Calnexin (CANX) is a type I single-pass integral membrane lectin chaperone of the endoplasmic reticulum and, together with the soluble paralog calreticulin, forms the central calnexin/calreticulin cycle of ER glycoprotein quality control. Its luminal globular lectin domain binds monoglucosylated N-glycans (Glc1Man9GlcNAc2) on nascent glycoproteins, while its extended proline-rich P domain (arm) recruits the oxidoreductase ERp57 (PDIA3) and the peptidyl-prolyl isomerase cyclophilin B (PPIB) to assist oxidative folding and assembly. Calnexin retains incompletely or incorrectly folded glycoproteins in the ER and triages terminally misfolded clients toward ER-associated degradation. It is a calcium-binding protein that contributes to ER calcium homeostasis. Calnexin is palmitoylated by ZDHHC6 on its cytoplasmic cysteines, which targets it to the perinuclear rough ER and couples it to the ribosome-translocon complex for co-translational capture of newly synthesized glycoproteins. It participates in MHC class I heavy-chain folding/assembly and in the maturation of many specific clients (e.g. ion channels, receptors, serpins).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: Protein folding is a core biological process for calnexin in the calnexin/calreticulin cycle. Reason: Phylogenetic transfer agrees with extensive experimental evidence that calnexin assists folding of nascent glycoproteins in the ER. Supporting Evidence: file:human/CANX/CANX-uniprot.txt in assisting protein assembly PMID:22314232 calnexin, a major ER chaperone involved in glycoprotein folding |
| GO:0036503 ERAD pathway | IBA GO_REF:0000033 | ACCEPT | Summary: The calnexin/calreticulin cycle triages terminally misfolded glycoproteins toward ER-associated degradation, so participation in the ERAD pathway is well supported. Reason: Calnexin retains incorrectly folded proteins and the cycle delivers persistent non-native clients to ERAD; this is an established core role. Supporting Evidence: file:human/CANX/CANX-uniprot.txt quality control apparatus of the ER |
| GO:0005509 calcium ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: Calcium ion binding is a core, conserved molecular function of calnexin. Reason: Calnexin binds Ca2+ via conserved high-capacity motifs and contributes to ER calcium handling. Supporting Evidence: PMID:8136357 Calnexin binds Ca2+ and may function as a chaperone in the transition of proteins from the ER to the outer cellular membrane. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic InterPro-based calcium ion binding annotation is consistent with the conserved calreticulin-family Ca2+-binding motifs. Reason: Same well-supported core molecular function as the IBA/TAS calcium annotations. Supporting Evidence: PMID:8136357 A subdomain containing four internal repeats binds Ca2+ with the highest affinity. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000120 | ACCEPT | Summary: ER localization is the core compartment for calnexin. Reason: Calnexin is a resident ER membrane protein; ER localization is supported by abundant experimental data. Supporting Evidence: PMID:8136357 Calnexin is a 90-kDa integral membrane protein of the endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: ER membrane is the precise core localization of this single-pass type I membrane chaperone. Reason: Topology (luminal lectin domain, single TM, cytoplasmic tail) and direct experimental localization place calnexin in the ER membrane. Supporting Evidence: file:human/CANX/CANX-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0006457 protein folding | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic protein folding annotation duplicates the well-supported core folding role. Reason: Consistent with experimental and phylogenetic evidence for chaperone-assisted glycoprotein folding. Supporting Evidence: PMID:22314232 calnexin, a major ER chaperone involved in glycoprotein folding |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: The bare mitochondrial membrane annotation overstates calnexin localization; calnexin is enriched at the ER side of mitochondria-associated ER membrane (MAM) contact sites, not in the mitochondrion proper. Reason: The supportable localization is the ER-mitochondria contact site (MAM); a generic mitochondrial membrane assignment for an ER chaperone is an over-call. |
| GO:0033162 melanosome membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Melanosome membrane localization derives from proteomic detection in melanosome fractions and is a secondary localization of an ER protein. Reason: Detected by mass spectrometry in melanosomes but not part of the core ER chaperone function. Supporting Evidence: file:human/CANX/CANX-uniprot.txt spectrometry in melanosome fractions from stage I to stage IV |
| GO:0098793 presynapse | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Presynapse localization is an inter-ontology inference tied to a speculative synaptic endocytosis role; not a core compartment for human calnexin. Reason: Based on logical inference rather than direct evidence; the conserved function of calnexin is ER glycoprotein quality control. |
