COL6A2

Summary: Retain collagen VI microfibril localization.

Reason: Retain collagen VI microfibril localization. The current ARBA rule has an exact target FunFam condition-set match, and independent collagen VI assembly literature supports extracellular beaded microfibrils. This is not an assignment to ordinary fibrillar collagen or proof that every alpha2 splice product incorporates identically.

Summary: Retain the established collagen VI microfibril location with independent target-chain context.

Reason: Collagen VI microfibril location is retained on independent canonical-chain and extracellular-assembly evidence summarized in PMID:23869615. The cited PMID:16893474 elastic-fibre review is authentic, but its exact alpha2 passage was not recovered. ACCEPT therefore reflects independently supported biology and curator deference, not verification of that original target-specific passage.

Summary: Preserve the positive human DISC1 association as non-core.

Reason: Three exact positive IntAct Y2H records support the human COL6A2–DISC1 association; canonical P12110 and Q9NRI5 sequence ROGIDs match the recorded participants. The original full paper remains unavailable and its abstract does not enumerate COL6A2; the evidence adjudicated here is the curated positive pair record, not an invented full-paper read. Tested fragment boundaries and physiological interaction remain unresolved. DISC1 identity and these records do not establish a more informative COL6A2 molecular activity. Retain supported binding as KEEP_AS_NON_CORE under the explicit user instruction in projects/CLINGEN_MENDELIAN.md, Curation instructions, lines 2976–2978, which takes precedence over the general informational-exclusion recommendation. This preserves the observed interaction without inventing a native pathway or specific activity.

Summary: Retain positive collagen-chain association from the original assembly experiment.

Reason: Original Methods, Results and Figure 9 identify endogenous human alpha1/alpha2 co-precipitating with engineered mouse alpha4 N6–C2 in secreted disulfide-linked assemblies. This positive collagen-chain association supports the existing collagen-binding annotation with P12109 preserved as its source partner. Separately, the isolated human major 2C2 alpha2 construct binds pepsin-solubilized collagen VI in the ligand assays of PMID:8168508. Neither experiment tests all alpha2 splice products; the assembly experiment does not isolate a binary alpha1–alpha2 interface.

Summary: Actual human aortic ECM proteomics identifies CO6A2_HUMAN in all three extraction tables.

Reason: Actual human aortic ECM proteomics identifies CO6A2_HUMAN in all three extraction tables. The exact rows report 4, 31 and 11 unique peptides in NaCl, guanidine and SDS extracts, respectively. Retain extracellular detection without converting fraction identification into a separate mechanical-force or signaling assay. The short quotation anchors sample provenance; the three exact peptide counts are in original Tables I–III, reproduced in the source-evidence index.

Summary: Retain the independently established extracellular location while preserving this human-vein proteomics source.

Reason: Extracellular location is independently supported by the exact human alpha2 aortic detections in PMID:20551380. The PMID:27068509 vein-extraction/MS Methods were read, but its accessible Figure 3 legend identifies alpha1/alpha3 and the exact alpha2 supplement link remains unverified. ACCEPT retains established location and the original curator assertion without claiming source-specific alpha2 differential abundance.

Summary: The original assembly source detects alpha1/alpha2-containing material in conditioned medium.

Reason: The original assembly source detects alpha1/alpha2-containing material in conditioned medium. Preserve actual extracellular secretion from human SaOs-2 cells with the engineered mouse alpha4 construct. Secreted disulfide-linked assembly is distinguished from demonstrated incorporation into a native extracellular microfibril and from tests of every alpha2 splice product.

Summary: Collagen VI is extracellular substrate material in the MMP2/MMP9/MMP11 degradation event; the proteases perform the cleavage.

Reason: Collagen VI is extracellular substrate material in the MMP2/MMP9/MMP11 degradation event; the proteases perform the cleavage. The actual event summary and complete target membership path were inspected; the annotation remains a location assertion.

Summary: The secretion event connects ER-luminal collagen precursors with extracellular collagen products; this row concerns the extracellular destination.

Reason: The secretion event connects ER-luminal collagen precursors with extracellular collagen products; this row concerns the extracellular destination. The actual event summary and complete target membership path were inspected; the annotation remains a location assertion.

Summary: The network-formation event explicitly describes collagen VI tetramers and beaded-filament associations, distinct from fibrillar collagen packing.

