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Curator prediction of NOT kinase activity

Valerie Wood val at sanger.ac.uk
Wed Mar 8 08:45:42 PST 2006


Sandra Orchard wrote:
> 
> I annotated both the mammalian Wnk kinases and the NRBP kinases (which
> are the set which started this argument). The Wnk kinases are identified
> as active by one of the ProSite patterns and only just fail the other,
> the NRBP kinases fail both so the Wnk kinases would have received the
> correct annotation even in the lack of experimental evidence, of which
> there is actually plenty. In the case of the Wnk kinases the catalytic
> site is slightly deformed and the catalytic lysine has just moved by a
> few residues, the NRBP kinases completely lack required catalytic
> residues and have a highly degraded ATP binding site site. It is
> possible to separate out an unusual kinase from an inactive one with a
> high degree of probability.

Sorry if I seem to be going round in circles here....

If it is possible for a person to separate these out, isn't it possible
to build hmms which are specific to these particular instances so 'NRBP
nuclear receptor binding proteins' were a separate family? but still
part of a the Protein kinase superfamily clan?  

This family would then be analogous to the other protein kinase
superfamily members which are unlikely to have protein kinase activity,
but have a similar fold, like ABC1
http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF03109


It just seems like these are subfamilies which are only distantly
related to protein kinases and should be separated out?

http://www.sanger.ac.uk/cgi-bin/Pfam/getallproteins.pl?name=Pfam-B_14955&acc=PB014955&type=full&verbose=true&zoom_factor=0.5&list=View+Graphic

I suppose this would just take too long on a case by case basis.....

