Genomes and Genes
Gene Symbol: Scm
Description: Sex comb on midleg
Alias: CG9495, Dmel\CG9495, SCM, Su(z)302, l(3)85Ef, scm, Sex comb on midleg, CG9495-PA, CG9495-PB, Scm-PA, Scm-PB, Sex combs on midleg, Sex combs on midlegs, sex comb on midleg
Species: fruit fly
- Oktaba K, Gutierrez L, Gagneur J, Girardot C, Sengupta A, Furlong E, et al. Dynamic regulation by polycomb group protein complexes controls pattern formation and the cell cycle in Drosophila. Dev Cell. 2008;15:877-89 pubmed publisher..Analysis of cell cycle regulators indicates that the PcG system also dynamically modulates the expression levels of certain genes, providing a possible explanation for the tumor phenotype of PcG mutants. ..
- Simon J, Chiang A, Bender W. Ten different Polycomb group genes are required for spatial control of the abdA and AbdB homeotic products. Development. 1992;114:493-505 pubmed..mutations in the genes Polycomb (Pc), extra sex combs (esc), Enhancer of zeste [E(z)], polyhomeotic (ph), Sex comb on midleg (Scm), Polycomb-like (Pcl), Sex comb extra (Sce), Additional sex combs (Asx), Posterior sex combs (Psc) and ..
- Peterson A, Mallin D, Francis N, Ketel C, Stamm J, Voeller R, et al. Requirement for sex comb on midleg protein interactions in Drosophila polycomb group repression. Genetics. 2004;167:1225-39 pubmedThe Drosophila Sex Comb on Midleg (SCM) protein is a transcriptional repressor of the Polycomb group (PcG). Although genetic studies establish SCM as a crucial PcG member, its molecular role is not known...
- Kim C, Sawaya M, Cascio D, Kim W, Bowie J. Structural organization of a Sex-comb-on-midleg/polyhomeotic copolymer. J Biol Chem. 2005;280:27769-75 pubmed..the interaction between the SAM domains of the polycomb group proteins polyhomeotic (Ph) and Sex-comb-on-midleg (Scm). Previously we showed that Ph-SAM polymerizes as a helical structure...
- Moazed D, O Farrell P. Maintenance of the engrailed expression pattern by Polycomb group genes in Drosophila. Development. 1992;116:805-10 pubmed
- Brown J, Fritsch C, Mueller J, Kassis J. The Drosophila pho-like gene encodes a YY1-related DNA binding protein that is redundant with pleiohomeotic in homeotic gene silencing. Development. 2003;130:285-94 pubmed..Pc, Psc, Scm, E(z) and Ph remain bound to polytene chromosomes at most sites in the absence of Pho and Pho-like...
- Salvaing J, Lopez A, Boivin A, Deutsch J, Peronnet F. The Drosophila Corto protein interacts with Polycomb-group proteins and the GAGA factor. Nucleic Acids Res. 2003;31:2873-82 pubmed..Moreover, we show by GST pull-down and two-hybrid experiments that Corto binds to E(Z), ESC, PH, SCM and GAGA and co-localizes with these proteins on a few sites on polytene chromosomes...
- Mishra R, Mihaly J, Barges S, Spierer A, Karch F, Hagstrom K, et al. The iab-7 polycomb response element maps to a nucleosome-free region of chromatin and requires both GAGA and pleiohomeotic for silencing activity. Mol Cell Biol. 2001;21:1311-8 pubmed..We show that GAGA and Pho interact with these sequences in vitro and that the consensus binding sites for the two proteins are critical for the silencing activity of the iab-7 PRE in vivo. ..
- Grimm C, de Ayala Alonso A, Rybin V, Steuerwald U, Ly Hartig N, Fischle W, et al. Structural and functional analyses of methyl-lysine binding by the malignant brain tumour repeat protein Sex comb on midleg. EMBO Rep. 2007;8:1031-7 pubmedb>Sex comb on midleg (Scm) is a member of the Polycomb group of proteins involved in the maintenance of repression of Hox and other developmental control genes in Drosophila...
- Peterson A, Kyba M, Bornemann D, Morgan K, Brock H, Simon J. A domain shared by the Polycomb group proteins Scm and ph mediates heterotypic and homotypic interactions. Mol Cell Biol. 1997;17:6683-92 pubmedThe Sex comb on midleg (Scm) and polyhomeotic (ph) proteins are members of the Polycomb group (PcG) of transcriptional repressors...
