Endoplasmic reticulum membrane protein complex

Last updated
Endoplasmic reticulum membrane protein complex
Identifiers
SymbolEMC
Membranome 637

The endoplasmic reticulum membrane protein complex (EMC) is a putative endoplasmic reticulum-resident membrane protein (co-)chaperone. [1] The EMC is evolutionarily conserved in eukaryotes (animals, plants, and fungi), and its initial appearance might reach back to the last eukaryotic common ancestor (LECA). [2] Many aspects of mEMC biology and molecular function remain to be studied.

Contents

Composition and structure

The EMC consists of up to 10 subunits (EMC1 - EMC4, MMGT1, EMC6 - EMC10), of which only two (EMC8/9) are homologous proteins. [3] [2] Seven out of ten (EMC1, EMC3, EMC4, MMMGT1, EMC6, EMC7, EMC10) subunts are predicted to contain at least one transmembrane domain (TMD), whereas EMC2, EMC8 and EMC9 do not contain any predicted transmembrane domains are herefore likely to interact with the rest of the EMC on the cytosolic face of the endoplasmic reticulum (ER). EMC proteins are thought to be present in the mature complex in a 1:1 stoichiometry. [4] [5]

Subunit primary structure

The majority of EMC proteins (EMC1/3/4/MMGT1/6/7/10) contain at least one predicted TMD. EMC1, EMC7 and EMC10 contain an N-terminal signal sequence.

EMC1

EMC1, also known as KIAA0090, contains a single TMD (aa 959-979) and Pyrroloquinoline quinone (PQQ)-like repeats (aa 21-252), which could form a β-propeller domain. [6] [7] The TMD is part of a domain a larger domain (DUF1620). [8] [7] The functions of the PQQ and DUF1620 domains in EMC1 remain to be determined.

EMC2

EMC2 (TTC35) harbours three tetratricopeptide repeats (TPR1/2/3). TPRs have been shown to mediate protein-protein interactions and can be found in a large variety of proteins of diverse function. [9] [10] [11] The function of TPRs in EMC2 is unknown.

EMC8 and EMC9

EMC8 and EMC9 show marked sequence identity (44.72%) on the amino acid level. Both proteins are members of the UPF0172 family, a member of which (e.g. TLA1) are involved in regulating the antenna size of chlorophyll-a. [12] [13] [14]

Posttranslational modifications

Several subunits of the mammalian EMC (mEMC) are posttranslationally modified. EMC1 contains three predicted N-glycosylation sites at positions 370, 818, and 913. [6] EMC10 features a predicted N-glycosylation consensus motif at position 182.

Evolutionary conservation

EMC proteins are evolutionarily conserved in eukaryotes. [2] No homologues are reported in prokaryotes. Therefore, the EMC has been suggested to have its evolutionary roots in the last eukaryote common ancestor (LECA). [2]

Function

Protein folding and degradation at the ER

The EMC was first identified in a genetic screen in yeast for factors involved in protein folding in the ER. [1] Accordingly, deletion of individual EMC subunits correlates with the induction of an ER stress response in various model organisms. [1] [15] [16] However, it is worth noting that in human osteosarcoma cells (U2OS cells), deletion of EMC6 does not appear to cause ER stress. [17] [18] When overexpressed, several subunits of the mammalian EMC orthologue (mEMC) have been found to physically interact with ERAD components (UBAC2, DER1, DER2) [3] Genetic screens in yeast have shown EMC subunits to be enriched in alongside ERAD genes. [19] [20] Taken together, these findings imply a role of the mEMC in protein homeostasis.

Chaperone

Maturation of polytopic membrane proteins

Several lines of evidence implicate the EMC in promoting the maturation of polytopic membrane proteins. The EMC is necessary to correctly and efficiently insert the first transmembrane domain (also called the signal anchor) of G-protein coupled receptors (GPCRs) such as the beta-adrenergic receptor. [21] Determining features of transmembrane domains that favour EMC involvement seem to be moderate hydrophobicity and ambiguous distribution of TMD flanking charges.

The substrate spectrum of the EMC appears to extend beyond GPCRs. Unifying properties of putative EMC clients are the presence of unusually hydrophilic transmembrane domains containing charged residues. [22] However, mechanistic detail of how the EMC assists in orienting and inserting such problematic transmembrane domains is lacking. In many cases, evidence implicating the EMC in the biogenesis of a certain protein consists of co-depletion when individual subunts of the EMC are disrupted.

