RefGenome Electronic Jamboree 2009-02 LONP1

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Orthoset

Ortholog set at PPOD

Participants

Name	Group	Organism(s)/Genome(s)	Notes
Li Ni	MGI	Mouse	Lonp1=MGI:1921392=UniProtKB:Q8CGK3
Rachael Huntley	GOA	Human	LONP1 (P36776)
Stan Laulederkind	RGD	Rat
Donghui Li	TAIR	A. thaliana
Ruth Lovering	BHF-UCL	Human	New GO term: oxidation-dependent protein catabolic processGO:0070407 For the annotation of LONP1, P36776 PMID:12198491 IMP
	ecoliwiki	E. coli	P0A9M0 (lon)
Valerie Wood	other	S. pombe	No papers Annotations up to date based on SGD ISS
Susan Tweedie	flyBase	D. melanogaster	Fly homolog is CG8798. Only one paper with experimental data (PMID:15834148) - no GO terms assigned from this.
Lakshmi Pillai	AgBase	G. gallus	No papers
Karen Christie	SGD	S. cerevisiae
Kimberly Van Auken	WormBase	C. elegans	WBGene00016391 (C34B2.6) - no experimental annotations
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LONP1

<ejamb> 573c5f77b3a094817c4e1c4a6f9b2c99.274339.B4989a9076ebbd

LONP1</ejamb>

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Group	Organism	Gene	Qualifier	GO ID	GO term name	Reference(s)	Evidence Code	with/from	Aspect	Notes	Status
MGI	Mouse	Lonp1		GO:0005739	mitochondrion	PMID:14651853	IDA: Inferred from Direct Assay		C		complete
MGI	Mouse	Lonp1		GO:0005739	mitochondrion	PMID:12657466	IDA: Inferred from Direct Assay		C		complete
MGI	Mouse	Lonp1		GO:0003697	single-stranded DNA binding	PMID:12657466	IDA: Inferred from Direct Assay		F		complete
MGI	Mouse	Lonp1		GO:0016887	ATPase activity	PMID:12657466	IDA: Inferred from Direct Assay		F		complete
MGI	Mouse	Lonp1		GO:0004176	ATP-dependent peptidase activity	PMID:12657466	IDA: Inferred from Direct Assay		F		complete
MGI	Mouse	Lonp1		GO:0006510	ATP-dependent proteolysis	PMID:12657466	IDA: Inferred from Direct Assay		P		complete
GOA	Human	LONP1		GO:0005739	mitochondrion	PMID:8248235	IDA: Inferred from Direct Assay		C		complete
MGI	Mouse	Lonp1		GO:0006200	ATP catabolic process	PMID:12657466	IDA: Inferred from Direct Assay		P		complete
GOA	Human	LONP1		GO:0005759	mitochondrial matrix	PMID:12198491	IMP: Inferred from Mutant Phenotype		C		complete
RGD	Rat	Lonp1		GO:0007568	aging	PMID:15560797	IEP: Inferred from Expression Pattern		P		complete
TAIR	Arabidopsis	Lon3/At3g05780		GO:0005739	mitochondrion	PMID:14671022	IDA: Inferred from Direct Assay		C		complete
RGD	Rat	Lonp1		GO:0010044	response to aluminum ion	PMID:19010380	IEP: Inferred from Expression Pattern		P		complete
TAIR	Arabidopsis	Lon4/At3g05790		GO:0009507	chloroplast	PMID:17478548	IDA: Inferred from Direct Assay		C	GFP fusion assay shows that this protein is located in both mitochondrion and chloroplast	complete
RGD	Rat	Lonp1		GO:0009725	response to hormone stimulus	PMID:10050756	IEP: Inferred from Expression Pattern		P		complete
TAIR	Arabidopsis	Lon4/At3g05790		GO:0005739	mitochondrion	PMID:17478548	IDA: Inferred from Direct Assay		C	GFP fusion assay shows that this protein is located in both mitochondrion and chloroplast	complete
RGD	Rat	Lonp1		GO:0001666	response to hypoxia	PMID:12082077	IEP: Inferred from Expression Pattern		P		complete
TAIR	Arabidopsis	Lon1/At5g26860		GO:0005739	mitochondrion	PMID:17478548	IDA: Inferred from Direct Assay		C	GFP fusion assay shows that this protein is located in mitochondrion but not in chloroplast	complete
RGD	Rat	Lonp1		GO:0005759	mitochondrial matrix	PMID:15560797	IDA: Inferred from Direct Assay		C		complete
TAIR	Arabidopsis	Lon1/At5g26860	NOT	GO:0009507	chloroplast	PMID:17478548	IDA: Inferred from Direct Assay		C	GFP fusion assay shows that this protein is located in mitochondrion but not in chloroplast	complete
RGD	Rat	Lonp1		GO:0007568	aging	PMID:15560797	IEP: Inferred from Expression Pattern		P		complete
RGD	Rat	Lonp1		GO:0007568	aging	PMID:15560797	IEP: Inferred from Expression Pattern		P		complete
RGD	Rat	Lonp1		GO:0010044	response to aluminum ion	PMID:19010380	IEP: Inferred from Expression Pattern		P		complete