Val 






> 
> Sandra
> 
> Valerie Wood wrote:
> 
> >>it is also possible that they use a modified
> >>catalytic mechanism that does not require these
> >>residues. This has been shown for the Wnk
> >>family, where Lys13 is thought to replace Lys30
> >>in adenosine triphosphate (ATP) binding (25)."
> >>
> >>In other words, nobody knows what they do, so we annotated to
> >>'unknown' since we were uncomfortable with 'protein kinase activity.'
> >>
> >>
> >>
> >
> >
> >In that case, because it is impossible for a curator to know whether
> >some family members have evolved to use alternative catalytic residues
> >to the ones they are familiar with, probably means it is best  to
> >reserve NOT for experimental codes......
> >
> >I am quite happy to see protein kinase family members annotated to
> >protein kinase activity 'with' ISS, even if they lack residues which are
> >presumed to be required (providing these fulfill other criteria for
> >family membership when clustered), because, presumably anybody doing an
> >experiment would test this, and the NOT would be added if this was shown
> >not to be the case....
> >
> >Although Karen, I can see your reasoning for annotating to function
> >unknown, but if somebody wanted to retrieve all proteins which were
> >likely to be kinases, based on sequence similarity wouldn't they also
> >want to retrieve these gene products? After all this is a reasonable
> >inference.....Sometimes using 'unknown' means these will not come to the
> >attention of people who may be interested in them as potential protein
> >kinases.
> >
> >Val
> >
> >
> >
> >>Karen
> >>
> >>At 07:54 AM 3/8/2006, Alexander D. Diehl wrote:
> >>
> >>
> >>
> >>>Hi,
> >>>
> >>>Sorry to be so late on this discussion, but I would like suggest
> >>>that perhaps the annotation is inappropriate on the grounds that NOT
> >>>annotations in general are very tricky assertions, and are best
> >>>based on actual experimental evidence, which itself is very
> >>>dependent on the experimental conditions used.  There's a universe
> >>>of proteins that I could provide NOT kinase activity for, but of
> >>>course most people would not confuse them with kinases.  The
> >>>question here is more whether the original algorithms for predicting
> >>>kinase activity need to be refined so that proteins lacking the
> >>>correct residues in the active site are not flagged as kinases in
> >>>the first place.  Such refinement, of course, ought best to be based
> >>>on experimental evidence (wet science) that feeds the computational
> >>>algorithm development, and that's where expert input is needed.
> >>>
> >>>I thus vote against any annotation at all in this case.
> >>>
> >>>-- Alex
> >>>
> >>>
> >>>Evelyn Camon wrote:
> >>>
> >>>
> >>>
> >>>>>what were the objections to a GO_REF, this would be unambiguous
> >>>>>
> >>>>>
> >>>>Hi,
> >>>>
> >>>>The issue of using the GO_REF vs extension of the evidence codes
> >>>>is on
> >>>>the GO Consortium meeting agenda.
> >>>>
> >>>>Arguments against GO_REF include:
> >>>>
> >>>>I don't think the users will read about GO_REF (is that our
> >>>>problem?)
> >>>>I don't think the users will even see GO_REF in most tools,
> >>>>microarray, we are also limited in UniProt ffl to 4 fields of GO
> >>>>information
> >>>>Users can filter on GO_REF plus evidence code but are we simply
> >>>>avoiding extending the number of useful GO evidence codes, for
> >>>>manual codes I can see that extending the codes might slow down
> >>>>curation but for more granular IEA codes, they are created
> >>>>electronically so no extra effort from curator required.
> >>>>Biology is complex. Although I don't like to see information lost
> >>>>I think we further complicate what was a simple annotation process
> >>>>and output.
> >>>>
> >>>>Arguments in favour GO_REF include:
