The DOI matches its Crossref record; 21 of the 22 references it cites were found in a registry or an index.
TRAM, LAG1 and CLN8: members of a novel family of lipid-sensing domains?
Abstract
A family of membrane-associated proteins related to yeast Lag1p and mammalian TRAM has been identified. The family includes the protein product of CLN8, a gene mutated in progressive epilepsy with mental retardation. Mouse CLN8 is also mutated in the mnd/mnd mouse, a model for neuronal ceroid lipofuscinoses. The identification of these homologues has potential implications for our understanding of ceramide synthesis, lipid regulation and protein translocation in the endoplasmic reticulum.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“There is a cysteine in an extension following the predicted prodomain barrel; taken together, these data are consistent with experimental data suggesting that the ADAM prodomain inhibits metalloprotease activity using a cysteine switch (26).”
From Accurate prediction of protein structures and interactions using a 3-track network (2021) · cites this paper as [26]
Citations
Cites
A comprehensive two-hybrid analysis to explore the yeast protein interactome
Ito, T., Chiba, T., Ozawa, R., Yoshida, M., Hattori, M., & Sakaki, Y. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061034498 · Cited by 3,566
Schäffer, A. A. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.14.2994 · Cited by 1,375
Shimano, H. (2001) · Progress in Lipid Research · doi:10.1016/s0163-7827(01)00010-8 · Cited by 763
Rost, B., Fariselli, P., & Casadio, R. (1996) · Protein Science · doi:10.1002/pro.5560050824 · Cited by 608
TRAPP, a highly conserved novel complex on the cis‐Golgi that mediates vesicle docking and fusion
Sacher, M., Jiang, Y., Barrowman, J., Scarpa, A., Burston, J., Zhang, L., Schieltz, D., Yates, J. R., Abeliovich, H., & Ferro-Novick, S. (1998) · EMBO Journal · doi:10.1093/emboj/17.9.2494 · Cited by 326
Ranta, S., Zhang, Y., Ross, B., Lonka, L., Takkunen, E., Messer, A. C., Sharp, J. D., Wheeler, R. B., Kusumi, K., Mole, S., et al. (1999) · Nature Genetics · doi:10.1038/13868 · Cited by 319
The sterol-sensing domain: multiple families, a unique role?
Kuwabara, P. E., & Labouesse, M. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(02)02640-9 · Cited by 285
Venkataraman, K., Riebeling, C., Bodennec, J., Riezman, H., Allegood, J. C., Sullards, M. C., Merrill, A. H., & Futerman, A. H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205211200 · Cited by 282
C26‐CoA‐dependent ceramide synthesis of Saccharomyces cerevisiae is operated by Lag1p and Lac1p
Guillas, I., Kirchman, P. A., Chuard, R., Pfefferli, M., Jiang, J. C., Jazwinski, S. M., & Conzelmann, A. (2001) · The EMBO Journal · doi:10.1093/emboj/20.11.2655 · Cited by 277
Schorling, S., Vallée, B., Barz, W. P., Riezman, H., & Oesterhelt, D. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.11.3417 · Cited by 276
Cited by
Sorted by citations
Accurate prediction of protein structures and interactions using a 3-track network
Baek, M., DiMaio, F., Anishchenko, I., Dauparas, J., Ovchinnikov, S., Lee, G. R., Wang, J., Cong, Q., Kinch, L. N., Schaeffer, R. D., et al. (2021) · doi:10.1101/2021.06.14.448402 · Cited by 5,549
“The RoseTTAFold CERS1 model for residues 98 to 304 (Pfam TLC domain) (26) includes six TMH that traverse the membrane in an up and down arrangement (Fig.”
Levy, M., & Futerman, A. H. (2010) · IUBMB Life · doi:10.1002/iub.319 · Cited by 632
“Subsequent bioinformatics analyses (13, 17, 18) revealed additional mammalian Lag homologs, originally characterized as translocating chain-associating membrane protein homologs (TRH) (8, 10), with the ceramides synthesized”
BackgroundCeramide synthases at the centre of sphingolipid metabolism and biology
Mullen, T. D., Hannun, Y. A., & Obeid, L. M. (2012) · Biochemical Journal · doi:10.1042/bj20111626 · Cited by 541
“CLN proteins are involved in the human neurodegenerative syndromes called CLNs [14].”
