COL6A1 encodes the alpha1 chain of collagen VI, a secreted extracellular matrix protein with a short triple-helical region flanked by von Willebrand factor A domains. Alpha1(VI) assembles with other collagen VI chains into triple-helical units that form disulfide-linked dimers and tetramers and extracellular beaded microfibrils. The canonical complex contains alpha1(VI), alpha2(VI) and alpha3(VI); alternative long chains support additional assembly contexts. Collagen VI provides matrix architecture around cells and connects tissue mechanics with cell adhesion and survival. Pathogenic COL6A1 variants cause collagen VI-related muscular dystrophies, including Bethlem and Ullrich phenotypes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001527 microfibril | IEA GO_REF:0000117 | ACCEPT | Reason: Microfibrillar extracellular localization is consistent with collagen VI assembly and beaded matrix architecture. The electronic assertion is supported by the established target-chain assembly literature and the collagen VI family review, without identifying these beaded microfibrils as ordinary fibrillar collagens. |
| GO:0001527 microfibril | TAS PMID:16893474 Elastic fibres in health and disease. | ACCEPT | Reason: Retain the established collagen VI microfibril location with curator deference and independent target evidence. The cited elastic-fibre review is authentic but only its abstract was recovered; its title does not demonstrate a target misattribution. It is not presented as a newly inspected COL6A1 localization experiment. |
| GO:0001649 osteoblast differentiation | HDA PMID:16210410 Differential expression profiling of membrane proteins by qu... | MARK AS OVER ANNOTATED | Reason: Human hMSC-TERT membrane proteomics measures increased COL6A1 abundance during calcitriol-induced osteoblast differentiation; the displayed collagen immunofluorescence assays type I, not VI. This is positive evidence for differentiation-associated matrix remodeling, but the source-specific osteoblast-process attribution is stronger than the demonstrated COL6A1 function. Mark the process annotation as over-annotated while retaining the genuine HDA observation. A structural matrix contribution remains plausible; the unresolved mechanism belongs in the biological questions, and no requirement for intrinsic cell-fate control is imposed. Supporting Evidence: PMID:16210410 changes in expression of membrane protein markers |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Reason: Two exact interaction records support COL6A1 association with COL9A1 in anti-tag affinity-purification/co-immunoprecipitation experiments in 293T and HCT116 cells. These are positive co-complex observations, but identification of a collagen partner alone does not establish that COL6A1 makes the collagen-binding contact. Retain the supported generic interaction as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions; withdraw the proposed GO:0005518 refinement for this source. The separate experimental collagen-binding annotation remains assessed on its own evidence. Supporting Evidence: |
| GO:0005518 collagen binding | IPI PMID:18400749 Three novel collagen VI chains, alpha4(VI), alpha5(VI), and ... | ACCEPT | Reason: Recovered original Methods/Results and Figure 9 show human endogenous alpha1(VI) and alpha2(VI) co-precipitating with engineered mouse alpha4(VI) N6–C2 in secreted disulfide-linked assemblies from SaOS-2 cells. This is positive collagen-chain association supporting collagen binding, with the source partner P12110 retained. The assay does not establish alpha1/alpha2 direct contact independently of the multichain assembly; the collagen-V-specific and cell-matrix-adhesion binding children do not fit this experiment. Supporting Evidence: PMID:18400749 trimeric collagen VI molecules |
| GO:0005576 extracellular region | HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | ACCEPT | Reason: Actual human vein extraction/MS Methods and Figure 3 legend identify CO6A1 in GuHCl extracellular-matrix extracts from six normal and six varicose saphenous veins. The legend scales CO6A1 and CO6A3 plotting intensities down fivefold; this is not a fivefold biological change. Retain positive extracellular detection without claiming an inspected supplemental target row or isolated vascular regulatory mechanism. Supporting Evidence: |
