CRB2 is a Crumbs-family cell-surface protein with a large extracellular EGF-repeat and laminin-G-domain region and a short cytoplasmic tail. Its terminal PDZ-binding motif and separate FERM-binding region connect it to epithelial polarity proteins. Membrane-associated CRB2 supports apical junction organization, maintenance and recovery, with prominent retinal and renal epithelial roles. In vertebrate models, Crb2 also coordinates epithelial cell behavior during gastrulation and supports photoreceptor organization and survival. A separate transmembrane-dependent interaction modulates gamma-secretase activity in human cell systems. Alternative products differ substantially in their extracellular regions and retention of the membrane anchor and cytoplasmic binding motifs.
Curated functional classes representing distinct biological activities. These may be splice variants, cleavage products, or other forms with different functions.
CRB2_PREDICTED_SECRETED| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001707 mesoderm formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CRB2 supports mesoderm formation during gastrulation. Reason: Mouse Crb2-null embryos have deficient mesoderm, and later live imaging shows that primitive-streak cells initiate apical constriction but fail to complete apical detachment and ingression (PMID:22072575; PMID:27870829). The protein participates in epithelial junction and cell-shape organization during the transition, rather than being merely a mesoderm marker. Retain the existing ortholog-derived developmental claim outside the principal polarity core; these are mouse experiments, not direct human embryonic perturbations. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. Supporting Evidence: PMID:22072575 impaired mesoderm and endoderm formation |
| GO:0001707 mesoderm formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CRB2 supports mesoderm formation during gastrulation. Reason: Mouse Crb2-null embryos have deficient mesoderm, and later live imaging shows that primitive-streak cells initiate apical constriction but fail to complete apical detachment and ingression (PMID:22072575; PMID:27870829). The protein participates in epithelial junction and cell-shape organization during the transition, rather than being merely a mesoderm marker. Retain the existing ortholog-derived developmental claim outside the principal polarity core; these are mouse experiments, not direct human embryonic perturbations. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0001756 somitogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Somite formation depends on the Crb2-dependent gastrulation context. Reason: The actual mouse knockout source shows absent or severely reduced somites and mesodermal organization (PMID:22072575). The later Poglut1 comparison independently examines Crb2-null embryos: Meox1-positive paraxial mesoderm is reduced and unsegmented, while a Notch target can remain expressed (PMID:26496195). This supports the broad developmental participation claim, without assigning CRB2 a segmentation-clock or Notch-enzyme function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0001756 somitogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Somite formation depends on the Crb2-dependent gastrulation context. Reason: The actual mouse knockout source shows absent or severely reduced somites and mesodermal organization (PMID:22072575). The later Poglut1 comparison independently examines Crb2-null embryos: Meox1-positive paraxial mesoderm is reduced and unsegmented, while a Notch target can remain expressed (PMID:26496195). This supports the broad developmental participation claim, without assigning CRB2 a segmentation-clock or Notch-enzyme function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0001895 retina homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CRB2 contributes to retinal tissue homeostasis. Reason: The exact mouse donor IMP in PMID:23001562 is supported by the original developmental conditional-knockout experiments: retinal disorganization, photoreceptor thinning, altered progenitor proliferation and cell death, and progressive functional impairment. Human RPE work separately supports junction maintenance (PMID:34262913). Retain the inherited tissue-homeostasis claim as non-core, with mouse tissue evidence distinguished from human cell assays. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. Supporting Evidence: PMID:23001562 disruption of adherens junctions between photoreceptors, Müller glia and progenitor cells |
| GO:0001895 retina homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CRB2 contributes to retinal tissue homeostasis. Reason: The exact mouse donor IMP in PMID:23001562 is supported by the original developmental conditional-knockout experiments: retinal disorganization, photoreceptor thinning, altered progenitor proliferation and cell death, and progressive functional impairment. Human RPE work separately supports junction maintenance (PMID:34262913). Retain the inherited tissue-homeostasis claim as non-core, with mouse tissue evidence distinguished from human cell assays. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Both exact InterPro entries map calcium ion binding: a calcium-binding EGF domain and its conserved-site signature. Reason: Both exact InterPro entries map calcium ion binding: a calcium-binding EGF domain and its conserved-site signature. Official CRB2 has multiple matched calcium-binding EGF repeats. This is a defensible domain inference, not a claimed direct human calcium-affinity measurement or calcium-sensing mechanism. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001881 SUPPORTS TRANSFER Actual target domain/signature and current InterPro-to-GO mapping support calcium binding; no direct affinity experiment is inferred. InterPro:IPR018097 SUPPORTS TRANSFER Actual target domain/signature and current InterPro-to-GO mapping support calcium binding; no direct affinity experiment is inferred. |