When Do Lasses (Longevity Assurance Genes) Become CerS (Ceramide Synthases)?
Pewzner-Jung, Y., Ben-Dor, S., & Futerman, A. H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.r600010200 · Cited by 435
Mammalian Lass6 and its related family members regulate synthesis of specific ceramides
Mizutani, Y., Kihara, A., & Igarashi, Y. (2005) · Biochemical Journal · doi:10.1042/bj20050291 · Cited by 376
Neuronal ceroid lipofuscinoses
Jalanko, A., & Braulke, T. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.11.004 · Cited by 341
“to have roles in biosynthesis, metabolism, transport, and sensing of lipids [174,175].”
BackgroundKousi, M., Lehesjoki, A., & Mole, S. (2011) · Human Mutation · doi:10.1002/humu.21624 · Cited by 330
“The TLC domain in CLN8 is composed of the residues p.62-262 [Winter and Ponting, 2002].”
BackgroundThe ins and outs of sphingolipid synthesis
Futerman, A. H., & Riezman, H. (2005) · Trends in Cell Biology · doi:10.1016/j.tcb.2005.04.006 · Cited by 338
Mole, S., Williams, R. E., & Goebel, H. H. (2005) · Neurogenetics · doi:10.1007/s10048-005-0218-3 · Cited by 307
“in CLN8 that cause vLINCL are located in a region of the CLN8 protein homologous to the TLC family of proteins, suggesting that mutations at these residues affect the TLC-specific function, whereas R24G that underlies Northern epilepsy is located prior to the TLC region of homology [166] in a region of the protein wit…”
BackgroundRiebeling, C., Allegood, J. C., Wang, E. L., Merrill, A. H., & Futerman, A. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307104200 · Cited by 292
Markham, J. E., Molino, D., Gissot, L., Bellec, Y., Hématy, K., Marion, J., Belcram, K., Palauqui, J., Satiat‐Jeunemaître, B., & Faure, J. (2011) · The Plant Cell · doi:10.1105/tpc.110.080473 · Cited by 227
The Neuronal Ceroid-Lipofuscinoses (Batten Disease)
Mole, S., & Haltia, M. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-410529-4.00070-x · Cited by 219
The Role and Metabolism of Sulfatide in the Nervous System
Eckhardt, M. (2008) · Molecular Neurobiology · doi:10.1007/s12035-008-8022-3 · Cited by 193
“Members of this protein family include ceramide synthases and membrane proteins involved in protein translocation at the endoplasmic reticulum [ 112 ].”
BackgroundHorizontal gene transfer of an entire metabolic pathway between a eukaryotic alga and its DNA virusPreprint
Monier, A., Pagarete, A., de Vargas, C., Allen, M. J., Read, B. A., Claverie, J., & Ogata, H. (2009) · Genome Research · doi:10.1101/gr.091686.109 · Cited by 183
Cell biology of the NCL proteins: What they do and don't do
Cárcel‐Trullols, J., Kovács, A., & Pearce, D. A. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.04.027 · Cited by 183
Ceramide Synthases: Roles in Cell Physiology and Signaling
Stiban, J., Tidhar, R., & Futerman, A. H. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-6741-1_4 · Cited by 175
Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants
van Hall, T., Wolpert, E. Z., van Veelen, P. A., Laban, S., van der Veer, M., Roseboom, M., Bres-Vloemans, S. A., Grufman, P., de Ru, A., Meiring, H. D., et al. (2006) · Nature Medicine · doi:10.1038/nm1381 · Cited by 160
Accurate prediction of protein structures and interactions using a three-track neural network
Baek, M., DiMaio, F., Anishchenko, I. V., Dauparas, J., Ovchinnikov, S., Lee, G. R., Wang, J., Cong, Q., Kinch, L. N., Schaeffer, R. D., et al. (2022) · Yearbook of pediatric endocrinology · doi:10.1530/ey.19.15.15 · Cited by 199
Cell biology and function of neuronal ceroid lipofuscinosis-related proteins
Kollmann, K., Uusi-Rauva, K., Scifo, E., Tyynelä, J., Jalanko, A., & Braulke, T. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.01.019 · Cited by 135
The enigma of ceramide synthase regulation in mammalian cells