| GO:0005576 extracellular region | IDA PMID:18400749 Three novel collagen VI chains, alpha4(VI), alpha5(VI), and ... | ACCEPT | Reason: The original source directly detects human alpha1(VI)/alpha2(VI)-containing engineered assemblies in conditioned medium. Retain secretion/extracellular location while separating secreted material from demonstrated incorporation into a native extracellular microfibril. Mouse alpha4 construct and endogenous human chains are distinguished. Supporting Evidence: |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1564112 | ACCEPT | Reason: The collagen VI degradation event contains extracellular collagen VI material as the substrate of MMP2, MMP9 and MMP11; those enzymes perform the proteolysis. Supporting Evidence: Reactome:R-HSA-1564112 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2089971 | ACCEPT | Reason: The secretion event links luminal precursors and exported collagen material; this assertion concerns the extracellular destination. Supporting Evidence: Reactome:R-HSA-2089971 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2213207 | ACCEPT | Reason: The network-formation summary explicitly includes collagen VI beaded filaments and their higher-order associations, distinct from fibrillar-collagen packing. Supporting Evidence: Reactome:R-HSA-2213207 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327695 | ACCEPT | Reason: The integrin-association event contains extracellular collagen VI in a broader collagen set; a target membership path is not an isolated alpha1(VI) affinity measurement for every listed integrin. Supporting Evidence: Reactome:R-HSA-2327695 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327909 | ACCEPT | Reason: Decorin association places collagen VI fibril material extracellularly; the target-chain path supports location without resolving an isolated alpha1(VI)-decorin interface. Supporting Evidence: Reactome:R-HSA-2327909 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2466106 | ACCEPT | Reason: Biglycan association contains collagen VI extracellular material; membership is not an independent alpha1(VI)-specific ligand assay. Supporting Evidence: Reactome:R-HSA-2466106 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-375151 | ACCEPT | Reason: The NCAM1 summary foregrounds other collagen types, whereas the actual current participant graph also reaches COL6A1 through a collagen set. Preserve the independently supported extracellular location without claiming a new direct COL6A1-NCAM1 experiment. Supporting Evidence: Reactome:R-HSA-375151 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-382054 | ACCEPT | Reason: The PDGF association event includes extracellular collagen material; the separate primary growth-factor-binding source is assessed at its own preparation/chain limits. Supporting Evidence: Reactome:R-HSA-382054 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4084903 | ACCEPT | Reason: The alpha10beta1 integrin event contains extracellular collagen VI/IX material; the target path supports location without assigning integrin signaling or every ligand contact to the isolated alpha1(VI) chain. Supporting Evidence: Reactome:R-HSA-4084903 |
| GO:0005589 collagen type VI trimer | IEA GO_REF:0000117 | ACCEPT | Reason: The established canonical collagen VI trimer contains alpha1, alpha2 and alpha3 chains, fitting the current GO definition. Retain this electronic complex assignment, while recognizing that the separate alpha4 experiment has a different composition and is reviewed separately. |
| GO:0005589 collagen type VI trimer | NAS PMID:2551668 Sequence analysis of alpha 1(VI) and alpha 2(VI) chains of h... | ACCEPT | Reason: Actual original human fibroblast/placental cDNA analysis and human amnion peptide work establish alpha1(VI) sequence/domain identity. The canonical alpha1/alpha2/alpha3 composition is contextual knowledge in this source rather than a newly purified assembly measurement. Retain its NAS membership assertion; the reported C-terminal splice variants concern alpha2(VI), not alternative human COL6A1 products. Supporting Evidence: |
| GO:0005589 collagen type VI trimer | TAS PMID:23869615 The expanded collagen VI family: new chains and new question... | ACCEPT | Reason: The actual family review describes canonical alpha1/alpha2/alpha3 collagen VI and additional long-chain possibilities. Retain the canonical complex assignment without claiming that each alternative combination was directly assembled from human proteins in this review. Supporting Evidence: |
| GO:0005604 basement membrane | IEA GO_REF:0000107 | ACCEPT | Reason: The exact current mouse Col6a1 donor has the same-term IDA record from PMID:31837950. Actual mouse lung immunostaining includes basal epithelial/subendothelial collagen VI distribution and appropriate antibody controls, consistent with basement-membrane-associated matrix. Retain this contextual structural location without requiring collagen VI to be an integral membrane protein. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q04857 · Col6a1 SUPPORTS TRANSFER The exact current mouse Col6a1 donor has the same-term IDA record from PMID:31837950. Actual mouse lung immunostaining includes basal epithelial/subendothelial collagen VI distribution and appropriate antibody controls, consistent with basement-membrane-associated matrix. Retain this contextual structural location without requiring collagen VI to be an integral membrane protein. Supporting Evidence: |