| GO:0005515 protein binding | IPI PMID:17920587 FERM protein EPB41L5 is a novel member of the mammalian CRB-... | MODIFY | Summary: The human retinal-cDNA intracellular CRB2 construct binds EPB41L5 in the actual 17920587 yeast/GST assays. Reason: The human retinal-cDNA intracellular CRB2 construct binds EPB41L5 in the actual 17920587 yeast/GST assays. The studied partner feature is its FERM domain; the detailed GTY deletion, truncated-FERM and retinal pull-down controls predominantly use CRB1, so do not relabel them as CRB2 perturbations. Domain-specific binding is justified; a finite current search did not establish a FERM-specific GO term. This is not PDZ binding to EPB41L5 and does not prove a cytoskeletal bridge. Proposed replacements: protein domain specific binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to GRID2IP PDZ domain constructs is directly measured. Reason: The 2 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of GRID2IP (A4D2P6) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 266 human PDZ-domains and the 448 human and viral PBMs |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to MPDZ PDZ domain constructs is directly measured. Reason: The 3 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of MPDZ (O75970) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to DLG4 PDZ domain constructs is directly measured. Reason: The 3 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of DLG4 (P78352) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to APBA1 PDZ domain constructs is directly measured. Reason: The 2 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of APBA1 (Q02410) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. One APBA1 participant record also preserves a mutation at position 655. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to TJP1 PDZ domain constructs is directly measured. Reason: The 2 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of TJP1 (Q07157) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to DLG1 PDZ domain constructs is directly measured. Reason: The 3 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of DLG1 (Q12959) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to IL16 PDZ domain constructs is directly measured. Reason: The 3 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of IL16 (Q14005) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to SCRIB PDZ domain constructs is directly measured. Reason: The 2 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of SCRIB (Q14160) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to DLG2 PDZ domain constructs is directly measured. Reason: The 2 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of DLG2 (Q15700) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to PDZK1 PDZ domain constructs is directly measured. Reason: The 3 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of PDZK1 (Q5T2W1) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to FRMPD2 PDZ domain constructs is directly measured. Reason: The 3 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of FRMPD2 (Q68DX3) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to MAGI2 PDZ domain constructs is directly measured. Reason: The 5 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of MAGI2 (Q86UL8) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to NHERF4 PDZ domain constructs is directly measured. Reason: The 2 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of NHERF4 (Q86UT5) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to PATJ PDZ domain constructs is directly measured. Reason: The 8 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of PATJ (Q8NI35) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to LNX1 PDZ domain constructs is directly measured. Reason: The 3 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of LNX1 (Q8TBB1) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to DLG3 PDZ domain constructs is directly measured. Reason: The 3 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of DLG3 (Q92796) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to MAGI1 PDZ domain constructs is directly measured. Reason: The 2 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of MAGI1 (Q96QZ7) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to APBA2 PDZ domain constructs is directly measured. Reason: The 2 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of APBA2 (Q99767) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to GRIP2 PDZ domain constructs is directly measured. Reason: The 5 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of GRIP2 (Q9C0E4) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to WHRN PDZ domain constructs is directly measured. Reason: The 3 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of WHRN (Q9P202) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CRB2 terminal-peptide binding to GRIP1 PDZ domain constructs is directly measured. Reason: The 5 exact positive IntAct records from PMID:36115835 pair the biotin-tagged CRB2 residues 1276–1285 with isolated IPR001478 PDZ constructs of GRIP1 (Q9Y3R0) in the holdup assay. The directly tested domain class supports GO:0030165 rather than generic binding. All literal features, tags, reference-sequence checksums and record joins are retained in the evidence index. Reference ROGID equality does not establish a full-length experimental construct, native cellular contact, or transfer of the partner protein's function to CRB2. Supplementary Data 1 was not recovered; the raw reported numeric affinity string is preserved without interpreting its missing exponent. Proposed replacements: PDZ domain binding |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The SL-0243 source belongs to official isoform 2, predicted secreted and lacking the canonical membrane helix/cytoplasmic tail. Reason: The SL-0243 source belongs to official isoform 2, predicted secreted and lacking the canonical membrane helix/cytoplasmic tail. Preserve the positive predicted extracellular context, without treating the extracellular domain of attached isoform 1 as a secreted product. Full-length ectodomain-release negatives in 20299451 do not test the distinct splice product. The predicted product scope is also encoded in the curated CRB2_PREDICTED_SECRETED class; no tested-product identifier is invented in the original GOA assertion. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0243 SUPPORTS TRANSFER Official predicted secreted product 2 supplies this source scope; full-length ectodomain-release assays do not test that splice product. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | MODIFY | Summary: The relevant cytoplasmic-region localization is the apical epithelial junction. Reason: The current Q80YA8 donor IDA points to PMID:26404741, whose actual mouse RPE imaging localizes CRB2 at the apicolateral membrane and tight-junction region. Cytoplasm is a broad anatomical assertion; the source-specific apical junction location is more useful. This is a precision change, not a claim that an intracellular biosynthetic pool cannot occur. Independent human RPE experiments corroborate peripheral junction localization (PMID:34262913). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER Actual UniProt subcellular-location mapping; positive epithelial localization is retained with the specific source and product limits in the reason. Proposed replacements: apical junction complex |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | MODIFY | Summary: The relevant cytoplasmic-region localization is the apical epithelial junction. Reason: The current Q80YA8 donor IDA points to PMID:26404741, whose actual mouse RPE imaging localizes CRB2 at the apicolateral membrane and tight-junction region. Cytoplasm is a broad anatomical assertion; the source-specific apical junction location is more useful. This is a precision change, not a claim that an intracellular biosynthetic pool cannot occur. Independent human RPE experiments corroborate peripheral junction localization (PMID:34262913). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. Proposed replacements: apical junction complex |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane localization is conserved within the Crumbs lineage. Reason: The actual PTN001526177 IBD is on the human CRB2 path in the current resolving PTHR24049 tree, with an exact 1285-residue target alignment and no target-path loss assertion. The displayed source family PTHR12916 and its current API tree differ from this resolving topology; the version boundary is retained explicitly. Mouse retinal and human RPE localization, the canonical transmembrane segment and fish ortholog evidence support this inherited membrane claim. It does not describe every splice product. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001526177 SUPPORTS TRANSFER Exact current IBD and ancestral path reconstructed in PTHR24049; human target MSA exact, no target-path IRD. Preserved PTHR12916 cache/current-xref boundary is separate. |
| GO:0007157 heterophilic cell-cell adhesion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The inherited heterophilic adhesion claim has direct ortholog experimental grounding. Reason: The PTN001526177 IBD is on the human target path. Its Q1A5L2 source has a genuine IPI annotation to PMID:22579223: recombinant zebrafish Crb2a/Crb2b extracellular-domain fusions coexpressed in Sf9 cells associate in lysate GST-pulldown assays, and human HEK cells expressing the fish proteins aggregate in extracellular-domain-dependent assays. These are not human CRB2 constructs. Human CRB1/CRB2 co-immunoprecipitation in PMID:38570189 supports association but is not itself a direct trans-cellular adhesion assay. Retain the considered evolutionary claim as non-core, without inventing an adhesion MF or inferring failure from donor count. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN001526177 SUPPORTS TRANSFER Exact current IBD and ancestral path reconstructed in PTHR24049; human target MSA exact, no target-path IRD. Preserved PTHR12916 cache/current-xref boundary is separate. |
| GO:0010470 regulation of gastrulation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CRB2 regulates cell behavior during gastrulation. Reason: The actual donor paper compares Crb2-null and Poglut1-null mouse embryos and measures broadened primitive streak, E-cadherin-positive cell accumulation and reduced mesodermal wings (PMID:26496195). Later live imaging directly identifies delayed or failed ingression in Crb2 mutants (PMID:27870829). These are positive process-level observations, not transfer of POGLUT1 catalytic activity or of its separate Notch-signaling defect to CRB2. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. Supporting Evidence: PMID:26496195 The gastrulation phenotypes of Poglut1 wsnp and Crumbs2 are indistinguishable |
| GO:0010470 regulation of gastrulation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CRB2 regulates cell behavior during gastrulation. Reason: The actual donor paper compares Crb2-null and Poglut1-null mouse embryos and measures broadened primitive streak, E-cadherin-positive cell accumulation and reduced mesodermal wings (PMID:26496195). Later live imaging directly identifies delayed or failed ingression in Crb2 mutants (PMID:27870829). These are positive process-level observations, not transfer of POGLUT1 catalytic activity or of its separate Notch-signaling defect to CRB2. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0010718 positive regulation of epithelial to mesenchymal transition | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CRB2 promotes the epithelial-to-mesenchymal transition at the primitive streak. Reason: Mouse Crb2 deletion causes E-cadherin-positive cells to accumulate at the primitive streak and disrupts mesoderm production; direct live imaging later shows failure of apical junction dissolution and detachment after apical constriction (PMID:22072575; PMID:27870829). The later study does not find a universal primary loss of classical polarity markers and argues that epithelial disorganization can be secondary to failed gastrulation. Retain the measured EMT role as contextual, without treating the earlier primary-polarity interpretation as settled. