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Source ontology files for the Gene Ontology
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'multi-function' inositol enzymes #2145

Closed gocentral closed 9 years ago

gocentral commented 19 years ago

Hi, I have an enzyme question:

Where an enzyme catalyses >1 different reactions, should separate GO function terms exist for each reaction?

Specifically:

1/ inositol-polyphosphate multikinase activity:

term: inositol-polyphosphate multikinase activity goid: GO:0050516 definition: Catalysis of the reaction: ATP + 1D-myo-inositol 1,4,5-trisphosphate = ADP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate. definition_reference: MetaCyc:2.7.1.151-RXN definition_reference: EC:2.7.1.151

The comment on IUBMB (http://www.chem.qmul.ac.uk/iubmb/enzyme/EC2/7/1/151.html) states: This enzyme also phosphorylates Ins(1,4,5)P3 to Ins(1,3,4,5)P4, Ins(1,3,4,5)P4 to Ins(1,3,4,5,6)P5, and Ins(1,3,4,5,6)P4 to Ins(PP)P4, isomer unknown.

There is an existing GO term (GO:0008440, EC:2.7.1.127) to describe Ins(1,4,5)P3 to Ins(1,3,4,5)P4.

Can I create a new term to describe Ins(1,3,4,5)P4 to Ins(1,3,4,5,6)P5

inositol or phosphatidylinositol kinase activity --%inositol-tetrakisphosphate 6-kinase activity ; GO:NEW

inositol-tetrakisphosphate 6-kinase activity ; GO:NEW Catalysis of the reaction: 1D-myo-insoitol 1,3,4,5-tetrakisphosphate + ATP = 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + ADP.


Similarly:

term: multiple inositol-polyphosphate phosphatase activity goid: GO:0004446 definition: Catalysis of the reaction: myo-inositol hexakisphosphate + H2O = myo-inositol pentakisphosphate (mixed isomers) + phosphate. definition_reference: EC:3.1.3.62

In the IUBMB comments, it says: Comments: This enzyme exists in two isoforms. It also acts on Ins(1,3,4,5)P4 to yield Ins(1,4,5)P3.

Can I have a new term to describe this extra function:

inositol tetrakisphosphate 3-phosphatase activity ; GO:NEW Catalysis of the reaction myo-inositol-1,3,4,5-tetrakisphosphate + H2O = myo-inositol-1,4,5-trisphosphate + phosphate.

In this case, should the new GO term get EC:3.1.3.62 as a x-ref?


2/ What about when IUBMB lists 2 reactions in the REACTIONS field (rather than as a note in the comments field?).

term: inositol-polyphosphate 5-phosphatase activity goid: GO:0004445 definition: Catalysis of the reaction: D-myo-inositol 1,4,5-trisphosphate + H2O = myo-inositol 1,4-bisphosphate + phosphate. definition_reference: EC:3.1.3.56

According to IUBMB there are 2 reactions catalysed catalysed by this enzyme, not just the one listed in the above definiton. See http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/1/3/56.html

Should the definition be expanded, or should a new term be created to cover this second reaction? If a new term is created to cover the 2nd reaction, should the term name of GO:0004445 be modified, and both GO:0004445 and the new term have 'inositol-polyphosphate 5-phosphatase activity' and EC:3.1.3.56 as a synonym/X-ref? eg:

term: inositol-trisphosphate 5-phosphatase activity ; GO:0004445 [NAME CHANGE] synonym: inositol-polyphosphate 5-phosphatase activity definition: Catalysis of the reaction: D-myo-inositol 1,4,5-trisphosphate + H2O = myo-inositol 1,4-bisphosphate + phosphate. definition_reference: EC:3.1.3.56 comment: inositol-polyphosphate 5-phosphatase catalyzes two reactions, described by GO:0004445 and GO:NEW.

term: inositol-tetrakisphosphate 5-phosphatase activity ; GO:NEW synonym: inositol-polyphosphate 5-phosphatase activity definition: Catalysis of the reaction: 1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo-inositol 1,3,4-trisphosphate + phosphate. definition_reference: EC:3.1.3.56 ?? comment: inositol-polyphosphate 5-phosphatase catalyzes two reactions, described by GO:0004445 and GO:NEW.

(Both reactions are needed for curation of PMID:1532211- see Fig 11).


term: inositol-hexakisphosphate kinase activity goid: GO:0050517 definition: Catalysis of the reaction: ATP + myo-inositol hexakisphosphate = ADP + diphospho-myo-inositol pentakisphosphate (isomeric configuration unknown). definition_reference: MetaCyc:2.7.1.152-RXN definition_reference: EC:2.7.4.21 comment: Note that this was EC:2.7.1.152.

According to IUBMB, there are 2 reactions catalysed by this enzyme: http://www.chem.qmul.ac.uk/iubmb/enzyme/EC2/7/4/21.html

Neither reaction matches exactly the definition given above.