> >>>>
> >>>>many different techniques not practical (or is it) to create ne
> >>>>evidence codes, helps to disambiguate annotations
> >>>>
> >>>>I am really not wishing to start a new thread here...can we leave
> >>>>GO_REF and codes to Consortium meeting, I am still collecting
> >>>>ideas..you could reply to me directly if you wish me to collect
> >>>>further 'for' and 'aganist' examples for discussion.
> >>>>
> >>>>cheers
> >>>>Evelyn
> >>>>
> >>>>
> >>>>
> >>>>
> >>>>>So all annotations which use
> >>>>>
> >>>>>NOT with the ISS evidence code and GO_REF:xxx and a dbxref to an
> >>>>>alignment
> >>>>>mean that:
> >>>>>
> >>>>>The curator or an expert have looked at  the alignment of this
> >>>>>sequence
> >>>>>to the associated database entry, protein family or hmm, and on
> >>>>>the
> >>>>>basis of the absence of critical residues have inferred that this
> >>>>>family
> >>>>>member is unlikely possess the associated activity.
> >>>>>
> >>>>>Or words to that effect.
> >>>>>
> >>>>>
> >>>>>
> >>>>>David Hill wrote:
> >>>>>
> >>>>>
> >>>>>
> >>>>>> I can see your point, but that would mean that every database
> >>>>>> should
> >>>>>> have an internal ISS reference. We have one, but it is only for
> >>>>>> orthology and subsequent inheritence of GO terms. Our's doesn't
> >>>>>> address
> >>>>>> this issue of a NOT. I think in either case, a User might be
> >>>>>> confused.
> >>>>>> If I were a naive User and I saw the annotation as you
> >>>>>> describe, I might
> >>>>>> think the NOT was a mistake becasue the proteins were so
> >>>>>> similar. If the
> >>>>>> protein in the with field is taken from the paper that
> >>>>>> discusses the
> >>>>>> critical residues, then maybe it would be less confusing. I'm
> >>>>>> not sure.
> >>>>>> I think we could generate confusion both ways.
> >>>>>>
> >>>>>> David
> >>>>>>
> >>>>>> Pascale Gaudet wrote:
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>>>Hi,
> >>>>>>>
> >>>>>>>Is this allowed? I thought that the reference had to directly
> >>>>>>>relate
> >>>>>>>to the annotation. In this case I would have used our
> >>>>>>>standard
> >>>>>>>'dictybase curators ISS' reference, because that's how the
> >>>>>>>annotation
> >>>>>>>was made.
> >>>>>>>
> >>>>>>>If I was to see the annotation as you describe it, I might be
> >>>>>>>tempted
> >>>>>>>to go and look at the reference, and I would be very confused
> >>>>>>>because
> >>>>>>>it doesn't talk about the protein at all.
> >>>>>>>
> >>>>>>>Pascale
> >>>>>>>
> >>>>>>>
> >>>>>>>At 07:49 AM 3/8/2006 -0500, David Hill wrote:
> >>>>>>>
> >>>>>>>
> >>>>>>>
> >>>>>>>
> >>>>>>>> This is a bit out of the ordinary, but what about an ISS
> >>>>>>>> evidence
> >>>>>>>> code with an active kinase and then a reference to a paper
> >>>>>>>> that
> >>>>>>>> identifies the critical residues for kinase activity?
> >>>>>>>>
> >>>>>>>> David
> >>>>>>>>
> >>>>>>>> Midori Harris wrote:
> >>>>>>>>
> >>>>>>>>
> >>>>>>>>
> >>>>>>>>
> >>>>>>>>>Seems to me it would be a valuable part of the story, but
> >>>>>>>>>not
> >>>>>>>>>necessarily the whole thing. It would tell you what the
> >>>>>>>>>important
> >>>>>>>>>residues are, but would miss out the part about observing
> >>>>>>>>>that those
> >>>>>>>>>residues are altered/absent in this particular protein.
> >>>>>>>>>Also, citing
> >>>>>>>>>only the important-residue reference could give the
> >>>>>>>>>impression that
> >>>>>>>>>that paper (or whatever it is) actually states that
> >>>>>>>>>protein XYZ
> >>>>>>>>>doesn't have the activity -- which I assume is not the
> >>>>>>>>>case.
> >>>>>>>>>
> >>>>>>>>>m
> >>>>>>>>>
> >>>>>>>>>On Wed, 8 Mar 2006, jyoti khadake wrote:
> >>>>>>>>>
> >>>>>>>>>
> >>>>>>>>>
> >>>>>>>>>
> >>>>>>>>>
> >>>>>>>>>
> >>>>>>>>>>Hi,
> >>>>>>>>>>
> >>>>>>>>>>In this particular instance would the reference which