Wegner, M.-S., Schiffmann, S., Parnham, M. J., Geißlinger, G., & Grösch, S. (2016) · Progress in Lipid Research · doi:10.1016/j.plipres.2016.03.006 · Cited by 135
Kühn, A. (2003) · Trends in Cell Biology · doi:10.1016/j.tcb.2003.08.005 · Cited by 136
A mutation in the CLN8 gene in English Setter dogs with neuronal ceroid-lipofuscinosis
Katz, M. L., Khan, S., Awano, T., Shahid, S. A., Siakotos, A. N., & Johnson, G. S. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.12.038 · Cited by 125
LASS5 Is a Bona Fide Dihydroceramide Synthase That Selectively Utilizes Palmitoyl-CoA as Acyl Donor
Lahiri, S., & Futerman, A. H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506485200 · Cited by 123
Necessary Role for the Lag1p Motif in (Dihydro)ceramide Synthase Activity
Spassieva, S., Seo, J.-G., Jiang, J. C., Bielawski, J., Alvarez-Vasquez, F., Jazwinski, S. M., Hannun, Y. A., & Obeid, L. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608092200 · Cited by 121
CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein
Mole, S., Michaux, G., Codlin, S., Wheeler, R. B., Sharp, J. D., & Cutler, D. F. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.04.042 · Cited by 116
The Genetic Spectrum of Human Neuronal Ceroid‐lipofuscinoses
Mole, S. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00500.x · Cited by 111
“ese 4 mutations are located within a region of the CLN8 protein homologous to the TLC family of proteins whereas R24 is located prior to the TLC region of homology (66) in a region of the protein with sequence unique to CLN8.”
BackgroundThe autosomal recessively inherited progressive myoclonus epilepsies and their genes
Ramachandran, N., Girard, J., Turnbull, J., & Minassian, B. A. (2009) · Epilepsia · doi:10.1111/j.1528-1167.2009.02117.x · Cited by 102
“5):29–36, 2009 doi: 10.1111/j.1528-1167.2009.02117.x et al., 2000), and its likely function is as an enzyme in the pathway of ceramide synthesis (Winter & Ponting, 2002).”
BackgroundInfluentialRanta, S., Topçu, M., Tegelberg, S., Tan, H., Üstübütün, A., Saatçi, I., Dufke, A., Enders, H., Pohl, K., Alembik, Y., et al. (2004) · Human Mutation · doi:10.1002/humu.20018 · Cited by 101
“Interestingly, the R204C change occurred in the absolutely conserved arginine residue in the recently identified and preliminarily characterized large family of proteins with lipid-sensing domains that CLN8 belongs to [Winter and Ponting, 2002].”
BackgroundHuman Homologues of LAG1 Reconstitute Acyl-CoA-dependent Ceramide Synthesis in Yeast
Guillas, I., Jiang, J. C., Vionnet, C., Roubaty, C., Uldry, D., Chuard, R., Wang, J., Jazwinski, S. M., & Conzelmann, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307554200 · Cited by 101
Functional biology of the neuronal ceroid lipofuscinoses (NCL) proteins
Kyttälä, A., Lahtinen, U., Braulke, T., & Hofmann, S. L. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2006.05.007 · Cited by 98
Immunogenomic Approaches to Study Host Immunity to Enteric Pathogens
Lillehoj, H. S., Kim, C. H., Keeler, C. L., & Zhang, S. (2007) · Poultry Science · doi:10.1093/ps/86.7.1491 · Cited by 94
“Also, CLN8 may play a role in protein secretion during immune activation (Winter and Ponting, 2002), and its defect has been associated with neuronal ceroid lipofuscinosis 8 disease, which is characterized by the accumulation of ATP synthase subunit C.”
BackgroundThe neuronal ceroid‐lipofuscinoses
Bennett, M. J., & Rakheja, D. (2013) · Developmental Disabilities Research Reviews · doi:10.1002/ddrr.1118 · Cited by 93
“The CLN8 protein is an integral endoplasmic reticulum membrane protein whose function is unknown, but it contains a peptide domain that is associated with lipid synthesis, transport, or sensing [Winter and Ponting, 2002].”
