Gliomedin is a Schwann-cell glycoprotein that links glial surfaces and perinodal extracellular matrix to axonal adhesion receptors. It is produced as a type-II membrane protein and released by proteolysis into extracellular assemblies. Its olfactomedin domain recognizes neurofascin and NrCAM. Together with glial NrCAM, gliomedin promotes sodium-channel clustering at developing heminodes; paranodal barriers provide a cooperating route to mature-node assembly. Gliomedin and NrCAM also support long-term nodal stability with overlapping contributions. Biallelic GLDN variants cause a severe inherited nodopathy associated with fetal akinesia and congenital contractures.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Reason: Retain the verified AN0 extracellular-region assertion. Gliomedin has an experimentally demonstrated released extracellular pool as well as a membrane precursor; these are compatible lifecycle locations. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Reason: The combined electronic extracellular-region assignment agrees with the experimentally established secreted pool. Membrane localization of the precursor does not invalidate extracellular localization after release. |
| GO:0005576 extracellular region | ISS GO_REF:0000024 | ACCEPT | Reason: The rat donor has a released extracellular form. This ISS location is biologically compatible with human gliomedin; preserve its original transfer evidence and unsuffixed product. Supporting Evidence: |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | KEEP AS NON CORE | Reason: The current HPA record reports supported plasma-membrane staining with antibody HPA050873 in U2OS cells. Other tested cell lines show vesicles; do not generalize one localization across every line or assign an isoform. Supporting Evidence: GO_REF:0000052 |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Reason: The electronic location fits the membrane precursor and human surface experiment. Retain this supported lifecycle location as non-core. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Reason: Retain the rat-derived membrane-precursor location as non-core; the released extracellular organizer defines the core. |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Reason: Retain the AN0/PTN000573635 assertion: the verified GLDN lineage descends from this node, with no established target-specific loss. The broad ancestral signaling inference is non-core; it does not assign MYOC-specific ErbB signaling to GLDN. Supporting Evidence: GO_REF:0000033 |
| GO:0009986 cell surface | IBA GO_REF:0000033 | ACCEPT | Reason: The AN480 placement and literal donor set are verified. The human self-donor is legitimate experimental grounding, corroborated by direct surface detection of expressed human gliomedin. |
| GO:0009986 cell surface | IDA PMID:27616481 Mutations in GLDN, Encoding Gliomedin, a Critical Component ... | ACCEPT | Reason: Human placental GLDN cDNA expressed in CHO cells was detected by live-cell surface staining, with permeabilized staining as total-expression comparison. Preserve the human protein/hamster host distinction and unspecified isoform. Supporting Evidence: |
| GO:0030424 axon | IEA GO_REF:0000044 | REMOVE | Reason: Rat immunogold and extracellular deposition support perinodal glial material, not an axonal compartment. The nodal-term boundary remains unresolved. Supporting Evidence: file:human/GLDN/GLDN-source-guide.md no gold particles were detected in the axon |
| GO:0034113 heterotypic cell-cell adhesion | IEA GO_REF:0000108 | ACCEPT | Reason: The inferred process matches the retained adhesion-associated molecular function. Binding experiments and genotype-defined neuron/Schwann-cell cocultures support physical participation beyond knockout necessity. Supporting Evidence: |
| GO:0086080 protein binding involved in heterotypic cell-cell adhesion | IEA GO_REF:0000107 | ACCEPT | Reason: Gliomedin binds axonal adhesion receptors and physically supports axoglial attachment. This adhesion-specific binding term is informative; retain the mouse ortholog transfer. |
| GO:0140149 non-collagenous component of interstitial matrix | TAS PMID:36399478 MatrisomeDB 2.0: 2023 updates to the ECM-protein knowledge d... | ACCEPT | Reason: The official human Matrisome masterlist places GLDN (HGNC:29514; Q6ZMI3) in Core matrisome / ECM Glycoproteins, consistent with its extracellular matrix role. Its collagen-like domain does not turn this category into the collagen category. No human peptide, tissue or proteoform-specific detection is claimed from the database article alone. Supporting Evidence: |
| GO:0045162 clustering of voltage-gated sodium channels | ISS PMID:20188654 A glial signal consisting of gliomedin and NrCAM clusters ax... | NEW | Reason: Propose an orthology-based human annotation for ligand-driven channel organization. Antibody-preclustered Gldn-Fc recruited sodium channels in mouse DRG neurons with NF186, including NrCAM-null neurons, but not NF186-null neurons. This establishes receptor-organizing participation beyond knockout necessity; it is not a human direct assay or an isoform-specific claim. Supporting Evidence: PMID:20188654 gliomedin provides a glial signal for Na+ channel clustering |
Loading supporting content…
Download this section (compressed HTML)Q: How does the naturally shorter Q6ZMI3-2 product reach its physiological compartment and contribute relative to the full-length precursor?
Suggested experts: Peripheral nerve biologists, UniProt curators
Q: Which human variant effects remain after matching cell-surface abundance, separating defective delivery from altered receptor recognition?
Suggested experts: Peripheral nerve biologists, Human geneticists
Q: How should a Schwann-cell/perinodal extracellular protein be represented at a node of Ranvier when GO:0033268 explicitly denotes an axon part?
Suggested experts: GO cellular-component curators
Experiment: Compare sequence-verified human products and disease variants at matched surface abundance, measuring receptor binding and neuron–Schwann-cell organization separately.
Hypothesis: Trafficking and receptor-recognition defects can be distinguished experimentally.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)