A number of putative EMC clients are listed below, but the manner in which the EMC engages them and whether they directly or indirectly depend on the EMC merits further investigation:

Loss of EMC function destabilises the enzyme sterol-O-acyltransferase 1 (SOAT1) and, in conjunction with overlooking the biogenesis of squalene synthase (SQS), helps to maintain cellular cholesterol homeostasis. [23] SOAT1 is an obligatory enzyme for cellular cholesterol storage and detoxification. For SQS, an enzyme controlling the committing step in cholesterol biosynthesis, the EMC has been shown to be sufficient for its integration into liposomes in vitro. [24]

Depletion of EMC6 and additional EMC proteins reduces the cell surface expression of the nicotinic Acetylcholine receptors in C. elegans. [15]

Knockdown of EMC2 has been observed to correlate with decreased CFTRΔF508 levels. [25] EMC2 contains three tetratricopeptide repeat domains (TRPs). TRPs have been shown to mediate protein-protein interaction and can be found in co-chaperones of Hsp90. Therefore, a role of EMC2 in mediating interactions with cytosolic chaperones is conceivable, but remains to be demonstrated.

Loss of EMC subunits in D. melanogaster correlates with strongly reduced cell surface expression of rhodopsin-1 (Rh1), an important polytopic light receptor in the plasma membrane. [16]

In yeast, the EMC has been implicated in maturation or trafficking defects of the polytopic model substrate Mrh1p-GFP. [26]

Recently, structural and functional studies have identified a holdase function for the EMC in the assembly and maturation of the voltage gated calcium channel CaV1.2. [27]

Insertion proteins into the ER

The EMC was shown to be involved in a pathway mediating the membrane integration of tail-anchored proteins containing an unusually hydrophilic or amphiphatic transmembrane domains. [24] This pathway appears to operate in parallel to the conventional Get/Trc40 targeting pathway.

Other suggested functions

Mitochondrial tethering

In S. cerevisiae , the EMC has been reported by Lahiri and colleagues to constitute a tethering complex between the ER and mitochondria. [28] Close apposition of both organelles is a prerequisite for phosphatidylcholine (PS) biosynthesis in which phosphatidylserine (PS) is imported from the ER into mitochondria, and this was previously proposed as evidence for a membrane tether between these two organelles by Jean Vance. [29] [30] Disruption of the EMC by genetic deletion of multiple of its subunits was shown to reduce ER-mitochondrial tethering and to impair transfer of phosphatidylserine (PS) from the ER. [28]

Autophagosome formation

EMC6 interacts with the small GTPase RAB5A and Beclin-1, regulators of autophagosome formation. [17] [18] This observation suggests that the mEMC, and not just EMC6, might be involved in regulating Rab5A and BECLIN-1. However, the molecular mechanism underlying the proposed modulation of autophagosome formation remains to be established.

Involvement in disease

The mEMC has repeatedly been implicated in a range of pathologies including susceptibility of cells to viral infection, cancer, and a congenital syndrome of severe physical and mental disability. None of these pathologies seem to be related by disruption of a single molecular pathway that might be regulated by the mEMC. Consequently, the involvement of the mEMC in these pathologies has only limited use for defining the primary function of this complex.

As a host factor in viral infections

Large-scale genetic screens imply several mEMC subunits in modulating the pathogenicity of flaviviruses such as West Nile virus (WNV), Zika virus (ZV), Dengue fever virus (DFV), and yellow fever virus (YFV). [20] [31] In particular, loss of several mEMC subunits (e.g. EMC2, EMC3) lead to inhibition of WNV-induced cell death. however, WNV was still able to infect and proliferate in cells lacking EMC subunits. [20] The authors made a similar observation of the role of the mEMC in the cell-killing capacity of Saint Louis Encephalitis Virus. The underlying cause for the resistance of EMC2/3-deficient cells to WNV-induced cytotoxicity remains elusive.

Cancer

Dysregulation of individual mEMC subunits correlates with the severity of certain types of cancer. Expression of h HSS1, a secreted splice variant of EMC10 (HSM1), reduces the proliferation and migration of glioma cell lines. [32]

Overexpression of EMC6 has been found to reduce cell proliferation of glioblastoma cells in vitro and in vivo, whereas its RNAi-mediated depletion has the opposite effect. [18] This indicates that the mEMC assumes (an) important function(s) in cancerous cells to establish a malignant tumour.

