DDR2

Summary: DDR2 signaling contributes to endochondral growth in the mouse ortholog.

Reason: The exact mouse Q62371 donor annotation traces to PMID:11375938. Ddr2-null mice have shortened long bones and reduced growth-plate chondrocyte proliferation; reduced proliferation, rather than increased apoptosis, explains the phenotype. This supports the existing ortholog inference as a developmental consequence of collagen receptor signaling, not a separate molecular core. The experiment is not a direct human bone-growth assay.

Summary: DDR2 signaling contributes to endochondral growth in the mouse ortholog.

Reason: The exact mouse Q62371 donor annotation traces to PMID:11375938. Ddr2-null mice have shortened long bones and reduced growth-plate chondrocyte proliferation; reduced proliferation, rather than increased apoptosis, explains the phenotype. This supports the existing ortholog inference as a developmental consequence of collagen receptor signaling, not a separate molecular core. The experiment is not a direct human bone-growth assay.

Summary: Refine the broad kinase-domain annotation to the established collagen receptor kinase activity.

Reason: The inspected InterPro kinase domains support an active protein kinase. Human DDR2 ligand-binding and full-length activation experiments establish the more specific collagen receptor activity already present in this annotation set. The refinement uses target evidence beyond the broad domain mapping.

Proposed replacements: protein tyrosine kinase collagen receptor activity

Summary: The target-specific collagen receptor kinase activity is more informative than the broad kinase class.

Reason: DDR2 is an active tyrosine kinase with a discoidin collagen-recognition domain. The original human receptor experiments support collagen-dependent kinase activation, so refine this broad automated assignment to the already represented collagen receptor activity. This does not add new functional coverage.

Proposed replacements: protein tyrosine kinase collagen receptor activity

Summary: Collagen-dependent DDR2 activation supports the collagen-specific receptor kinase term.

Reason: The original human DDR2 study combines soluble-domain collagen binding with full-length wild-type versus W52A receptor activation in HEK293 cells. Figure 6B measures receptor phosphotyrosine after collagen I stimulation. This supports the collagen-specific receptor kinase activity; it does not by itself distinguish every autophosphorylation event from Src-mediated phosphorylation. The specific activity is already represented elsewhere in this review; this is source-row refinement, not new coverage.

Proposed replacements: protein tyrosine kinase collagen receptor activity

Summary: The target-specific collagen receptor kinase activity is more informative than the broad kinase class.

Reason: DDR2 is an active tyrosine kinase with a discoidin collagen-recognition domain. The original human receptor experiments support collagen-dependent kinase activation, so refine this broad automated assignment to the already represented collagen receptor activity. This does not add new functional coverage.

Proposed replacements: protein tyrosine kinase collagen receptor activity

Summary: Refine the broad receptor kinase annotation to collagen receptor kinase activity.

Reason: The accessible original abstract explicitly identifies both DDR receptors as collagen-activated kinases and describes a DDR2-dependent response. The full 1997 article could not be recovered from the publisher, so its construct-level details have not been independently verified. The target function is firmly supported by the later human structure and activation experiments. Refine to the existing collagen-specific activity rather than retaining a separate generic kinase core.

Proposed replacements: protein tyrosine kinase collagen receptor activity

Summary: The original experiment directly supports collagen binding.

Reason: The full original reports human DDR2 residues 26–186 expressed in Pichia and tested against bovine nasal-septum collagen II by SPR and NMR transferred cross-saturation. Refine the generic protein-binding term to collagen binding. The imported P13942 supporting entity is preserved, but it must not be read as a direct human COL11A2 assay: the two retrieved MINT records carry that human mapping, whereas the actual Methods identify bovine collagen II. The original Results give a 25 micromolar monomeric-domain dissociation constant; no human COL11A2 affinity is inferred.

Proposed replacements: collagen binding

Summary: The source-specific HSP90AB1 association supports Hsp90 protein binding.

Reason: The literal DDR2–P08238 records in PMID:22939624 include co-immunoprecipitation and LUMIER in HEK293T cells. P08238 is HSP90AB1, a protein-folding Hsp90 chaperone. The original LUMIER Methods and curated target records support this partner-class refinement, without assigning chaperone activity to DDR2 or inferring an untagged native interface. The supplementary target table was not independently recovered.