Reason: The network-formation event explicitly describes collagen VI tetramers and beaded-filament associations, distinct from fibrillar collagen packing. The actual event summary and complete target membership path were inspected; the annotation remains a location assertion.

Summary: The integrin-association event includes collagen VI within a broader extracellular collagen set; it is not an isolated alpha2 affinity measurement for every listed integrin.

Reason: The integrin-association event includes collagen VI within a broader extracellular collagen set; it is not an isolated alpha2 affinity measurement for every listed integrin. The actual event summary and complete target membership path were inspected; the annotation remains a location assertion.

Summary: Decorin association contains extracellular collagen VI material; target-chain membership does not isolate the alpha2-decorin interface.

Reason: Decorin association contains extracellular collagen VI material; target-chain membership does not isolate the alpha2-decorin interface. The actual event summary and complete target membership path were inspected; the annotation remains a location assertion.

Summary: Biglycan association contains extracellular collagen VI material, supporting location without resolving a purified alpha2-specific ligand contact.

Reason: Biglycan association contains extracellular collagen VI material, supporting location without resolving a purified alpha2-specific ligand contact. The actual event summary and complete target membership path were inspected; the annotation remains a location assertion.

Summary: The NCAM1 summary names other collagen types, whereas the current participant graph also reaches COL6A2 through a collagen set.

Reason: The NCAM1 summary names other collagen types, whereas the current participant graph also reaches COL6A2 through a collagen set. Retain the independently supported extracellular location without inventing a direct alpha2-NCAM1 experiment. The actual event summary and complete target membership path were inspected; the annotation remains a location assertion.

Summary: The PDGF association event includes extracellular collagen material; the graph does not establish that isolated alpha2 executes PDGF signaling or give it the receptor activity.

Reason: The PDGF association event includes extracellular collagen material; the graph does not establish that isolated alpha2 executes PDGF signaling or give it the receptor activity. The actual event summary and complete target membership path were inspected; the annotation remains a location assertion.

Summary: The alpha10beta1 association event includes collagen VI/IX material.

Reason: The alpha10beta1 association event includes collagen VI/IX material. Its target-chain path supports extracellular location, not a universal isolated-alpha2 integrin-binding measurement. The actual event summary and complete target membership path were inspected; the annotation remains a location assertion.

Summary: Retain canonical alpha1(VI)/alpha2(VI)/alpha3(VI) trimer membership.

Reason: Retain canonical alpha1(VI)/alpha2(VI)/alpha3(VI) trimer membership. The current rule matches the target through its FunFam branch even though another PANTHER branch does not match. The official term explicitly specifies those three chains; the separate engineered alpha4-containing assembly is reviewed under a broader collagen-trimer class.

Summary: The full family review explicitly describes canonical alpha1/alpha2/alpha3 collagen VI trimers and their higher-order assembly.

Reason: The full family review explicitly describes canonical alpha1/alpha2/alpha3 collagen VI trimers and their higher-order assembly. Retain that canonical complex assertion. Discussion of alternative long chains is distinguished from direct testing of every native chain combination or all alpha2 C-terminal splice forms.

Summary: Dimerization of collagen VI precursor units is an intracellular luminal assembly stage.

Reason: Dimerization of collagen VI precursor units is an intracellular luminal assembly stage. Retain the source-specific biosynthetic location outside the principal mature extracellular structural core, without assigning synthesis, processing or transport-enzyme activity to COL6A2.

Summary: Tetramerization of collagen VI dimers occurs before secretion in the ER-luminal pathway.

Reason: Tetramerization of collagen VI dimers occurs before secretion in the ER-luminal pathway. Retain the source-specific biosynthetic location outside the principal mature extracellular structural core, without assigning synthesis, processing or transport-enzyme activity to COL6A2.

Summary: The triple-helix event contains COL6A2 as a structural chain being assembled; the chaperones and isomerases supply their own activities.

Reason: The triple-helix event contains COL6A2 as a structural chain being assembled; the chaperones and isomerases supply their own activities. Retain the source-specific biosynthetic location outside the principal mature extracellular structural core, without assigning synthesis, processing or transport-enzyme activity to COL6A2.

Summary: The secretion event has ER-luminal precursor material and extracellular output at different stages; this row preserves the former.

Reason: The secretion event has ER-luminal precursor material and extracellular output at different stages; this row preserves the former. Retain the source-specific biosynthetic location outside the principal mature extracellular structural core, without assigning synthesis, processing or transport-enzyme activity to COL6A2.