| GO:0005764 lysosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: The exact mouse donor record points to PMID:28604699, whose actual experiments include collagen VI uptake/degradation in human RPE1 cells and patient fibroblasts, with bafilomycin-sensitive degradation. This supports a lysosomal cargo location outside the principal extracellular structural core. The gifted uptake tetramers have unspecified species in Methods; the separate binding reagent is explicitly pepsinized human-tissue collagen VI. Cargo presence is retained without assigning lysosomal catalytic activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q04857 · Col6a1 SUPPORTS TRANSFER The exact mouse donor record points to PMID:28604699, whose actual experiments include collagen VI uptake/degradation in human RPE1 cells and patient fibroblasts, with bafilomycin-sensitive degradation. This supports a lysosomal cargo location outside the principal extracellular structural core. The gifted uptake tetramers have unspecified species in Methods; the separate binding reagent is explicitly pepsinized human-tissue collagen VI. Cargo presence is retained without assigning lysosomal catalytic activity. Supporting Evidence: |
| GO:0005765 lysosomal membrane | HDA PMID:17897319 Integral and associated lysosomal membrane proteins. | KEEP AS NON CORE | Reason: Actual original human placental fractionation identifies COL6A1-associated peptides in a lysosomal-membrane preparation. The authors specifically discuss terminal-domain/degradation debris as an explanation for collagen VI detection. Retain the positive fraction-associated observation as non-core; it does not establish an intact integral membrane topology. The target row was inspected, but unlabeled numeric columns are not interpreted without its complete header. Supporting Evidence: |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: The signal-bearing precursor enters the ER for modification and chain assembly. Retain this broad biosynthetic location outside the principal mature extracellular structural core; the existing luminal source assertions give the more precise stage-specific context. Luminal residence does not make the collagen a chaperone or export-machine component. Supporting Evidence: Reactome:R-HSA-2022073 Reactome:R-HSA-8944247 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-1614460 | KEEP AS NON CORE | Reason: Collagen VI dimers form from assembled precursor units in the ER lumen. Supporting Evidence: Reactome:R-HSA-1614460 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-1614461 | KEEP AS NON CORE | Reason: Tetramerization of collagen VI precursor units is an ER-luminal assembly stage before secretion. Supporting Evidence: Reactome:R-HSA-1614461 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2022073 | KEEP AS NON CORE | Reason: The target participates as a structural chain in luminal triple-helix formation; the cited chaperones and isomerases perform their own catalytic steps. Supporting Evidence: Reactome:R-HSA-2022073 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2089971 | KEEP AS NON CORE | Reason: The secretion event includes luminal precursor material as well as extracellular material at a later stage. Supporting Evidence: Reactome:R-HSA-2089971 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8944247 | KEEP AS NON CORE | Reason: Procollagen VI association involves chain alignment/assembly in the ER lumen. Supporting Evidence: Reactome:R-HSA-8944247 |
| GO:0009653 anatomical structure morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: Retain the broad electronic morphogenesis association as contextual matrix biology. Mouse collagen VI deficiency alters lung architecture and muscle development/integrity, providing a coherent structural contribution to anatomical form. These phenotypes do not identify a separate morphogen enzyme or a universal developmental signaling pathway. |
| GO:0009888 tissue development | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: The collagen VI matrix contributes a structural environment for tissue development and maintenance, consistent with actual mouse lung and vertebrate muscle phenotypes. Preserve the broad electronic developmental association as non-core, without treating every secondary tissue response as an independently executed molecular activity. |
| GO:0016020 membrane | HDA PMID:16210410 Differential expression profiling of membrane proteins by qu... | KEEP AS NON CORE | Reason: Original human hMSC-TERT Methods use a membrane-enriched ultracentrifugation/carbonate-treated fraction and identify COL6A1 by mass spectrometry during osteogenic induction. Preserve that positive fraction association as non-core; it does not establish a transmembrane helix or a membrane-specific catalytic activity. The type I collagen immunofluorescence image is not relabeled as a type VI localization assay. Supporting Evidence: |
