RefGenome Electronic Jamboree 2009-02 LONP1

From GONUTS

See the talk page for tips on editing the tables and for misc. discussion.

Orthoset

Ortholog set at PPOD

Participants

LONP1

Notes

New terms requested;
oxidized protein catabolic process GO:0070407 (BHF-UCL)
mitochondrial light strand promoter anti-sense binding GO:0070361 (GOA)
mitochondrial light strand promoter sense binding GO:0070363 (GOA)
mitochondrial heavy strand promoter anti-sense binding GO:0070362 (GOA)
mitochondrial heavy strand promoter sense binding GO:0070364 (GOA)

discussion topics

1. modification-dependent protein catabolic process (GO:0019941) -Suggestion to rename as modification-initiated protein catabolic process (UK curation groups)

2. Why don’t all ATP-x activity terms have ATP binding as a child? (Val)

3. Annotation inconsistency query with regards to an EcoliWiki annotation – why annotate to GO:0017111 nucleoside-triphosphatase activity from PMID:6458036 but not the child terms ATPase activity or CTPase activity? (UK curation groups)

Minutes

Karen was concerned about the level of granularity for some process terms she was able to assign to this gene. For example, ATP dependent proteolysis is at a high level in the tree as a direct child of proteolysis (it is not even a child of cellular proteolysis). This term isn't really necessary as a process term as ATP-dependence is captured by the function, ‘ATP-dependent peptidase’ and if ATP-dept proteolysis did not add anything then it should be merged with proteolysis and perhaps terms such as ‘cellular catabolic process’ should be used in annotations instead.

AI: Karen to create SourceForge item regarding the validity of the ‘ATP dependent proteolysis’ term


Val: Additional granularity should be provided by being able to represent mitochondrial-specific events.

Harold: The current take on things appears to be that new terms based on a specific subcellular location are only made if there is a fundamental difference in the reaction mechanism at that site. Annotating concurrently with a generic process term together with the cellular component term mitochondrion captures the full annotation.

Val argued that if it is a different set of protein involved in the process then it is distinct enough to merit a separate term. Val also argued for having the location within a more granular term because it makes it easier for users to get meaningful results with term enrichment analysis tools which don't work with a combination of terms - without a single granular term you couldn't use over-representation to pull out genes involved the mitochondrial process.

Harold pointed out that several mitochondrial specific terms had previously existed but were removed because the reaction mechanism wasn't distinct. However there does seem to be some inconsistency with the was this is handle at the moment. [Example given was amino acylate tRNA synthetase genes with and without leader - working in both mitochondria and cytoplasm terms with terms for each even though the reaction is the same wherever it occurs?? - can't find these terms is correct?]. [RL-maybe this is what is meant:GO:0070127 tRNA aminoacylation for mitochondrial protein translation]

AI: Karen to GO email list with a view to clarifying this policy. Should we make organelle specific terms for processes [and functions?] that aren't mechanistically different but use different gene sets? GOC agenda item [?]

MGI raised the issue that there was an apparent conflict between mouse and human in terms of the specificity of binding to mitochondrial promoters. Some negative results had not been captured from mouse data that apparently conflicted with the human annotations. At least some of this was explained by the fact that the human annotations are qualified with NOT but this is not shown on the summary table used to compare species. Conclusion was that MGI would add the negative annotations to the mouse protein and assume any remaining conflicts are a true reflection of the data.

There are annotations for both 'ATP-dependent peptidase activity' and 'ATP-dependent proteolysis' - is there a difference between these? Pointless if there is no distinction e.g. peptide v protein. Do we need both terms?

RL- both terms are needed-one is process one is function but the key thing is to standardise the use of peptidolysis v proteolysis and peptidase v protease. Following pressure from protein community HGNC had to change all gene names from protease to peptidase.

AI: [Karen?] Does this term need to be there and is it in the right place? -> source forge

Both ATP-dependent terms imply ATP binding but this annotation is not always made. Karen doesn't do it unless it is shown directly. Some discussion about whether there should be an explicit relationship between such terms. Apparently were was at some point but this caused TPV problems. Concurrent annotations now used instead. RL-notes The explicit relationship between ATP binding and ATP-dependent terms was not made because in some protein complexes one protein binds the ATP and another protein has the ATP-dependent activity.

