DPY19L2

Summary: Retain the broad ancestral mannosyltransferase inference, without claiming demonstrated human chemistry.

Reason: The literal PAINT IBD places GO:0000030 at PANTHER:PTN001266774, and the human Q6NUT2 leaf descends from that node. Experimental donor grounding is present for mouse Dpy19l1 and Dpy19l3 (PMID:28202721), human DPY19L3 (PMID:29405629), and worm dpy-19 (PMID:23562325); donor count is not the criterion for this phylogenetic judgment. The 2017 full original also tests expressed mouse Dpy19l2: it does not rescue UNC5A surface export and no C-mannosylation of the tested UNC5A substrate was demonstrated. The authors explicitly leave substrate and cellular-context specificity unresolved; the unavailable supplementary Figure S6 is not claimed as read. The 2023 original experimentally characterizes worm DPY19 and compares predicted human DPY19L2 substrate-binding architecture, explicitly without a demonstrated human DPY19L2 substrate. These findings do not establish a target-specific universal loss that overturns the broad curated inference. Retain the existing MF, but do not refine it to a specific C-mannosyltransferase reaction or equate the inferred reaction with the observed acrosome-attachment role.

Summary: Refine the positive nuclear-fraction detection to the independently supported inner nuclear membrane compartment.

Reason: The author thesis linked to PMID:21630459 contains the study-specific Annex 8.2 table (printed page 198; PDF page 199), which lists DPY19L2/Q6NUT2 with 8.7% coverage and five peptides among proteins detected in isolated human sperm nuclei. This is positive target evidence, not merely absence of a localization contradiction. The fractionation/table do not resolve an inner membrane, authenticate a natural isoform, or establish chromatin binding. The more specific gene-level location is supported independently by endogenous mouse localization/immunogold and the explicitly human tagged DPY19L2 construct in PMID:22764053. The refinement preserves that distinction in resolution and is nonexclusive: HPA cell-line nucleoplasm/mitochondria observations and the different 2011 mature-sperm immunoblot result are retained as separate contexts rather than dismissed or silently reconciled.

Proposed replacements: nuclear inner membrane

Summary: Retain phylogenetically supported inner nuclear membrane localization.

Reason: The literal IBD at PANTHER:PTN001266831 is grounded in experimental mouse Dpy19l2 (MGI:2444662; P0CW70), and the human target is a descendant of that node. The original mouse localization and immunogold evidence supports the inner nuclear membrane, with human tagged-protein nuclear-envelope localization providing corroboration rather than identical ultrastructural resolution. The target lineage also carries an IRD for the ancestral ER-membrane term; that distinct location transition is preserved and is not treated as a loss of the separate mannosyltransferase MF. The imported is_active_in qualifier remains unchanged.

Summary: Retain the combined electronic inference of inner nuclear membrane localization.

Reason: The literal sources comprise the mouse ortholog P0CW70, its Ensembl protein record, and UniProt subcellular-location SL-0179. The current donor annotation is experimentally grounded by mouse inner nuclear membrane localization in PMID:22764053 and PMID:34471926, while the former also explicitly uses a human tagged DPY19L2 construct in host-cell localization experiments. These identifiers are components of a combined automated inference, not three independent localization assays. The conserved compartment is supported, with neither exclusivity nor a fully established human membrane topology asserted.

Summary: Retain the curator-transferred inner nuclear membrane location from mouse Dpy19l2.

Reason: The literal ISS donor P0CW70 is mouse Dpy19l2, whose endogenous inner nuclear membrane localization is experimentally supported. PMID:22764053 distinguishes those mouse ultrastructural experiments from explicitly human DPY19L2-GFP expression in HEK293 and NIH3T3 host cells. The human and mouse evidence supports the conserved location without inferring construct species from the host or authenticating an experimental natural isoform. Two raw current GOA records differ only in identifier/date and are represented by this single normal-seeded source object; both raw records are preserved in the source-coverage record.

Summary: Retain the phylogenetically conserved spermatid-development role.

Reason: The target descends from the spermatid-development IBD at PANTHER:PTN001266831. Its experimental grounding includes mouse Dpy19l2 loss-of-function and human DPY19L2 genetic evidence. Human Q6NUT2 appearing among the descendant sources is legitimate target experimental grounding, not circular propagation. Human deletion-associated globozoospermia and mouse acrosome/nuclear-envelope phenotypes support participation in spermatid development; these experiments do not identify a specific catalytic substrate or establish the proposed LINC molecular interface.

Summary: Retain the human genetic evidence for spermatid development.

Reason: The full original describes homozygous DPY19L2 deletions, segregation and affected human sperm with globozoospermia. Its immature-germ-cell microscopy reports absent proacrosomal vesicles despite otherwise appropriate polarity/chromatoid-body placement, and its discussion separates the spermiogenesis phenotype from earlier germ-cell proliferation. These observations support the broad developmental assertion. They do not by themselves demonstrate human DPY19L2 enzymatic chemistry, direct molecular anchoring, or a universal polarity defect inferred from the worm family member.

Summary: Retain the independent human deletion-associated spermatid-development annotation.

Reason: The original human deletion cohort links DPY19L2 loss to failed sperm-head elongation and acrosome formation. Testis immunoblot and mature-sperm observations are distinct assay contexts; the proposed acroplaxome mechanism in this 2011 paper is a hypothesis rather than a demonstrated molecular bridge. The broader developmental function is supported directly by human genetics and corroborated by the later mouse ortholog experiments. The original experimental citation and qualifier are preserved.

Summary: Replace the broad membrane location with the supported inner nuclear membrane compartment.

Reason: InterPro:IPR018732 genuinely maps this Dpy19-like family to membrane, and the official DPY19L2 sequence contains predicted membrane-spanning segments. The mapping is correct but does not specify the relevant membrane. Independent target/ortholog localization in PMID:22764053 supports the more informative inner nuclear membrane term. This is a gene-level specificity refinement of the existing broad location, not a claim that InterPro measured subcellular localization or that all DPY19 family members share this compartment. Other observed cellular pools are not excluded.

Proposed replacements: nuclear inner membrane