Pathologies

Mutations in the EMC1 gene have been associated with retinal dystrophy and a severe systemic disease phenotype involving developmental delay, cerebellar atrophy, scoliosis and hypotonia. [33]

Similarly, a homozygous missense mutation (c.430G>A, p.Ala144Thr) within the EMC1 gene has been correlated with the development of retinal dystrophy. [34]

Even though a set of disease-causing mutations in EMC1 has been mapped, their effect on EMC1 function and structure remain to be studied.

Related Research Articles

<span class="mw-page-title-main">Endoplasmic reticulum</span> Cell organelle that synthesizes, folds and processes proteins

The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum (RER), and smooth endoplasmic reticulum (SER). The endoplasmic reticulum is found in most eukaryotic cells and forms an interconnected network of flattened, membrane-enclosed sacs known as cisternae, and tubular structures in the SER. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum is not found in red blood cells, or spermatozoa.

<span class="mw-page-title-main">COPI</span> Protein complex

COPI is a coatomer, a protein complex that coats vesicles transporting proteins from the cis end of the Golgi complex back to the rough endoplasmic reticulum (ER), where they were originally synthesized, and between Golgi compartments. This type of transport is retrograde transport, in contrast to the anterograde transport associated with the COPII protein. The name "COPI" refers to the specific coat protein complex that initiates the budding process on the cis-Golgi membrane. The coat consists of large protein subcomplexes that are made of seven different protein subunits, namely α, β, β', γ, δ, ε and ζ.

<span class="mw-page-title-main">Calnexin</span> Mammalian protein found in Homo sapiens

Calnexin (CNX) is a 67kDa integral protein of the endoplasmic reticulum (ER). It consists of a large N-terminal calcium-binding lumenal domain, a single transmembrane helix and a short, acidic cytoplasmic tail. In humans, calnexin is encoded by the gene CANX.

<span class="mw-page-title-main">Signal recognition particle receptor</span>

Signal recognition particle (SRP) receptor, also called the docking protein, is a dimer composed of 2 different subunits that are associated exclusively with the rough ER in mammalian cells. Its main function is to identify the SRP units. SRP is a molecule that helps the ribosome-mRNA-polypeptide complexes to settle down on the membrane of the endoplasmic reticulum.

<span class="mw-page-title-main">Endoplasmic-reticulum-associated protein degradation</span>

Endoplasmic-reticulum-associated protein degradation (ERAD) designates a cellular pathway which targets misfolded proteins of the endoplasmic reticulum for ubiquitination and subsequent degradation by a protein-degrading complex, called the proteasome.

<span class="mw-page-title-main">Ribophorin</span>

Ribophorins are dome shaped transmembrane glycoproteins which are located in the membrane of the rough endoplasmic reticulum, but are absent in the membrane of the smooth endoplasmic reticulum. There are two types of ribophorines: ribophorin I and II. These act in the protein complex oligosaccharyltransferase (OST) as two different subunits of the named complex. Ribophorin I and II are only present in eukaryote cells.

<span class="mw-page-title-main">ATF6</span> Protein-coding gene in the species Homo sapiens

Activating transcription factor 6, also known as ATF6, is a protein that, in humans, is encoded by the ATF6 gene and is involved in the unfolded protein response.

<span class="mw-page-title-main">Valosin-containing protein</span> Protein-coding gene in the species Homo sapiens

Valosin-containing protein (VCP) or transitional endoplasmic reticulum ATPase also known as p97 in mammals and CDC48 in S. cerevisiae, is an enzyme that in humans is encoded by the VCP gene. The TER ATPase is an ATPase enzyme present in all eukaryotes and archaebacteria. Its main function is to segregate protein molecules from large cellular structures such as protein assemblies, organelle membranes and chromatin, and thus facilitate the degradation of released polypeptides by the multi-subunit protease proteasome.

<span class="mw-page-title-main">Binding immunoglobulin protein</span> Protein-coding gene in the species Homo sapiens

Binding immunoglobulin protein (BiPS) also known as 78 kDa glucose-regulated protein (GRP-78) or heat shock 70 kDa protein 5 (HSPA5) is a protein that in humans is encoded by the HSPA5 gene.

