GDAP1 is a tail-anchored protein with a glutathione-transferase-like fold that associates with mitochondrial and peroxisomal membranes. Cellular evidence supports contributions to mitochondrial and peroxisomal fission. Its intrinsic catalytic activity and endogenous ligand remain unresolved. Pathogenic variants cause recessive and dominant peripheral neuropathies.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000266 mitochondrial fission | IBA GO_REF:0000033 | ACCEPT | Summary: The ancestral fission assertion is retained. Reason: Actual tree/alignment replay places the exact human sequence below the asserted node, without an intervening negative placement. The human self-donor is legitimate experimental grounding, not circularity. The inspected fission phenotype supports this conserved placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002544728 SUPPORTS TRANSFER Literal fission IBD at AN0/PTN002544728 descends to human AN53/PTN002544735; Q8TB36 is a genuine target-self donor. Supporting Evidence: GO_REF:0000033 |
| GO:0000266 mitochondrial fission | IDA PMID:15772096 GDAP1, the protein causing Charcot-Marie-Tooth disease type ... | ACCEPT | Summary: Retain the experimental fission assertion. Reason: The original full assay remains inaccessible, but independent perturbation evidence supports GDAP1-mediated fission. Retain the curator assertion without claiming that its abstract reproduces the experiment. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Retain the TMEM218 interaction evidence; remove the uninformative generic-binding annotation. Reason: The literal HuRI pair uses TMEM218 ORF 54962 and GDAP1 ORF 2560. The official partner record describes a membrane protein with a proposed ciliary role supported by similarity; it supplies no established molecular class that justifies a more informative binding replacement here. Binding a ciliary membrane component does not demonstrate that GDAP1 performs ciliogenesis. This decision removes the generic term while preserving the positive pair and source construct limits. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Refine the demonstrated ABHD16A interaction to lipase binding. Reason: HuRI identifies ABHD16A O95870-1, ORF 8110, paired with GDAP1 ORF 2560; current IntAct retains this positive association. The reviewed human ABHD16A record independently establishes monoacylglycerol lipase activity through PMID:25290914. Its phosphatidylserine-specific role is separately marked by similarity. GO:0035473 describes binding to a lipase and is a descendant of enzyme binding and protein binding, making it a justified refinement of this existing assertion. This does not assign lipase catalysis, lipid signaling, or physiological regulation of ABHD16A to GDAP1. Proposed replacements: lipase binding Supporting Evidence: UniProtKB:O95870 file:human/GDAP1/GDAP1-external-evidence.md Also has monoacylglycerol lipase activity |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the apolipoprotein D pair without inferring binding to an enzyme or a lipoprotein particle. Reason: The positive pair uses APOD ORF 4506. The official APOD record describes ligand binding and transport and association with lecithin-cholesterol acyltransferase; association with that enzyme does not make APOD itself an enzyme. The binary APOD construct is also not evidence of interaction with an assembled lipoprotein particle. No supported specific binding replacement was identified, so remove only the uninformative generic term and retain the actual association and source context. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Refine the CLCN7 interaction to transmembrane transporter binding. Reason: HuRI identifies CLCN7 P51798-1, ORF 6673, with GDAP1 ORF 2560; the current IntAct records retain the positive pair. The official CLCN7 record describes proton-coupled chloride exchange across the lysosomal membrane. The current GO:0044325 definition covers binding to a protein that enables transfer across a membrane, and its primary label is transmembrane transporter binding; ion channel binding is a narrower synonym. This established partner class supports a more informative binding assertion without treating the exchanger as a conventional chloride channel or transferring its transport activity, localization, or lysosomal function to GDAP1. Proposed replacements: transmembrane transporter binding Supporting Evidence: UniProtKB:P51798 file:human/GDAP1/GDAP1-external-evidence.md exchange of chloride ions against protons |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Retain the PNLIPRP1 interaction without assigning lipase binding from family membership alone. Reason: HuRI identifies PNLIPRP1 P54315-1, ORF 8421. The reviewed record explicitly distinguishes this inactive lipase-related protein from active pancreatic lipases: the cited human work reports no milk-fat hydrolysis in vitro, while broader low or undetectable substrate activity is marked by similarity. These findings do not prove inactivity under every possible condition, but they do not establish the active lipase class needed for GO:0035473. Preserve the positive interaction and remove only GO:0005515 as uninformative. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the FAM114A1/NOXP20 pair without a speculative functional binding class. Reason: The literal pair uses Q8IWE2-1, ORF 13409. The official record proposes a neuronal-development role by similarity but does not establish an enzyme, receptor, transcription factor or other informative partner class for this interaction. The developmental suggestion is not a molecular activity and cannot be transferred to GDAP1. Remove the generic binding assertion while preserving the positive assay result and source construct identities. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Keep the STARD4 interaction evidence without calling lipid transfer enzyme activity. Reason: HuRI identifies STARD4 Q96DR4-1, ORF 100080785. The official record establishes intracellular cholesterol transfer and sterol binding. Its Rhea transport equation moves unchanged cholesterol between compartments; the CATALYTIC ACTIVITY heading alone does not establish chemical catalysis or justify enzyme binding. STARD4 is a soluble lipid-transfer protein rather than a transmembrane transporter, so GO:0044325 is also unsuitable. No supported specific replacement was identified. Preserve the pair and remove only the generic protein-binding assertion. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the isoform-2 DCBLD2 pair and its construct features without inventing receptor activity. Reason: Both GOA and HuRI explicitly name DCBLD2 Q96PD2-2, ORF 8198. Current IntAct records annotate a sufficient partner region 47-789, while the official variant VSP_010715 describes its sequence difference from the displayed product. These identifiers and features must remain distinct from a verified full construct sequence. A single-pass topology and discoidin/CUB/LCCL domains do not themselves establish a receptor molecular activity suitable for receptor-binding refinement. Retain the five current IntAct positive rows and six original HuRI rows, including their distinct assay records; remove only the generic binding term. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Retain the TMEM14B pair without inferring an enzyme or transcriptional-regulator binding role. Reason: The positive HuRI interaction identifies TMEM14B Q9NUH8-1, ORF 14338. The official record describes a cortical-development role and proposes effects mediated through IQGAP1 translocation. Promoting phosphorylation or nuclear translocation of another protein does not establish intrinsic kinase activity or transcription-factor activity in TMEM14B. No supported specific binding class follows from this record. Preserve the experimental pair and remove the uninformative generic assertion, without transferring cortical-development function to GDAP1. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to cytoskeletal regulatory protein binding. Reason: BIRC5 directly organizes spindle microtubules through the chromosome-passenger machinery and the RANβTPX2 scaffold described in its official FUNCTION record. This is a cytoskeletal regulatory protein class, rather than an inference from its apoptosis phenotype. The replacement describes the partner class only; it assigns neither spindle regulation nor anti-apoptotic activity to GDAP1. Proposed replacements: cytoskeletal regulatory protein binding Supporting Evidence: UniProtKB:O15392 file:human/GDAP1/GDAP1-external-evidence.md participates in the organization of the center spindle |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: The reported partner is MSH5 isoform O43196-2. Its mismatch-recognition and meiotic roles do not establish a more informative GDAP1 activity from this interaction. ATP binding or membership in the MutS family alone is not a demonstrated ATPase class for this tested product. Remove the generic binding term without assigning DNA repair, complex membership or a negative interaction result. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: SNX2 is a membrane-remodeling and trafficking protein. Binding one SNX-BAR component does not establish binding to the assembled retromer complex, membrane deformation by GDAP1 or a direct GTPase-regulatory activity. The observed partner is neither the lipid it binds nor the enzymes recruited by its network. Remove the generic term while retaining the source interaction. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to DNA-binding transcription factor binding. Reason: HOXC4 is independently described as a sequence-specific DNA-binding transcription factor. The Haenig pair therefore supports the partner-class refinement as measured binding capacity. Its curated nuclear location differs from GDAP1βs usual cytosol-facing membrane domain: native colocalization is not established, and no transport or relocalization mechanism is inferred. The screen does not demonstrate transcriptional regulation or DNA binding by GDAP1. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: UniProtKB:P09017 file:human/GDAP1/GDAP1-external-evidence.md Sequence-specific transcription factor |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to phosphatidylinositol 3-kinase regulatory subunit binding. Reason: The literal partner P27986-2 is a PIK3R1 regulatory product, not the p110 catalytic subunit. Its official alternative sequence changes the amino terminus while retaining the regulatory SH2-containing region. Use the term specifically defined for a phosphatidylinositol 3-kinase regulatory subunit; do not assign kinase catalysis to this partner or GDAP1. Exact experimental clone sequence and isoform-exclusive binding remain unestablished. Proposed replacements: phosphatidylinositol 3-kinase regulatory subunit binding Supporting Evidence: UniProtKB:P27986 file:human/GDAP1/GDAP1-external-evidence.md Belongs to the PI3K p85 subunit family |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to cytoskeletal protein binding. Reason: Human TAGLN2 constructs associate with actin structures, and recombinant protein cosediments with F-actin in PMID:25869671. This primary evidence supports a cytoskeletal protein partner independently of GO annotations. The Haenig pair supports binding to that class, without transferring actin binding, immune function or cytoskeletal remodeling to GDAP1. No product-specific interaction is established. Proposed replacements: cytoskeletal protein binding Supporting Evidence: UniProtKB:P37802 file:human/GDAP1/GDAP1-external-evidence.md TAGLN2 associates with F-actin |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to ubiquitin-specific protease binding. Reason: ATXN3 is an experimentally characterized deubiquitinating protease: its official catalytic record specifies hydrolysis of ubiquitin-linked bonds. Ubiquitin-specific protease binding is therefore more informative than generic protein binding. This does not make GDAP1 a deubiquitinase, an inhibitor of ATXN3 or an established physiological ATXN3 substrate. Proposed replacements: ubiquitin-specific protease binding Supporting Evidence: UniProtKB:P54252 file:human/GDAP1/GDAP1-external-evidence.md Deubiquitinating enzyme involved in protein homeostasis maintenance |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: SPACA3 is a sperm-surface protein with a proposed adhesion/receptor role; its official record explicitly reports no detectable bacteriolytic activity for the processed form. A lysozyme-related name or fold does not establish an enzyme-binding subtype, and the proposed receptor role is not sufficient to manufacture a signaling-receptor-binding claim here. Retain the interaction without assigning fertilization or catalytic activity to GDAP1. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: The literal partner is ZNF638 isoform Q14966-2. Its documented VSP_014803 deletion removes canonical residues 815β1978, including the experimentally mapped DNA-binding region at 1353β1477. A transcription-factor-binding refinement based on the long canonical protein would therefore overstate the tested product evidence. This is not evidence against the interaction, nor a claim that the shorter product has no function; remove only the uninformative generic term. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: The partner is Q16637-3, the SMN-delta7 product. The original network table names SMN1/GeneID6606; the current shared protein record also cross-references SMN2/GeneID6607, and neither fact proves clone-sequence uniqueness. SMN-complex assembly roles do not make this single partner a catalytic enzyme or establish binding to the whole complex. Remove generic binding while retaining these product and gene-identity limits. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to protease binding. Reason: CLPP independently has peptide-cleaving activity, supporting protease binding for the reported Haenig pair. Mature CLPP is in the mitochondrial matrix, separated by membranes from GDAP1βs usual cytosol-facing domain. Thus the assay supports binding capacity without establishing access between the mature native proteins. No relocalization, precursor interaction, protease regulation or physiological substrate relationship is inferred. Proposed replacements: protease binding Supporting Evidence: UniProtKB:Q16740 file:human/GDAP1/GDAP1-external-evidence.md Protease component of the ClpXP complex that cleaves peptides |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: CEP55 recruits cytokinetic machinery to the midbody. This establishes a cellular adaptor role but does not identify an enzyme class, binding to a complete complex or a GDAP1 cytokinesis activity. The scaffold-protein-binding definition specifically concerns tethering signaling-pathway members; cytokinetic recruitment alone is not used to impose that subtype. Remove generic protein binding and preserve the interaction record. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: The official ZNF697 function is RNA interaction and a damage-associated muscle response. A zinc-finger name is not sufficient evidence of a DNA-binding transcription factor, and RNA binding by the partner would not establish RNA binding by GDAP1. No verified specific partner-class subtype is supported by the inspected functional record; remove the generic binding term. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: IQSEC1 isoform Q6DN90-2 is an ARF guanine-nucleotide exchange factor whose amino-terminal deletion leaves the annotated SEC7 region. It is not itself an ARF GTPase, and exchange-factor activity is not equated with ATP hydrolysis or kinase catalysis. Without a verified suitable exchange-factor-binding subtype, preserve the pair without assigning an enzyme or downstream trafficking activity to GDAP1. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to DNA-binding transcription factor binding. Reason: FOXR1βs curated FUNCTION record identifies a transcription factor. Its location record includes both nucleus and cytoplasm, so a nuclear-only exclusion is unwarranted. The Haenig pair supports the measured partner-class interaction, while native colocalization and physiological relevance remain unestablished. It does not establish transcriptional regulation, DNA binding or stress protection by GDAP1. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: UniProtKB:Q6PIV2 file:human/GDAP1/GDAP1-external-evidence.md Transcription factor which acts as both an activator and a repressor |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: The inspected SPATA12 record does not establish a specific molecular partner class beyond the named protein. Its spermatogenesis-associated name does not justify assigning a reproductive process, receptor role, enzyme class or transcription-factor interaction to GDAP1. Remove generic protein binding without disputing the reported pair or claiming that SPATA12 is biologically inactive. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: KRTAP8-1 contributes to the matrix surrounding hair keratin filaments. It is a keratin-associated matrix protein, not a keratin itself; binding this protein is not evidence that GDAP1 binds keratin filaments or controls hair-shaft assembly. No more specific molecular partner class is established by the inspected record, so remove the generic binding term. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to enzyme binding. Reason: ZDHHC17 is independently characterized as a protein acyltransferase, with explicit palmitoyl-CoA-dependent catalytic reactions in its official record. Enzyme binding captures that documented partner class. The interaction does not by itself establish that GDAP1 is palmitoylated, that it regulates ZDHHC17, or that it catalyzes acyl transfer. Proposed replacements: enzyme binding Supporting Evidence: UniProtKB:Q8IUH5 file:human/GDAP1/GDAP1-external-evidence.md Palmitoyltransferase that catalyzes the addition of palmitate |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to cytoskeletal protein binding. Reason: IQUB anchors radial-spoke complex RS1 to the axonemal A microtubule, identifying a cytoskeletal partner. Axonemal association does not itself place IQUB in a membrane-separated lumen. The Haenig interaction supports binding capacity without establishing native encounter or a ciliary role for GDAP1; no trafficking mechanism, motility function or microtubule binding is transferred. Proposed replacements: cytoskeletal protein binding Supporting Evidence: UniProtKB:Q8NA54 file:human/GDAP1/GDAP1-external-evidence.md Adapter protein that anchors the radial spoke 1 (RS1) complex |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: VPS37A is an ESCRT-I component involved in sorting ubiquitinated cargo. A binary interaction with this subunit does not establish binding to the assembled ESCRT complex, ubiquitin binding or a cargo-sorting function for GDAP1. No independent enzymatic or other supported specific partner-class binding subtype is established here; remove the generic term. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: The original table name C4orf49 and current MGARP record map to the same GeneID84709. Its role concerns mitochondrial transport and positioning along microtubules, which does not by itself make MGARP a motor enzyme or a structural microtubule component. Retain the identity-resolved interaction without inferring motor binding, mitochondrial transport or a new GDAP1 activity. