regions of plasma membrane remodeling via the endocytic pathway. Here, we show that GTP-bound ARF6 interacts with Sec10, a subunit of the exocyst complex involved in docking of vesicles with the plasma membrane. We found that Sec10 localization in the perinuclear region is not restricted to the trans-Golgi network, but extends to recycling endosomes. In addition, we report that depletion of Sec5 exocyst subunit or dominant inhibition of Sec10 affects the function and the morphology of the recycling pathway. Sec10 is found to redistribute to ruffling areas of the plasma membrane in cells expressing GTP-ARF6, whereas dominant inhibition of Sec10 interferes with ARF6-induced cell spreading. Our paper suggests that ARF6 specifies delivery and insertion of recycling membranes to regions of dynamic reorganization of the plasma membrane through interaction with the vesicle-tethering exocyst complex.

    The Journal of cell biology 2003;163;5;1111-21

  • The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin.

    Inoue M, Chang L, Hwang J, Chiang SH and Saltiel AR

    Life Sciences Institute, Departments of Internal Medicine and Physiology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.

    Insulin stimulates glucose transport by promoting exocytosis of the glucose transporter Glut4 (refs 1, 2). The dynamic processes involved in the trafficking of Glut4-containing vesicles, and in their targeting, docking and fusion at the plasma membrane, as well as the signalling processes that govern these events, are not well understood. We recently described tyrosine-phosphorylation events restricted to subdomains of the plasma membrane that result in activation of the G protein TC10 (refs 3, 4). Here we show that TC10 interacts with one of the components of the exocyst complex, Exo70. Exo70 translocates to the plasma membrane in response to insulin through the activation of TC10, where it assembles a multiprotein complex that includes Sec6 and Sec8. Overexpression of an Exo70 mutant blocked insulin-stimulated glucose uptake, but not the trafficking of Glut4 to the plasma membrane. However, this mutant did block the extracellular exposure of the Glut4 protein. So, the exocyst might have a crucial role in the targeting of the Glut4 vesicle to the plasma membrane, perhaps directing the vesicle to the precise site of fusion.

    Nature 2003;422;6932;629-33

  • Ral-GTPase influences the regulation of the readily releasable pool of synaptic vesicles.

    Polzin A, Shipitsin M, Goi T, Feig LA and Turner TJ

    Department of Biochemistry, Tufts University School of Medicine, Tufts-New England Medical Center, Boston, MA 02111, USA.

    The Ral proteins are members of the Ras superfamily of GTPases. Because they reside in synaptic vesicles, we used transgenic mice expressing a dominant inhibitory form of Ral to investigate the role of Ral in neurosecretion. Using a synaptosomal secretion assay, we found that while K(+)-evoked secretion of glutamate was normal, protein kinase C-mediated enhancement of glutamate secretion was suppressed in the mutant mice. Since protein kinase C effects on secretion have been shown to be due to enhancement of the size of the readily releasable pool of synaptic vesicles docked at the plasma membrane, we directly measured the refilling of this readily releasable pool of synaptic vesicles after Ca(2+)-triggered exocytosis. Refilling of the readily releasable pool was suppressed in synaptosomes from mice expressing dominant inhibitory Ral. Moreover, we found that protein kinase C and calcium-induced phosphorylation of proteins thought to influence synaptic vesicle function, such as MARCKS, synapsin, and SNAP-25, were all reduced in synaptosomes from these transgenic mice. Concomitant with these studies, we searched for new functions of Ral by detecting proteins that specifically bind to it in cells. Consistent with the phenotype of the transgenic mice described above, we found that active but not inactive RalA binds to the Sec6/8 (exocyst) complex, whose yeast counterpart is essential for targeting exocytic vesicles to specific docking sites on the plasma membrane. These findings demonstrate a role for Ral-GTPase signaling in the modulation of the readily releasable pool of synaptic vesicles and suggest the possible involvement of Ral-Sec6/8 (exocyst) binding in modulation of synaptic strength.

    Molecular and cellular biology 2002;22;6;1714-22

  • The brain exocyst complex interacts with RalA in a GTP-dependent manner: identification of a novel mammalian Sec3 gene and a second Sec15 gene.

    Brymora A, Valova VA, Larsen MR, Roufogalis BD and Robinson PJ

    Children's Medical Research Institute, 214 Hawkesbury Road, Westmead NSW 2145, Australia.

