NTPase (Drosophila melanogaster, O76268) notes

2026-10-21 — Full re-review, independent of the ProtNLM2 predictions

ProtNLM2 output was not opened or used for this review.

O76268 is NTPase-PA (FBpp0077367, 461 aa). The gene has five transcripts and four distinct
polypeptides: PE (Q9VQI8, 464 aa), PF (M9PBV2, 524 aa, the GCRP canonical), and PC/PD (Q8IPZ6,
271 aa). All four are unreviewed TrEMBL entries, and none is Swiss-Prot reviewed.
Comparison (NTPase-bioinformatics/compare_isoforms_rereview.py, RESULTS-rereview.md):
PA is full-length, with the TM helix at 38-57, ACR1 DAGSTGS, and the predicted proton acceptor
E202. PE differs only in its first residues. PF additionally carries an insertion of about 63
residues after the TM helix. PC/PD equals PA 191-461 and lacks the TM helix and ACR1.
The residues named in the cloning paper (C42 in the TM domain, C447 in the exoplasmic domain)
match PA numbering, so O76268 is the experimentally characterised product
PMID:19467631.
Conclusion: O76268 is not a fragment. It is a full-length alternative isoform, and it is the
characterised one. The gene-level review in this folder is complete. No same-gene canonical entry
needs a separate review: PF/M9PBV2 is the GCRP representative, but it is unreviewed, it carries the
same GO set, and its function is not separately characterised.

PANTHER PTHR11782:SF127 ("NTPASE, ISOFORM F") contains fly NTPase and C. elegans uda-1 (Q9XU84,
Swiss-Prot reviewed). Human ENTPD5 (SF35) and ENTPD6 (SF99) are in different subfamilies.
Global identity is about 42% to each of the three, so pairwise identity does not resolve them. The
"NTPDase6" name in the literature is a family-level analogy, not one-to-one orthology.
uda-1 is a UDP/GDPase with a luminal active site, induced by ER stress through ire-1
PMID:15102851. This matches the fly
substrate profile and topology, so the luminal NDPase function is conserved within SF127.
PANTHER family review interpro/panther/PTHR11782/PTHR11782-review.yaml lists O76268 as the SF127
representative. It agrees with the placement used here.
There are no IBA rows for this gene in GOA, so there is no PAINT node to argue with.

cytoplasm (IDA): KEEP_AS_NON_CORE changed to MODIFY with endoplasmic reticulum as the
replacement, because the paper reports the ER directly.
plasma membrane (ARBA): UNDECIDED changed to REMOVE. Activity is latent in intact cells, the
protein is in the ER, and the enzyme resists inhibitors of the surface NTPDases.
extracellular region (ARBA): UNDECIDED changed to MARK_AS_OVER_ANNOTATED. No isoform has a
secretion signal, and secreted relatives are in other subfamilies.
Golgi (ARBA): kept UNDECIDED. UDA-1 fractionates with intermediate ER/Golgi vesicles, but no fly
data address a Golgi pool.
MF rows unchanged in substance. No NEW biological-process term was added: glycoprotein processing
is a hypothesis from the paper and from the uda-1 analogy, and no fly loss-of-function test exists.
Core function now also gives the location as ER. The description was rewritten.
No modules under modules/ include NTPase. The dmel glycosylation modules do not list it.