Proposed replacements: Hsp90 protein binding

Summary: The CDC37 association is supported; the narrower folding-chaperone binding class remains unresolved.

Reason: The literal PMID:25036637 DDR2–Q16543 LUMIER record documents a tagged-protein association in human HEK293T cells. CDC37 recognizes kinase clients and promotes their recruitment to HSP90, with resulting stabilization. The original study distinguishes co-chaperone recognition of flexible, partly recognizable domains from HSP70 recognition of unfolded polypeptides. The inspected evidence therefore supports this positive CDC37 association, but leaves unresolved whether CDC37 itself meets the complete nascent/unfolded-polypeptide folding-chaperone definition required by GO:0051087. Retain the generic interaction as non-core under the project policy for supported interactions without a justified narrower class. This does not imply DDR2 chaperone activity, activation of either partner, or a false interaction.

Summary: The BioPlex DDR1–DDR2 association supports receptor tyrosine kinase binding.

Reason: The exact PMID:33961781 record is DDR1 bait Q08345 with DDR2 prey Q16832 in HEK293T affinity-capture experiments. DDR1 is a collagen receptor tyrosine kinase. Refine by the independently established partner class, while retaining that this is tagged cellular co-complex evidence, not purified direct binding, collagen-induced heterodimerization, or evidence that DDR2 phosphorylates DDR1.

Proposed replacements: receptor tyrosine kinase binding

Summary: The RTK interactome independently supports Hsp90 protein binding.

Reason: The exact PMID:35384245 record pairs DDR2 with HSP90AB1 in affinity-purification mass spectrometry. The original study used C-terminal MAC-tagged receptors and pervanadate-treated HEK cells. Hsp90 is an established chaperone class, supporting the narrower binding term. The experiment does not establish physiological ligand dependence, a direct interface, or Hsp90 activity by DDR2.

Proposed replacements: Hsp90 protein binding

Summary: The DDR1 association supports receptor tyrosine kinase binding.

Reason: The PMID:35384245 source has a DDR2–DDR1 AP-MS record and a distinct co-immunoprecipitation record with V5-tagged DDR1. DDR1 is independently established as a receptor tyrosine kinase. Retain the positive association at that binding-class specificity, without transferring receptor activation, substrate phosphorylation, or a native collagen-dependent heterocomplex mechanism from the assay.

Proposed replacements: receptor tyrosine kinase binding

Summary: The NTRK3 association supports receptor tyrosine kinase binding.

Reason: The PMID:35384245 literal DDR2–NTRK3 Q16288 pair has an AP-MS record and a separate anti-tag co-immunoprecipitation record (Figure EV1E, lane 18). The study used C-terminally MAC-tagged RTKs in HEK293-derived cells, with pervanadate treatment for the AP-MS screen; the separate RTK–RTK validation co-expressed MAC- and V5-tagged constructs in HEK293 cells. NTRK3 curated FUNCTION and kinase-family evidence establish that the partner is a receptor tyrosine kinase, satisfying the binding-partner class of GO:0030971. Tagged cellular co-complex capture does not establish a purified direct interface, native tissue colocalization, ligand-triggered DDR2–NTRK3 cross-talk, or activation of either receptor by the other. These limits qualify the positive association without negating the supported binding-class refinement.

Proposed replacements: receptor tyrosine kinase binding

Summary: The CDC37 association is supported; the narrower folding-chaperone binding class remains unresolved.

Reason: PMID:35384245 supplies both CDC37 proximity-labeling and independent AP-MS records for DDR2, so support is not proximity alone. CDC37 is an established kinase-client co-chaperone, but the inspected functional and primary evidence leaves unresolved whether CDC37 itself meets the stricter nascent/unfolded-polypeptide folding-chaperone definition of GO:0051087. Retain the positive association as non-core under the project policy for supported interactions without a justified narrower class. C-terminal tagging, cellular co-complex capture and pervanadate treatment limit native-interface and physiological interpretation; the association does not itself establish DDR2 activation or a folding function.