<span class="mw-page-title-main">SOAT1</span> Protein-coding gene in the species Homo sapiens

Sterol O-acyltransferase 1, also known as SOAT1, is an enzyme that in humans is encoded by the SOAT1 gene.

<span class="mw-page-title-main">HERPUD1</span> Protein-coding gene in the species Homo sapiens

Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein is a protein that in humans is encoded by the HERPUD1 gene.

<span class="mw-page-title-main">SEC61B</span> Mammalian protein found in Homo sapiens

Protein transport protein Sec61 subunit beta is a protein that in humans is encoded by the SEC61B gene.

<span class="mw-page-title-main">NFE2L1</span> Protein-coding gene in the species Homo sapiens

Nuclear factor erythroid 2-related factor 1 (Nrf1) also known as nuclear factor erythroid-2-like 1 (NFE2L1) is a protein that in humans is encoded by the NFE2L1 gene. Since NFE2L1 is referred to as Nrf1, it is often confused with nuclear respiratory factor 1 (Nrf1).

<span class="mw-page-title-main">Derlin-1</span> Protein involved in retrotranslocation of specific misfolded proteins and in ER stress

Derlin-1 also known as degradation in endoplasmic reticulum protein 1 is a membrane protein that in humans is encoded by the DERL1 gene. Derlin-1 is located in the membrane of the endoplasmic reticulum (ER) and is involved in retrotranslocation of specific misfolded proteins and in ER stress. Derlin-1 is widely expressed in thyroid, fat, bone marrow and many other tissues. The protein belongs to the Derlin-family proteins consisting of derlin-1, derlin-2 and derlin-3 that are components in the endoplasmic reticulum-associated protein degradation (ERAD) pathway. The derlins mediate degradation of misfolded lumenal proteins within ER, and are named ‘der’ for their ‘Degradation in the ER’. Derlin-1 is a mammalian homologue of the yeast DER1 protein, a protein involved in the yeast ERAD pathway. Moreover, derlin-1 is a member of the rhomboid-like clan of polytopic membrane proteins.

<span class="mw-page-title-main">Sec61 alpha 1</span>

Protein transport protein Sec61 subunit alpha isoform 1 is a protein that in humans is encoded by the SEC61A1 gene.

<span class="mw-page-title-main">Hepatitis C virus envelope glycoprotein E1</span>

E1 is one of two subunits of the envelope glycoprotein found in the hepatitis C virus. The other subunit is E2. This protein is a type 1 transmembrane protein with a highly glycosylated N-terminal ectodomain and a C-terminal hydrophobic anchor. After being synthesized the E1 glycoproteins associates with the E2 glycoprotein as a noncovalent heterodimer.

<span class="mw-page-title-main">DPM2</span> Protein-coding gene in the species Homo sapiens

Dolichol phosphate-mannose biosynthesis regulatory protein is a protein that in humans is encoded by the DPM2 gene.

<span class="mw-page-title-main">Gram domain containing 1a</span> Protein that is encoded by the GRAMD1A gene

GRAM domain containing 1A also known as Aster-A is a protein that is encoded by the GRAMD1A gene. It contains a transmembrane region, a GRAM domain and a VASt domain that can bind cholesterol. GRAMD1A has four paralogs: GRAMD1B and GRAMD1C and two without VASt domains, GRAMD2A and GRAMD2B. These proteins are mammalian representatives of the yeast lipid transfer proteins anchored at a membrane contact site (LAM) family.

<span class="mw-page-title-main">CREB3L1</span> Protein-coding gene in the species Homo sapiens

CAMP responsive element binding protein 3 like 1 is a responsive element binding protein that in humans is encoded by the CREB3L1 gene.

<span class="mw-page-title-main">GRAMD1C</span> Protein that is encoded by the GRAMD1C gene

GRAM domain containing 1C also known as Aster-C is a cholesterol transport protein that is encoded by the GRAMD1C gene. It contains a transmembrane region, a GRAM domain and a VASt domain. It is anchored to the endoplasmic reticulum through its transmembrane domain.