Debbie: Claims documentation says not to annotate to binding of a substrate (such as ATP).

AI: Debbie: to circulate where in the documentation it says not to annotate to binding

Harold and Karen are in favour of only annotating with exp evidence when there is a binding curve, or other such direct binding evidence, instead of just assuming it binds to ATP as it is included in the in vitro reaction mixture. Emily - what a protein binds to in an in vitro situation may not always be an accurate representation of what it binds in vivo (e.g. inclusion of certain metal ions)

There was concern about the aging annotation based on IEP in rat. Is it really involved in the process? Cause and effect hard to prove. Ruth argues it should be IC from the fact it degrades oxidised proteins. Is aging a valid process at all? Include senescence which is. General consensus is that this annotation is not valid. IEP-evidence should be used for expression of a gene being annotated and not the expression of targets.

Modification-dependent protein catabolic process (GO:0019941) was assigned to human LONP1 even though it isn't strictly modification-dependent (LONP1 also works on unmodified protein to some extent). The definition states catabolism is 'initiated by the covalent modification of the target protein' so it was suggested that the term be renamed modification-initiated protein catabolic process to reflect the definition more accurately. Seems like there may be a baseline of unmodified protein catabolism so it isn't really dependent. It was pointed out the baseline may be due to recognition of mis-folded proteins. There was concern about changing this based on one paper - there is a whole slew of related terms. Also the current term name is more consistent with what is talked about in the literature.

AI: Ruth: add 'modification-initiated protein catabolic process' as a synonym instead and also add a synonym that includes the word proteolysis.

Annotation inconsistency query with regards to an EcoliWiki annotation – why annotate to GO:0017111 nucleoside-triphosphatase activity from PMID:6458036 but not the child terms ATPase activity or CTPase activity? This was simply an error.

AI: Debbie to add specific terms.

References

See Help:References for how to manage references in GONUTS.