Summary: Collagen recognition is a central DDR2 receptor activity.

Reason: The PAINT assertion at PTN002400507 lies on the reconstructed human lineage and agrees with direct human DDR2 collagen-binding experiments. The target in WITH/FROM supplies direct descendant evidence, not circular support. Accept collagen binding as the recognition component of the receptor activity, without adding a duplicate standalone core.

Summary: Direct structural and biochemical experiments establish collagen binding.

Reason: Human DDR2 DS 26–190 was crystallized with a synthetic triple-helical collagen-like peptide. Soluble ectodomain W52A failed to bind collagen I, while full-length W52A failed collagen-induced activation in HEK293 cells. The synthetic peptide replaces methionine with norleucine; it is not an endogenous collagen isoform. These experiments directly establish the collagen-recognition function.

Summary: Collagen binding is supported by both the matched rule and direct human experiments.

Reason: ARBA00086883 has a fully matched target condition set containing the inspected kinase and discoidin FunFam signatures. Human DDR2 structural and biochemical experiments independently establish collagen binding, so the rule is corroboration rather than the sole biological justification. This recognition activity belongs within the collagen receptor core.

Summary: ATP binding is required for DDR2 kinase catalysis.

Reason: DDR2 is an active receptor tyrosine kinase with ATP-dependent phosphotransfer activity. The broad kinase-domain mapping is consistent with the official ATP-binding residues and direct DDR2 autophosphorylation evidence. Accept this cofactor-binding property; do not create a separate ATP-binding core or claim that the predicted residue coordinates were experimentally mapped.

Summary: The conserved receptor plasma-membrane location is supported on the target lineage.

Reason: The literal positive IBD at PTN001230349 lies on the human DDR2 path. The reconstructed alignment is identical to the official 855-residue sequence, and positive experimental donor records map to descendant leaves. The target has the expected extracellular–transmembrane–cytoplasmic architecture and direct intact-cell receptor activation evidence. No on-lineage loss assertion was found.

Summary: The HPA record supports plasma-membrane localization.

Reason: The current HPA DDR2 subcellular data record reports supported plasma-membrane staining with antibody HPA070112 in SH-SY5Y and U2OS cells. This agrees with the receptor topology and intact-cell activation studies. The HPA data record was inspected, not the underlying microscopy pixels; its separate uncertain actin-filament signal is not converted into a new annotation.

Summary: The curated cell-membrane mapping is consistent with the receptor mechanism.

Reason: The UniProt subcellular-location mapping agrees with DDR2 single-pass topology, HPA plasma-membrane data and collagen-triggered activation of full-length human DDR2. Accept the cellular location without claiming that all expressed or trafficking receptor molecules are confined to the surface.

Summary: DDR2 acts as a cell-surface transmembrane receptor.

Reason: The source establishes a collagen-responsive receptor at the cell surface, consistent with the official extracellular, transmembrane and cytoplasmic domain organization and later intact-cell activation assays. Full 1997 construct-level Methods remain inaccessible; the location is nevertheless independently consistent with the receptor mechanism.

Summary: Reactome explicitly places mature DDR2 at the plasma membrane.

Reason: The actual R-HSA-2465890 input and product paths reach human DDR2 reference Q16832 through the DDR2 dimer and collagen-associated complex. Entity R-HSA-211419 specifies residues 22–855 in the plasma membrane. These selected positive target paths support the location; they do not constitute a reconstruction of every branch of the broader pathway.

Summary: DDR2 was reproducibly detected in isolated human fibroblast focal adhesions.

Reason: The recovered original author-hosted Supplementary Table 1 lists DDR2 in both the detectable and reproducible HFF1 focal-adhesion protein sets. The original isolation and MudPIT Methods support a contextual localization. Fractionation can retain associated material, so this does not establish a stable structural focal-adhesion role or a direct integrin-binding mechanism. It is positive source-specific evidence, not an inference from the paper title.

Summary: The cited source does not yet establish an adhesion role independently of receptor signaling.