> >>>>>>>>>>identifies
> >>>>>>>>>>residues important for the kinase activity in members of
> >>>>>>>>>>the family
> >>>>>>>>>>be the appropriate reference?
> >>>>>>>>>>
> >>>>>>>>>>JK
> >>>>>>>>>>
> >>>>>>>>>>Midori Harris wrote:
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>> The reference has to identify the source of the
> >>>>>>>>>>> information. In
> >>>>>>>>>>> this case,
> >>>>>>>>>>> it comes from what the curator knows, and from the work
> >>>>>>>>>>> she did
> >>>>>>>>>>> examining
> >>>>>>>>>>> the protein sequence. So I don't think the protein ID
> >>>>>>>>>>> would suffice,
> >>>>>>>>>>> because it would capture nothing of the curator's
> >>>>>>>>>>> involvement. The
> >>>>>>>>>>> advantage of a GO_REF is that we could include
> >>>>>>>>>>> everything the
> >>>>>>>>>>> curator did,
> >>>>>>>>>>> and make it unambiguous ... but it's not for me to
> >>>>>>>>>>> decide whether
> >>>>>>>>>>> that
> >>>>>>>>>>> advantage outweighs the problems (btw, what are the
> >>>>>>>>>>> arguments
> >>>>>>>>>>> against a
> >>>>>>>>>>> GO_REF?)
> >>>>>>>>>>>
> >>>>>>>>>>> m
> >>>>>>>>>>>
> >>>>>>>>>>> On Wed, 8 Mar 2006, Emily Dimmer wrote:
> >>>>>>>>>>>
> >>>>>>>>>>>
> >>>>>>>>>>>
> >>>>>>>>>>>
> >>>>>>>>>>>
> >>>>>>>>>>>
> >>>>>>>>>>>
> >>>>>>>>>>>>So if using the ISS code with these kinds of
> >>>>>>>>>>>>annotations, what
> >>>>>>>>>>>>reference information should be provided? Should the
> >>>>>>>>>>>>reference
> >>>>>>>>>>>>field refer back to the protein's identifier? Or to a
> >>>>>>>>>>>>specific
> >>>>>>>>>>>>GO_REF (which isn't ideal)
> >>>>>>>>>>>>e.g.
> >>>>>>>>>>>>UniProt     P12345      GO:0004672
> >>>>>>>>>>>>UniProt:P12345
> >>>>>>>>>>>>ISS   F
> >>>>>>>>>>>>protein    taxon:9606 20060308       UniProt
> >>>>>>>>>>>>
> >>>>>>>>>>>>Midori Harris wrote:
> >>>>>>>>>>>>
> >>>>>>>>>>>>
> >>>>>>>>>>>>
> >>>>>>>>>>>>
> >>>>>>>>>>>>
> >>>>>>>>>>>>
> >>>>>>>>>>>>
> >>>>>>>>>>>>
> >>>>>>>>>>>>>The documentation for ISS says that it can be used
> >>>>>>>>>>>>>for predicted
> >>>>>>>>>>>>>or observed sequence features, and that in such
> >>>>>>>>>>>>>cases the 'with'
> >>>>>>>>>>>>>field can be left blank. If we choose to regard
> >>>>>>>>>>>>>altered 'active'
> >>>>>>>>>>>>>site residues as features -- which seems reasonable
> >>>>>>>>>>>>>-- ISS will
> >>>>>>>>>>>>>work.
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>Also, using IC would not solve the reference
> >>>>>>>>>>>>>problem, so you
> >>>>>>>>>>>>>would still have to either (a) make a GO_REF entry
> >>>>>>>>>>>>>or (b) think
> >>>>>>>>>>>>>of something else to use as the reference.
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>m
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>On Wed, 8 Mar 2006, Evelyn Camon wrote:
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>> ok..so sequence similar to what?? the
> >>>>>>>>>>>>>> sequence/domain for the
> >>>>>>>>>>>>>> active kinase??? or could we have Inferred by
> >>>>>>>>>>>>>> Curator from
> >>>>>>>>>>>>>> Sequence (ICS??)..hmmm
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>> Ev
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>> Valerie Wood wrote:
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>I think I prefer ISS, because this is
> >>>>>>>>>>>>>>>essentially a judgement
> >>>>>>>>>>>>>>>which has
> >>>>>>>>>>>>>>>been made by assessing the sequence.....
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>Evelyn Camon wrote:
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>> Hi,
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>> I'm not keen on the GO_REF idea I'm
> >>>>>>>>>>>>>>>> afraid...could we propose
> >>>>>>>>>>>>>>>> that IC
> >>>>>>>>>>>>>>>> could be used without GO ID on these odd
> >>>>>>>>>>>>>>>> occasions...not sure
> >>>>>>>>>>>>>>>> what