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to scaffold protein binding. Reason: OPTN is independently described as recruiting TBK1 at the Golgi and organizing its activation in innate signaling. This supports the signaling-scaffold class defined by the replacement term. The reported Q96CV9-2 product has an internal six-residue deletion; the record does not establish isoform-exclusive binding or a GDAP1 effect on this signaling pathway. Autophagy-receptor terminology is not substituted for signaling-receptor binding. Proposed replacements: scaffold protein binding Supporting Evidence: UniProtKB:Q96CV9 file:human/GDAP1/GDAP1-external-evidence.md Mechanistically, recruits TBK1 at the Golgi apparatus |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to protein kinase binding. Reason: MAP3K5 is an experimentally characterized serine/threonine protein kinase, with explicit protein-phosphorylation reactions. Protein kinase binding is the appropriate partner-class refinement. It does not establish that GDAP1 is phosphorylated by MAP3K5, activates or inhibits it, or propagates its stress-response pathways. Proposed replacements: protein kinase binding Supporting Evidence: UniProtKB:Q99683 file:human/GDAP1/GDAP1-external-evidence.md Serine/threonine kinase which acts as an essential component |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: The literal partner Q9BY12-3 is a SCAPER product. Its CCNA2/CDK2 regulatory role does not make it the kinase itself, and binding a regulator is not equivalent to binding CDK2 or the assembled kinase complex. No source-supported catalytic or other informative molecular subtype is established for this pair. Remove generic binding without assigning a cell-cycle function to GDAP1. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: The tableβs WDR61 and the current SKIC8 record share GeneID80349. The record describes membership in both the SKI and PAF1 complexes; the extensive catalytic and transcriptional statements concern those complexes. They do not independently assign an isolated enzyme or a DNA-binding transcription-factor class to this partner. Binding one subunit does not establish GDAP1 binding to either whole complex or performing RNA decay or transcriptional regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: The original C11orf67 and current AAMDC names resolve to GeneID28971. Its possible adipogenic role does not identify a molecular enzyme, receptor or transcription-factor class, and a domain name alone is insufficient. Preserve this identity-resolved interaction while removing the generic GO term; no lack of biological activity is asserted. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: The literal DAZ3 product Q9NR90-2 is an RNA-binding regulator with a documented internal deletion. RNA binding or translational regulation by a partner does not imply those activities for GDAP1, and DAZ3 is not classified as a translation-initiation factor from the inspected record. No supported informative binding subtype is established here, so remove the generic term without disputing the pair. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to ATPase binding. Reason: DDX20 has independently recorded ATP-hydrolysis activity with UniProt experimental attribution to PMID:10383418 and PMID:20510246. ATPase binding states that measured partner class without relying on the stronger, partly inferred RNA-helicase assignment. The interaction does not establish ATP hydrolysis by GDAP1, modulation of DDX20 catalysis or recruitment to the SMN complex. Proposed replacements: ATPase binding Supporting Evidence: UniProtKB:Q9UHI6 file:human/GDAP1/GDAP1-external-evidence.md ATP + H2O = ADP + phosphate + H(+) |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to cytoskeletal regulatory protein binding. Reason: EVL directly enhances actin nucleation and polymerization and is therefore a cytoskeletal regulatory protein. Its literal Q9UI08-2 product is named isoform1 in UniProt; the declared change is an amino-terminal MAT sequence and does not delete the actin-regulatory EVH2 region. Preserve that naming distinction and refine only the partner class, without assigning actin regulation or isoform-exclusive binding to GDAP1. Proposed replacements: cytoskeletal regulatory protein binding Supporting Evidence: UniProtKB:Q9UI08 file:human/GDAP1/GDAP1-external-evidence.md EVL enhances actin nucleation and polymerization |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to transmembrane transporter binding. Reason: Original PMID:26949185 reports recombinant BOK-dependent vesicle permeabilization; the human BOK FUNCTION record independently describes membrane permeabilization. These support a pore-forming partner class without relying on DR GO. The inspected main Methods do not resolve the recombinant species/sequence; no natural human full-length channel preparation is claimed. The Haenig pair supports transporter-class binding, not pore formation or BOK regulation by GDAP1. Proposed replacements: transmembrane transporter binding Supporting Evidence: UniProtKB:Q9UMX3 file:human/GDAP1/GDAP1-external-evidence.md BOK is a pore-forming protein |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Refine to cytoskeletal regulatory protein binding. Reason: BAIAP2 is independently described as regulating actin reorganization, with its IMD region able to induce bundling and protrusions. The reported Q9UQB8-6 changes lie outside that amino-terminal IMD region. This supports the cytoskeletal regulatory partner class without treating the screen as evidence that GDAP1 activates Rac/CDC42 pathways, reorganizes actin or binds this product uniquely. Proposed replacements: cytoskeletal regulatory protein binding Supporting Evidence: UniProtKB:Q9UQB8 file:human/GDAP1/GDAP1-external-evidence.md Necessary for CDC42-mediated reorganization of the actin cytoskeleton |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove an uninformative generic binding term. Reason: MRFAP1 is documented as associating with MORF4-family proteins and an RB1-containing complex. Such association alone does not make it a DNA-binding transcription factor, a catalytic enzyme or the whole complex. No suitable specific molecular partner class is established from the inspected record; retain the positive interaction while removing generic protein binding. |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | UNDECIDED | Summary: Sperm-specific nuclear detection remains unresolved without the GDAP1-specific proteomic evidence. Reason: PMID:21630459 reports mass spectrometry of purified human sperm nuclei; it is not a generic somatic-nucleus claim. Preserve the original part_of(CL:0000019) context, whose current CL label is sperm. The abstract describes nuclear purification and proteomic identification, but the GDAP1 entry, peptide assignments and localization controls have not been recovered. Established mitochondrial and peroxisomal localization does not disprove a specialized sperm-nuclear pool. Keep the curator assertion undecided; do not call it contamination or a wrong-gene annotation. Supporting Evidence: |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | MODIFY | Summary: Refine the broad location to independently supported cytosolic and organellar compartments. Reason: The ARBA/UniProt mapping is compatible with cytoplasm, but cytosol, mitochondrial outer membrane and peroxisomal membrane provide more informative supported locations. Actual is_a/part_of paths place these compartments within cytoplasm. HPA metadata and the human PEX19 model support a cytosolic pool; topology and localization studies support the membranes. This refinement uses the combined evidence and does not treat the electronic mapping as an experiment resolving each compartment. These replacement locations are already carried in the current GOA. Supporting Evidence: GO_REF:0000120 UniProtKB:Q8TB36 Reactome:R-HSA-9603804 GO_REF:0000052 |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | MODIFY | Summary: Refine the broad location to independently supported cytosolic and organellar compartments. Reason: Mouse O88741 supports the broad cytoplasmic location, which includes organelles. Independent GDAP1 localization and human PEX19-model evidence support cytosol, mitochondrial outer membrane and peroxisomal membrane, connected to cytoplasm by verified is_a/part_of paths. Refine to those informative compartments without presenting the original orthology assertion as three direct human assays or implying exclusively soluble GDAP1. These replacement locations are already carried in the current GOA. Supporting Evidence: GO_REF:0000024 UniProtKB:O88741 Reactome:R-HSA-9603804 GO_REF:0000052 |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: The original MitoCoP data identify GDAP1 as a mitochondrial membrane-associated protein group. Reason: PMID:34800366 supplementary Table S2 sheet A row404 identifies group8465 (Q8TB36;Q8TB36-2;E5RGI2), with positive mitochondrial preselection across subtractive, spatial and importomics approaches. GDAP1 is in subtractive class1, spatial cluster1 and importomics class1; the latter has log2 TOMM40-knockdown/mock of -0.9614. The membrane-association measurements classify the group as integral. Retain the mitochondrial location at protein-group resolution. Pre-existing GO columns in the table are annotation metadata, not new measurements of a submitochondrial compartment. Supporting Evidence: |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: HPA supports a mitochondrial GDAP1 pool in human cultured cells. Reason: The current official HPA record labels mitochondria as the main subcellular location and cytosol as an additional location, with supported reliability. Its assay metadata reports mitochondrial and cytosolic staining in A-549 and U2OS and cytosolic staining in PC-3. This supports the original mitochondrion term without asserting that the HPA assay alone resolves the outer membrane or excludes cell-dependent cytosolic localization. Supporting Evidence: GO_REF:0000052 UniProtKB:Q8TB36 |