Reason: The accessible 1997 abstract demonstrates collagen binding and kinase activation, but does not describe a mammalian cell-adhesion assay. Its statement about aggregation concerns the Dictyostelium discoidin family background. Full original Methods/Results could not be recovered, so this TAS annotation is not rejected on abstract-only evidence. A role in attaching cells to matrix should be distinguished from sensing collagen and regulating downstream adhesion.

Summary: The demonstrated signal is collagen-triggered receptor tyrosine kinase signaling.

Reason: The broad signaling annotation can be refined to the collagen-activated pathway, supported by the source abstract and the direct DDR2 activation/autophosphorylation studies. This receptor performs the ligand-recognition and kinase steps itself. The refined process is already present in the annotation set.

Proposed replacements: collagen-activated tyrosine kinase receptor signaling pathway

Summary: Retain the valid receptor-kinase inference with collagen-specific process scope.

Reason: The positive IBD at PTN001230349 is on the human target lineage, so there is no off-clade-transfer finding. Human DDR2 experiments identify collagen as the initiating ligand and establish the more informative collagen-activated pathway. The refinement concerns target specificity, not donor count or target self-support.

Proposed replacements: collagen-activated tyrosine kinase receptor signaling pathway

Summary: Refine the receptor-family signaling mapping to the collagen-activated pathway.

Reason: The inspected InterPro receptor kinase signatures support the broader pathway class. Actual human DDR2 experiments identify collagen recognition and receptor phosphorylation, supporting the existing collagen-activated signaling term. The target-specific refinement does not imply that every kinase-family member senses collagen.

Proposed replacements: collagen-activated tyrosine kinase receptor signaling pathway

Summary: DDR2 regulates matrix breakdown through downstream cellular responses.

Reason: ARBA00085209 condition set 0 matches the actual DDR2 FunFam signatures. Independent mouse knockout and rescue evidence links DDR2 signaling to MMP-2 activity and matrix migration, supporting a regulatory role. DDR2 is not itself a collagenase, and this contextual response is not a second catalytic core.

Summary: The review-level matrix-remodeling claim is supported by a relevant original study.

Reason: The cited DDR-family review discusses extracellular-matrix remodeling; its full text was not independently recovered. The mouse DDR2 knockout/rescue study separately reports reduced MMP-2 activity and migration through Matrigel, supporting contextual regulation of matrix disassembly. This corroboration does not turn the review citation into a newly read direct human assay.

Summary: Mouse DDR2 promotes fibroblast migration through extracellular matrix.

Reason: The current Q62371 donor records trace to PMID:11723120. Its complete abstract reports impaired chemotactic migration through Matrigel in Ddr2-null skin fibroblasts and rescue by receptor re-expression, while ordinary cell motility was unaffected. Retain this ortholog-supported contextual response with that matrix-dependent scope; no direct human migration assay is asserted.

Summary: Mouse DDR2 promotes fibroblast migration through extracellular matrix.

Reason: The current Q62371 donor records trace to PMID:11723120. Its complete abstract reports impaired chemotactic migration through Matrigel in Ddr2-null skin fibroblasts and rescue by receptor re-expression, while ordinary cell motility was unaffected. Retain this ortholog-supported contextual response with that matrix-dependent scope; no direct human migration assay is asserted.

Summary: Fibroblast matrix migration is a supported contextual DDR2 response.

Reason: The cited review-level assertion is independently corroborated by the mouse DDR2 knockout/rescue abstract, which distinguishes migration through Matrigel from unchanged simple motility. Retain the regulatory role while keeping the review source and the experimental corroboration separate.

Summary: Membrane is a valid but unnecessarily broad location.

Reason: The InterPro membrane-receptor mapping is compatible with DDR2 biology, but accepted plasma-membrane assertions already describe the experimentally supported receptor location. Retain the positive source evidence while treating this ancestor location as too general.

Summary: The apical location is a specific rat renal context.

Reason: The B1WC09 donor record is grounded in PMID:15218324, whose complete abstract describes apical DDR2 localization in selected rat nephron segments. Retain this ortholog-supported polarized-cell context without making apical localization the universal human receptor location or erasing the broader plasma-membrane evidence.

