update DDAH2 branch of PTHR12737 = DIMETHYLARGININE DIMETHYLAMINOHYDROLASE

[krchristie]

I am creating this ticket on behalf of Dr. Vinitha Ragavan who submitted a request for correction of Ddah2 annotations via MGI's help desk. Her email is included below.

• PTHR ID & PTN node:

PTHR12737 = DIMETHYLARGININE DIMETHYLAMINOHYDROLASE node = SF16-N(G),N(G)-DIMETHYLARGININE DIMETHYLAMINOHYDROLASE 2 (AN9)

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

Here are the sequences with annotations to the MF term "dimethylargininase activity" or to BP terms under "arginine metabolism". There may be additional BP problem annotations that don't map up to "arginine metabolism"

I have already deleted the single annotation MGI annotation which was based on the sequence alighment with DDAH1 and its enzymatic function of "dimethylargininase activity". I have also deleted the PINC annotations as these often do not meet current standards and some were redundant with UniProt annotations from the same paper.

Taxon name	Feature ID	Symbol	Gene name	Aspect	GO ID	GO term	Contributor	Ev Code	With	Reference	Date
Mus musculus	MGI:MGI:1859016	Ddah2	dimethylarginine dimethylaminohydrolase 2	P	GO:0006527	arginine catabolic process	MGI	ISA	EMBL:AF004106	PMID:10493931	20000616
Rattus norvegicus	RGD:1302955	Ddah2	dimethylarginine dimethylaminohydrolase 2	F	GO:0016403	dimethylargininase activity	RGD	IDA		PMID:17322279|RGD:1625578	20070614
Rattus norvegicus	RGD:1302955	Ddah2	dimethylarginine dimethylaminohydrolase 2	P	GO:0006525	arginine metabolic process	RGD	IDA		PMID:17322279|RGD:1625578	20070614
Rattus norvegicus	RGD:1302955	Ddah2	dimethylarginine dimethylaminohydrolase 2	F	GO:0016403	dimethylargininase activity	UniProt	ISS	UniProtKB:O95865	GO_REF:0000024|RGD:1600115	20100804
Homo sapiens	UniProtKB:O95865	DDAH2	N(G),N(G)-dimethylarginine dimethylaminohydrolase 2	F	GO:0016403	dimethylargininase activity	UniProt	IDA		PMID:10493931	20100804
Homo sapiens	UniProtKB:O95865	DDAH2	N(G),N(G)-dimethylarginine dimethylaminohydrolase 2	F	GO:0016403	dimethylargininase activity	Reactome	TAS		Reactome:R-HSA-5693373	20220504
Homo sapiens	UniProtKB:O95865	DDAH2	N(G),N(G)-dimethylarginine dimethylaminohydrolase 2	P	GO:0006527	arginine catabolic process	PINC	TAS		PMID:10493931	20030904
Bos taurus	UniProtKB:Q3SX44	DDAH2	N(G),N(G)-dimethylarginine dimethylaminohydrolase 2	F	GO:0016403	dimethylargininase activity	UniProt	ISS	UniProtKB:O95865	GO_REF:0000024	20100804

• Type of Issue: Erroneous source or erroneous propagation, or other issue

New experimental work clarifying a situation which has had conflicting experimental results:

Date: Tuesday, July 11, 2023 at 6:30 AM Vinitha Ragavan's Comments:

Dear Mouse Genome Informatics Help Team,

With this email we are informing you about a major discrepancy between the information in your database and the current state of knowledge regarding the function of dimethylarginine dimethylaminohydrolase 2 (DDAH2), Access # - MGI:1859016 (https://www.informatics.jax.org/go/marker/MGI:1859016?header=hydrolase) It has just been shown in the multicenter consortium study that DDAH2 has nothing to do with metabolism of the endogenous dimethylarginines (https://pubmed.ncbi.nlm.nih.gov/37296100/). The international consortium involved 14 different universities worldwide and the consortium paper was published in Nature Communications. As a result, the current substrate of DDAH2 is unknown. We kindly ask you to correct the database to avoid unnecessary confusion.

Sincerely, Vinitha Ragavan

• New annotations to incorporate

I have curated the paper Dr. Ragavan brought to our attention, PMID:37296100, and generated NOT annotations for both the human DDAH2 (in Protein2GO) and mouse Ddah2 genes (in Noctua). Since I have curated the human and mouse annotations in different curation interfaces, they will likely become available for use in PAINT at different times.

• Add the label 'high priority' if needed. Generally high priority issues affect a lot of proteins, and annotations are incorrect (as opposed to just imprecise).

[marcfeuermann]

Thanks Karen for sharing this. I've blocked all corresponding annotations at the DDAH2 branch. This is a nice example of ancient duplication followed by loss of function. We will close this ticket once all experimental annotations will be corrected. Best regards, Marc.

[krchristie]

Thanks for getting to this so quickly Marc,

Best regards,

Karen

[deustp01]

Reactome annotation to DDAH2 has been removed - change will become visible with our next release in September.