> >>>>>>>>>>>>>>>> publication you would use though...
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>> Ev
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>> Sandra Orchard wrote:
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>Most kinase recognition patterns are HMMs
> >>>>>>>>>>>>>>>>>which can only
> >>>>>>>>>>>>>>>>>predict a
> >>>>>>>>>>>>>>>>>domain but will not tell you if it is active
> >>>>>>>>>>>>>>>>>or not. The
> >>>>>>>>>>>>>>>>>kinases in
> >>>>>>>>>>>>>>>>>these examples were hit by the HMMs. The only
> >>>>>>>>>>>>>>>>>method which
> >>>>>>>>>>>>>>>>>will give any
> >>>>>>>>>>>>>>>>>indication of activity are ProSite patterns
> >>>>>>>>>>>>>>>>>which
> >>>>>>>>>>>>>>>>>specifically say a
> >>>>>>>>>>>>>>>>>particular residue needs to be in a particulr
> >>>>>>>>>>>>>>>>>position. The
> >>>>>>>>>>>>>>>>>HMMs are
> >>>>>>>>>>>>>>>>>correct in that these are part of the kinase
> >>>>>>>>>>>>>>>>>family, but are
> >>>>>>>>>>>>>>>>>inactive
> >>>>>>>>>>>>>>>>>members of it, they are not false positives
> >>>>>>>>>>>>>>>>>in that sense.
> >>>>>>>>>>>>>>>>>This is true
> >>>>>>>>>>>>>>>>>for many different classes of enzyme.
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>And I do not remove enzyme InterPro2GO
> >>>>>>>>>>>>>>>>>annotation just
> >>>>>>>>>>>>>>>>>because a family
> >>>>>>>>>>>>>>>>>contains a few inactive members - all the big
> >>>>>>>>>>>>>>>>>enzyme
> >>>>>>>>>>>>>>>>>families do and
> >>>>>>>>>>>>>>>>>they can only really be recognised by manual
> >>>>>>>>>>>>>>>>>annotation.
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>Sandra
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>Valerie Wood wrote:
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>Hi Emily,
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>A few comments which may be relevant:
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>Out of interest, which protein kinase family
> >>>>>>>>>>>>>>>>>>is this (i.e.
> >>>>>>>>>>>>>>>>>>which
> >>>>>>>>>>>>>>>>>>Interpro domain). Is it a family where some
> >>>>>>>>>>>>>>>>>>(but not all)
> >>>>>>>>>>>>>>>>>>members are
> >>>>>>>>>>>>>>>>>>protein kinases, in
> >>>>>>>>>>>>>>>>>>which case the mapping should be removed?
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>Alternatively, if this appears to be a
> >>>>>>>>>>>>>>>>>>spurious hit,
> >>>>>>>>>>>>>>>>>>instead of adding a
> >>>>>>>>>>>>>>>>>>NOT annotation, you can get spurious matches
> >>>>>>>>>>>>>>>>>>suppressed by
> >>>>>>>>>>>>>>>>>>Interpro as
> >>>>>>>>>>>>>>>>>>false positives (I often do this for S.
> >>>>>>>>>>>>>>>>>>pombe).
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>Or, could it be a sequencing or gene
> >>>>>>>>>>>>>>>>>>predicition error?
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>Val
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>Midori Harris wrote:
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>> Hi,
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>> I think there's no doubt whatsoever that
> >>>>>>>>>>>>>>>>>>> this information
> >>>>>>>>>>>>>>>>>>> should be
> >>>>>>>>>>>>>>>>>>> captured. The question is what to put for
> >>>>>>>>>>>>>>>>>>> reference and
> >>>>>>>>>>>>>>>>>>> evidence. The
> >>>>>>>>>>>>>>>>>>> best
> >>>>>>>>>>>>>>>>>>> evidence code is probably TAS, although
> >>>>>>>>>>>>>>>>>>> one could possibly
> >>>>>>>>>>>>>>>>>>> also make a
> >>>>>>>>>>>>>>>>>>> case for ISS (note that IC is restricted
> >>>>>>>>>>>>>>>>>>> to inferences
> >>>>>>>>>>>>>>>>>>> from other GO
> >>>>>>>>>>>>>>>>>>> annotations, so isn't suitable).
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>> For a reference, one possibility is to add
> >>>>>>>>>>>>>>>>>>> an item to the
> >>>>>>>>>>>>>>>>>>> GO_REF
> >>>>>>>>>>>>>>>>>>> collection; then there would be an ID to