Schlank, a member of the ceramide synthase family controls growth and body fat in Drosophila
Bauer, R., Voelzmann, A., Breiden, B., Schepers, U., Farwanah, H., Hahn, I., Eckardt, F., Sandhoff, K., & Hoch, M. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.305 · Cited by 94
“Rather, the gene product of CG11642 seems more homologous to members of the translocating chain-associated membrane (TRAM) protein family (Figure 2A), which are not involved in ceramide synthesis (Jiang et al, 1998; Winter and Ponting, 2002; Spassieva et al, 2006).”
BackgroundThe CLN9 Protein, a Regulator of Dihydroceramide Synthase
Schulz, A., Mousallem, T. I., Venkataramani, M., Persaud‐Sawin, D., Zucker, A., Luberto, C., Bielawska, A. E., Bielawski, J., Holthuis, J. C. M., Jazwinski, S. M., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509483200 · Cited by 88
Molecular genetics of the NCLs — status and perspectives
Siintola, E., Lehesjoki, A., & Mole, S. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2006.05.006 · Cited by 84
Sassa, T., Hirayama, T., & Kihara, A. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.695858 · Cited by 84
“homology domain (45), shown as black and gray regions, respectively.”
BackgroundEbel, P., Dorp, K. V., Petrasch‐Parwez, E., Zlomuzica, A., Kinugawa, K., Mariani, J., Minich, D. J., Ginkel, C., Welcker, J., Degen, J., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.479907 · Cited by 83
“The lag1 domain, which is shared by all CerS, is located within the TLC (tram-lag-CLN8) domain in the center of the protein and is part of the active center of the enzymes (8).”
BackgroundLyly, A., von Schantz, C., Heine, C., Schmiedt, M.-L., Sipilä, T., Jalanko, A., & Kyttälä, A. (2009) · BMC Cell Biology · doi:10.1186/1471-2121-10-83 · Cited by 80
“In general, accumulating evidence has indicated dysregulated lipid metabolism in different forms of NCLs and several NCL proteins have been functionally linked to lipid metabolism [[48,49], reviewed in [50-52]].”
Impaired cell adhesion and apoptosis in a novel CLN9 Batten disease variant
Schulz, A., Dhar, S., Rylova, S. N., Dbaibo, G. S., Alroy, J., Hagel, C., Artacho, I., Kohlschütter, A., Lin, S. M., & Boustany, R. (2004) · Annals of Neurology · doi:10.1002/ana.20187 · Cited by 79
Ceramide synthase 4 deficiency in mice causes lipid alterations in sebum and results in alopecia
Ebel, P., Imgrund, S., Dorp, K. V., Hofmann, K., Maier, H., Drake, H., Degen, J., Dörmann, P., Eckhardt, M., Franz, T., et al. (2014) · Biochemical Journal · doi:10.1042/bj20131242 · Cited by 74
Cerantola, V., Guillas, I., Roubaty, C., Vionnet, C., Uldry, D., Knudsen, J., & Conzelmann, A. (2009) · Molecular Microbiology · doi:10.1111/j.1365-2958.2009.06628.x · Cited by 73
“1), which are members of a large gene family with homologues present throughout the eukaryotic kingdom (Winter and Ponting, 2002; Obeid and Hannun, 2003).”
BackgroundEleven residues determine the acyl chain specificity of ceramide synthases
Tidhar, R., Zelnik, I. D., Volpert, G., Ben‐Dor, S., Kelly, S. L., Merrill, A. H., & Futerman, A. H. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.001936 · Cited by 71
“Since the identification of the first mammalian CerS in 2002 (8), some effort has been invested in attempting to determine the basis for the acyl chain specificity of the mammalian CerS; thus, it is known that the amino acids involved in acyl chain specificity are located in the Tram-Lag-CLN8 (TLC) domain (9), a regio…”
BackgroundTidhar, R., Ben‐Dor, S., Wang, E. L., Kelly, S. L., Merrill, A. H., & Futerman, A. H. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.280271 · Cited by 69
“TheLag1pmotif has been suggested to be essential for CerS activity (16, 17) and contains a number of residues, including two conserved histidines, which may be involved in catalysis or substrate binding (13).”