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0010718 positive regulation of epithelial to mesenchymal transition | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CRB2 promotes the epithelial-to-mesenchymal transition at the primitive streak. Reason: Mouse Crb2 deletion causes E-cadherin-positive cells to accumulate at the primitive streak and disrupts mesoderm production; direct live imaging later shows failure of apical junction dissolution and detachment after apical constriction (PMID:22072575; PMID:27870829). The later study does not find a universal primary loss of classical polarity markers and argues that epithelial disorganization can be secondary to failed gastrulation. Retain the measured EMT role as contextual, without treating the earlier primary-polarity interpretation as settled. This source identity represents two literal GOA records: UniProt assigned on 2017-03-07 and CAFA assigned on 2013-10-07; their distinct assigners and dates remain in the evidence index. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0010951 negative regulation of endopeptidase activity | IMP PMID:20299451 Human CRB2 inhibits gamma-secretase cleavage of amyloid prec... | KEEP AS NON CORE | Summary: Human CRB2 overexpression and endogenous SH-SY5Y knockdown alter APP cleavage products; CHAPSO membrane assays corroborate reduced endopeptidase output. Reason: Human CRB2 overexpression and endogenous SH-SY5Y knockdown alter APP cleavage products; CHAPSO membrane assays corroborate reduced endopeptidase output. This is positive context-dependent regulation, not merely an APP-expression phenotype; in vivo brain relevance and exact complex mechanism remain unresolved. Supporting Evidence: PMID:20299451 CRB2 inhibition of gamma-cleavage was also detected in cell-free assays. |
| GO:0014028 notochord formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notochord formation is affected in Crb2-null embryos. Reason: The mouse source shows discontinuous Shh-positive axial mesoderm/notochord organization, with an independently observed discontinuous Brachyury-positive midline in the Crb2 comparison (PMID:22072575; PMID:26496195). Retain this existing developmental annotation at the broad morphogenetic scope; it does not establish a notochord-specific receptor or autonomous lineage-specification mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0014028 notochord formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Notochord formation is affected in Crb2-null embryos. Reason: The mouse source shows discontinuous Shh-positive axial mesoderm/notochord organization, with an independently observed discontinuous Brachyury-positive midline in the Crb2 comparison (PMID:22072575; PMID:26496195). Retain this existing developmental annotation at the broad morphogenetic scope; it does not establish a notochord-specific receptor or autonomous lineage-specification mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the apical membrane localization at gene-level homologous context, with mouse Q80YA8 transfer provenance and independent human RPE polarity/junction evidence. Reason: Retain the apical membrane localization at gene-level homologous context, with mouse Q80YA8 transfer provenance and independent human RPE polarity/junction evidence. Do not transfer membrane topology or localization to the predicted secreted isoform 2. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. UniProtKB-SubCell:SL-0015 SUPPORTS TRANSFER Actual UniProt subcellular-location mapping; positive epithelial localization is retained with the specific source and product limits in the reason. |
| GO:0016324 apical plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the apical membrane localization at gene-level homologous context, with mouse Q80YA8 transfer provenance and independent human RPE polarity/junction evidence. Reason: Retain the apical membrane localization at gene-level homologous context, with mouse Q80YA8 transfer provenance and independent human RPE polarity/junction evidence. Do not transfer membrane topology or localization to the predicted secreted isoform 2. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0016324 apical plasma membrane | NAS PMID:26404741 CRB2 completes a fully expressed Crumbs complex in the Retin... | MODIFY | Summary: The actual NAS paper 26404741 localizes mouse CRB2 to a narrow apicolateral RPE membrane region above p120-catenin by confocal z-stacks. Reason: The actual NAS paper 26404741 localizes mouse CRB2 to a narrow apicolateral RPE membrane region above p120-catenin by confocal z-stacks. Its HEK construct/antibody tests do not constitute human RPE imaging. Apicolateral membrane is the precise location at this source scope; human 34262913 separately corroborates junctional peripheral localization. Proposed replacements: apicolateral plasma membrane Supporting Evidence: PMID:26404741 CRB2 is restricted to the apicolateral membrane of RPE cells |
| GO:0016327 apicolateral plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: The specific apicolateral membrane claim agrees with actual mouse RPE imaging in 26404741 and conserved epithelial context. Reason: The specific apicolateral membrane claim agrees with actual mouse RPE imaging in 26404741 and conserved epithelial context. Preserve the exact mouse-derived Compara premise; this is not an independent human retinal microscopy assertion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0019828 aspartic-type endopeptidase inhibitor activity | IMP PMID:20299451 Human CRB2 inhibits gamma-secretase cleavage of amyloid prec... | KEEP AS NON CORE | Summary: 20299451 supports binding-associated inhibition of the aspartyl protease complex through a CRB2 transmembrane-dependent interaction and cell/membrane cleavage assays, satisfying the actual inhibitor definition. Reason: 20299451 supports binding-associated inhibition of the aspartyl protease complex through a CRB2 transmembrane-dependent interaction and cell/membrane cleavage assays, satisfying the actual inhibitor definition. No purified binary inhibition, active-site occlusion, identified direct binding subunit or universal aspartyl-protease inhibition is demonstrated. Retain the positive activity outside the principal polarity core. |
