IPR012259 glycine metabolism?

[ValWood]

• InterPro ID / label

IPR012259

• Example sequences with problematic annotation (ID + gene/protein name):

https://www.pombase.org/gene/SPCC1223.08c

• Description of issue

Glycine biosynthetic process seems to be too indirect. DHFR itself doesn't directly participate in glycine metabolism, the overall folate cycle, in which DHFR is a key enzyme, is interconnected with glycine metabolism through the transfer of one-carbon units

[deustp01]

Glycine biosynthetic process seems to be too indirect.

MetaCyc disagrees - this reaction sequence shows up in a variety of pathways (depending how one draws pathway boundaries) but is a major source of glycine:

General Background

The proteinogenic amino acid glycine can biosynthesized via several different pathways. The main pathway in most organisms is the production of glycine from L-serine via EC 2.1.2.1, glycine hydroxymethyltransferase. Eukaryotic organisms have both a cytosolic enzyme (SHMT2) and a mitochondrial enzyme (SHMT1) (see glycine biosynthesis I). The two isoforms were reported to work in opposite directions depending on the culture conditions [Kastanos97].

[ValWood]

OK I assumed that since DHFR generates THF, and THF is a contactor in the interconversion, this would make DHFR indirect (causally upstream).

I'm never sure how the boundaries should be drawn.

[pgaudet]

The InterPro entry seems clear that this is part of glycine synthesis, but in individual entries there seems to be reactions in other pathways: https://www.uniprot.org/uniprotkb/Q86XF0/entry https://www.uniprot.org/uniprotkb/P0ABQ4/entry

So I agree it's safer not to have it as an InterPro mapping.

[pgaudet]

@blazaropinto @sarach06 @tony787

What do you think, should these mappings be removed?

[blazaropinto]

Thanks for pointing this out. I agree. I removed the term. The changes will be visible in the next release.

Best, Beatriz