    Ral is a small GTPase involved in critical cellular signaling pathways. The two isoforms, RalA and RalB, are widely distributed in different tissues, with RalA being enriched in brain. The best characterized RalA signaling pathways involve RalBP1 and phospholipase D. To investigate RalA signaling in neuronal cells we searched for RalA-binding proteins in brain. We found at least eight proteins that bound RalA in a GTP-dependent manner. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) identified these as the components of the exocyst complex. The yeast exocyst is a regulator of polarized secretion, docking vesicles to regions of the plasma membrane involved in active exocytosis. We identified the human FLJ10893 protein as the mammalian homologue of the yeast exocyst protein Sec3p. The exocyst complex did not contain the previously identified exocyst component rSec15, but a new homologue of both yeast Sec15p and rSec15, called KIAA0919. Western blots confirmed that two rat exocyst proteins, rSec6 and rSec8, bound active RalA in nerve terminals, as did RalBP1. Phospholipase D bound RalA in a nucleotide-independent manner. This places the RalA signaling system in mammalian nerve terminals, where the exocyst may act as an effector for activated RalA in directing sites of exocytosis.

    The Journal of biological chemistry 2001;276;32;29792-7

  • Subunit composition, protein interactions, and structures of the mammalian brain sec6/8 complex and septin filaments.

    Hsu SC, Hazuka CD, Roth R, Foletti DL, Heuser J and Scheller RH

    Howard Hughes Medical Institute, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, California 94305, USA.

    Both the sec6/8 complex and septin filaments have been implicated in directing vesicles and proteins to sites of active membrane addition in yeast. The rat brain sec6/8 complex coimmunoprecipitates with a filament composed of four mammalian septins, suggesting an interaction between these complexes. One of the septins, CDC10, displays broad subcellular and tissue distributions and is found in postmitotic neurons as well as dividing cells. Electron microscopic studies showed that the purified rat brain septins form filaments of 8.25 nm in diameter; the lengths of the filaments are multiples of 25 nm. Glutaraldehyde-fixed rat brain sec6/8 complex adopts a conformation resembling the letter "T" or "Y". The sec6/8 and septin complexes likely play an important role in trafficking vesicles and organizing proteins at the plasma membrane of neurons.

    Neuron 1998;20;6;1111-22

  • Subunit structure of the mammalian exocyst complex.

    Kee Y, Yoo JS, Hazuka CD, Peterson KE, Hsu SC and Scheller RH

    Howard Hughes Medical Institute, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford CA 94305-5428, USA.

    The exocyst is a protein complex required for the late stages of secretion in yeast. Unlike the SNAREs (SNAP receptors), important secretory proteins that are broadly distributed on the target membrane, the exocyst is specifically located at sites of vesicle fusion. We have isolated cDNAs encoding the rexo70, rsec5, and rsec15 subunits of the mammalian complex. The amino acid sequences encoded by these genes are between 21% and 24% identical to their yeast homologs. All three genes are broadly expressed and multiple transcripts are observed for rexo70 and rsec15. Characterization of cDNAs encoding the 84-kDa subunit of the mammalian complex revealed a novel protein. mAbs were generated to the mammalian rsec6 subunit of the exocyst complex. rsec6 immunoreactivity is found in a punctate distribution at terminals of PC12 cell processes at or near sites of granule exocytosis.

    Proceedings of the National Academy of Sciences of the United States of America 1997;94;26;14438-43

  • Identification and characterization of homologues of the Exocyst component Sec10p.

    Guo W, Roth D, Gatti E, De Camilli P and Novick P

    Yale University School of Medicine, Department of Cell Biology, New Haven, CT 06510, USA.

    The SEC10 gene product is a member of the Exocyst complex essential for exocytosis in the budding yeast Saccharomyces cerevisiae. We report here the cloning and characterization of human Sec10p (hSec10p; GenBank accession number U85946). hSec10p is a 77-kDa protein with 23% amino acid identity to yeast Sec10p and 37% identity to a C. elegans protein found in the database. Northern and Western blot analyses indicate that hSec10 has a broad tissue distribution. Immunofluorescence staining of COS cells cotransfected with hSec10p and a mammalian Sec8p demonstrates that these two proteins have an identical distribution in the cell including a localization in the peripheral cytoplasm. These data suggest that hSec10p is a component of the mammalian counterpart of the yeast Exocyst complex essential for post-Golgi traffic.

    FEBS letters 1997;404;2-3;135-9

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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