| GO:0030010 establishment of cell polarity | IEA GO_REF:0000107 | MODIFY | Summary: Developmental mouse retinal evidence supports establishment of epithelial apicobasal polarity. Reason: Mouse Crb2 deletion in the developing retina disrupts adherens junctions and the orientation of newly born photoreceptors; ectopic photoreceptors fail to form normal segments and can be immature, nonpolarized or misoriented (PMID:23001562, developmental Results). These findings support the formation component of epithelial apicobasal polarity in the existing mouse establishment assertion. Refine to GO:0045198 at that developmental inference scope. The study also reports maintenance defects and does not isolate a direct molecular initiation step. Human RPE PMID:34262913 independently supports maintenance and recovery, not de novo establishment, and is not used to establish this replacement. Repeated terms from distinct source assertions are allowed; avoiding duplicate coverage is not the justification for this refinement. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. Proposed replacements: establishment of epithelial cell apical/basal polarity |
| GO:0030010 establishment of cell polarity | ISS GO_REF:0000024 | MODIFY | Summary: Developmental mouse retinal evidence supports establishment of epithelial apicobasal polarity. Reason: Mouse Crb2 deletion in the developing retina disrupts adherens junctions and the orientation of newly born photoreceptors; ectopic photoreceptors fail to form normal segments and can be immature, nonpolarized or misoriented (PMID:23001562, developmental Results). These findings support the formation component of epithelial apicobasal polarity in the existing mouse establishment assertion. Refine to GO:0045198 at that developmental inference scope. The study also reports maintenance defects and does not isolate a direct molecular initiation step. Human RPE PMID:34262913 independently supports maintenance and recovery, not de novo establishment, and is not used to establish this replacement. Repeated terms from distinct source assertions are allowed; avoiding duplicate coverage is not the justification for this refinement. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. Proposed replacements: establishment of epithelial cell apical/basal polarity |
| GO:0030054 cell junction | IEA GO_REF:0000107 | MODIFY | Summary: Retinal and RPE source evidence concerns apically located epithelial junction organization. Reason: Retinal and RPE source evidence concerns apically located epithelial junction organization. Use apical junction complex as the specific anatomical unit, without claiming that every protein contact is a molecular Crumbs complex. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. Proposed replacements: apical junction complex |
| GO:0030513 positive regulation of BMP signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse source supports an indirect, contextual positive influence on BMP signaling. Reason: The exact Q80YA8 IMP source is PMID:22072575. Original Results show reduced embryonic Bmp4 expression from E7 to E7.75, with Bmp4 retained in amnion/allantois and Brachyury/Fgf8 expression unchanged; gross morphological abnormalities become apparent later in this interval. This stage- and region-selective response supports the existing indirect positive-regulation inference. It does not directly measure downstream BMP output or resolve how CRB2 affects Bmp4 expression, and altered cell composition remains a possible contributor. Retain the ortholog-derived signaling context as non-core without requiring an autonomous CRB2 signaling reaction, asserting a pSMAD assay, or claiming a universal direct CRB2-to-BMP4 mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 IMP source 22072575 has stage/region-selective Bmp4-expression changes with retained comparison markers. Indirect regulation is defensible; downstream output, mechanism and cell-composition contribution are unresolved. |
| GO:0030513 positive regulation of BMP signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse source supports an indirect, contextual positive influence on BMP signaling. Reason: The exact Q80YA8 IMP source is PMID:22072575. Original Results show reduced embryonic Bmp4 expression from E7 to E7.75, with Bmp4 retained in amnion/allantois and Brachyury/Fgf8 expression unchanged; gross morphological abnormalities become apparent later in this interval. This stage- and region-selective response supports the existing indirect positive-regulation inference. It does not directly measure downstream BMP output or resolve how CRB2 affects Bmp4 expression, and altered cell composition remains a possible contributor. Retain the ortholog-derived signaling context as non-core without requiring an autonomous CRB2 signaling reaction, asserting a pSMAD assay, or claiming a universal direct CRB2-to-BMP4 mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 IMP source 22072575 has stage/region-selective Bmp4-expression changes with retained comparison markers. Indirect regulation is defensible; downstream output, mechanism and cell-composition contribution are unresolved. |
| GO:0032991 protein-containing complex | IBA GO_REF:0000033 | ACCEPT | Summary: Retain participation in a protein-containing polarity complex at the inherited gene-level scope. Reason: CRB2 participates in protein-containing assemblies in polarity systems and in a separate gamma-secretase-associated context. The actual PTN001526177 complex IBD is on the human target path and includes human CRB2 IDA evidence from PMID:20299451; this self-descendant evidence is legitimate. The broad evolutionary assertion is not restricted to the gamma-secretase-associated pool, and a fixed stoichiometric molecular Crumbs-complex identifier is not assigned. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001526177 SUPPORTS TRANSFER Exact current IBD and ancestral path reconstructed in PTHR24049; human target MSA exact, no target-path IRD. Preserved PTHR12916 cache/current-xref boundary is separate. |
