#1247 PAINT:Ionotropic Glutamate Receptors. PTN001056595 & PTN001056621

[Helen Attrill]

Hi,

The PAINT annotations for Ionotropic Glutamate Receptors (iGluR) & Ionotrpic Receptors (IR) in D.mel have a mixture of problems - inappropriate NOT annotations, highly specific molecular functions, IRs with iGluR terms and vice versa.

Drosophila have the typical iGluRs that fall into the kainate, AMPA, NMDA subclasses and Ionotropic Receptors (IR). IRs are a variant subfamily of ionotropic glutamate receptors which lack conserved glutamate-interacting residues found throughout the protostome lineage. They can been dived into two subgroups: (1) antennal - olfactory receptors expressed in the antenna and, (2) divergent - largely species-specific, with low amino acid sequence identity. Expressed in gustatory organs, they are believed to be taste receptors.

PMID:21220098 has a good evolutionary tree.

Issues:

A. Ionotropic Receptors being given NOT annotations for iGluR attributes.

As these receptors are known to not bind glutamate, it's misleading to give this annotation - they are a distinct class in their own right. NOTs are perhaps not appropriate for PAINT - we would only use them when it is surprising that X does not do Y using IKR or experimental evidence codes and to point to conflicting evidence.

e.g. Ir100 from PANTHER:PTN001056595
NOT GO:0004970 ionotropic glutamate receptor activity
NOT GO:0005234 extracellular-glutamate-gated ion channel
NOT GO:0008328 ionotropic glutamate receptor complex
NOT GO:0035235 ionotropic glutamate receptor signaling pathway
NOT GO:0035249 synaptic transmission, glutamatergic
NOT GO:0045211 postsynaptic membrane

(D.mel genes: Ir100a, Ir10a, Ir21a, Ir40a, Ir41a, Ir52c, Ir60a, Ir60e, Ir64a, Ir67b, Ir67c, Ir68a, Ir75d, Ir76a, Ir76b, Ir7c, Ir7e, Ir7g, Ir87a, Ir92a, Ir93a)

B. Ionotropic Receptors being given iGluR annotations.
PANTHER:PTN001056621
e.g. Ir94d

GO:0005234 extracellular-glutamate-gated ion channel
GO:0035235 ionotropic glutamate receptor signaling pathway
GO:0035249 synaptic transmission, glutamatergic
GO:0045211 postsynaptic membrane

(D.mel genes: Ir11a, Ir25a, Ir31a, Ir54a, Ir75a, Ir75b, Ir75c, Ir7a, Ir7b, Ir7d, Ir7f, Ir8a, Ir94d)

C. Annotation with "extracellular ammonia-gated ion channel activity" GO:0036081

This is based on one D.mel IR - Ir92a. As far as I know, this is the only ammonia-gated IR. But all annotations for PANTHER:PTN001056595 have this.
(D.mel genes: Ir100a, Ir10a, Ir21a, Ir40a, Ir41a, Ir52c, Ir60a, Ir60e, Ir64a, Ir67b, Ir67c, Ir68a, Ir75d, Ir76a, Ir76b, Ir7c, Ir7e, Ir7g, Ir87a, Ir92a, Ir93a).

Not really happy with any IBA annotation made from just one source - I would regard a 1:1 relationship such as this as an ISS, with all the associated background work to confirm its orthology/homology. But this one is really very specific, so shouldn't happen.

D. iGluRs annotated with NOT annotations for iGluR attributes and extracellular ammonia-gated ion channel activity. Again from PANTHER:PTN001056595.

CG11155 - Kainate iGluR family
CG9935 - kainate iGluR family

NOT GO:0004970 ionotropic glutamate receptor activity
NOT GO:0005234 extracellular-glutamate-gated ion channel
NOT GO:0008328 ionotropic glutamate receptor complex
NOT GO:0035235 ionotropic glutamate receptor signaling pathway
NOT GO:0035249 synaptic transmission, glutamatergic
NOT GO:0045211 postsynaptic membrane

Regards,

Helen

p.s. I've just cleaned-up the D.mel IRs annotation, removing a few old incorrect ISS/NAS and up-dated the experimental-based annotations.

[Helen Attrill]

Also, adding

Ir54a
Ir75b
Ir94d
Ir31a
Ir75a
Ir11a
Ir7b
Ir7a

which have been given

GO:0032281 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid selective glutamate receptor complex
GO:0004971 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity

From PANTHER:PTN000438080

Interestingly, I came across a research paper (PMID:19695344) that says that in D.mel, the division into AMPA and Kainate receptors for iGluRs is flawed and should be just grouped as non-NMDA receptors. I am going to leave our annotation to these groups for now as they don't do any direct binding assays and put an internal note for future review.