References

  1. 1 2 3 Jonikas MC, Collins SR, Denic V, Oh E, Quan EM, Schmid V, Weibezahn J, Schwappach B, Walter P, Weissman JS, Schuldiner M (March 2009). "Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum". Science. 323 (5922): 1693–7. Bibcode:2009Sci...323.1693J. doi:10.1126/science.1167983. PMC   2877488 . PMID   19325107.
  2. 1 2 3 4 Wideman JG (25 August 2015). "The ubiquitous and ancient ER membrane protein complex (EMC): tether or not?". F1000Research. 4: 624. doi: 10.12688/f1000research.6944.2 . PMC   4602282 . PMID   26512320.
  3. 1 2 Christianson JC, Olzmann JA, Shaler TA, Sowa ME, Bennett EJ, Richter CM, Tyler RE, Greenblatt EJ, Harper JW, Kopito RR (November 2011). "Defining human ERAD networks through an integrative mapping strategy". Nature Cell Biology. 14 (1): 93–105. doi:10.1038/ncb2383. PMC   3250479 . PMID   22119785.
  4. Li GW, Burkhardt D, Gross C, Weissman JS (April 2014). "Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources". Cell. 157 (3): 624–35. doi:10.1016/j.cell.2014.02.033. PMC   4006352 . PMID   24766808.
  5. Hein MY, Hubner NC, Poser I, Cox J, Nagaraj N, Toyoda Y, Gak IA, Weisswange I, Mansfeld J, Buchholz F, Hyman AA, Mann M (October 2015). "A human interactome in three quantitative dimensions organized by stoichiometries and abundances". Cell. 163 (3): 712–23. doi: 10.1016/j.cell.2015.09.053 . PMID   26496610.
  6. 1 2 Ninagawa S, Okada T, Sumitomo Y, Horimoto S, Sugimoto T, Ishikawa T, Takeda S, Yamamoto T, Suzuki T, Kamiya Y, Kato K, Mori K (November 2015). "Forcible destruction of severely misfolded mammalian glycoproteins by the non-glycoprotein ERAD pathway". The Journal of Cell Biology. 211 (4): 775–84. doi:10.1083/jcb.201504109. PMC   4657166 . PMID   26572623.
  7. 1 2 Kopec KO, Lupas AN (15 October 2013). "β-Propeller blades as ancestral peptides in protein evolution". PLOS ONE. 8 (10): e77074. Bibcode:2013PLoSO...877074K. doi: 10.1371/journal.pone.0077074 . PMC   3797127 . PMID   24143202.
  8. Ghosh M, Anthony C, Harlos K, Goodwin MG, Blake C (February 1995). "The refined structure of the quinoprotein methanol dehydrogenase from Methylobacterium extorquens at 1.94 A". Structure. 3 (2): 177–87. doi: 10.1016/s0969-2126(01)00148-4 . PMID   7735834.
  9. Goebl M, Yanagida M (May 1991). "The TPR snap helix: a novel protein repeat motif from mitosis to transcription". Trends in Biochemical Sciences. 16 (5): 173–7. doi:10.1016/0968-0004(91)90070-c. PMID   1882418.
  10. Lamb JR, Tugendreich S, Hieter P (July 1995). "Tetratrico peptide repeat interactions: to TPR or not to TPR?". Trends in Biochemical Sciences. 20 (7): 257–9. doi: 10.1016/s0968-0004(00)89037-4 . PMID   7667876.
  11. Das AK, Cohen PW, Barford D (March 1998). "The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions". The EMBO Journal. 17 (5): 1192–9. doi:10.1093/emboj/17.5.1192. PMC   1170467 . PMID   9482716.
  12. Mitra M, Melis A (February 2010). "Genetic and biochemical analysis of the TLA1 gene in Chlamydomonas reinhardtii". Planta. 231 (3): 729–40. doi:10.1007/s00425-009-1083-3. PMC   2806527 . PMID   20012986.
  13. Mitra M, Kirst H, Dewez D, Melis A (December 2012). "Modulation of the light-harvesting chlorophyll antenna size in Chlamydomonas reinhardtii by TLA1 gene over-expression and RNA interference". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 367 (1608): 3430–43. doi:10.1098/rstb.2012.0229. PMC   3497077 . PMID   23148270.