| GO:0005515 protein binding | IPI PMID:16546175 Rescue of functional delF508-CFTR channels in cystic fibrosi... | MARK AS OVER ANNOTATED | Summary: Bare protein binding is uninformative; this CFTR-rescue study reflects the chaperone-client relationship already captured by folding terms. Reason: Per curation guidelines, generic protein binding does not convey calnexin's molecular function. |
| GO:0005515 protein binding | IPI PMID:17110338 Hsp90 cochaperone Aha1 downregulation rescues misfolding of ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a CFTR/Aha1 study; uninformative for calnexin function. Reason: Bare protein binding should not be treated as a meaningful molecular function. |
| GO:0005515 protein binding | IPI PMID:17220478 Proteomics analysis of the interactome of N-myc downstream r... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from an NDRG1 interactome study; uninformative. Reason: Bare protein binding is not an informative molecular function. |
| GO:0005515 protein binding | IPI PMID:17380188 Simultaneous induction of the four subunits of the TRAP comp... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a TRAP-complex ER-stress study; uninformative. Reason: Bare protein binding does not capture a specific calnexin function. |
| GO:0005515 protein binding | IPI PMID:20528919 Human delta opioid receptor biogenesis is regulated via inte... | MARK AS OVER ANNOTATED | Summary: This reflects calnexin chaperoning the delta opioid receptor (a glycoprotein client), but the bare protein binding term is uninformative. Reason: The underlying biology is client chaperoning, already represented by ER protein-folding terms; generic protein binding adds nothing. |
| GO:0005515 protein binding | IPI PMID:22190034 Global landscape of HIV-human protein complexes. | MARK AS OVER ANNOTATED | Summary: Generic protein binding from an HIV-host complex screen; uninformative. Reason: High-throughput host-virus interaction; bare protein binding is not informative. |
| GO:0005515 protein binding | IPI PMID:22314232 Palmitoylated calnexin is a key component of the ribosome-tr... | MARK AS OVER ANNOTATED | Summary: The underlying interaction is calnexin association with the ribosome-translocon component SSR1, more informatively captured as ER protein folding than as bare protein binding. Reason: Generic protein binding obscures the specific translocon-coupling biology reported here; the functional content is the folding/translocon role. Supporting Evidence: PMID:22314232 palmitoylation mediates the association of calnexin with the ribosome-translocon complex (RTC) |
| GO:0005515 protein binding | IPI PMID:22872700 Inherited genetic variants in autism-related CNTNAP2 show pe... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a CNTNAP2 trafficking/ATF6 study; uninformative. Reason: Bare protein binding does not convey a specific calnexin function. |
| GO:0005515 protein binding | IPI PMID:25170080 HIV-1 protein Nef inhibits activity of ATP-binding cassette ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from an HIV-1 Nef/ABCA1/calnexin study; uninformative as a function term. Reason: Bare protein binding is not an informative molecular function. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a quantitative interactome map; uninformative. Reason: High-throughput interactome hit; bare protein binding does not convey function. |
| GO:0005515 protein binding | IPI PMID:26618866 βF508 CFTR interactome remodelling promotes rescue of cystic... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a CFTR-interactome study; uninformative. Reason: Bare protein binding is not informative for curation. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a proteome-scale interactome; uninformative. Reason: High-throughput interaction; bare protein binding adds no functional information. |
| GO:0005515 protein binding | IPI PMID:29568061 An AP-MS- and BioID-compatible MAC-tag enables comprehensive... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a MAC-tag interaction/localization map; uninformative. Reason: Bare protein binding is not an informative molecular function. |
| GO:0005515 protein binding | IPI PMID:29924966 A Proteomic Variant Approach (ProVarA) for Personalized Medi... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a proteomic-variant study; uninformative. Reason: Bare protein binding does not convey a specific function. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a histone crosslinking-MS study; uninformative and likely incidental. Reason: Bare protein binding is not informative; an ER chaperone-histone crosslink is not a meaningful function. |
| GO:0005515 protein binding | IPI PMID:31324722 Inhibition of calpain 1 restores plasma membrane stability t... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a CFTR/calpain rescue study; uninformative. Reason: Bare protein binding is not an informative molecular function. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a dual proteome-scale network; uninformative. Reason: High-throughput interactome hit; bare protein binding adds no function information. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from OpenCell endogenous tagging; uninformative. Reason: Bare protein binding is not informative for curation. |
| GO:0005515 protein binding | IPI PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from CFTR proximity-labeling; uninformative. Reason: Bare protein binding does not convey a specific function. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a multimodal cell-map study; uninformative. Reason: Bare protein binding is not an informative molecular function. |