| GO:0005741 mitochondrial outer membrane | EXP PMID:16172208 Ganglioside-induced differentiation associated protein 1 is ... | ACCEPT | Summary: Inspected experiments support outer-membrane topology. Reason: Original topology experiments support an integral outer-membrane protein; the construct was mouse cDNA, not silently human. Supporting Evidence: |
| GO:0005741 mitochondrial outer membrane | EXP PMID:16857173 Functional characterisation of ganglioside-induced different... | ACCEPT | Summary: Retain the established outer-membrane compartment. Reason: The cited human biochemical paper is abstract-only in the inspected scope. Its localization details remain uninspected; independent evidence supports retaining the existing EXP assertion. |
| GO:0005741 mitochondrial outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The ancestral outer-membrane placement is retained. Reason: The exact target sequence inherits the actual outer-membrane IBD, with no path-specific negative placement. Independent compartment evidence agrees. Preserve the original activity-location relation and the valid human self-donor. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002544728 SUPPORTS TRANSFER Literal GO:0005741 IBD at AN0/PTN002544728 reaches human AN53/PTN002544735; the inspected topology shows no intervening IRD or NOT. Supporting Evidence: GO_REF:0000033 |
| GO:0005741 mitochondrial outer membrane | IDA PMID:15772096 GDAP1, the protein causing Charcot-Marie-Tooth disease type ... | ACCEPT | Summary: Retain outer-membrane localization. Reason: The cited abstract establishes mitochondrial targeting; independent evidence resolves the compartment. Retain the experimental curation without inventing an inspected topology assay in this paper. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The subcellular-location mapping correctly captures GDAP1 mitochondrial outer-membrane localization. Reason: SL-0172 maps to mitochondrial outer membrane. The official human record and the independently read tail-anchor/localization experiments support GDAP1 as an outer-membrane protein. The cytoplasm-facing domain and C-terminal membrane anchor are compatible with this location. Retain the mapping without interpreting the broader HPA or MitoCoP observations as direct subcompartment-resolution experiments. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9603775 | ACCEPT | Summary: Reactome explicitly places GDAP1 in the peroxisomal membrane after PEX19-mediated delivery. Reason: R-HSA-9603775 releases a class-I peroxisomal membrane-protein set (R-HSA-9603802) whose actual GDAP1 member R-HSA-9603788 is Q8TB36 residues1-358 in the peroxisomal membrane. This is a gene-specific entity trace, not inference from a pathway title. PMID:23628762 additionally supports a peroxisomal GDAP1 pool, PEX19-dependent targeting and a role in peroxisome division. Retain the location while distinguishing it from the predominant mitochondrial pool. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9603775 | KEEP AS NON CORE | Summary: The cytosolic assignment represents a delivery intermediate in the peroxisomal insertion reaction. Reason: The input of R-HSA-9603775 is membrane-associated complex R-HSA-9603793, containing cytosolic PEX19:cargo complex R-HSA-9603787. That complex contains set R-HSA-9603783 and its GDAP1 member R-HSA-9603796, Q8TB36 residues1-358 annotated in cytosol. The product target becomes membrane-localized R-HSA-9603788. Retain this modeled pre-insertion cytosolic state as non-core localization; it does not establish a distinct soluble catalytic role or imply that all cytosolic GDAP1 is explained by this route. Supporting Evidence: Reactome:R-HSA-9603775 Reactome:R-HSA-9603804 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9603784 | KEEP AS NON CORE | Summary: The cytosolic GDAP1 entity is cargo in the PEX19-to-PEX3 docking step. Reason: R-HSA-9603784 consumes cytosolic PEX19:cargo complex R-HSA-9603787 before docking to membrane PEX3. Its component set R-HSA-9603783 explicitly contains GDAP1 R-HSA-9603796, Q8TB36 residues1-358 in cytosol. Retain this trafficking-state localization as non-core. Cargo status does not mean GDAP1 itself catalyzes peroxisomal protein import, and no such process annotation is proposed. Supporting Evidence: Reactome:R-HSA-9603784 Reactome:R-HSA-9603804 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9603804 | KEEP AS NON CORE | Summary: Newly synthesized cytosolic GDAP1 is represented as PEX19 cargo. Reason: R-HSA-9603804 explicitly names GDAP1 among class-I peroxisomal membrane proteins bound by PEX19. The input set R-HSA-9603783 contains R-HSA-9603796, Q8TB36 residues1-358 in cytosol. Retain the modeled cytosolic pre-insertion pool as non-core localization. The current HPA record also allows an additional cytosolic pool, but neither observation proves that this is a separate soluble enzymatic role. |