BackgroundHermansson, M., Käkelä, R., Berghäll, M., Lehesjoki, A., Somerharju, P. J., & Lahtinen, U. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03376.x · Cited by 67
Ruiz, M., Bodhicharla, R. K., Svensk, E., Devkota, R., Busayavalasa, K., Palmgren, H., Ståhlman, M., Borén, J., & Pilon, M. (2018) · eLife · doi:10.7554/elife.40686 · Cited by 67
“…1E) that belong to a protein family characterized by the presence of a TLC domain and that includes the ER-localized ceramide synthases as well as translocation associated membrane proteins involved in membrane protein synthesis in the rough ER (Pewzner-Jung et al., 2006; Winter and Ponting, 2002).”
InfluentialA New Functional Motif in Hox Domain-containing Ceramide Synthases
Mesika, A., Ben‐Dor, S., Laviad, E. L., & Futerman, A. H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703487200 · Cited by 67
Sociale, M., Wulf, A., Breiden, B., Klee, K., Thielisch, M., Eckardt, F., Sellin, J., Bülow, M. H., Loebbert, S., Weinstock, N., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.090 · Cited by 63
“All CerSs contain a TLC domain, a conserved lipid-sensing domain (Winter and Ponting, 2002), which also determines acyl chain specificity of CerSs (Tidhar et al.”
BackgroundMoving towards a new era of genomics in the neuronal ceroid lipofuscinoses
Butz, E. S., Chandrachud, U., Mole, S. E., & Cotman, S. L. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.165571 · Cited by 62
Wallace, S. W., Singhvi, A., Liang, Y., Lu, Y., & Shaham, S. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.03.051 · Cited by 61
“5 encodes a transmembrane protein with a conserved TLC (TRAM, LAG1, and CLN8) domain, which have general roles in lipid metabolism and in mammals regulate calcium channel activity (Papanayotou et al., 2013; Winter and Ponting, 2002), and F31D5.”
CLN 5 and CLN 8 protein association with ceramide synthase: B iochemical and proteomic approaches
Haddad, S. E., Khoury, M., Daoud, M., Kantar, R. S., Harati, H., Mousallem, T. I., Álzate, Ó., Meyer, B. F., & Boustany, R. (2012) · Electrophoresis · doi:10.1002/elps.201200472 · Cited by 60
Ceramide, Stress, and a "LAG" in Aging
Obeid, L. M., & Hannun, Y. A. (2003) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2003.39.pe27 · Cited by 60
Ceramide synthases in biomedical research
Cingolani, F., Futerman, A. H., & Casas, J. (2015) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2015.07.026 · Cited by 61
Vantaggiato, C., Redaelli, F. C., Falcone, S., Perrotta, C., Tonelli, A., Bondioni, S., Morbin, M., Riva, D., Saletti, V., Bonaglia, M. C., et al. (2009) · Human Mutation · doi:10.1002/humu.21012 · Cited by 58
“CLN8 contains a TLC (TRAM-LAG1-CLN8) domain of 200 aa (62–262 aa) found in a family of membrane associated proteins that was proposed to have a role in sensing, biosynthesis, and metabolism of lipids [Winter and Ponting, 2002].”
BackgroundShacka, J. J. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2012.03.003 · Cited by 59
The 16p11.2 homologs fam57ba and doc2a generate certain brain and body phenotypes
McCammon, J. M., Blaker, A. L., Chen, X., & Sive, H. L. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx255 · Cited by 57
“Fam57b has a Tram-Lag1-Cln8 (TLC) domain associated with ceramide synthases (86), and is capable of ceramide synthesis in vitro (46).”
BackgroundInteractions of the proteins of neuronal ceroid lipofuscinosis: clues to function
Getty, A. L., & Pearce, D. A. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0468-6 · Cited by 56
“larity with yeast Lag1p, a protein involved in longevity and aging [211] and TRAM, a regulator of translocation into the ER [212], and through these similarities, functions for CLN8 were suggested in lipid synthesis, proteolipid trafficking, or lipid sensing [213], though these suggestions have not been tested directl…”
Cannelli, N., Cassandrini, D., Bertini, E., Striano, P., Fusco, L., Gaggero, R., Specchio, N., Biancheri, R., Vigevano, F., Bruno, C., et al. (2006) · Neurogenetics · doi:10.1007/s10048-005-0024-y · Cited by 54
“Although the protein’s function is largely unknown, CLN8 is a member of the TLC protein family (TRAM-LAG1-CLN8) that may contain lipid-sensing domains [16], which suggests that this NCL may be caused by defects in lipid biosynthesis or transport.”