Summary: Collagen activation is accompanied by receptor tyrosine phosphorylation.

Reason: Figure 6B of the original study measures full-length human DDR2 phosphotyrosine after collagen I stimulation in HEK293 cells, with W52A as a binding-defective comparator. This is consistent with the receptor kinase function. The blot alone does not assign every site to DDR2 rather than Src; the independent biochemical autophosphorylation study establishes DDR2-performed phosphotransfer.

Summary: A mouse DDR2 ectodomain construct alters collagen fibril organization.

Reason: The Q62371 donor assertion traces to PMID:19900459. The actual study expressed a secreted mouse DDR2 Met1–Ile400 V5/His-tagged ectodomain in MC3T3-E1 cells and found altered fibrillogenesis. This is positive gene-product-domain evidence, but it does not establish that an endogenous shed human ectodomain performs the same role. The article explicitly lacks direct evidence for natural DDR2 shedding. Retain as contextual, not as a distinct natural product or core.

Summary: A mouse DDR2 ectodomain construct alters collagen fibril organization.

Reason: The Q62371 donor assertion traces to PMID:19900459. The actual study expressed a secreted mouse DDR2 Met1–Ile400 V5/His-tagged ectodomain in MC3T3-E1 cells and found altered fibrillogenesis. This is positive gene-product-domain evidence, but it does not establish that an endogenous shed human ectodomain performs the same role. The article explicitly lacks direct evidence for natural DDR2 shedding. Retain as contextual, not as a distinct natural product or core.

Summary: DDR2 signaling affects mineralization in an osteogenic experimental context.

Reason: The original Methods and Results distinguish human osteoblastic cells from mouse differentiation systems. Matrix mineralization was assayed in mouse C3H10T1/2 cultures, whereas human MG63 knockdown supported osteogenic marker regulation. Retain the curated human-associated regulatory assertion with these model limits, without describing the mineralization images as a direct human assay.

Summary: The donor experiment supports a biomineralization context with a construct limitation.

Reason: The mouse Q62371 donor term comes from the ectodomain-overexpression study PMID:19900459. Its soluble Met1–Ile400 construct changed matrix organization and mineralization in mouse osteoblast cultures. This supports a non-core contextual annotation; the experiment does not demonstrate a normal secreted human DDR2 isoform or isolate full-length receptor signaling as the cause.

Summary: The donor experiment supports a biomineralization context with a construct limitation.

Reason: The mouse Q62371 donor term comes from the ectodomain-overexpression study PMID:19900459. Its soluble Met1–Ile400 construct changed matrix organization and mineralization in mouse osteoblast cultures. This supports a non-core contextual annotation; the experiment does not demonstrate a normal secreted human DDR2 isoform or isolate full-length receptor signaling as the cause.

Summary: Collagen production can be regulated downstream of DDR2 in rat cell models.

Reason: The B1WC09 donor records include rat cardiac-fibroblast and chondrocyte studies. The complete PMID:26674152 abstract links DDR2 knockdown to impaired ERK-dependent collagen production, while PMID:24938620 describes a separate chondrocyte/collagen-II context. Retain the ortholog inference as a tissue-dependent regulatory effect, not collagen synthesis performed by DDR2 itself.

Summary: Activating human DDR2 variants implicate receptor signaling in tissue remodeling.

Reason: The original patient-fibroblast experiments show enhanced receptor phosphorylation for the studied activating variants, alongside a progressive connective-tissue phenotype. They do not directly measure every normal remodeling step, nor show increased downstream AKT/ERK signaling in those conditions. Retain contextual regulation with the variant and clinical scope explicit; do not infer a new extracellular-matrix catalytic activity.

Summary: DDR2 promotes chondrocyte proliferation in the mouse growth plate.

Reason: The Q62371 donor term is supported by PMID:11375938, which directly compares Ddr2-null and wild-type growth plates. Reduced proliferation, without increased growth-plate apoptosis, accompanies impaired endochondral growth. Retain this developmental ortholog inference without converting it into direct human cell-cycle kinetics.