| GO:0016020 membrane | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Generic membrane is correct but uninformatively broad; the specific compartment is the ER membrane. Reason: A bare membrane term is subsumed by the more precise ER membrane annotation. |
| GO:0031965 nuclear membrane | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Nuclear membrane localization most likely reflects continuity of the ER membrane with the nuclear envelope rather than a distinct functional pool. Reason: Likely a contiguity artifact; the functional compartment is the ER membrane. |
| GO:0044322 endoplasmic reticulum quality control compartment | IEA GO_REF:0000107 | ACCEPT | Summary: Localization to the ER quality control compartment is consistent with calnexin's role in retaining and triaging misfolded glycoproteins. Reason: Directly aligned with calnexin's core ER quality-control function. Supporting Evidence: file:human/CANX/CANX-uniprot.txt quality control apparatus of the ER |
| GO:0048488 synaptic vesicle endocytosis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: A synaptic vesicle endocytosis role is a speculative, ortholog-derived inference (via SGIP1) noted as possible in UniProt, not an established human function. Reason: Only suggested ("may play a role") and not supported by direct human evidence; not the core ER function. |
| GO:0072583 clathrin-dependent endocytosis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Clathrin-dependent endocytosis is the same speculative synaptic/endocytic inference and is not a core calnexin function. Reason: Ortholog-derived and speculative; not supported by direct evidence for human calnexin. |
| GO:0044183 protein folding chaperone | TAS Reactome:R-HSA-9683772 | ACCEPT | Summary: Protein folding chaperone is an accurate core molecular function for calnexin. Reason: Calnexin is a bona fide molecular chaperone for nascent glycoproteins. Supporting Evidence: PMID:22314232 calnexin, a major ER chaperone involved in glycoprotein folding |
| GO:0005783 endoplasmic reticulum | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence-based ER localization is consistent with the established core compartment. Reason: ER residence is a core property of calnexin. Supporting Evidence: PMID:8136357 Calnexin is a 90-kDa integral membrane protein of the endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:22314232 Palmitoylated calnexin is a key component of the ribosome-tr... | ACCEPT | Summary: Experimental evidence places calnexin in the ER membrane, with palmitoylation directing it to the perinuclear rough ER and the translocon. Reason: Direct experimental support for the core ER membrane localization. Supporting Evidence: PMID:22314232 This modification leads to the preferential localization of calnexin to the perinuclear rough ER, at the expense of ER tubules. |
| GO:0031966 mitochondrial membrane | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Sequence/orthology transfer of mitochondrial membrane localization overstates a MAM (ER-mitochondria contact) association. Reason: Calnexin localizes to the ER side of MAM contact sites; the generic mitochondrial membrane term is an over-call. |
| GO:0033162 melanosome membrane | EXP PMID:12643545 Proteomic analysis of early melanosomes: identification of n... | KEEP AS NON CORE | Summary: Melanosome proteomics detected calnexin; a secondary localization of an ER protein. Reason: Real proteomic detection in melanosomes but not part of the core ER chaperone function. Supporting Evidence: file:human/CANX/CANX-uniprot.txt spectrometry in melanosome fractions from stage I to stage IV |
| GO:0033162 melanosome membrane | EXP PMID:17081065 Proteomic and bioinformatic characterization of the biogenes... | KEEP AS NON CORE | Summary: Independent melanosome proteomics again detected calnexin; secondary localization. Reason: Consistent secondary melanosomal detection; non-core relative to ER function. Supporting Evidence: file:human/CANX/CANX-uniprot.txt spectrometry in melanosome fractions from stage I to stage IV |
| GO:0019082 viral protein processing | TAS Reactome:R-HSA-9683686 | KEEP AS NON CORE | Summary: Viral protein processing (e.g. SARS-CoV-2 spike maturation) is a client-specific application of the calnexin chaperone cycle, not a distinct core function. Reason: Calnexin folds viral glycoproteins as it folds other clients; retain as a context-specific application rather than core function. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9932913 | ACCEPT | Summary: Reactome ER membrane localization is consistent with the core compartment. Reason: Matches the well-supported ER membrane localization. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9932988 | ACCEPT | Summary: Reactome ER membrane localization (CDH1 processing pathway) is consistent with the core compartment. Reason: Matches the well-supported ER membrane localization. |
| GO:0098553 lumenal side of endoplasmic reticulum membrane | TAS Reactome:R-HSA-983145 | ACCEPT | Summary: The lectin/chaperone domain of calnexin faces the ER lumen, so luminal-side ER membrane localization is accurate. Reason: Topology places the functional globular and P domains on the luminal side of the ER membrane. Supporting Evidence: file:human/CANX/CANX-uniprot.txt TOPO_DOM 21..481 |