Summary: Association of procollagen VI involves chain alignment in the ER lumen before higher-order assembly and secretion.

Reason: Association of procollagen VI involves chain alignment in the ER lumen before higher-order assembly and secretion. Retain the source-specific biosynthetic location outside the principal mature extracellular structural core, without assigning synthesis, processing or transport-enzyme activity to COL6A2.

Summary: The current official HPA page reports additional plasma-membrane localization as supported, separately from uncertain cytosol localization and its overall uncertain summary.

Reason: The current official HPA page reports additional plasma-membrane localization as supported, separately from uncertain cytosol localization and its overall uncertain summary. Preserve the positive immunofluorescence-derived source as non-core. No image pixels were independently inspected, and peripheral collagen association is not evidence of a transmembrane helix or universal intracellular topology.

Summary: Retain the plasma-membrane-associated electronic location as non-core.

Reason: Retain the plasma-membrane-associated electronic location as non-core. The current ARBA rule has an exact FunFam branch matching COL6A2, HPA retains a supported plasma-membrane signal, and the original NG2 abstract describes cell-surface anchoring of secreted collagen VI. These support association rather than integral insertion or an additional membrane-specific activity.

Summary: The exact rat Col6a2 donor carries an IEP response-to-glucose record from PMID:8494053.

Reason: The exact rat Col6a2 donor carries an IEP response-to-glucose record from PMID:8494053. Its original abstract reports increased alpha1/alpha2/alpha3 mRNAs and collagen VI fibril accumulation in rat nerve connective-tissue cultures exposed to high glucose. Gene-expression change fits the actual response term; retain this contextual response without assigning glucose sensing, glucose metabolism or the diabetic phenotype itself as a separate COL6A2 activity.

Summary: The actual membrane definition includes attached proteins, not only embedded proteins.

Reason: The actual membrane definition includes attached proteins, not only embedded proteins. Official COL6A2 subcellular annotation and the original NG2 experiments support peripheral association of secreted collagen VI with the cell surface. Preserve that contextual location without asserting that alpha2 itself spans a membrane or that the original whole-collagen preparation resolves all three alpha2 products.

Summary: Original marrow ECM workbooks identify COL6A2 in the healthy/donor group; the inspected disease-group cells are not detected or zero.

Reason: Original marrow ECM workbooks identify COL6A2 in the healthy/donor group; the inspected disease-group cells are not detected or zero. This preserves condition-specific identification rather than universal multiple-myeloma detection. Retain the independently established collagen VI structural class under the current collagen convention; proteomic detection is not an isolated tensile-force assay.

Summary: The exact pig Q1T7A6 donor is COL6A2 and carries the same structural term by RCA from PMID:22261194.

Reason: The exact pig Q1T7A6 donor is COL6A2 and carries the same structural term by RCA from PMID:22261194. The genuine abstract describes porcine cardiac ECM proteomics after ischemia/reperfusion, with later human validation context. Retain the homologous alpha2 structural role with independent collagen VI assembly support; no isolated force measurement or exact human alpha2 target experiment is inferred from that abstract.

Summary: Actual aortic Methods and the three exact target rows identify CO6A2_HUMAN in extracellular extracts.

Reason: Actual aortic Methods and the three exact target rows identify CO6A2_HUMAN in extracellular extracts. Retain the independently established collagen VI structural class under the current collagen convention; proteomic detection is not an isolated tensile-force assay.

Summary: Actual human colon/liver ECM Methods and the COL6A2 protein group in both original workbook sheets were inspected; the two sheets are views of the same dataset, not independent experiments.

Reason: Actual human colon/liver ECM Methods and the COL6A2 protein group in both original workbook sheets were inspected; the two sheets are views of the same dataset, not independent experiments. Retain the independently established collagen VI structural class under the current collagen convention; proteomic detection is not an isolated tensile-force assay.

Summary: Recovered original human atrial Methods and Table 1 detect alpha2(VI) in GuHCl input and the glycopeptide column, with the glycoprotein-enrichment column blank.

Reason: Recovered original human atrial Methods and Table 1 detect alpha2(VI) in GuHCl input and the glycopeptide column, with the glycoprotein-enrichment column blank. Retain the independently established collagen VI structural class under the current collagen convention; proteomic detection is not an isolated tensile-force assay.

Summary: Recovered original cell-derived ECM Methods and Table 1 group COL6A1/2/3 as beaded-filament-forming collagen VI.