RGD	Rat	Lonp1		GO:0009725	response to hormone stimulus	PMID:10050756	IEP: Inferred from Expression Pattern		P		complete
RGD	Rat	Lonp1		GO:0001666	response to hypoxia	PMID:12082077	IEP: Inferred from Expression Pattern		P		complete
RGD	Rat	Lonp1		GO:0005759	mitochondrial matrix	PMID:15560797	IDA: Inferred from Direct Assay		C		complete
TAIR	Arabidopsis	Lon1/At5g26860		GO:0005524	ATP binding	PMID:17137349	IDA: Inferred from Direct Assay		F	affinity chromatography shows that this protein binds to ATP	complete
BHF-UCL	Human	LONP1		GO:0042645	mitochondrial nucleoid	PMID:18063578	IDA: Inferred from Direct Assay		C		complete
GOA	Human	LONP1		GO:0051260	protein homooligomerization	PMID:14739292	IDA: Inferred from Direct Assay		P		complete
GOA	Human	LONP1		GO:0006510	ATP-dependent proteolysis	PMID:17420247	IDA: Inferred from Direct Assay		P		complete
GOA	Human	LONP1		GO:0006510	ATP-dependent proteolysis	PMID:8248235	IDA: Inferred from Direct Assay		P		complete
GOA	Human	LONP1		GO:0001666	response to hypoxia	PMID:17418790	IEP: Inferred from Expression Pattern		P		complete
GOA	Human	LONP1		GO:0007005	mitochondrion organization	PMID:15683722	IMP: Inferred from Mutant Phenotype		P		complete
GOA	Human	LONP1		GO:0034599	cellular response to oxidative stress	PMID:12198491	IC: Inferred by Curator	GO:0019941	P		complete
GOA	Human	LONP1		GO:0034599	cellular response to oxidative stress	PMID:17420247	IDA: Inferred from Direct Assay		P		complete
GOA	Human	LONP1		GO:0070407		PMID:12198491	IMP: Inferred from Mutant Phenotype			New term: oxidized protein catabolic process	required field missing
GOA	Human	LONP1		GO:0004176	ATP-dependent peptidase activity	PMID:17420247	IDA: Inferred from Direct Assay		F		complete
GOA	Human	LONP1		GO:0051880	G-quadruplex DNA binding	PMID:18174225	IDA: Inferred from Direct Assay		F		complete
GOA	Human	LONP1		GO:0043565	sequence-specific DNA binding	PMID:14739292	IDA: Inferred from Direct Assay		F		complete
GOA	Human	LONP1		GO:0043531	ADP binding	PMID:14739292	IDA: Inferred from Direct Assay		F		complete
GOA	Human	LONP1		GO:0005524	ATP binding	PMID:14739292	IDA: Inferred from Direct Assay		F		complete
GOA	Human	LONP1		GO:0004176	ATP-dependent peptidase activity	PMID:8248235	IDA: Inferred from Direct Assay		F		complete
GOA	Human	LONP1		GO:0003727	single-stranded RNA binding	PMID:14739292	IDA: Inferred from Direct Assay		F		complete
GOA	Human	LONP1		GO:0005515	protein binding	PMID:14739292	IPI: Inferred from Physical Interaction	Q96RR1	F		complete
GOA	Human	LONP1		GO:0070182	DNA polymerase binding	PMID:14739292	IPI: Inferred from Physical Interaction	P54098	F		complete
EcoliWiki	E. coli	lon		GO:0006510	ATP-dependent proteolysis	PMID:6458036	IDA: Inferred from Direct Assay		P	Purified Lon was assayed for release of radiolabeled Pi from [gamma-32P]ATP and an acid insoluble form of the [3H]-alpha-casein substrate. Release of the products was measured after TCA precipitation by scintillation counting at time points over 4 hours	complete
EcoliWiki	E. coli	lon		GO:0006508	proteolysis	PMID:6458036	IDA: Inferred from Direct Assay		P		complete
EcoliWiki	E. coli	lon		GO:0017111	nucleoside-triphosphatase activity	PMID:6458036	IDA: Inferred from Direct Assay		F	ATPase activity of purified Lon was measured by addition of radiolabeled ATP, either [gamma-32P]ATP or [purine-3H]ATP, and analysis of released Pi by TLC	complete
EcoliWiki	E. coli	lon		GO:0008233	peptidase activity	PMID:9720920	IDA: Inferred from Direct Assay		F	Full-length Lon (Lon-NAP) and its proteolytic domain (Lon-P) were each tagged with a GST moeity, expressed from a plasmid and purified using GST tag, which was subsequently removed by thrombin cleavage. LonNAP and Lon-P were then assayed for proteolytic activity using a radiolabeled protein, [14C]acetyl-alpha-casein, or peptidase activity using melittin, a 26aa peptide, as the substrate in the presence or absence of ATP. The products were separated by HPLC and LonNAP was shown to require ATP for proteolysis and peptidase activity, while LonP retained only peptidase activity, even without the addition of ATP.	complete