BackgroundZelnik, I. D., Rozman, B., Rosenfeld-Gur, E., Ben‐Dor, S., & Futerman, A. H. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-21162-2_4 · Cited by 55
Sphingolipids and neuronal degeneration in lysosomal storage disorders
Grassi, S., Chiricozzi, E., Mauri, L., Sonnino, S., & Prinetti, A. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14540 · Cited by 50
Schmiedt, M.-L., Blom, T., Blom, T., Kopra, O., Wong, A. P., von Schantz, C., Ikonen, E., Kuronen, M., Jauhiainen, M., Cooper, J. D., et al. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.12.009 · Cited by 49
Ahtiainen, L., Kolikova, J., Mutka, A., Luiro, K., Gentile, M., Ikonen, E., Khiroug, L., Jalanko, A., & Kopra, O. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.06.012 · Cited by 48
Guo, J., Johnson, G. S., Brown, H. A., Provencher, M., da Costa, R. C., Mhlanga-Mutangadura, T., Taylor, J. F., Schnabel, R. D., O’Brien, D. P., & Katz, M. L. (2014) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2014.05.014 · Cited by 49
Lonka, L., Salonen, T., Siintola, E., Kopra, O., Lehesjoki, A., & Jalanko, A. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20133 · Cited by 47
“CLN8 has been linked to a TLC (TRAM, Lag1, and CLN8 homology domains) superfamily of proteins proposed to have a role in sensing, biosynthesis, and metabolism of lipids (Winter and Ponting, 2002).”
BackgroundYeast sphingolipids do not need to contain very long chain fatty acids
Cerantola, V., Vionnet, C., Aebischer, O. F., Jenny, T. A., Knudsen, J., & Conzelmann, A. (2006) · Biochemical Journal · doi:10.1042/bj20061128 · Cited by 43
Reinhardt, K., Grapp, M., Schlachter, K., Brück, W., Gärtner, J., & Steinfeld, R. (2009) · Clinical Genetics · doi:10.1111/j.1399-0004.2009.01285.x · Cited by 42
“70C>G occurs in an N -terminal region upstream of the TLC domain not conserved among TLC homologs (22).”
BackgroundInfluentialThe longevity assurance homologue of yeast lag1 (Lass) gene family (Review)
Teufel (1998) · International Journal of Molecular Medicine · doi:10.3892/ijmm_00000110 · Cited by 42
“As the ER is the site of ceramide synthesis Lass proteins would be expected to localize to this organelle and in fact the subcellular localization of yeast lag1 was the ER membrane (3).”
The Intracellular Location and Function Of Proteins Of Neuronal Ceroid Lipofuscinoses
Ezaki, J., & Kominami, E. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00501.x · Cited by 42
Chen, Q., Denard, B., Lee, C.-E., Han, S., Ye, J. S., & Ye, J. (2016) · Molecules and Cells · doi:10.1016/j.molcel.2016.06.032 · Cited by 41
“…membrane protein 1 (TRAM1), a translocon-associated protein (Görlich et al., 1992; Görlich and Rapoport, 1993) that also contains a TRAM/LAG1/CLN8 homology (TLC) domain, which is shared by ceramide synthase and is postulated to bind ceramide or related sphingolipids (Winter and Ponting, 2002).”
BackgroundInfluentialCalfacilitin is a calcium channel modulator essential for initiation of neural plate development
Papanayotou, C., Almeida, I. D., Liao, P. H., Oliveira, N. M. M., Lu, S., Kougioumtzidou, E., Zhu, L., Shaw, A. D., Sheng, G., Streit, A., et al. (2013) · Nature Communications · doi:10.1038/ncomms2864 · Cited by 39
Garić, D., Sanctis, J. B. D., Shah, J., Dumut, D. C., & Radzioch, D. (2019) · Progress in Lipid Research · doi:10.1016/j.plipres.2019.03.001 · Cited by 39
Integrative Genetic Analysis of Allergic Inflammation in the Murine Lung
Kelada, S. N. P., Carpenter, D. E., Aylor, D. L., Chines, P. S., Rutledge, H. R., Chesler, E. J., Churchill, G. A., de Villena, F. P., Schwartz, D. A., & Collins, F. S. (2014) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2013-0501oc · Cited by 34
“candidate gene in that TLC domain– containing proteins are thought to act as sphingolipid sensors (39) that are involved”
BackgroundPassantino, R., Cascio, C., Deidda, I., Galizzi, G., Russo, D., Spedale, G., & Guarneri, P. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.10.030 · Cited by 36
Takada, N., & Appel, B. (2010) · Developmental Dynamics · doi:10.1002/dvdy.22338 · Cited by 34
Ye, J. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.012669 · Cited by 32
Riedelsheimer, C., Brotman, Y., Méret, M., Melchinger, A. E., & Willmitzer, L. (2013) · Scientific Reports · doi:10.1038/srep02479 · Cited by 32
Yamashita-Sugahara, Y., Tokuzawa, Y., Nakachi, Y., Kanesaki-Yatsuka, Y., Matsumoto, M., Mizuno, Y., & Okazaki, Y. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.440792 · Cited by 32
“1C) (47), we focused on this gene and performed a detailed characterization.”