Summary: DDR2 promotes chondrocyte proliferation in the mouse growth plate.

Reason: The Q62371 donor term is supported by PMID:11375938, which directly compares Ddr2-null and wild-type growth plates. Reduced proliferation, without increased growth-plate apoptosis, accompanies impaired endochondral growth. Retain this developmental ortholog inference without converting it into direct human cell-cycle kinetics.

Summary: The chondrocyte-proliferation review claim has direct mouse corroboration.

Reason: Although the cited DDR review is available only as an abstract here, the independently recovered mouse knockout original shows reduced growth-plate chondrocyte proliferation. Retain the contextual developmental assertion with source and species limits, rather than rejecting a sound function because the review text is inaccessible.

Summary: Positive rat expression-response evidence is preserved; the source-specific human transfer remains unresolved.

Reason: The exact rat B1WC09 donor is an IEP annotation from PMID:16087782. Its complete abstract reports increased DDR2 mRNA and protein after cyclic stretch of rat vascular smooth-muscle cells, with angiotensin/TGF-beta/p38/Myc-dependent induction. The GO definition includes changes in gene expression, and GO guidance permits response-to-stimulus IEP annotations in appropriate contexts; this positive rat observation is not a curator error merely because it concerns expression. The previous non-core retention is revised because the detailed original experiments and the biological basis for transferring this context-dependent response to human DDR2 could not be verified. Full original Methods/Results remain inaccessible, so neither additional participation assays nor their absence can be established. Retain the rat observation while leaving the human inference undecided; lack of a direct human assay alone is not evidence of false orthology or functional loss.

Summary: The conserved collagen-specific receptor kinase activity is directly supported in human DDR2.

Reason: The literal positive IBD at PTN002400507 lies on the reconstructed DDR2 lineage. Independent human ligand-binding and activation experiments support the same activity, and no target-specific loss is evident. Target self-inclusion in the source list is valid descendant experimental grounding.

Summary: Collagen acts as the activating ligand for DDR2 kinase signaling.

Reason: The original abstract explicitly demonstrates collagen binding and activation of DDR2. The full original article remains unavailable; the specific activity is independently corroborated by later human ligand-binding and intact-cell activation experiments. Accept the direct experimental annotation while retaining this access limitation.

Summary: The matched ARBA rule agrees with the experimentally established collagen receptor activity.

Reason: ARBA00088048 has two matched condition sets for the inspected DDR2 family/domain and taxonomic features. Independent human ligand-binding and activation studies establish the activity itself, so the unvetted automated rule is not treated as stand-alone experimental support.

Summary: Src-dependent activation and DDR2 autophosphorylation form part of collagen receptor signaling.

Reason: The accessible original abstract distinguishes Src phosphorylation of DDR2 activation-loop Tyr736/Tyr740/Tyr741 from subsequent DDR2 cis-autophosphorylation and Shc recruitment. It reports collagen-independent signaling by Y740F. Full Methods remain inaccessible, so no additional construct species or in vivo stoichiometry is asserted. This supports the existing pathway annotation with curator deference.

Summary: The mouse donor supports the conserved collagen-activated receptor pathway.

Reason: The exact Q62371 donor records support collagen-responsive receptor signaling, and the human target independently has direct collagen-binding and activation evidence. This is a conserved central mechanism, not a transfer based solely on family-name similarity.

Summary: DDR2 can promote survival in a rat hepatic-stellate context.

Reason: The B1WC09 donor assertion is grounded in PMID:23409069. The original shRNA experiments used immortalized rat HSC-T6 cells and an alcoholic-liver-disease rat model, with increased apoptosis following DDR2 suppression. Retain the contextual anti-apoptotic response; it is not universal across tissues or a separate intrinsic apoptosis enzyme function.

Summary: DDR2 participates in a signaling receptor complex.

Reason: The positive signaling-receptor-complex IBD at PTN001230349 is on the target lineage. The source-specific DDR2 literature also describes phosphorylated DDR2–Shc assemblies. Accept the broad complex membership; do not infer a named heterocomplex, universal composition, or a ligand-induced dimerization mechanism from a family label or a static DS-domain crystal.