- Lopez A, Higuet D, Rosset R, Deutsch J, Peronnet F. corto genetically interacts with Pc-G and trx-G genes and maintains the anterior boundary of Ultrabithorax expression in Drosophila larvae. Mol Genet Genomics. 2001;266:572-83 pubmed..polyhomeotic, mutations in corto enhance the extra-sex-comb phenotype of multi sex combs, Polycomb-like and Sex combs on midleg. corto also genetically interacts with a number of trx-G genes (ash1, kismet, kohtalo, moira, osa, ..
- Kennison J, Tamkun J. Dosage-dependent modifiers of polycomb and antennapedia mutations in Drosophila. Proc Natl Acad Sci U S A. 1988;85:8136-40 pubmed..e., Sex combs reduced (Scr), Brista (Ba), trithorax (trx), Polycomb (Pc), Polycomblike (Pcl), and Sex comb on midleg (Scm)]...
- Muller M, Hagstrom K, Gyurkovics H, Pirrotta V, Schedl P. The mcp element from the Drosophila melanogaster bithorax complex mediates long-distance regulatory interactions. Genetics. 1999;153:1333-56 pubmed..Finally, this pairing element can also mediate long-distance interactions between enhancers and promoters, activating mini-white expression. ..
- Mihaly J, Hogga I, Gausz J, Gyurkovics H, Karch F. In situ dissection of the Fab-7 region of the bithorax complex into a chromatin domain boundary and a Polycomb-response element. Development. 1997;124:1809-20 pubmed
- Finley J, Miller A, Herman T. Polycomb group genes are required to maintain a binary fate choice in the Drosophila eye. Neural Dev. 2015;10:2 pubmed publisher..Here, we show that loss of the PcG genes Sce, Scm, or Pc specifically affects one of the three binary fate choices that R7 precursors must make: mutant R7s derepress ..
- Ng C, Kopp A. Sex combs are important for male mating success in Drosophila melanogaster. Behav Genet. 2008;38:195-201 pubmed publisher..Rapid evolution of sex comb morphology may be driven either by changes in female preferences, or by co-evolution between sex combs and female external genitalia. ..
- Atchison L, Ghias A, Wilkinson F, Bonini N, Atchison M. Transcription factor YY1 functions as a PcG protein in vivo. EMBO J. 2003;22:1347-58 pubmed..Finally, we found that YY1, as well as Polycomb, required the co-repressor protein CtBP for repression in vivo. These results provide a mechanism for recruitment of vertebrate PcG complexes to DNA and demonstrate new functions for YY1. ..
- Cheng N, Sinclair D, Campbell R, Brock H. Interactions of polyhomeotic with Polycomb group genes of Drosophila melanogaster. Genetics. 1994;138:1151-62 pubmed..for a temperature-sensitive allele, ph2, are lethal when heterozygous with mutants in Asx, Pc, Pcl, Psc, Sce and Scm, and with E(Pc) and Su(z)2...
- Nuzhdin S, Reiwitch S. Are the same genes responsible for intra- and interspecific variability for sex comb tooth number in Drosophila?. Heredity (Edinb). 2000;84 ( Pt 1):97-102 pubmed..One intraspecific QTL mapped to the same interval as the QTL for interspecific differences between D. simulans and D. mauritiana. Whether or not these effects result from the same genes requires further examination. ..
- Kang H, McElroy K, Jung Y, Alekseyenko A, Zee B, Park P, et al. Sex comb on midleg (Scm) is a functional link between PcG-repressive complexes in Drosophila. Genes Dev. 2015;29:1136-50 pubmed publisher..BioTAP-Enhancer of zeste [E(z)], we captured all PcG-repressive complex 1 (PRC1) or PRC2 core components and Sex comb on midleg (Scm) as the only protein strongly enriched with both complexes...
- Smulders Srinivasan T, Szakmary A, Lin H. A Drosophila chromatin factor interacts with the Piwi-interacting RNA mechanism in niche cells to regulate germline stem cell self-renewal. Genetics. 2010;186:573-83 pubmed publisher..These results reveal a novel epigenetic mechanism involving Corto and Piwi that defines the fate and signaling function of niche cells in maintaining GSCs. ..