| GO:0008053 mitochondrial fusion | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Fusion propagation overextends the inspected disease-variant evidence. Reason: The target genuinely descends from this IBD, and self-donation is valid. However, the traced human experiment measures inhibition by dominant pathogenic variants; it does not identify wild-type GDAP1 performing mitochondrial merger. That source-to-ancestral-function extension is not established. Preserve the observed phenotype without concluding that physiological fusion involvement is impossible. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN002544728 SOURCE WEAK OR INFERRED The inspected human mutant fusion experiments do not sufficiently establish the normal-function assertion used at the ancestral node; the corresponding experimental human fusion row is also marked over-annotated. The target sequence, ancestry and legitimate self-donor remain valid. |
| GO:0008053 mitochondrial fusion | IMP PMID:21753178 Dominant GDAP1 mutations cause predominantly mild CMT phenot... | MARK AS OVER ANNOTATED | Summary: Pathogenic inhibition does not establish normal fusion participation. Reason: Human A156G and R120W impair the measured fusion endpoint; wild-type and recessive R120Q behave like controls. These positive mutant results establish disturbed dynamics, without identifying normal GDAP1 as a merger participant. Unchanged fusion under wild-type overexpression alone neither proves nor disproves a physiological fusion role. Supporting Evidence: |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MODIFY | Summary: Refine membrane to the supported mitochondrial outer and peroxisomal membranes. Reason: The original human YTS membrane-proteome abstract does not recover the GDAP1 table row or distinguish organelles. The existing broad assertion is independently supported by tail-anchor topology, mitochondrial/peroxisomal localization and MitoCoP integration evidence. Refine to the two established organellar membranes, both is_a descendants of membrane. These replacements use independent evidence, not an invented subcellular resolution of PMID:19946888; no plasma-membrane localization is asserted. These replacement locations are already carried in the current GOA. Proposed replacements: mitochondrial outer membrane peroxisomal membrane Supporting Evidence: UniProtKB:Q8TB36 Reactome:R-HSA-9603804 |
| GO:0071305 cellular response to vitamin D | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Rat GDAP1 protein induction by vitamin D does not establish a conserved human response function. Reason: The two WITH/FROM alternatives trace to rat GDAP1, not two independent functional experiments. The recovered RGD donor annotation is IEP from PMID:25449168: the abstract explicitly identifies increased Gdap1 protein abundance in 1,25-dihydroxyvitamin-D3-treated INS-1 cells, measured by quantitative proteomics. This is positive evidence of stimulus-dependent protein abundance in that rat cell model, but it does not show that GDAP1 executes the vitamin-D response or that its stimulus regulation is conserved in human cells. Mark the human process projection as over-annotated while retaining the donor observation. Do not infer a vitamin-D-receptor interaction, transcriptional mechanism, or insulin-secretory function. |
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Download this section (compressed HTML)Q: Does membrane-embedded full-length GDAP1 catalyze glutathione conjugation under a physiological activation state, and which endogenous substrate would establish that role?
Q: Is thapsic acid an endogenous GDAP1 ligand, or an experimental probe of a pocket whose physiological ligand remains unidentified?
Q: How does the natural 290-residue product differ from the displayed protein in localization and organelle remodeling?
Experiment: Compare sequence-verified natural products with T288X, T318X and soluble ΞTM controls in membrane reconstitution. Measure conjugated products directly alongside ligand binding and membrane remodeling, using substrate-free, inactive-enzyme and membrane-only controls to distinguish these activities.
Type: Matched natural-product and construct comparison
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The intrinsic catalytic activity and endogenous ligand of membrane-embedded full-length GDAP1 remain unresolved.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: Organelle remodeling and construct-dependent glutathione conjugation or lipid binding are supported. These findings do not identify a physiological catalytic reaction of the native protein.
Significance: Resolving this chemistry would connect the GST-like fold to membrane remodeling and disease mechanisms.
What would resolve it: Compare sequence-verified natural products in defined membranes, measuring substrate turnover and products independently of ligand binding and membrane deformation.
Provenance (the field's own admissions):
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