EcoliWiki	E. coli	lon		GO:0004176	ATP-dependent peptidase activity	PMID:9720920	IDA: Inferred from Direct Assay		F		complete
EcoliWiki	E. coli	lon		GO:0005737	cytoplasm	PMID:8995294	IDA: Inferred from Direct Assay		C	After sonication, Lon was isolated from the supernatant of a centrifugation performed at 27 000 x g for 60 minutes at 4oC and purified over a Q-sepharose, heparin-sepharose and DNA affinity column in KCl buffer.	complete
EcoliWiki	E. coli	lon		GO:0003677	DNA binding	PMID:8995294	IDA: Inferred from Direct Assay		F	Lon was present in the eluant (and N-terminally sequenced) after DNA affinity chromatography (see Figures 2 & 4) and was shown to bind a double-stranded DNA by a SouthWestern blotting.	complete
EcoliWiki	E. coli	lon		GO:0006950	response to stress	PMID:6330035	IEP: Inferred from Expression Pattern		P	The relative rate of synthesis of Lon, measured over a time course of 10 minutes, rapidly increased upon shifting a culture from 28oC to 42oC. Additionally, B strains of E. coli are generally lon- and when shifted to 45oC from 28oC, do not show an increase in the spot corresponding to Lon. In contrast, a K-12 strain has a much more obvious increase in spot size corresponding to Lon.	complete
EcoliWiki	E. coli	lon		GO:0004252	serine-type endopeptidase activity	PMID:15606774	IMP: Inferred from Mutant Phenotype		F	Wild-type Lon, Lon-S679A and Lon-K722Q were assayed for proteolytic and peptidase activity using beta-casein and a thioester as substrates, respectively. Ser679 was identified as the catalytic serine and mutation to Ala at this position resulted in no enzymatic activity. Mutation of conserved Lys722 also resulted in no catalytic activity.	complete
EcoliWiki	E. coli	lon		GO:0005524	ATP binding	PMID:15037242	IPI: Inferred from Physical Interaction		F	Crystal structure of the alpha domain of E. coli Lon with the ATP analog, AMP-PNP.	complete
GOA	Human	LONP1		GO:0070361	mitochondrial light strand promoter anti-sense binding	PMID:9485316	IDA: Inferred from Direct Assay		F		complete
GOA	Human	LONP1		GO:0070362	mitochondrial heavy strand promoter anti-sense binding	PMID:9485316	IDA: Inferred from Direct Assay		F		complete
GOA	Human	LONP1	NOT	GO:0070363	mitochondrial light strand promoter sense binding	PMID:9485316	IDA: Inferred from Direct Assay		F		complete
GOA	Human	LONP1	NOT	GO:0070364	mitochondrial heavy strand promoter sense binding	PMID:9485316	IDA: Inferred from Direct Assay		F		complete
SGD	S. cerevisiae	PIM1		GO:0004176	ATP-dependent peptidase activity	PMID:8146662|PMID:8276800	IMP: Inferred from Mutant Phenotype		F		complete
SGD	S. cerevisiae	PIM1		GO:0006515	misfolded or incompletely synthesized protein catabolic process	PMID:7957078	IGI: Inferred from Genetic Interaction	SGD:SSC1	P		complete
SGD	S. cerevisiae	PIM1		GO:0006515	misfolded or incompletely synthesized protein catabolic process	PMID:7957078	IMP: Inferred from Mutant Phenotype		P		complete
MGI	Mouse	Lonp1		GO:0070361	mitochondrial light strand promoter anti-sense binding	PMID:12657466	IDA: Inferred from Direct Assay		F		complete
SGD	S. cerevisiae	PIM1		GO:0034619	cellular chaperone-mediated protein complex assembly	PMID:8810243	IGI: Inferred from Genetic Interaction	SGD:YTA12|SGD:AFG3	P		complete
SGD	S. cerevisiae	PIM1		GO:0005759	mitochondrial matrix	PMID:8146662|PMID:8276800	IMP: Inferred from Mutant Phenotype		C		complete
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Notes

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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

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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

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