| GO:0016529 sarcoplasmic reticulum | IEA GO_REF:0000107 | REMOVE | Reason: The exact mouse IMP donor traces to PMID:22024752, whose knockout-muscle TEM shows dilated sarcoplasmic reticulum and altered organelle homeostasis. The measured structure is an affected organelle, not a demonstrated collagen VI location. Transferring that pathology as a specific location for this secreted extracellular structural chain is unlikely to be correct. Remove this electronic inference; retain the independently supported broad ER/ER-lumen biosynthetic locations. This does not dispute the knockout phenotype or infer absence from all intracellular compartments. Propagation Review Root cause: SOURCE BAD Sources checked: UniProtKB:Q04857 · Col6a1 SOURCE BAD The current mouse IMP donor is genuine. Its inspected experiment measures downstream compartment pathology rather than locating collagen VI at that structure; SOURCE_BAD identifies this source-to-location inference, not a false experiment. Supporting Evidence: PMID:22024752 altered sarcoplasmic reticulum |
| GO:0030016 myofibril | IEA GO_REF:0000107 | REMOVE | Reason: The exact mouse IMP donor traces to PMID:20716577. Original Results and Methods measure tropomyosin oxidation, MAO activity and recovery of muscle contractility after MAO inhibition in collagen-VI-deficient mice; the relevant immunoblots assay tropomyosin and MAO. Myofibrils are the intracellular contractile actin-myosin apparatus, whereas the established collagen VI role is extracellular matrix support. The electronic transfer confuses damage to that apparatus with a site occupied by COL6A1 and is unlikely to be correct. Remove this localization inference while retaining the genuine muscle-homeostasis findings. Propagation Review Root cause: SOURCE BAD Sources checked: UniProtKB:Q04857 · Col6a1 SOURCE BAD The current mouse IMP donor is genuine. Its inspected experiment measures downstream compartment pathology rather than locating collagen VI at that structure; SOURCE_BAD identifies this source-to-location inference, not a false experiment. Supporting Evidence: PMID:20716577 oxidation of myofibrillar proteins |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | ISS GO_REF:0000024 | ACCEPT | Reason: The exact pig Q1T7A8 source resolves to COL6A1 and has the corresponding structural record from PMID:22261194. The original abstract describes porcine cardiac ECM remodeling after ischemia/reperfusion; no isolated tensile experiment is claimed. The GO collagen convention and independently established collagen VI matrix assembly support the transferred structural function. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q1T7A8 · COL6A1 SUPPORTS TRANSFER Official pig COL6A1 identity and exact current same-term record are verified; original porcine ECM-proteomics abstract and independent human structural/location evidence support transfer. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Reason: Actual human aortic extraction/MS Methods and Table II identify CO6A1_HUMAN. Retain the independently established collagen structural activity. Proteomic identification/classification is not an isolated tensile-force measurement, and missing table access is not contrary evidence. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Reason: Actual human colon/liver ECM Methods and the exact COL6A1 row in both complete and Matrisome workbook sheets were inspected; these are two views of one dataset. Retain the independently established collagen structural activity. Proteomic identification/classification is not an isolated tensile-force measurement, and missing table access is not contrary evidence. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Reason: Separately recovered original human atrial Methods/Table 1 identify alpha1(VI) in GuHCl input and the glycopeptide column, with the glycoprotein-enrichment column blank. Retain the independently established collagen structural activity. Proteomic identification/classification is not an isolated tensile-force measurement, and missing table access is not contrary evidence. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Reason: Recovered original cell-derived ECM Methods/Table 1 groups COL6A1/2/3 as beaded-filament-forming collagen VI; this is not chain-resolved quantitative peptide evidence. Retain the independently established collagen structural activity. Proteomic identification/classification is not an isolated tensile-force measurement, and missing table access is not contrary evidence. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Reason: Original human tissue ECM extraction/MS Methods and Results were recovered, but exact target supplementary workbook access remains incomplete: attempted XLSX downloads returned HTML. Retain the independently established collagen structural activity. Proteomic identification/classification is not an isolated tensile-force measurement, and missing table access is not contrary evidence. |