Reason: Recovered original cell-derived ECM Methods and Table 1 group COL6A1/2/3 as beaded-filament-forming collagen VI. This classification is not individual-chain quantitation. Retain the independently established collagen VI structural class under the current collagen convention; proteomic detection is not an isolated tensile-force assay.

Summary: Actual original human-tissue ECM extraction/MS Methods and Results were read, but attempted supplementary XLSX responses were HTML challenges and the exact alpha2 target row remains unverified.

Reason: The exact alpha2 target link in PMID:28675934 remains UNVERIFIED: original human-tissue ECM extraction/MS Methods and Results were read, but the attempted supplementary XLSX responses were HTML challenges. ACCEPT rests on the independently established collagen VI structural role and the current collagen convention, supported by PMID:23869615, not an isolated tensile-force measurement in this proteomics paper.

Summary: Actual human aortic ECM extraction/MS Methods and all three target table rows identify CO6A2_HUMAN.

Reason: Actual human aortic ECM extraction/MS Methods and all three target table rows identify CO6A2_HUMAN. Retain direct matrix-fraction detection, distinguishing location from isolated mechanical measurement or a new vascular regulatory activity.

Summary: Original Table 1 identifies COL6A2 in human placental stromal fibroblast and immortalized placental fibroblast ECM (normalized values 0.980 and 4.49), with HUES1 not detected.

Reason: Original Table 1 identifies COL6A2 in human placental stromal fibroblast and immortalized placental fibroblast ECM (normalized values 0.980 and 4.49), with HUES1 not detected. A mouse feeder group is also positive; the exact mixed-species column headers were inspected. Retain matrix localization without claiming human ESC-matrix detection or a COL6A2-specific stem-cell induction step. The quotation anchors cell identity; the numerical values and column assignments are from original Table 1 in the source-evidence index.

Summary: Actual human colon/liver ECM Methods and the COL6A2 protein group in both original workbook sheets were inspected; the two sheets are views of the same dataset, not independent experiments.

Reason: Actual human colon/liver ECM Methods and the COL6A2 protein group in both original workbook sheets were inspected; the two sheets are views of the same dataset, not independent experiments. Retain the established extracellular matrix location at that exact access and sample scope. The quotation anchors patient sample context; the alpha2 identification is in original Additional file 2, row 102 in each sheet, indexed separately.

Summary: Recovered original human atrial Methods and Table 1 detect alpha2(VI) in GuHCl input and the glycopeptide column, with the glycoprotein-enrichment column blank.

Reason: Recovered original human atrial Methods and Table 1 detect alpha2(VI) in GuHCl input and the glycopeptide column, with the glycoprotein-enrichment column blank. Retain the established extracellular matrix location at that exact access and sample scope.

Summary: Recovered original cell-derived ECM Methods and Table 1 group COL6A1/2/3 as beaded-filament-forming collagen VI.

Reason: Recovered original cell-derived ECM Methods and Table 1 group COL6A1/2/3 as beaded-filament-forming collagen VI. This classification is not individual-chain quantitation. Retain the established extracellular matrix location at that exact access and sample scope.

Summary: Original marrow ECM workbooks identify COL6A2 in the healthy/donor group; the inspected disease-group cells are not detected or zero.

Reason: Original marrow ECM workbooks identify COL6A2 in the healthy/donor group; the inspected disease-group cells are not detected or zero. This preserves condition-specific identification rather than universal multiple-myeloma detection. Retain the established extracellular matrix location at that exact access and sample scope.

Summary: Actual original human-tissue ECM extraction/MS Methods and Results were read, but attempted supplementary XLSX responses were HTML challenges and the exact alpha2 target row remains unverified.

Reason: The exact alpha2 target link in PMID:28675934 remains UNVERIFIED: original human-tissue ECM extraction/MS Methods and Results were read, but the attempted supplementary XLSX responses were HTML challenges. ACCEPT rests on independently established extracellular collagen VI assembly summarized in PMID:23869615, not verification of the unavailable target-table row.

Summary: Retain the curated PAINT extracellular-matrix placement, consistent with alpha2 matrix biology and direct target proteomics.

Reason: Retain the curated PAINT extracellular-matrix placement, consistent with alpha2 matrix biology and direct target proteomics. Exact current MGI and UniProt descendant identities and same-term records were inspected; they include experimentally supported extracellular matrix proteins. IBA is a historical ancestral-node judgment, not a donor-count vote. The historical PTN tree/MSA was not reconstructed, so its exact placement remains unresolved rather than alleged wrong or circular.