1. ↑ ^{1.0 1.1 1.2 1.3} Bota DA & Davies KJ (2002) Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism. Nat Cell Biol 4: 674-80 PubMed GONUTS page
2. ↑ Laviolette MJ et al. (2005) A genetic screen for suppressors of Drosophila NSF2 neuromuscular junction overgrowth. Genetics 170: 779-92 PubMed GONUTS page
3. ↑ Mootha VK et al. (2003) Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria. Cell 115: 629-40 PubMed GONUTS page
4. ↑ ^{4.0 4.1 4.2 4.3 4.4 4.5 4.6} Lu B et al. (2003) The ATP-dependent Lon protease of Mus musculus is a DNA-binding protein that is functionally conserved between yeast and mammals. Gene 306: 45-55 PubMed GONUTS page
5. ↑ ^{5.0 5.1 5.2} Wang N et al. (1993) A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease. Proc Natl Acad Sci U S A 90: 11247-51 PubMed GONUTS page
6. ↑ ^{6.0 6.1 6.2 6.3 6.4} Delaval E et al. (2004) Age-related impairment of mitochondrial matrix aconitase and ATP-stimulated protease in rat liver and heart. Eur J Biochem 271: 4559-64 PubMed GONUTS page
7. ↑ Heazlewood JL et al. (2004) Experimental analysis of the Arabidopsis mitochondrial proteome highlights signaling and regulatory components, provides assessment of targeting prediction programs, and indicates plant-specific mitochondrial proteins. Plant Cell 16: 241-56 PubMed GONUTS page
8. ↑ ^{8.0 8.1} Kumar V et al. (2009) Susceptibility of mitochondrial superoxide dismutase to aluminium induced oxidative damage. Toxicology 255: 117-23 PubMed GONUTS page
9. ↑ ^{9.0 9.1 9.2 9.3} Ostersetzer O et al. (2007) Multiple intracellular locations of Lon protease in Arabidopsis: evidence for the localization of AtLon4 to chloroplasts. Plant Cell Physiol 48: 881-5 PubMed GONUTS page
10. ↑ ^{10.0 10.1} Luciakova K et al. (1999) Enhanced mitochondrial biogenesis is associated with increased expression of the mitochondrial ATP-dependent Lon protease. FEBS Lett 444: 186-8 PubMed GONUTS page
11. ↑ ^{11.0 11.1} Hori O et al. (2002) Transmission of cell stress from endoplasmic reticulum to mitochondria: enhanced expression of Lon protease. J Cell Biol 157: 1151-60 PubMed GONUTS page
12. ↑ Ito J et al. (2006) Analysis of the soluble ATP-binding proteome of plant mitochondria identifies new proteins and nucleotide triphosphate interactions within the matrix. J Proteome Res 5: 3459-69 PubMed GONUTS page
13. ↑ Bogenhagen DF et al. (2008) The layered structure of human mitochondrial DNA nucleoids. J Biol Chem 283: 3665-75 PubMed GONUTS page
14. ↑ ^{14.0 14.1 14.2 14.3 14.4 14.5 14.6} Liu T et al. (2004) DNA and RNA binding by the mitochondrial lon protease is regulated by nucleotide and protein substrate. J Biol Chem 279: 13902-10 PubMed GONUTS page
15. ↑ ^{15.0 15.1 15.2} Lu B et al. (2007) Roles for the human ATP-dependent Lon protease in mitochondrial DNA maintenance. J Biol Chem 282: 17363-74 PubMed GONUTS page
16. ↑ Fukuda R et al. (2007) HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 129: 111-22 PubMed GONUTS page
17. ↑ Bota DA et al. (2005) Downregulation of the human Lon protease impairs mitochondrial structure and function and causes cell death. Free Radic Biol Med 38: 665-77 PubMed GONUTS page
18. ↑ Chen SH et al. (2008) Thermodynamic characterization of specific interactions between the human Lon protease and G-quartet DNA. Nucleic Acids Res 36: 1273-87 PubMed GONUTS page
19. ↑ ^{19.0 19.1 19.2} Charette MF et al. (1981) ATP hydrolysis-dependent protease activity of the lon (capR) protein of Escherichia coli K-12. Proc Natl Acad Sci U S A 78: 4728-32 PubMed GONUTS page
20. ↑ ^{20.0 20.1} Rasulova FS et al. (1998) The isolated proteolytic domain of Escherichia coli ATP-dependent protease Lon exhibits the peptidase activity. FEBS Lett 432: 179-81 PubMed GONUTS page
21. ↑ ^{21.0 21.1} Fu GK et al. (1997) Bacterial protease Lon is a site-specific DNA-binding protein. J Biol Chem 272: 534-8 PubMed GONUTS page
22. ↑ Phillips TA et al. (1984) lon gene product of Escherichia coli is a heat-shock protein. J Bacteriol 159: 283-7 PubMed GONUTS page
23. ↑ Rotanova TV et al. (2004) Classification of ATP-dependent proteases Lon and comparison of the active sites of their proteolytic domains. Eur J Biochem 271: 4865-71 PubMed GONUTS page
24. ↑ Botos I et al. (2004) Crystal structure of the AAA+ alpha domain of E. coli Lon protease at 1.9A resolution. J Struct Biol 146: 113-22 PubMed GONUTS page
25. ↑ ^{25.0 25.1 25.2 25.3} Fu GK & Markovitz DM (1998) The human LON protease binds to mitochondrial promoters in a single-stranded, site-specific, strand-specific manner. Biochemistry 37: 1905-9 PubMed GONUTS page
26. ↑ ^{26.0 26.1} Suzuki CK et al. (1994) Requirement for the yeast gene LON in intramitochondrial proteolysis and maintenance of respiration. Science 264: 273-6 PubMed GONUTS page
27. ↑ ^{27.0 27.1} Van Dyck L et al. (1994) PIM1 encodes a mitochondrial ATP-dependent protease that is required for mitochondrial function in the yeast Saccharomyces cerevisiae. J Biol Chem 269: 238-42 PubMed GONUTS page
28. ↑ ^{28.0 28.1} Wagner I et al. (1994) Molecular chaperones cooperate with PIM1 protease in the degradation of misfolded proteins in mitochondria. EMBO J 13: 5135-45 PubMed GONUTS page
29. ↑ Rep M et al. (1996) Promotion of mitochondrial membrane complex assembly by a proteolytically inactive yeast Lon. Science 274: 103-6 PubMed GONUTS page