| GO:0030154 cell differentiation | IEA GO_REF:0000117 | UNDECIDED | Reason: ARBA00027429 genuinely predicts this term through condition set 214, requiring three FunFams present in human P12109. The current response establishes applicability but does not expose the historical experimental or training premise. The broad cell-differentiation claim is not necessarily limited to the two expression studies assessed separately. Actual collagen-VI matrix effects on airway epithelial spreading and barrier maturation leave the developmental transition unresolved, and the authors do not establish its ontogeny. Retain UNDECIDED because the broader rule-derived functional attribution remains unadjudicated; rule firing alone neither proves that function nor establishes over-annotation. |
| GO:0031012 extracellular matrix | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Reason: Actual human aortic ECM-enrichment Methods and Table II directly identify the alpha1(VI) target in extracellular preparations. Retain matrix location; extraction/deposition evidence is kept distinct from a purified structural mechanics assay. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:23658023 Comparative proteomic analysis of supportive and unsupportiv... | ACCEPT | Reason: Actual original ECM proteomics Table 1 detects COL6A1 in human placental stromal fibroblast feeder matrices, while the HUES1 MS entry is not detected; weaker immunofluorescence is a distinct assay. Retain extracellular-matrix localization without claiming universal target detection in all tested cell types or a positive endoderm-induction experiment. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Reason: Actual human colon/liver ECM Methods and the exact COL6A1 row in both complete and Matrisome workbook sheets were inspected; these are two views of one dataset. Retain the well-established extracellular matrix location at the actual source access scope. |
| GO:0031012 extracellular matrix | HDA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Reason: Separately recovered original human atrial Methods/Table 1 identify alpha1(VI) in GuHCl input and the glycopeptide column, with the glycoprotein-enrichment column blank. Retain the well-established extracellular matrix location at the actual source access scope. |
| GO:0031012 extracellular matrix | HDA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Reason: Recovered original cell-derived ECM Methods/Table 1 groups COL6A1/2/3 as beaded-filament-forming collagen VI; this is not chain-resolved quantitative peptide evidence. Retain the well-established extracellular matrix location at the actual source access scope. |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Reason: Original human tissue ECM extraction/MS Methods and Results were recovered, but exact target supplementary workbook access remains incomplete: attempted XLSX downloads returned HTML. Retain the well-established extracellular matrix location at the actual source access scope. |
| GO:0031012 extracellular matrix | IBA GO_REF:0000033 | ACCEPT | Reason: Retain the PAINT extracellular-matrix placement. Current resolved descendant identities and same-term records are consistent with extracellular collagen/matrilin/cochlin biology; the target itself also has substantial direct ECM grounding. IBA represents a curated ancestral-node placement rather than a pairwise donor vote. The historical tree/MSA was not reconstructed and no placement failure is alleged. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002544439 UNRESOLVED Historical PAINT node/tree not reconstructed; current descendant records and direct target ECM evidence support the inherited placement without treating donor count as a confidence score. |
| GO:0031012 extracellular matrix | IEA GO_REF:0000107 | ACCEPT | Reason: The exact mouse Col6a1 donor has multiple current ECM records and target-concordant matrix evidence. Actual mouse lung collagen VI distribution and independently detected human extracellular material support the transfer. The separate lysosomal/vesicular observations do not negate extracellular matrix residence. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q04857 · Col6a1 SUPPORTS TRANSFER The exact mouse Col6a1 donor has multiple current ECM records and target-concordant matrix evidence. Actual mouse lung collagen VI distribution and independently detected human extracellular material support the transfer. The separate lysosomal/vesicular observations do not negate extracellular matrix residence. |
| GO:0031012 extracellular matrix | ISS PMID:22261194 Proteomics analysis of cardiac extracellular matrix remodeli... | ACCEPT | Reason: Retain the pig-to-human ECM transfer. The official pig Q1T7A8 identity and its current source record are resolved, and the authentic original abstract concerns porcine cardiac extracellular matrix proteomics. Human target ECM detection independently corroborates location; no claim is made that the original study directly measured every human COL6A1 peptide. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q1T7A8 · COL6A1 SUPPORTS TRANSFER Official pig COL6A1 identity and exact current same-term record are verified; original porcine ECM-proteomics abstract and independent human structural/location evidence support transfer. |
