CG8841 encodes the Drosophila HID1 protein, an 837-residue member of the conserved HID1/Ecm30 family (PANTHER PTHR21575:SF12) that is about 69% identical to mammalian HID1 and retains the N-terminal Gly2 myristoylation motif and the conserved C-terminal region. It is unrelated to the DMC1 meiotic recombinase despite carrying Dmc1 as a database gene name. By orthology to experimentally studied HID1 proteins, it is expected to be a myristoylated peripheral membrane protein that cycles between the cytosol and the cytosolic face of the medial and trans Golgi, where it supports Golgi organization and, in neuroendocrine and peptidergic cells, the biogenesis and maturation of dense-core secretory granules, including trans-Golgi network acidification, cargo sorting and homotypic fusion of immature granules. No catalytic or specific binding activity is known for any HID1 protein, and the fly protein has not itself been studied experimentally.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000138 Golgi trans cisterna | IBA GO_REF:0000033 | ACCEPT | Summary: Trans-Golgi residence is the experimentally established location of HID1 orthologs and is inherited from the eukaryote-level PAINT node. Reason: PAINT placed this term at PTN000491103 seeded by human HID1 and C. elegans HID-1. Human HID1 localizes to medial and trans Golgi in a myristoylation-dependent manner (PMID:21337012), and the CG8841 sequence is a full-length SF12 member that retains the Gly2 myristoylation motif and about 69% identity to human HID1 (bioinformatics RESULTS). PAINT negated the term only in a fission-yeast clade, not in Metazoa, so the inheritance applies to the fly protein. Supporting Evidence: PMID:21337012 mammalian HID-1 localized to the medial- and trans- Golgi apparatus as well as the cytosol file:DROME/CG8841/CG8841-bioinformatics/RESULTS.md CG8841 is a full-length HID1 protein, about 69% identical to the mammalian HID1 |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: No molecular activity is known for CG8841 or for any HID1-family protein. Reason: Literature searches found no CG8841-specific study, and work on HID1 orthologs establishes localization and cell-biological roles but no catalytic reaction, transport substrate or specific binding partner. The ND annotation therefore remains accurate. Supporting Evidence: file:DROME/CG8841/CG8841-deep-research-falcon.md No catalytic reaction, active site, transported substrate, or ligand specificity has been established. |
| GO:0005794 Golgi apparatus | ISS GO_REF:0000024 | MODIFY | Summary: Golgi localization is correct but less specific than the medial and trans Golgi cisterna terms the gene already carries. Reason: The ISS source, human HID1, is localized specifically to medial and trans Golgi (PMID:21337012). CG8841 already carries GO:0005797 Golgi medial cisterna and GO:0000138 Golgi trans cisterna by IBA; those descendants express the supported location more precisely. Proposed replacements: Golgi medial cisterna Golgi trans cisterna Supporting Evidence: PMID:21337012 mammalian HID-1 localized to the medial- and trans- Golgi apparatus as well as the cytosol |
| GO:0005797 Golgi medial cisterna | IBA GO_REF:0000033 | ACCEPT | Summary: Medial-Golgi residence is supported for HID1 orthologs and inherited by CG8841. Reason: Same PAINT node and evidence as the trans cisterna annotation; human HID1 associates with medial and trans Golgi and the fly protein conserves the membrane-targeting N-terminus. Supporting Evidence: PMID:21337012 mammalian HID-1 localized to the medial- and trans- Golgi apparatus as well as the cytosol |
| GO:0005829 cytosol | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: A cytosolic pool is real for HID1 orthologs but represents the reservoir of a protein that acts on Golgi membranes. Reason: Human HID1 shuttles dynamically between the Golgi and the cytosol (PMID:21337012), so a cytosolic pool is expected for CG8841. The functional site is the Golgi membrane, so the cytosol term is retained as a true but non-core location. Supporting Evidence: PMID:21337012 HID-1 was a peripheral membrane protein and dynamically shuttled between the Golgi apparatus and the cytosol |
| GO:0006886 intracellular protein transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: HID1 orthologs influence sorting of secretory cargo at the trans-Golgi network, which is a form of intracellular protein transport, but the mechanism is unresolved. Reason: Loss of HID-1 in rat neuroendocrine cells impairs sorting of regulated-secretory cargo and dense-core formation (PMID:29074564), and the human localization study proposed a role in intra-Golgi trafficking (PMID:21337012). Whether HID1 participates directly in a transport step or acts indirectly through TGN acidification is not known, so a more specific transport term is not justified. The broad term is kept as non-core; the granule-maturation term better captures the core role. Supporting Evidence: PMID:29074564 Loss of HID-1 causes a reduction in the number of LDCVs and affects their morphology and biochemical properties, due to impaired cargo sorting and dense core formation. PMID:21337012 We propose that HID-1 is probably involved in the intracellular trafficking within the Golgi region. |