Lysosomal Storage Diseases: Is Impaired Apoptosis a Pathogenic Mechanism?
Tardy, C., Andrieu‐Abadie, N., Salvayre, R., & Levade, T. (2004) · Neurochemical Research · doi:10.1023/b:nere.0000021232.05175.38 · Cited by 32
“Finally, members of the TLC (TRAM-Lag1pCLN8)-domain family, including CLN8 (which is mutated in a NCL form called progressive epilepsy with mental retardation), may be involved in ceramide synthesis (93), providing a possible (and tantalizing) pathogenic link between (sphingo)lipid metabolism, apoptotic cell death, an…”
BackgroundJanevska, S., Ferling, I., Jojić, K., Rautschek, J., Hoefgen, S., Proctor, R. H., Hillmann, F., & Valiante, V. (2020) · mBio · doi:10.1128/mbio.00455-20 · Cited by 30
“An analysis of the deduced amino acid sequences of Fum17 and Fum18 revealed that both proteins have a TRAM/LAG1/CLN8 (TLC) protein domain (IPR006634), a domain that is present in all eukaryotic ceramide synthases described to date (26).”
The neuronal ceroid lipofuscinoses program: A translational research experience in Argentina
Kohan, R., Pesaola, F. N., Guelbert, N. B., Pons, P., Ramírez, A. M. O., Rautenberg, G. E., Becerra, A., Sims, K. B., Xin, W. W., Cismondi, I. A., et al. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.05.003 · Cited by 29
Deficient mitochondrial Ca2+ buffering in the Cln8 mouse model of neuronal ceroid lipofuscinosis
Kolikova, J., Afzalov, R. A., Surin, A. M., Lehesjoki, A., & Khiroug, L. S. (2011) · Cell Calcium · doi:10.1016/j.ceca.2011.08.004 · Cited by 28
Monogenic neurological disorders of sphingolipid metabolism
Sabourdy, F., Astudillo, L. M., Colacios, C., Dubot, P., Mrad, M., Ségui, B., Andrieu‐Abadie, N., & Levade, T. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2015.01.010 · Cited by 29
Yang, B., Thorogood, D., Armstead, I. P., Franklin, F. C. H., & Barth, S. (2009) · Plant Molecular Biology · doi:10.1007/s11103-009-9501-2 · Cited by 27
“TLC-domain containing proteins have been reported in yeast, mammalians and humans with various lipid metabolism functions such as lipid synthesis activation, protecting proteins from proteolysis, lipid transport and lipid sensing (Winter and Ponting 2002).”
BackgroundPeraza-Echeverría, S., Santamaría, J. M., Fuentes, G., Menéndez-Cerón, M. D. L. Á., Vallejo-Reyna, M. Á., & Herrera-Valencia, V. A. (2012) · Genes & Genomics · doi:10.1007/s13258-011-0218-7 · Cited by 26
“…GTP-binding protein (Table 3) which are implicated in different physiological processes such as chloroplast homeostasis (Meskauskiene et al., 2009), lipid metabolism (Winter and Ponting, 2002), disease resistance (van der Hoorn, 2008) and signal transduction (Yuksel and Memon, 2008), respectively.”