| GO:0032991 protein-containing complex | IPI PMID:18400749 Three novel collagen VI chains, alpha4(VI), alpha5(VI), and ... | MODIFY | Reason: Refine the generic protein-containing complex assertion to GO:0140158, the VWA-domain-rich collagen trimer class. PMID:18400749 tests endogenous human alpha1/alpha2 with engineered mouse alpha4 N6–C2 in SaOS-2 cells; reciprocal precipitation and reducing/nonreducing analysis support secreted disulfide-linked assemblies. GO:0005589 specifically enumerates alpha1/alpha2/alpha3 and therefore does not describe the chain composition of this assay. The recorded partner P12110 identifies alpha2, not the complete stoichiometry. This source supports a more specific class than GO:0032991 without establishing a native human alpha1/alpha2/alpha4 microfibril. Proposed replacements: von-Willerbrand-factor-A-domain-rich collagen trimer Supporting Evidence: PMID:18400749 mouse alpha4(VI)N6-C2 chain co-assembled with endogenous alpha1(VI) and alpha2(VI) chains |
| GO:0035987 endodermal cell differentiation | IEP PMID:23154389 Regulation of endodermal differentiation of human embryonic ... | MARK AS OVER ANNOTATED | Reason: The original human ESC study measures increased endogenous COL6A1 expression during endoderm induction. Its exogenous collagen screen tests types I, III, IV and V, and the receptor knockdowns address fibronectin/vitronectin; these interventions do not test collagen VI. Retain the positive IEP observation but mark the source-specific endodermal-process attribution as over-annotated: the measured expression response does not distinguish a differentiation contribution from production of matrix by differentiating cells. This assessment preserves possible structural participation without presenting expression correlation as a resolved COL6A1 function. Supporting Evidence: PMID:23154389 we measured endogenous ECMP gene expression |
| GO:0042383 sarcolemma | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: The exact mouse donor has a current sarcolemma IDA record from the biglycan/muscle study. The official GO sarcolemma definition includes its covering basement membrane and collagen network, so an extracellular pericellular matrix component is not excluded. Retain this contextual muscle-surface location; only the authentic source abstract was recovered, and the precise target localization image was not independently inspected. No plasma-membrane insertion is inferred. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q04857 · Col6a1 SUPPORTS TRANSFER The exact mouse donor has a current sarcolemma IDA record from the biglycan/muscle study. The official GO sarcolemma definition includes its covering basement membrane and collagen network, so an extracellular pericellular matrix component is not excluded. Retain this contextual muscle-surface location; only the authentic source abstract was recovered, and the precise target localization image was not independently inspected. No plasma-membrane insertion is inferred. Supporting Evidence: |
| GO:0048407 platelet-derived growth factor binding | IDA PMID:8900172 Type I, II, III, IV, V, and VI collagens serve as extracellu... | KEEP AS NON CORE | Reason: The complete authentic abstract directly includes type VI collagen and constituent-chain binding to PDGF isoforms, with competition and retained growth-factor stimulation after collagen binding. Retain this extracellular ligand interaction outside the principal structural core. Full preparation Methods and an alpha1(VI)-specific affinity were not recovered; the pooled 4–22 nM range is not assigned to this chain, and COL6A1 is not a PDGF receptor kinase. Supporting Evidence: |
| GO:0048741 skeletal muscle fiber development | IBA GO_REF:0000033 | KEEP AS NON CORE | Reason: Retain the contextual PAINT muscle-development placement. The exact MGI mouse and ZFIN zebrafish identities are resolved and carry current direct same-term records. The mouse study reports collagen VI deficiency, autophagy defects and myofiber degeneration; the original zebrafish study tests col6a1 disruption and rescue of muscle structure/motility. These support a matrix-dependent muscle role, not collagen-catalyzed autophagy. The ancestral node/tree was not reconstructed; donor number is not used to challenge its placement. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002770521 UNRESOLVED Historical PAINT node/tree not reconstructed. Exact mouse MGI and zebrafish ZFIN identities and direct current same-term records were verified; source-specific muscle evidence supports a contextual structural role. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Reason: Recovered original Methods isolate a high-speed urinary vesicle fraction from healthy human donors, with DTT treatment to reduce uromodulin trapping and mass-spectrometric identification. Preserve the curated positive exosome-associated observation as non-core. The exact COL6A1 supplementary row was not recovered, so no chain-resolved intact-vesicle topology or functional exosome role is asserted. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Reason: Recovered original Methods use a high-speed human parotid-saliva exosome preparation from one donor with MudPIT identification. Retain the source-curated positive detection as non-core. The target workbook remains unavailable; the authors discuss possible secreted-protein carryover generally, which is not a demonstrated COL6A1-specific contaminant result or grounds to discard the annotation. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Reason: Actual original Methods analyze pooled human expressed-prostatic-secretion urine vesicle preparations using differential centrifugation and mass spectrometry. Retain positive exosome-associated detection as non-core; exact target supplementary-table access is incomplete. General sample-composition caveats do not prove the COL6A1 observation false, and no vesicle signaling mechanism or transmembrane topology is inferred. Supporting Evidence: |
| GO:0097708 intracellular vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: The exact mouse donor points to actual immunogold, microsome and secretion experiments in bronchial epithelial cells. Collagen VI occurs in WT intracellular vesicles, with altered late-Golgi/VAMP2-associated accumulation in the knockout context and tested mouse Col6a1-GFP secretion. Retain genuine vesicle/cargo location as non-core without transferring ANXA2 or SNARE machinery activity to the collagen chain. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q04857 · Col6a1 SUPPORTS TRANSFER The exact mouse donor points to actual immunogold, microsome and secretion experiments in bronchial epithelial cells. Collagen VI occurs in WT intracellular vesicles, with altered late-Golgi/VAMP2-associated accumulation in the knockout context and tested mouse Col6a1-GFP secretion. Retain genuine vesicle/cargo location as non-core without transferring ANXA2 or SNARE machinery activity to the collagen chain. Supporting Evidence: |
| GO:0160108 animal gross anatomical part developmental process | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: Retain the broad electronic developmental association as contextual structural biology. Matrix architecture supports lung and skeletal-muscle formation/integrity in actual vertebrate studies, but those observations do not establish a separate universal developmental signaling function for COL6A1. |
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Download this section (compressed HTML)Q: Which human tissues contain alpha1/alpha2 trimers with alternative long collagen VI chains, and how do these assemblies differ from canonical alpha1/alpha2/alpha3 microfibrils?
Q: Which alpha1(VI) domains contribute to PDGF retention in native matrix, and how does this compare with binding by isolated chains or modified collagen preparations?
Q: What proportions of intracellular or vesicle-associated COL6A1 represent secretory precursors, endocytosed intact assemblies or degradation fragments?
Q: Does collagen VI itself contribute a defined matrix-dependent step to osteoblast or endoderm differentiation beyond the observed expression change?
Q: How does extracellular collagen VI architecture influence muscle autophagy and contractile integrity without requiring the collagen chain to reside in SR or myofibrils?
Experiment: Reconstitute sequence-defined human alpha1/alpha2 with each long-chain partner, and separately measure trimer composition, disulfide-linked oligomers, secretion and extracellular microfibril architecture.
Hypothesis: Alternative long chains alter higher-order assembly without changing the basic structural contribution of alpha1(VI).
Experiment: Combine domain-specific pulse-chase imaging, extracellular labeling and protease protection with intact-chain mass spectrometry in secretory and uptake models.
Hypothesis: Intracellular COL6A1 signals comprise distinguishable precursor, uptake and degradation pools.
Experiment: Perturb COL6A1 and rescue with sequence-defined assembled collagen VI in the original osteoblast/endoderm induction systems while controlling matrix abundance and receptor engagement.
Hypothesis: Expression changes can be separated from a matrix-performed differentiation step.
Experiment: Measure PDGF binding to purified human alpha1(VI), defined heterotrimers and microfibrils with matched preparation and competition controls.
Hypothesis: Growth-factor retention depends on chain assembly and accessible domains rather than a single pooled collagen affinity.
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