| GO:0007030 Golgi organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Golgi organization is an ancestral HID1-family role inherited from the eukaryote-level node. Reason: PAINT placed this term at the eukaryote node PTN000491103 seeded by the fission-yeast Golgi-resident HID1 ortholog SPAC17A5.16, whose mutant lacks stacked Golgi (PMID:40899782); negations were applied only to fungal clades. CG8841 descends from this node, so the inheritance is retained. The seed is distant (about 26-30% identity to CG8841) and no metazoan Golgi-structure phenotype is documented in the cited evidence, so the term is kept as a non-core family-level role rather than the core metazoan function. Supporting Evidence: PMID:40899782 Transmission electron microscopy revealed that the SPAC17A5.16 mutant lacks a stacked Golgi apparatus (GA) form, suggesting a role in maintaining GA structure. file:DROME/CG8841/CG8841-bioinformatics/RESULTS.md Fungal members of the same subfamily are much more distant (25-30%) |
| GO:0016020 membrane | IBA GO_REF:0000033 | MODIFY | Summary: Membrane association is correct, but the supported membrane is the Golgi membrane, to which HID1 binds peripherally through N-terminal myristoylation. Reason: Human HID1 is a peripheral membrane protein whose Golgi binding requires the conserved N-terminal myristoylation site (PMID:21337012); the same motif is required for membrane association of nematode HID-1 (PMID:21115972) and is conserved in CG8841. Golgi membrane is the specific supported location. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000491103 · HID1 family eukaryote-level node SUPPORTS TRANSFER Membrane association is soundly inherited; the seeds' evidence specifies peripheral Golgi membrane binding, so the refinement is Golgi membrane. UniProtKB:Q8IV36 · human HID1 SUPPORTS TRANSFER Myristoylation-dependent peripheral Golgi membrane protein (PMID:21337012). Proposed replacements: Golgi membrane Supporting Evidence: PMID:21337012 we verified that a conserved N-terminal myristoylation site was required for HID-1 binding to the Golgi apparatus PMID:21115972 a conserved N-terminal myristoylated motif of both invertebrate and vertebrate HID-1 is essential for its association with intracellular membranes in nematodes and PC12 cells file:DROME/CG8841/CG8841-bioinformatics/RESULTS.md Q0E9B5 length 837; N-terminus MGNTDSKL; Gly2=True |
| GO:0061792 secretory granule maturation | IBA GO_REF:0000033 | ACCEPT | Summary: Secretory granule maturation is the best-characterized metazoan HID1 function and is inherited by CG8841 from a PAINT node below the eukaryote root. Reason: PAINT placed this term at PTN001090684, a node distinct from the eukaryote-level PTN000491103 from which CG8841 also descends (GOA propagates it to the fly protein), seeded by mouse Hid1, whose beta-cell knockout blocks homotypic fusion of immature secretory granules (PMID:27751232). Rat HID-1 knockout cells show defective dense-core vesicle formation and TGN acidification (PMID:29074564), and C. elegans HID-1 is a component of the dense-core-vesicle neurosecretory pathway (PMID:21115972). CG8841 is within SF12 and about 69% identical to mouse Hid1; the IBA is accepted as the core inferred process, while recognising that no Drosophila experiment has tested it. Supporting Evidence: PMID:27751232 HID-1 deficiency prevented secretory granule maturation by blocking homotypic fusion of immature secretory granules PMID:29074564 HID-1 KO cells also exhibit defects in TGN acidification together with mislocalization of the Golgi-enriched vacuolar H+-ATPase subunit isoform a2. PMID:21115972 our findings indicate that HID-1 is a novel component of a DCV-based neurosecretory pathway |
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Download this section (compressed HTML)Q: Does CG8841 localize to the medial/trans Golgi in Drosophila peptidergic neurons and endocrine cells, and is this localization dependent on Gly2 myristoylation?
Q: What is the molecular activity of HID1 proteins, for example whether they position the V-ATPase a2 subunit at the trans-Golgi network directly or act through another partner?
Experiment: Generate a CG8841 null allele and a Gly2-to-Ala rescue construct, and assay dense-core-vesicle number, neuropeptide storage and release, and Golgi-associated V-ATPase a-subunit localization in peptidergic neurons or the larval ring gland.
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