- Eissenberg J. Divided loyalties: transdetermination and the genetics of tissue regeneration. Bioessays. 2006;28:574-7 pubmed..The data identify key mechanisms that control developmental homeostasis and cell fate restriction that could be manipulated to make somatic stem-cell engineering possible. ..
- Sinclair D, Clegg N, Antonchuk J, Milne T, Stankunas K, Ruse C, et al. Enhancer of Polycomb is a suppressor of position-effect variegation in Drosophila melanogaster. Genetics. 1998;148:211-20 pubmed..However, E(Pc) appears to be an important link between the two groups. We discuss why Asx might act as an enhancer of PEV. ..
- Georgiev P. Identification of mutations in three genes that interact with zeste in the control of white gene expression in Drosophila melanogaster. Genetics. 1994;138:733-9 pubmed..The products of these three genes may represent, together with zeste, a group of proteins involved in the organization of long-distance interactions between DNA sequences...
- Ng J, Hart C, Morgan K, Simon J. A Drosophila ESC-E(Z) protein complex is distinct from other polycomb group complexes and contains covalently modified ESC. Mol Cell Biol. 2000;20:3069-78 pubmed..distinct from previously described complexes containing the PcG proteins Polyhomeotic, Polycomb, and Sex comb on midleg. In addition, we present evidence that ESC is phosphorylated in vivo and that this modified ESC is ..
- Kapoun A, Kaufman T. Regulatory regions of the homeotic gene proboscipedia are sensitive to chromosomal pairing. Genetics. 1995;140:643-58 pubmed..Interestingly, the intronic PS regions contain positive regulatory sequences for pb, whereas the upstream PS sites contain pb negative regulatory elements. ..
- Breen T, Duncan I. Maternal expression of genes that regulate the bithorax complex of Drosophila melanogaster. Dev Biol. 1986;118:442-56 pubmed..The genes studied include Additional sex combs (Asx), Polycomblike (Pcl), Sex comb extra (Sce), Sex comb on midleg (Scm), and lethal(4)29 [l(4)29]...
- Paro R. Imprinting a determined state into the chromatin of Drosophila. Trends Genet. 1990;6:416-21 pubmed
- Pirrotta V. PcG complexes and chromatin silencing. Curr Opin Genet Dev. 1997;7:249-58 pubmed..How such a complex interferes with transcriptional activity is not entirely clear but current evidence suggests that they compete with the chromatin structure required for the binding of activators. ..
- Salvaing J, Decoville M, Mouchel Vielh E, Bussiere M, Daulny A, Boldyreva L, et al. Corto and DSP1 interact and bind to a maintenance element of the Scr Hox gene: understanding the role of Enhancers of trithorax and Polycomb. BMC Biol. 2006;4:9 pubmed..The presence of a given combination of ETPs on an ME would control the recruitment of either PcG or TrxG complexes, propagating the silenced or active state. ..
- Belenkaya T, Soldatov A, Nabirochkina E, Biryukova I, Birjukova I, Georgieva S, et al. P-Element insertion at the polyhomeotic gene leads to formation of a novel chimeric protein that negatively regulates yellow gene expression in P-element-induced alleles of Drosophila melanogaster. Genetics. 1998;150:687-97 pubmed..The P-PH, Polycomb (PC), and Posterior sex combs (PSC) proteins were immunohistochemically detected on polytene chromosomes in the regions of P-element insertions. ..
- O Connell S, Wang L, Robert S, Jones C, Saint R, Jones R. Polycomblike PHD fingers mediate conserved interaction with enhancer of zeste protein. J Biol Chem. 2001;276:43065-73 pubmed..We discuss the implications of PCL association with ESC.E(Z) complexes and the possibility that PCL may either be a subunit of a subset of ESC.E(Z) complexes or a subunit of a separate complex that interacts with ESC.E(Z) complexes. ..
- Calvo MartÃn J, Librado P, AguadÃ© M, Papaceit M, Segarra C. Adaptive selection and coevolution at the proteins of the Polycomb repressive complexes in Drosophila. Heredity (Edinb). 2016;116:213-23 pubmed publisher..These clusters include well-established binary interactions among PcG proteins as well as new putative interactions. ..