Summary: The exact mouse Col6a2 donor has current same-term IDA and HDA records, including the original muscle-development study and feeder-matrix proteomics.

Reason: The exact mouse Col6a2 donor has current same-term IDA and HDA records, including the original muscle-development study and feeder-matrix proteomics. Retain the orthologous extracellular-matrix location with independent human target support. Current descendant records support the transfer premise but do not reconstruct the historical Compara mapping.

Summary: The exact pig COL6A2 donor Q1T7A6 has a same-term HDA record from this porcine cardiac ECM study.

Reason: The exact pig COL6A2 donor Q1T7A6 has a same-term HDA record from this porcine cardiac ECM study. Retain the transferred matrix location with independent human alpha2 detection. The original abstract was read, but no exact pig target table or separate human alpha2 measurement is claimed.

Summary: Refine the broad complex to the vWA-domain-rich collagen trimer class supported by the actual source.

Reason: The actual PMID:18400749 Methods, Results and Figure 9C show endogenous human alpha1/alpha2 co-assembling with the engineered mouse alpha4 N6–C2 chain in secreted disulfide-linked heterotrimers. GO:0140158 defines a family of collagens containing multiple vWA domains and is placed under collagen trimer; its child GO:0005589 explicitly specifies alpha1(VI)/alpha2(VI)/alpha3(VI). The child therefore misdescribes this particular alpha4-containing experiment. Retain MODIFY from generic GO:0032991 to the supported source-specific trimer class, while retaining independent canonical alpha3-complex assertions. The ancestor/descendant exclusion for NEW annotations does not erase distinct existing source assertions or force them to name an untested chain. Human COL6A4 disruption and the native alternative-chain uncertainties discussed in PMID:23869615 limit physiological extrapolation; they do not negate the observed human alpha2 coassembly in the engineered assay. No native human alpha4 complex, all-product equivalence or catalytic activity is asserted.

Proposed replacements: von-Willerbrand-factor-A-domain-rich collagen trimer

Summary: The exact mouse Col6a2 source has the same sarcolemma IDA annotation from PMID:16810681.

Reason: The exact mouse Col6a2 source has the same sarcolemma IDA annotation from PMID:16810681. The authentic abstract includes collagen VI colocalization with biglycan in embryonic tendon, but the full original localization images were not recovered. Retain the curated muscle-associated matrix location as non-core with that limit: the official sarcolemma definition includes the covering basement membrane and collagen network, so extracellular identity does not contradict it.

Summary: Original ACS Table S2 row 334 identifies COL6A2/IPI00304840.3 in a human parotid exosome-rich fraction, reporting five sequences, five spectra and 5% coverage.

Reason: Original ACS Table S2 row 334 identifies COL6A2/IPI00304840.3 in a human parotid exosome-rich fraction, reporting five sequences, five spectra and 5% coverage. Table S1 rows 4116-4120 contain four distinct peptide sequences across five entries; all map to alpha2, and AAVFHEK maps to the major 2C2 C terminus but not either shorter product. Preserve this positive single-donor fraction detection as non-core, without an all-product, quantitative isoform, vesicle-biogenesis or target-specific imaging claim. Actual isolation/MS Methods and the authors contamination discussion were read separately from the shorter protected cache. The short quotation records the authors' general fraction-contamination caveat; it neither identifies COL6A2 as contamination nor substitutes for the exact target/peptide rows in the original supplements.

Summary: The original public PXD000608 MaxQuant proteinGroups row 855 identifies the COL6A2 group containing P12110, P12110-2 and P12110-3, with ten peptides in each of the two EV pools and a low soluble-fraction signal.

Reason: The original public PXD000608 MaxQuant proteinGroups row 855 identifies the COL6A2 group containing P12110, P12110-2 and P12110-3, with ten peptides in each of the two EV pools and a low soluble-fraction signal. The archived parameter file uses 1% peptide and protein FDR; the target is not flagged reverse or contaminant. Retain positive human CSF EV-fraction detection as non-core. This grouped assignment is not evidence that all three products were independently detected, that the protein lies inside vesicles, or that COL6A2 executes vesicle biogenesis. The original abstract and authentic deposited output were read; full article Methods were not recovered.