> >>>>>>>>>>>>>>>>>>> plug into the file.
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>> m
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>> On Wed, 8 Mar 2006, Emily Dimmer wrote:
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>>Hi,
> >>>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>>One of our annotators, who is an expert
> >>>>>>>>>>>>>>>>>>>>on protein
> >>>>>>>>>>>>>>>>>>>>kinases, has looked
> >>>>>>>>>>>>>>>>>>>>at the sequence of a putative protein
> >>>>>>>>>>>>>>>>>>>>kinase and from
> >>>>>>>>>>>>>>>>>>>>noticing a couple
> >>>>>>>>>>>>>>>>>>>>of amino acids changes at its active
> >>>>>>>>>>>>>>>>>>>>site, has predicted
> >>>>>>>>>>>>>>>>>>>>that it does
> >>>>>>>>>>>>>>>>>>>>not possess any kinase activity - she
> >>>>>>>>>>>>>>>>>>>>did not use any
> >>>>>>>>>>>>>>>>>>>>software and
> >>>>>>>>>>>>>>>>>>>>there
> >>>>>>>>>>>>>>>>>>>>is no published work on this protein.
> >>>>>>>>>>>>>>>>>>>>Do you think this type of annotation
> >>>>>>>>>>>>>>>>>>>>should be
> >>>>>>>>>>>>>>>>>>>>represented in GO (we
> >>>>>>>>>>>>>>>>>>>>feel this annotation is of high quality
> >>>>>>>>>>>>>>>>>>>>and adds valuable
> >>>>>>>>>>>>>>>>>>>>information to
> >>>>>>>>>>>>>>>>>>>>a protein which has not yet been
> >>>>>>>>>>>>>>>>>>>>characterized), and if
> >>>>>>>>>>>>>>>>>>>>so how should
> >>>>>>>>>>>>>>>>>>>>this annotation be shown?
> >>>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>>Thanks,
> >>>>>>>>>>>>>>>>>>>>Emily
> >>>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>> --
> >>>>>>>>>>>>>>>> Evelyn Camon
> >>>>>>>>>>>>>>>> GOA Coordinator
> >>>>>>>>>>>>>>>> Senior Scientific Curator
> >>>>>>>>>>>>>>>> European Bioinformatics Institute
> >>>>>>>>>>>>>>>> Tel:01223-494465
> >>>>>>>>>>>>>>>> Fax:01223-494468
> >>>>>>>>>>>>>>>> E-mail: camon at ebi.ac.uk
> >>>>>>>>>>>>>>>> URL: http://www.ebi.ac.uk/goa
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>>>
> >>>>>>>>>>>>>> -- Evelyn Camon
> >>>>>>>>>>>>>> GOA Coordinator
> >>>>>>>>>>>>>> Senior Scientific Curator
> >>>>>>>>>>>>>> European Bioinformatics Institute
> >>>>>>>>>>>>>> Tel:01223-494465
> >>>>>>>>>>>>>> Fax:01223-494468
> >>>>>>>>>>>>>> E-mail: camon at ebi.ac.uk
> >>>>>>>>>>>>>> URL: http://www.ebi.ac.uk/goa
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>>>>>>>
> >>>>>>>> --
> >>>>>>>> David P. Hill, Ph.D.
> >>>>>>>> Senior Scientific Curator
> >>>>>>>> Mouse Genome Informatics
> >>>>>>>> Gene Ontology Consortium
> >>>>>>>> The Jackson Laboratory
> >>>>>>>> 600 Main Street
> >>>>>>>> Bar Harbor, ME 04609-1500
> >>>>>>>> tel:207-288-6430
> >>>>>>>> htpp://www.informatics.jax.org
> >>>>>>>> http://www.geneontology.org
> >>>>>>>>
> >>>>>>>>
> >>>>>>>
> >>>>>>>
> >>>>>>>
> >>>>>> --
> >>>>>> David P. Hill, Ph.D.
> >>>>>> Senior Scientific Curator
> >>>>>> Mouse Genome Informatics
> >>>>>> Gene Ontology Consortium
> >>>>>> The Jackson Laboratory
> >>>>>> 600 Main Street
> >>>>>> Bar Harbor, ME 04609-1500
> >>>>>> tel:207-288-6430
> >>>>>> htpp://www.informatics.jax.org
> >>>>>> http://www.geneontology.org
> >>>>>>
> >>>>>>
> >>>>>
> >>>>>
> >>>--
> >>>Alexander Diehl, Ph.D.
> >>>Scientific Curator
> >>>Mouse Genome Informatics
> >>>The Jackson Laboratory
> >>>600 Main Street
> >>>Bar Harbor, ME  04609
> >>>
> >>>email:  adiehl at informatics.jax.org
> >>>work:  +1 (207) 288-6427
> >>>fax:  +1 (207) 288-6131
> >>>
> >>>
> >>>
> >
> >
> >

-- 
----------------------------------------------------------------------------------
Valerie Wood		       Tel: 01223 494954
S. pombe Genome Project	       Fax: 01223 494919 		       
The Sanger Institute           email: val at sanger.ac.uk
Wellcome Trust Genome Campus   http://www.sanger.ac.uk/Projects/S_pombe 
Cambridge                      
CB10 1SA



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