- Maeda R, Karch F. The ABC of the BX-C: the bithorax complex explained. Development. 2006;133:1413-22 pubmed..This primer attempts to distill and explain our current knowledge about this classic, complex locus. ..
- Frey F, Sheahan T, Finkl K, Stoehr G, Mann M, Benda C, et al. Molecular basis of PRC1 targeting to Polycomb response elements by PhoRC. Genes Dev. 2016;30:1116-27 pubmed publisher..We show that the Sfmbt subunit of the DNA-binding Pho-repressive complex (PhoRC) and the Scm subunit of the canonical Polycomb-repressive complex 1 (PRC1) directly bind each other through their SAM domains...
- Gambetta M, MÃ¼ller J. O-GlcNAcylation prevents aggregation of the Polycomb group repressor polyhomeotic. Dev Cell. 2014;31:629-39 pubmed publisher..We propose that O-GlcNAcylation is needed for Ph to form functional, ordered assemblies via its SAM domain. ..
- Langlais K, Brown J, Kassis J. Polycomb group proteins bind an engrailed PRE in both the "ON" and "OFF" transcriptional states of engrailed. PLoS ONE. 2012;7:e48765 pubmed publisher..These results show that PcG binding per se does not determine the transcriptional state of engrailed. ..
- Bengani H, Mendiratta S, Maini J, Vasanthi D, Sultana H, Ghasemi M, et al. Identification and Validation of a Putative Polycomb Responsive Element in the Human Genome. PLoS ONE. 2013;8:e67217 pubmed publisher..Taken together, our results strongly suggest that PRE-PIK3C2B functions as a site of interaction for polycomb proteins. ..
- Gebuhr T, Bultman S, Magnuson T. Pc-G/trx-G and the SWI/SNF connection: developmental gene regulation through chromatin remodeling. Genesis. 2000;26:189-97 pubmed..genesis 26:189-197, 2000. ..
- McKeon J, Slade E, Sinclair D, Cheng N, Couling M, Brock H. Mutations in some Polycomb group genes of Drosophila interfere with regulation of segmentation genes. Mol Gen Genet. 1994;244:474-83 pubmed..These results support a role for Pc genes in regulation of some segmentation genes, and suggest that esc may act differently from other Pc group genes. ..
- Muller J. Transcriptional silencing by the Polycomb protein in Drosophila embryos. EMBO J. 1995;14:1209-20 pubmed..The extent of DNA over which the Pc-G machinery acts is quite selective, as silencing established on one enhancer does not necessarily 'spread' to a juxtaposed synthetic enhancer...
- Adler P, Charlton J, Brunk B. Genetic interactions of the suppressor 2 of zeste region genes. Dev Genet. 1989;10:249-60 pubmed..However, we have found that mutations in Su(z)2 do interact in a variety of interesting ways with mutations in Pc group genes. ..
- Chen S, Birve A, Rasmuson Lestander A. In vivo analysis of Drosophila SU(Z)12 function. Mol Genet Genomics. 2008;279:159-70 pubmed..In addition, we analyzed the binding pattern of Heterochromatin Protein 1 (HP1) and found that SU(Z)12 and HP1 do not co-localize. ..
- Landecker H, Sinclair D, Brock H. Screen for enhancers of Polycomb and Polycomblike in Drosophila melanogaster. Dev Genet. 1994;15:425-34 pubmed..We also show that spalt enhances Polycomb group mutations. These results are discussed with respect to previous estimates of Polycomb group gene number. ..
- Kennison J. The Polycomb and trithorax group proteins of Drosophila: trans-regulators of homeotic gene function. Annu Rev Genet. 1995;29:289-303 pubmed..The ZESTE protein may help to activate transcription by bringing distant cis-regulatory elements closer to promoter-bound proteins. ..
- Estella C, Mckay D, Mann R. Molecular integration of wingless, decapentaplegic, and autoregulatory inputs into Distalless during Drosophila leg development. Dev Cell. 2008;14:86-96 pubmed publisher..The "trigger-maintenance" model describes a mechanism by which secreted morphogens act combinatorially to induce the stable expression of target genes. ..
- Taillebourg E, Dura J. A novel mechanism for P element homing in Drosophila. Proc Natl Acad Sci U S A. 1999;96:6856-61 pubmed..We also suggest that P element homing could be a more frequent phenomenon than generally assumed and that it could become a powerful tool of Drosophila reverse genetics, for which there is no other described gene targeting technique. ..