| GO:0032991 protein-containing complex | IDA PMID:20299451 Human CRB2 inhibits gamma-secretase cleavage of amyloid prec... | MODIFY | Summary: 20299451 combines endogenous monkey-brain co-IP of all four gamma-secretase components, human-cell native/overexpression BN complex sizes, and transmembrane-dependent association/inhibition. Reason: 20299451 combines endogenous monkey-brain co-IP of all four gamma-secretase components, human-cell native/overexpression BN complex sizes, and transmembrane-dependent association/inhibition. GO0070765 explicitly permits regulatory subunits in addition to the four core components. This supports a CRB2-associated regulatory pool, not a fixed stoichiometric catalytic-core subunit, direct contact with a specified component, or universal membership in all gamma-secretase complexes. Reciprocal IP was uninterpretable due to background; the native brain species is monkey. Proposed replacements: gamma-secretase complex |
| GO:0032991 protein-containing complex | IEA GO_REF:0000117 | ACCEPT | Summary: Broad protein-containing complex participation is biologically sound for CRB2 polarity assemblies. Reason: The complete current ARBA00028902 rule emits GO:0032991 and its condition set 165 matches the actual CRB2 features/taxon. This establishes current rule applicability, separately from biological validity. Independent polarity-complex and human CRB1/CRB2 association evidence supports the broad complex claim (PMID:17920587; PMID:38570189). The rule does not specify gamma-secretase membership or an exact Crumbs-complex stoichiometry. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028902 SUPPORTS TRANSFER All condition sets evaluated; current ARBA00028902 set 165 matches and emits GO:0032991. Biological support is independently assessed. |
| GO:0035003 subapical complex | IEA GO_REF:0000107 | MODIFY | Summary: The current subapical-complex definition explicitly describes an invertebrate epithelial compartment. Reason: The current subapical-complex definition explicitly describes an invertebrate epithelial compartment. Mammalian subapical staining does not establish that taxon-specific term. Apical junction complex has an explicit vertebrate anatomical definition and matches the measured mouse/human epithelial context; preserve the mouse source and describe shared term-scope mismatch rather than target-specific evolutionary loss. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:Q80YA8 UNRESOLVED Mouse subapical staining is genuine, but GO:0035003 explicitly defines an invertebrate compartment; the anatomical scope is corrected for both source and human target. Proposed replacements: apical junction complex |
| GO:0043296 apical junction complex | NAS PMID:26404741 CRB2 completes a fully expressed Crumbs complex in the Retin... | ACCEPT | Summary: 26404741 directly supports mouse apical junction-region localization and compares p120-catenin/PALS1; 34262913 independently supports human RPE tight-junction maintenance. Reason: 26404741 directly supports mouse apical junction-region localization and compares p120-catenin/PALS1; 34262913 independently supports human RPE tight-junction maintenance. This is anatomical junction localization, not a defined stoichiometric molecular complex or a direct human perturbation in the 2015 paper. Supporting Evidence: PMID:26404741 in the tight junctions |
| GO:0044877 protein-containing complex binding | IMP PMID:20299451 Human CRB2 inhibits gamma-secretase cleavage of amyloid prec... | KEEP AS NON CORE | Summary: The human CRB2 construct interacts with a gamma-secretase-containing assembly and its transmembrane replacement removes complex association and inhibition. Reason: The human CRB2 construct interacts with a gamma-secretase-containing assembly and its transmembrane replacement removes complex association and inhibition. The actual complex-binding term is supported even though the directly contacted subunit remains unidentified. No gamma-secretase-specific binding descendant was established in the finite current search. |
| GO:0045177 apical part of cell | IEA GO_REF:0000107 | MODIFY | Summary: Apical membrane localization is more informative than an unspecified apical cell region and matches the transmembrane product and homologous retinal/epithelial evidence. Reason: Apical membrane localization is more informative than an unspecified apical cell region and matches the transmembrane product and homologous retinal/epithelial evidence. Retain source-specific transfer and isoform limits. The exact donor PMID:25636444 uses a pan-Crb antibody recognizing the shared CRB1/2/3 tail; its staining alone is not CRB2-specific. The refinement also uses independent CRB2-specific mouse RPE and human RPE localization, rather than silently assigning all pan-Crb signal to CRB2. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Current IDA source 25636444 uses pan-Crb antibody; independent target-specific localization supports the refinement without assigning all pan-Crb signal to Crb2. Proposed replacements: apical plasma membrane |
| GO:0045197 establishment or maintenance of epithelial cell apical/basal polarity | IBA GO_REF:0000033 | ACCEPT | Summary: The broad inherited epithelial polarity role agrees with direct human RPE maintenance/recovery and independent mouse developmental polarity evidence. Reason: The PTN001526177 epithelial-polarity IBD lies on the actual human CRB2 path. Direct human RPE maintenance/recovery and independent mouse developmental retinal polarity evidence support the broad establishment-or-maintenance role. Fish donor annotations are retained with their actual experimental/access scopes. Neither donor count nor lack of a single resolved scaffold mechanism defeats the inherited biological process. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001526177 SUPPORTS TRANSFER Exact current IBD and ancestral path reconstructed in PTHR24049; human target MSA exact, no target-path IRD. Preserved PTHR12916 cache/current-xref boundary is separate. |
| GO:0045197 establishment or maintenance of epithelial cell apical/basal polarity | NAS PMID:26404741 CRB2 completes a fully expressed Crumbs complex in the Retin... | ACCEPT | Summary: The 2015 mouse localization study discusses the epithelial polarity role as a non-traceable statement, rather than demonstrating a knockdown mechanism there. Reason: The 2015 mouse localization study discusses the epithelial polarity role as a non-traceable statement, rather than demonstrating a knockdown mechanism there. Independent human 2021 perturbation now corroborates the broad establishment-or-maintenance term. Keep those evidence scopes distinct. Supporting Evidence: PMID:26404741 establishment and maintenance of cell-cell junctions |