Summary: DDR2 supports osteogenic differentiation through p38-linked signaling.

Reason: The original study includes human MG63 knockdown with reduced osteogenic markers and mouse osteogenic differentiation models. These observations support the curated regulatory role with mixed-model scope. They do not imply that DDR2 directly binds DNA or that every osteogenic assay used human cells.

Summary: DDR2 can promote p38 kinase-pathway activity during osteogenic differentiation.

Reason: The original study links DDR2 perturbation to p38 phosphorylation and uses p38 inhibition or suppression to interrupt downstream Runx2/osteocalcin activation. Retain this secondary signaling response. It is distinct from DDR2 intrinsic tyrosine kinase catalysis and does not establish direct DDR2 phosphorylation of p38.

Summary: DDR2 catalyzes autophosphorylation after activation.

Reason: The source abstract explicitly separates Src-catalyzed activation-loop phosphorylation from DDR2 cis-autophosphorylation of additional residues. This establishes that DDR2 performs the latter reaction itself, satisfying the participation requirement. Full Methods remain inaccessible; accept the curator annotation without adding unverified construct or phosphorylation-site claims.

Summary: Mouse fibroblast proliferation depends on DDR2 kinase signaling.

Reason: The Q62371 donor records trace to PMID:11375938 and PMID:11723120. The recovered first original shows slower mutant fibroblast proliferation and rescue by wild-type but not kinase-dead DDR2. Retain the contextual ortholog inference, with no claim that every human fibroblast population requires the same response.

Summary: Mouse fibroblast proliferation depends on DDR2 kinase signaling.

Reason: The Q62371 donor records trace to PMID:11375938 and PMID:11723120. The recovered first original shows slower mutant fibroblast proliferation and rescue by wild-type but not kinase-dead DDR2. Retain the contextual ortholog inference, with no claim that every human fibroblast population requires the same response.

Summary: PI3K/Akt regulation is a plausible inherited but context-dependent signaling output.

Reason: The literal positive IBD at PTN008618212 lies on the DDR2 lineage. Its current experimental donors include tree-matched rat and human receptor-kinase descendants; no on-lineage loss was recovered. This supports retaining the phylogenetic judgment as a non-core downstream output. The absence of elevated AKT in the particular activating-variant fibroblast study does not prove a universal target loss, and the IBA is not evidence that every DDR2 condition activates Akt.

Summary: The rat cardiac-fibroblast response supports contextual ERK activation.

Reason: The exact B1WC09 donor record traces to PMID:26674152. Its abstract reports that DDR2 knockdown suppresses AngII-induced ERK1/2 activation and collagen production. Retain that ortholog-supported signaling output, without generalizing it to every tissue or contradicting the negative ERK result in a different human variant-fibroblast context.

Summary: Rat vascular smooth-muscle DDR2 responds to hypoxic culture conditions.

Reason: The B1WC09 donor is supported by PMID:18664364, whose abstract reports hypoxia-associated DDR2 induction and a DDR2-dependent migration/MMP2 response. Retain the existing ortholog inference with this cell-culture scope. It does not establish DDR2 as the oxygen sensor or a universal human hypoxia effector.

Summary: Positive rat expression-response evidence is preserved; the source-specific human transfer remains unresolved.

Reason: The exact rat B1WC09 donor is an IEP annotation from PMID:16087782. Its complete abstract reports DDR2 induction after exogenous TGF-beta1 and inhibition of stretch-induced expression by a TGF-beta1 antibody. The GO definition includes changes in gene expression, and GO guidance permits response-to-stimulus IEP annotations in appropriate contexts. The previous non-core retention is revised because the detailed original experiments and the basis for transferring this context-dependent response to human DDR2 could not be verified. Full original Methods/Results remain inaccessible; the abstract does not establish whether further participation experiments were performed. Preserve the positive rat expression response without treating it as proof of a conserved human response, DDR2 TGF-beta-receptor activity, or a demonstrated annotation error.

Summary: Mouse DDR2 signaling promotes matrix breakdown through MMP regulation.