- Wu C, Jones R, Lasko P, Gelbart W. Homeosis and the interaction of zeste and white in Drosophila. Mol Gen Genet. 1989;218:559-64 pubmed..This report details the observations that several of these mutations also have homeotic effects. ..
- Mishra K, Chopra V, Srinivasan A, Mishra R. Trl-GAGA directly interacts with lola like and both are part of the repressive complex of Polycomb group of genes. Mech Dev. 2003;120:681-9 pubmed..These observations suggest a possible mechanism of how Trl-GAGA plays a role in maintaining the repressed state of target genes involving lolal, which may function as a mediator to recruit PcG complexes. ..
- Wang L, Jahren N, Miller E, Ketel C, Mallin D, Simon J. Comparative analysis of chromatin binding by Sex Comb on Midleg (SCM) and other polycomb group repressors at a Drosophila Hox gene. Mol Cell Biol. 2010;30:2584-93 pubmed publisherb>Sex Comb on Midleg (SCM) is a transcriptional repressor in the Polycomb group (PcG), but its molecular role in PcG silencing is not known...
- Bello B, Holbro N, Reichert H. Polycomb group genes are required for neural stem cell survival in postembryonic neurogenesis of Drosophila. Development. 2007;134:1091-9 pubmed..in postembryonic neuroblast clones is dramatically reduced in the absence of Polycomb, Sex combs extra, Sex combs on midleg, Enhancer of zeste or Suppressor of zeste 12...
- Schultz J, Ponting C, Hofmann K, Bork P. SAM as a protein interaction domain involved in developmental regulation. Protein Sci. 1997;6:249-53 pubmed..A conserved tyrosine in the SAM sequences of the EPH related RPTKs is likely to mediate cell-cell initiated signal transduction via the binding of SH2 containing proteins to phosphotyrosine. ..
- Bornemann D, Miller E, Simon J. The Drosophila Polycomb group gene Sex comb on midleg (Scm) encodes a zinc finger protein with similarity to polyhomeotic protein. Development. 1996;122:1621-30 pubmedThe Sex comb on midleg (Scm) gene is a member of the Polycomb group (PcG) of genes in Drosophila melanogaster. The PcG genes encode transcriptional repressors required for proper spatial expression of homeotic genes...
- Tillib S, Petruk S, Sedkov Y, Kuzin A, Fujioka M, Goto T, et al. Trithorax- and Polycomb-group response elements within an Ultrabithorax transcription maintenance unit consist of closely situated but separable sequences. Mol Cell Biol. 1999;19:5189-202 pubmed..Our results show that long-range maintenance of Ultrabithorax expression requires a complex element composed of cooperating modules, each capable of interacting with both positive and negative chromatin regulators. ..
- Mollaaghababa R, Sipos L, Tiong S, Papoulas O, Armstrong J, Tamkun J, et al. Mutations in Drosophila heat shock cognate 4 are enhancers of Polycomb. Proc Natl Acad Sci U S A. 2001;98:3958-63 pubmed..HSC4 might be needed for the proper folding of a component of the Polycomb repression complex, or it may be a functional member of that complex...
- Ringrose L, Paro R. Remembering silence. Bioessays. 2001;23:566-70 pubmed..The authors' interpretation of these results is discussed here. ..
- Pelegri F, Lehmann R. A role of polycomb group genes in the regulation of gap gene expression in Drosophila. Genetics. 1994;136:1341-53 pubmed..Because Pc-G genes are thought to control gene expression by regulating chromatin, we propose that imprinting at the chromatin level underlies the determination of anteroposterior polarity in the early embryo. ..
- Lu J, Ruhf M, Perrimon N, Leder P. A genome-wide RNA interference screen identifies putative chromatin regulators essential for E2F repression. Proc Natl Acad Sci U S A. 2007;104:9381-6 pubmed..These findings suggest that potential chromatin regulation mediated by Domino and PcG-like factors plays an important role in controlling E2F activity and cell growth. ..
- Ruhf M, Braun A, Papoulas O, Tamkun J, Randsholt N, Meister M. The domino gene of Drosophila encodes novel members of the SWI2/SNF2 family of DNA-dependent ATPases, which contribute to the silencing of homeotic genes. Development. 2001;128:1429-41 pubmed..Altogether, the data lead us to propose that domino acts as a repressor by interfering with chromatin structure. This activity is likely to be performed as a subunit of a chromatin-remodeling complex. ..