| GO:0045199 maintenance of epithelial cell apical/basal polarity | IEA GO_REF:0000107 | ACCEPT | Summary: Maintenance of epithelial apicobasal polarity is supported by mouse tissue studies and directly by human fetal RPE CRB2 knockdown, junction ultrastructure and delayed calcium-switch recovery. Reason: Maintenance of epithelial apicobasal polarity is supported by mouse tissue studies and directly by human fetal RPE CRB2 knockdown, junction ultrastructure and delayed calcium-switch recovery. This does not establish universal loss of all polarity markers or de novo initiation in every tissue; the exact donor mapping is recorded in the evidence index. The source donor IMP points to the earlier PMID:22072575; PMID:27870829 subsequently separates its measured gastrulation defect from a proposed universal primary polarity defect. The human maintenance evidence is independent of that contested embryonic mechanism. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0045199 maintenance of epithelial cell apical/basal polarity | ISS GO_REF:0000024 | ACCEPT | Summary: Maintenance of epithelial apicobasal polarity is supported by mouse tissue studies and directly by human fetal RPE CRB2 knockdown, junction ultrastructure and delayed calcium-switch recovery. Reason: Maintenance of epithelial apicobasal polarity is supported by mouse tissue studies and directly by human fetal RPE CRB2 knockdown, junction ultrastructure and delayed calcium-switch recovery. This does not establish universal loss of all polarity markers or de novo initiation in every tissue; the exact donor mapping is recorded in the evidence index. The source donor IMP points to the earlier PMID:22072575; PMID:27870829 subsequently separates its measured gastrulation defect from a proposed universal primary polarity defect. The human maintenance evidence is independent of that contested embryonic mechanism. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0045494 photoreceptor cell maintenance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CRB2 helps maintain photoreceptors within retinal tissue. Reason: The original conditional mouse retinal deletion study documents progressive photoreceptor-layer thinning, rod photoreceptor cell death and impaired electroretinographic responses (PMID:23001562). Junction and tissue organization contribute to photoreceptor survival. Retain the ortholog-derived maintenance process as non-core, without claiming a direct anti-apoptotic enzyme or transferring every CRB1 phenotype. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0045494 photoreceptor cell maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CRB2 helps maintain photoreceptors within retinal tissue. Reason: The original conditional mouse retinal deletion study documents progressive photoreceptor-layer thinning, rod photoreceptor cell death and impaired electroretinographic responses (PMID:23001562). Junction and tissue organization contribute to photoreceptor survival. Retain the ortholog-derived maintenance process as non-core, without claiming a direct anti-apoptotic enzyme or transferring every CRB1 phenotype. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0046549 retinal cone cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CRB2 supports normal cone-cell maturation and organization. Reason: The full indexed original of PMID:23001562 includes mislocalized cone markers and direct cone outer-segment length measurements in developing conditional-mutant mouse retina: shortened segments at P15 and a larger deficit at P21. This is positive cone-development evidence in the source, despite the title foregrounding human CRB1 disease. It is not a claim that CRB2 specifies the cone lineage or that the experiment was conducted in human retina. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0046549 retinal cone cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CRB2 supports normal cone-cell maturation and organization. Reason: The full indexed original of PMID:23001562 includes mislocalized cone markers and direct cone outer-segment length measurements in developing conditional-mutant mouse retina: shortened segments at P15 and a larger deficit at P21. This is positive cone-development evidence in the source, despite the title foregrounding human CRB1 disease. It is not a claim that CRB2 specifies the cone lineage or that the experiment was conducted in human retina. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0055111 ingression involved in gastrulation with mouth forming second | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CRB2 participates in ingression during deuterostome gastrulation. Reason: PMID:27870829 directly films mouse primitive-streak cells: mutant cells constrict apically and move their cell bodies basally but retain apical attachments and fail to complete ingression, with lineage-restricted deletion and mosaic experiments separating cell and neighborhood context. The participation is in cell-surface/junction organization during ingression. Retain this existing developmental process, while the proposed molecular link to Myosin IIB remains incompletely resolved. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. Supporting Evidence: PMID:27870829 in the absence of CRB2, apical junctions do not dissolve |