(1) ATP + 1D-myo-inositol hexakisphosphate = ADP + 5-diphospho-1D-myo-inositol (1,2,3,4,6)pentakisphosphate

(2) ATP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate = ADP + diphospho-1D-myo-inositol tetrakisphosphate (isomeric configuration unknown)

[inositol hexakisphosphate kinases (IP6 kinases) use IP5 and IP6 as substrates to generate inositol pyrophosphate species]


a couple more new term requests to curate PMID:1532211

inositol or phosphatidylinositol phosphatase activity ; GO:0004437 --%inositol bisphosphate phosphatase activity ; GO:0016312 --%inositol trisphosphate phosphatase activity ; GO:0046030 --%inositol tetrakisphosphate phosphatase activity ; GO:NEW ----%inositol-1,4,5,6-tetrakisphosphate 6-phosphatase activity ; GO:0030352

inositol tetrakisphosphate phosphatase activity ; GO:NEW Catalysis of the removal of one of the four phosphate groups of an inositol tetrakisphosphate molecule.

inositol or phosphatidylinositol kinase activity --%inositol pentakisphosphate 2-kinase activity ; GO:NEW --%inositol tetrakisphosphate 3-kinase activity ; GO:NEW

inositol pentakisphosphate 2-kinase activity ; GO:NEW Catalysis of the reaction myo-inositol (1,3,4,5,6)-pentakisphosphate + ATP = myo-inositol (1,2,3,4,5,6)-hexakisphosphate + ADP.

inositol tetrakisphosphate 3-kinase activity ; GO:NEW Catalysis of the reaction myo-inositol (1,4,5,6)-tetrakisphosphate + ATP = myo-inositol (1,3,4,5,6)-pentakisphosphate + ADP.


thanks, Becky

Reported by: beckyfoulger

Original Ticket: "geneontology/ontology-requests/2152":https://sourceforge.net/p/geneontology/ontology-requests/2152

gocentral commented 19 years ago

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Number 1 in my list: EC 2.7.1.151 (inositol-polyphosphate multikinase) is actually a case where 2 reactions are listed in the 'Reaction' field of IUBMB. So should a new GO term be created, or should the definition be expanded?

Original comment by: beckyfoulger

gocentral commented 19 years ago

Logged In: YES user_id=579762

Hi Becky,

Funnily enough, I'm curating one of these enzymes myself right now. Could you fold it into your updates?

PMID: 9126335

inositol 1,3,4 trisphosphate 5/6-kinase

it does both

inositol 1,3,4 trisphosphate -> 1,3,4,6-tetrakisphosphate

and

inositol 1,3,4 trisphosphate -> 1,3,4,5-tetrakisphosphate

Thanks alot,

Tanya

Original comment by: tberardini

gocentral commented 19 years ago

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Will do Tanya!

Emailed the GO group about how to handle these- ie whether to expand the current definitions to cover both reactions, or whether to make separate terms. Amelia replied saying:

Strictly speaking I think that it would be better to create separate function terms for each, since they're two different reactions. However, when the substrate molecules are very similar and the catalytic activity is the same (in this case, a phosphorylation of polyphosphorylated inositol), it might not be worthwhile making a separate term. I'm sure there are examples of both the separate terms and the expanded defs in the function ontology. Perhaps if there are any other enzymes that catalyze one reaction but not the other, you could create separate terms; otherwise, expand the existing term def?

Original comment by: beckyfoulger

gocentral commented 19 years ago

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Judy's and Suzi's comments agreed with Amelia:

I think Amelia strikes the right balance between separate terms and expanded definitions with the idea that if there are enzymes that catalyze one but not the other, then separate terms. Might look to microbial annotations to determine this.

Judy

I strongly feel that if the activity is the same then it is a single term. Function is distinguished by what it does not what it acts upon. Usually, of course, the 2 go together (different substrate== different activity), but not always. If these are not 'different' in the functional activity sense, then separate terms are not called for. Otherwise we are including more (substrates too) than we intend aren't we?

my 2 cents (why isn't there a cents chararcter on keyboards?)

-S

Therefore where the IUBMB site lists multiple reactions in the 'Reactions' field, I shall go ahead and expand the GO definitions of these enzymes to cover >1 reaction, and make a new term for Tanyas enzyme activity.

Becky

Original comment by: beckyfoulger

gocentral commented 19 years ago

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Expanded the definitions of inositol-polyphosphate multikinase activity ; GO:0050516 ; EC:2.7.1.151 inositol-polyphosphate 5-phosphatase activity ; GO:0004445 ; EC:3.1.3.56 inositol-hexakisphosphate kinase activity ; GO:0050517 ; EC:2.7.4.21

to cover both reactions listed in IUBMB.

Made the following new terms: inositol pentakisphosphate 2-kinase activity ; GO:0035299 inositol trisphosphate 5/6-kinase activity ; GO:0035300

Original comment by: beckyfoulger

gocentral commented 19 years ago

Original comment by: beckyfoulger