- Hagstrom K, Muller M, Schedl P. A Polycomb and GAGA dependent silencer adjoins the Fab-7 boundary in the Drosophila bithorax complex. Genetics. 1997;146:1365-80 pubmed..The iab-7 PRE silencer is contained within a 0.8-kb fragment that spans a nuclease hypersensitive site, and silencing appears to depend on the chromatin remodeling protein, the GAGA factor. ..
- Alfieri C, Gambetta M, Matos R, Glatt S, Sehr P, Fraterman S, et al. Structural basis for targeting the chromatin repressor Sfmbt to Polycomb response elements. Genes Dev. 2013;27:2367-79 pubmed publisher..Our results support a model where DNA tethering of Sfmbt by Pho and multivalent interactions of Sfmbt with histone modifications and other PcG proteins create a hub for PcG protein complex assembly at PREs. ..
- Smith M, Mallin D, Simon J, Courey A. Small ubiquitin-like modifier (SUMO) conjugation impedes transcriptional silencing by the polycomb group repressor Sex Comb on Midleg. J Biol Chem. 2011;286:11391-400 pubmed publisherThe Drosophila protein Sex Comb on Midleg (Scm) is a member of the Polycomb group (PcG), a set of transcriptional repressors that maintain silencing of homeotic genes during development...
- Stankunas K, Berger J, Ruse C, Sinclair D, Randazzo F, Brock H. The enhancer of polycomb gene of Drosophila encodes a chromatin protein conserved in yeast and mammals. Development. 1998;125:4055-66 pubmed
- Yamaguchi M, Yoshida H, Hirose F, Inoue Y, Hayashi Y, Yamagishi M, et al. Ectopic expression of BEAF32A in the Drosophila eye imaginal disc inhibits differentiation of photoreceptor cells and induces apoptosis. Chromosoma. 2001;110:313-21 pubmed..The transgenic flies established in this study should be useful to identify targets of BEAF32A and its positive or negative regulators in Drosophila. ..
- Bai X, Larschan E, Kwon S, Badenhorst P, Kuroda M. Regional control of chromatin organization by noncoding roX RNAs and the NURF remodeling complex in Drosophila melanogaster. Genetics. 2007;176:1491-9 pubmed..Together, these results demonstrate the importance of a local balance between modifying activities that promote and antagonize chromatin compaction within defined chromatin domains in higher organisms. ..
- Ali J, Bender W. Cross-regulation among the polycomb group genes in Drosophila melanogaster. Mol Cell Biol. 2004;24:7737-47 pubmed..These multiple pathways of cross-regulation help to explain the large size of the Polycomb group family of genes, but they complicate the genetic analysis of any single member. ..
- Bienz M, Muller J. Transcriptional silencing of homeotic genes in Drosophila. Bioessays. 1995;17:775-84 pubmed..We propose that this complex consists of specific non-histone proteins, the so-called Polycomb group proteins, and that it is anchored at SIL-M elements and at the promoter. ..
- Remillieux Leschelle N, Santamaria P, Randsholt N. Regulation of larval hematopoiesis in Drosophila melanogaster: a role for the multi sex combs gene. Genetics. 2002;162:1259-74 pubmed..We propose that mxc provides one of the regulatory inputs in larval hematopoiesis that control normal rates of plasmatocyte and crystal lineage proliferation as well as normal rates and timing of hemocyte differentiation. ..
- Mallin D, Myung J, Patton J, Geyer P. Polycomb group repression is blocked by the Drosophila suppressor of Hairy-wing [su(Hw)] insulator. Genetics. 1998;148:331-9 pubmed..These studies suggest that one role of the su(Hw) protein may be to restrict the range of action of repressors, such as the Polycomb group proteins, throughout the euchromatic regions of the genome...
- Saget O, Forquignon F, Santamaria P, Randsholt N. Needs and targets for the multi sex combs gene product in Drosophila melanogaster. Genetics. 1998;149:1823-38 pubmed..We discuss these data in view of the numerous functions of PcG genes during development. ..
- Pirrotta V. Transvection and chromosomal trans-interaction effects. Biochim Biophys Acta. 1999;1424:M1-8 pubmed