Reason: The Q62371 donor records are supported by PMID:11723120. The complete abstract reports reduced MMP-2 activity and matrix migration in mutant fibroblasts, rescued by receptor re-expression. This supports positive regulation of matrix disassembly, not proteolysis catalyzed by DDR2. Retain the tissue-dependent ortholog inference outside the compact receptor core.

Summary: Mouse DDR2 signaling promotes matrix breakdown through MMP regulation.

Reason: The Q62371 donor records are supported by PMID:11723120. The complete abstract reports reduced MMP-2 activity and matrix migration in mutant fibroblasts, rescued by receptor re-expression. This supports positive regulation of matrix disassembly, not proteolysis catalyzed by DDR2. Retain the tissue-dependent ortholog inference outside the compact receptor core.

Summary: DDR2 contributes to a fibroblast wound-response model.

Reason: The B1WC09 donor annotation is grounded in PMID:26674152, which reports DDR2-dependent AngII-driven wound healing in cardiac-fibroblast experiments. Retain this contextual ortholog inference with the in-vitro migration/repair scope; it is not a direct demonstration of all stages of human wound repair.

Summary: DDR2-dependent signaling can promote G1/S progression in cardiac fibroblasts.

Reason: The B1WC09 donor assertion traces to PMID:32412792. Its abstract describes DDR2/ERK/SRF-dependent Skp2 induction and p27 degradation, with Rb phosphorylation, PCNA and flow-cytometry readouts. Retain this source-positive regulatory inference while keeping the rat donor and cell-type context explicit; no direct cyclin-dependent kinase activity is assigned to DDR2.

Summary: The rat cardiac-fibroblast source supports oxidative-stress survival signaling.

Reason: The exact B1WC09 donor annotation traces to PMID:32412792, whose abstract reports DDR2-dependent ERK/SRF/cIAP2 signaling that protects cardiac fibroblasts against oxidative injury. Retain the curator-specific hydrogen-peroxide response with donor and access limits; the precise treatment protocol was not independently read, and this is not a constitutive anti-death core.

Summary: Angiotensin-responsive DDR2 regulation is supported in rat cells.

Reason: The B1WC09 donor records include PMID:26674152, whose abstract directly places DDR2 in an AngII-induced collagen/ERK response. Retain the contextual ortholog inference without proposing angiotensin binding by DDR2; the collagen receptor acts within the cellular response rather than replacing the angiotensin receptor.

Summary: The specific smooth-muscle proliferation claim remains unresolved at the cited donor source.

Reason: The exact B1WC09 donor IMP annotation points to PMID:16087782. The accessible abstract directly establishes stretch-dependent DDR2 expression in rat vascular smooth-muscle cells, but does not describe the proliferation experiment. Publisher full-text access failed. Other cell types provide proliferation evidence, but that does not recover this source-specific vascular assay; retain uncertainty rather than alleging a wrong annotation or transferring fibroblast results into it.

Summary: The rat vascular smooth-muscle source supports a migration response.

Reason: The B1WC09 donor record traces to PMID:18664364. Its abstract reports inhibition of hypoxia-induced MMP2 expression and cell migration by DDR2 siRNA. Retain the contextual ortholog inference without inferring an independent direct human vascular assay or a receptor-independent motility mechanism.

Summary: DDR2 promotes proliferation and activation in a rat stellate-cell disease model.

Reason: The B1WC09 donor assertions are grounded in PMID:23409069. Actual HSC-T6 and rat alcoholic-liver-disease experiments support decreased stellate-cell proliferation/activation after DDR2 suppression, with increased apoptosis. Retain these source-positive ortholog inferences as contextual, rather than treating fibrosis or the immortalized-cell model as proof of a universal physiological human role.

Summary: DDR2 promotes proliferation and activation in a rat stellate-cell disease model.

Reason: The B1WC09 donor assertions are grounded in PMID:23409069. Actual HSC-T6 and rat alcoholic-liver-disease experiments support decreased stellate-cell proliferation/activation after DDR2 suppression, with increased apoptosis. Retain these source-positive ortholog inferences as contextual, rather than treating fibrosis or the immortalized-cell model as proof of a universal physiological human role.