| GO:0055111 ingression involved in gastrulation with mouth forming second | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CRB2 participates in ingression during deuterostome gastrulation. Reason: PMID:27870829 directly films mouse primitive-streak cells: mutant cells constrict apically and move their cell bodies basally but retain apical attachments and fail to complete ingression, with lineage-restricted deletion and mosaic experiments separating cell and neighborhood context. The participation is in cell-surface/junction organization during ingression. Retain this existing developmental process, while the proposed molecular link to Myosin IIB remains incompletely resolved. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: CRB2 was detected in a human urinary-exosome preparation. Reason: The original-linked NHLBI protein table lists CRB2/NP_775960 with one peptide and reference 2, PMID:19056867. The paper describes pooled normal human urine, ultracentrifugation/DTT fractionation and LC-MS/MS. Retain the existing fraction-localization claim at that detection scope, not as a principal cellular location or a demonstrated role in exosome biogenesis, sorting or function. Supporting Evidence: PMID:19056867 the analysis identified 1132 proteins unambiguously |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | UNDECIDED | Summary: The second exosome screen remains unresolved at the target-table level. Reason: PMID:23533145 describes pooled expressed-prostatic-secretion urine fractions and quantitative mass spectrometry, but the target-bearing supplementary Table 2 could not be recovered through the bounded original-source routes. The apparent workbook downloads were HTML/XML challenge or error content. The original experimental annotation is preserved without asserting target absence or confusing this cohort with normal urine in PMID:19056867. Its CRB2 identification and fraction specificity remain the unresolved source question. |
| GO:0070161 anchoring junction | IEA GO_REF:0000044 | MODIFY | Summary: The supported location is the epithelial apical junction region, with mouse retinal adherens-junction disruption and RPE tight-junction context. Reason: The supported location is the epithelial apical junction region, with mouse retinal adherens-junction disruption and RPE tight-junction context. Apical junction complex captures that measured anatomical context. This does not deny anchoring-junction localization or infer a direct mechanical cytoskeletal role merely from a location annotation. The replacement is a contextual refinement, not a claim that its ontology closure is identical to anchoring junction. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0038 SUPPORTS TRANSFER Actual UniProt subcellular-location mapping; positive epithelial localization is retained with the specific source and product limits in the reason. Proposed replacements: apical junction complex |
| GO:0070161 anchoring junction | ISS GO_REF:0000024 | MODIFY | Summary: The supported location is the epithelial apical junction region, with mouse retinal adherens-junction disruption and RPE tight-junction context. Reason: The supported location is the epithelial apical junction region, with mouse retinal adherens-junction disruption and RPE tight-junction context. Apical junction complex captures that measured anatomical context. This does not deny anchoring-junction localization or infer a direct mechanical cytoskeletal role merely from a location annotation. The replacement is a contextual refinement, not a claim that its ontology closure is identical to anchoring junction. Propagation Review Root cause: SOURCE STALE OR MISSING Sources checked: UniProtKB:Q80YA8 SOURCE STALE OR MISSING No exact GO:0070161 entry occurs in the complete current mouse source capture; preserve historical transfer and use directly read retinal/RPE evidence for the apical-junction replacement. Proposed replacements: apical junction complex |
| GO:0072359 circulatory system development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CRB2-dependent morphogenesis contributes to circulatory development. Reason: PMID:22072575 reports failure of normal heart-tube formation during severe gastrulation defects. The independent Crb2-null comparison in PMID:26496195 shows that Nkx2.5-positive cardiac mesoderm is specified, but the heart fields are abnormally shaped and fail to fuse. Retain the broad existing developmental annotation as non-core; this does not assign CRB2 a cardiac differentiation factor, vascular receptor or blood-cell function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
| GO:0072359 circulatory system development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CRB2-dependent morphogenesis contributes to circulatory development. Reason: PMID:22072575 reports failure of normal heart-tube formation during severe gastrulation defects. The independent Crb2-null comparison in PMID:26496195 shows that Nkx2.5-positive cardiac mesoderm is specified, but the heart fields are abnormally shaped and fail to fuse. Retain the broad existing developmental annotation as non-core; this does not assign CRB2 a cardiac differentiation factor, vascular receptor or blood-cell function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q80YA8 SUPPORTS TRANSFER Mouse Crb2 ortholog; current same-term experimental records and source-specific primary access are separately recorded. Human cellular corroboration does not convert mouse assays to human experiments. |
Loading supporting content…
Download this section (compressed HTML)Q: Which CRB2 PDZ/FERM contacts are required for junction recovery in human RPE, and how are they coordinated with actomyosin remodeling? Would a specific FERM-domain binding term better represent the experimentally supported EPB41L5 interaction than the current domain-specific binding term?
Q: Does the predicted secreted second product have a distinct extracellular role, and does product 3 preserve the polarity and gamma-secretase effects of the displayed membrane product?
Q: Which gamma-secretase component directly contacts CRB2, and how much of the endogenous human complex pool contains it?
Experiment: Combine endogenous CRB2 depletion with matched-expression rescue by the displayed product, PDZ-motif/FERM-region mutants and official alternative products in polarized human RPE. Measure junction localization, ultrastructure and calcium-switch recovery separately from total barrier resistance.
Experiment: Resolve CRB2-containing gamma-secretase assemblies with endogenous crosslinking or structural approaches and calibrated stoichiometry, retaining native-cell and purified membrane-assay distinctions.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)