  14. Dunkley TP, Hester S, Shadforth IP, Runions J, Weimar T, Hanton SL, Griffin JL, Bessant C, Brandizzi F, Hawes C, Watson RB, Dupree P, Lilley KS (April 2006). "Mapping the Arabidopsis organelle proteome". Proceedings of the National Academy of Sciences of the United States of America. 103 (17): 6518–23. Bibcode:2006PNAS..103.6518D. doi: 10.1073/pnas.0506958103 . PMC   1458916 . PMID   16618929.
  15. 1 2 Richard M, Boulin T, Robert VJ, Richmond JE, Bessereau JL (March 2013). "Biosynthesis of ionotropic acetylcholine receptors requires the evolutionarily conserved ER membrane complex". Proceedings of the National Academy of Sciences of the United States of America. 110 (11): E1055–63. doi: 10.1073/pnas.1216154110 . PMC   3600456 . PMID   23431131.
  16. 1 2 Satoh T, Ohba A, Liu Z, Inagaki T, Satoh AK (February 2015). "dPob/EMC is essential for biosynthesis of rhodopsin and other multi-pass membrane proteins in Drosophila photoreceptors". eLife. 4. doi: 10.7554/eLife.06306 . PMC   4341237 . PMID   25715730.
  17. 1 2 Li Y, Zhao Y, Hu J, Xiao J, Qu L, Wang Z, Ma D, Chen Y (February 2013). "A novel ER-localized transmembrane protein, EMC6, interacts with RAB5A and regulates cell autophagy". Autophagy. 9 (2): 150–63. doi:10.4161/auto.22742. PMC   3552880 . PMID   23182941.
  18. 1 2 3 Shen X, Kan S, Hu J, Li M, Lu G, Zhang M, Zhang S, Hou Y, Chen Y, Bai Y (January 2016). "EMC6/TMEM93 suppresses glioblastoma proliferation by modulating autophagy". Cell Death & Disease. 7 (1): e2043. doi:10.1038/cddis.2015.408. PMC   4816184 . PMID   26775697.
  19. Raj S, Krishnan K, Askew DS, Helynck O, Suzanne P, Lesnard A, Rault S, Zeidler U, d'Enfert C, Latgé JP, Munier-Lehmann H, Saveanu C (December 2015). "The Toxicity of a Novel Antifungal Compound Is Modulated by Endoplasmic Reticulum-Associated Protein Degradation Components". Antimicrobial Agents and Chemotherapy. 60 (3): 1438–49. doi:10.1128/aac.02239-15. PMC   4775935 . PMID   26666917.
  20. 1 2 3 Ma H, Dang Y, Wu Y, Jia G, Anaya E, Zhang J, Abraham S, Choi JG, Shi G, Qi L, Manjunath N, Wu H (July 2015). "A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death". Cell Reports. 12 (4): 673–83. doi:10.1016/j.celrep.2015.06.049. PMC   4559080 . PMID   26190106.
  21. Chitwood, Patrick J.; Juszkiewicz, Szymon; Guna, Alina; Shao, Sichen; Hegde, Ramanujan S. (2018-11-29). "EMC Is Required to Initiate Accurate Membrane Protein Topogenesis". Cell. 175 (6): 1507–1519.e16. doi:10.1016/j.cell.2018.10.009. ISSN   1097-4172. PMC   6269167 . PMID   30415835.
  22. Shurtleff, Matthew J.; Itzhak, Daniel N.; Hussmann, Jeffrey A.; Schirle Oakdale, Nicole T.; Costa, Elizabeth A.; Jonikas, Martin; Weibezahn, Jimena; Popova, Katerina D.; Jan, Calvin H. (May 29, 2018). "The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins". eLife. 7. doi: 10.7554/eLife.37018 . ISSN   2050-084X. PMC   5995541 . PMID   29809151.
  23. Volkmar, Norbert; Thezenas, Maria-Laetitia; Louie, Sharon M.; Juszkiewicz, Szymon; Nomura, Daniel K.; Hegde, Ramanujan S.; Kessler, Benedikt M.; Christianson, John C. (2019-01-16). "The ER membrane protein complex promotes biogenesis of sterol-related enzymes maintaining cholesterol homeostasis". Journal of Cell Science. 132 (2): jcs223453. doi:10.1242/jcs.223453. ISSN   1477-9137. PMC   6362398 . PMID   30578317.
  24. 1 2 Guna A, Volkmar N, Christianson JC, Hegde RS (January 2018). "The ER membrane protein complex is a transmembrane domain insertase". Science. 359 (6374): 470–473. Bibcode:2018Sci...359..470G. doi:10.1126/science.aao3099. PMC   5788257 . PMID   29242231.