BackgroundClinical and electrophysiological features of epilepsy in Italian patients with CLN8 mutations
Striano, P., Specchio, N., Biancheri, R., Cannelli, N., Simonati, A., Cassandrini, D., Rossi, A., Bruno, C., Fusco, L., Gaggero, R., et al. (2006) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2006.10.009 · Cited by 26
Ceramide synthases: Reflections on the impact of Dr. Lina M. Obeid
Kim, J. L., Mestre, B., Shin, S.-H., & Futerman, A. H. (2021) · Cellular Signalling · doi:10.1016/j.cellsig.2021.109958 · Cited by 25
Greiner-Tollersrud, O. K., & Berg, T. (2007) · Springer eBooks · doi:10.1007/0-387-28957-7_6 · Cited by 27
Petkevicius, K., Palmgren, H., Glover, M. S., Ahnmark, A., Andréasson, A., Madeyski-Bengtson, K., Kawana, H., Allman, E. L., Kaper, D., Uhrbom, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33735-6 · Cited by 24
NCLs and ER: A stressful relationship
Marotta, D., Tinelli, E., & Mole, S. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.04.003 · Cited by 24
Bickert, A., Kern, P., van Uelft, M., Herresthal, S., Ulas, T., Gutbrod, K., Breiden, B., Degen, J., Sandhoff, K., Schultze, J. L., et al. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2018.04.006 · Cited by 24
Dawson, K., Toone, W. M., Jones, N., & Wilkinson, C. R. M. (2008) · Eukaryotic Cell · doi:10.1128/ec.00037-08 · Cited by 24
Alexander, S., & Alexander, H. (2010) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2010.10.005 · Cited by 23
Bender, K. O., Ng, C. L., & Tortorella, D. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807568200 · Cited by 24
The neuronal ceroid-lipofuscinoses (Batten disease)
Mole, S., Schulz, A., & Haltia, M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813866-3.00004-7 · Cited by 23
Si, W., Hang, T., Guo, M., Chen, Z., Liang, Q., Gu, L., & Ding, T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215484 · Cited by 22
A novel C-terminal DxRSDxE motif in ceramide synthases involved in dimer formation
Kim, J. L., Ben‐Dor, S., Rosenfeld-Gur, E., & Futerman, A. H. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101517 · Cited by 23
“A full length view of the logo of the CerS clade (209 sequences from 84 species), where the Lag1p motif (13, 24, 26), the putative active site, can be seen in lines 9 to 10, and the DxRSDxE motif (highlighted in Fig.”
BackgroundInfluentialStructure and mechanism of a eukaryotic ceramide synthase complex
Xie, T., Fang, Q., Zhang, Z., Wang, Y., Dong, F., & Gong, X. (2023) · The EMBO Journal · doi:10.15252/embj.2023114889 · Cited by 24
Cunningham, D., Swartzlander, D. B., Liyanarachchi, S., Davuluri, R. V., & Herman, G. E. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m400462-jlr200 · Cited by 19
Structural basis of the mechanism and inhibition of a human ceramide synthase
Pascoa, T. C., Pike, A. C. W., Tautermann, C. S., Chi, G., Traub, M., Quigley, A., Chalk, R., Štefanić, S., Thamm, S., Pautsch, A., et al. (2025) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01414-3 · Cited by 25
Kuronen, M., Hermansson, M., Manninen, O., Zech, I., Talvitie, M., Laitinen, T., Gröhn, O. H. J., Somerharju, P. J., Eckhardt, M., Cooper, J. D., et al. (2011) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2011.01233.x · Cited by 19
Vionnet, C., Roubaty, C., Ejsing, C. S., Knudsen, J., & Conzelmann, A. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.176875 · Cited by 19
Metadata
- Authors
- Winter, E., & Ponting, C. P.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Ponting, Chris P
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 27
- Issue
- 8
- Pages
- 381-383
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W2016874659
- Cited by
- 181
- References
- 22
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 4 · 2022: 4 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 8 · 2017: 4 · 2016: 11 · 2015: 4 · 2014: 5 · 2013: 10 · 2012: 16
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- tram, CLN8, membrane-associated proteins, ceramide synthesis, lipid regulation, neuronal ceroid lipofuscinosis, protein families
- MeSH terms
- Amino Acid Sequence, Animals, Fungal Proteins, Humans, Membrane Glycoproteins, Membrane Proteins, Molecular Sequence Data, Mutation, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Membrane Transport Proteins, Saccharomyces cerevisiae Proteins, Lipid Metabolism, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