  25. Louie RJ, Guo J, Rodgers JW, White R, Shah N, Pagant S, Kim P, Livstone M, Dolinski K, McKinney BA, Hong J, Sorscher EJ, Bryan J, Miller EA, Hartman JL (December 2012). "A yeast phenomic model for the gene interaction network modulating CFTR-ΔF508 protein biogenesis". Genome Medicine. 4 (12): 103. doi: 10.1186/gm404 . PMC   3906889 . PMID   23270647.
  26. Bircham PW, Maass DR, Roberts CA, Kiew PY, Low YS, Yegambaram M, Matthews J, Jack CA, Atkinson PH (September 2011). "Secretory pathway genes assessed by high-throughput microscopy and synthetic genetic array analysis". Molecular BioSystems. 7 (9): 2589–98. doi:10.1039/c1mb05175j. PMID   21731954.
  27. Chen, Zhou; Mondal, Abhisek; Abderemane-Ali, Fayal; Jang, Seil; Niranjan, Sangeeta; Montaño, José L.; Zaro, Balyn W.; Minor, Daniel L. (July 2023). "EMC chaperone–CaV structure reveals an ion channel assembly intermediate". Nature. 619 (7969): 410–419. Bibcode:2023Natur.619..410C. doi:10.1038/s41586-023-06175-5. PMID   37196677. S2CID   258763550.
  28. 1 2 Lahiri S, Chao JT, Tavassoli S, Wong AK, Choudhary V, Young BP, Loewen CJ, Prinz WA (October 2014). "A conserved endoplasmic reticulum membrane protein complex (EMC) facilitates phospholipid transfer from the ER to mitochondria". PLOS Biology. 12 (10): e1001969. doi: 10.1371/journal.pbio.1001969 . PMC   4196738 . PMID   25313861.
  29. Vance JE (May 1990). "Phospholipid synthesis in a membrane fraction associated with mitochondria". The Journal of Biological Chemistry. 265 (13): 7248–56. doi: 10.1016/S0021-9258(19)39106-9 . PMID   2332429.
  30. Vance, J. E. (1991-01-05). "Newly made phosphatidylserine and phosphatidylethanolamine are preferentially translocated between rat liver mitochondria and endoplasmic reticulum". The Journal of Biological Chemistry. 266 (1): 89–97. doi: 10.1016/S0021-9258(18)52406-6 . ISSN   0021-9258. PMID   1898727.
  31. Savidis G, McDougall WM, Meraner P, Perreira JM, Portmann JM, Trincucci G, John SP, Aker AM, Renzette N, Robbins DR, Guo Z, Green S, Kowalik TF, Brass AL (June 2016). "Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics". Cell Reports. 16 (1): 232–246. doi: 10.1016/j.celrep.2016.06.028 . PMID   27342126.
  32. Junes-Gill KS, Gallaher TK, Gluzman-Poltorak Z, Miller JD, Wheeler CJ, Fan X, Basile LA (April 2011). "hHSS1: a novel secreted factor and suppressor of glioma growth located at chromosome 19q13.33". Journal of Neuro-Oncology. 102 (2): 197–211. doi:10.1007/s11060-010-0314-6. PMC   3052511 . PMID   20680400.
  33. Harel T, Yesil G, Bayram Y, Coban-Akdemir Z, Charng WL, Karaca E, Al Asmari A, Eldomery MK, Hunter JV, Jhangiani SN, Rosenfeld JA, Pehlivan D, El-Hattab AW, Saleh MA, LeDuc CA, Muzny D, Boerwinkle E, Gibbs RA, Chung WK, Yang Y, Belmont JW, Lupski JR (March 2016). "Monoallelic and Biallelic Variants in EMC1 Identified in Individuals with Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy". American Journal of Human Genetics. 98 (3): 562–570. doi:10.1016/j.ajhg.2016.01.011. PMC   4800043 . PMID   26942288.
  34. Abu-Safieh L, Alrashed M, Anazi S, Alkuraya H, Khan AO, Al-Owain M, Al-Zahrani J, Al-Abdi L, Hashem M, Al-Tarimi S, Sebai MA, Shamia A, Ray-Zack MD, Nassan M, Al-Hassnan ZN, Rahbeeni Z, Waheeb S, Alkharashi A, Abboud E, Al-Hazzaa SA, Alkuraya FS (February 2013). "Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes". Genome Research. 23 (2): 236–47. doi:10.1101/gr.144105.112. PMC   3561865 . PMID   23105016.