| GO:0098553 lumenal side of endoplasmic reticulum membrane | TAS Reactome:R-HSA-983146 | ACCEPT | Summary: Luminal-side ER membrane localization (MHC I assembly pathway) matches calnexin topology. Reason: The functional luminal lectin domain is on the luminal side of the ER membrane. |
| GO:0005515 protein binding | IPI PMID:32783947 NACHO Engages N-Glycosylation ER Chaperone Pathways for Ξ±7 N... | MARK AS OVER ANNOTATED | Summary: This reflects calnexin's role in NACHO-dependent Ξ±7 nicotinic receptor assembly (a glycoprotein client), but bare protein binding is uninformative. Reason: The functional content is client chaperoning that requires calnexin chaperone activity; generic protein binding does not capture it. Supporting Evidence: PMID:32783947 NACHO-mediated effects on Ξ±7 assembly and channel function require N-glycosylation and calnexin chaperone activity. |
| GO:0005515 protein binding | IPI PMID:31735293 TMX2 Is a Crucial Regulator of Cellular Redox State, and Its... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a TMX2 redox study; uninformative. Reason: Bare protein binding does not convey a specific calnexin function. |
| GO:0005515 protein binding | IPI PMID:30188326 Deletion of Tmtc4 activates the unfolded protein response an... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a TMTC4/UPR study; uninformative. Reason: Bare protein binding is not an informative molecular function. |
| GO:0005783 endoplasmic reticulum | IDA PMID:30188326 Deletion of Tmtc4 activates the unfolded protein response an... | ACCEPT | Summary: Direct ER localization consistent with the core compartment. Reason: Reinforces the established ER localization of calnexin. |
| GO:0005515 protein binding | IPI PMID:29765154 The cancer-associated microprotein CASIMO1 controls cell pro... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a CASIMO1/squalene epoxidase study; uninformative. Reason: Bare protein binding does not convey a specific function. |
| GO:0005783 endoplasmic reticulum | IDA PMID:24454821 Transmembrane and coiled-coil domain family 1 is a novel pro... | ACCEPT | Summary: Direct ER localization consistent with the core compartment. Reason: Reinforces the established ER localization. |
| GO:0005515 protein binding | IPI PMID:21205830 A systematic search for endoplasmic reticulum (ER) membrane-... | MARK AS OVER ANNOTATED | Summary: This reflects the ZNRF4-calnexin interaction regulating calnexin stability, but bare protein binding is uninformative. Reason: The biology is regulation of calnexin stability/ubiquitination by ZNRF4; generic protein binding does not capture it. Supporting Evidence: PMID:21205830 Nixin/ZNRF4 as a regulator of calnexin stability and ER homeostasis |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:23814182 Tracking a refined eIF4E-binding motif reveals Angel1 as a n... | ACCEPT | Summary: Direct ER membrane localization consistent with the core compartment. Reason: Matches the established ER membrane localization. |
| GO:0034975 protein folding in endoplasmic reticulum | TAS PMID:22013210 The unfolded protein response: integrating stress signals th... | ACCEPT | Summary: Protein folding in the ER is the precise core biological process for calnexin. Reason: This is the most accurate BP term for calnexin's chaperone activity in the ER. Supporting Evidence: PMID:22314232 calnexin, a major ER chaperone involved in glycoprotein folding |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:20531390 Suppression of the novel ER protein Maxer by mutant ataxin-1... | ACCEPT | Summary: Direct ER membrane localization consistent with the core compartment. Reason: Matches the established ER membrane localization. |
| GO:0005783 endoplasmic reticulum | IDA PMID:22572157 Sensitive detection of idiotypic platelet-reactive alloantib... | ACCEPT | Summary: Direct ER localization consistent with the core compartment. Reason: Reinforces the established ER localization. |
| GO:0005515 protein binding | IPI PMID:24764305 TMTC1 and TMTC2 are novel endoplasmic reticulum tetratricope... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a TMTC1/TMTC2 calcium-homeostasis study; uninformative. Reason: Bare protein binding is not an informative molecular function. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | MARK AS OVER ANNOTATED | Summary: High-throughput exosome proteomics detected calnexin; an incidental/non-core localization for an ER membrane protein. Reason: Calnexin is commonly used as a negative (non-exosomal) marker; HDA exosome detection is likely contamination and not a genuine functional location. |
| GO:0070062 extracellular exosome | IDA NOT PMID:21235781 Human saliva, plasma and breast milk exosomes contain RNA: u... | ACCEPT | Summary: This NOT annotation states calnexin is absent from these exosomes, consistent with its use as a non-exosomal ER marker. Reason: The negation is biologically appropriate; calnexin is an ER-resident protein typically excluded from exosomes. |
| GO:0044233 mitochondria-associated endoplasmic reticulum membrane contact site | IDA PMID:23455425 Autophagosomes form at ER-mitochondria contact sites. | KEEP AS NON CORE | Summary: Calnexin localizes to MAM contact sites, the accurate description of its ER-mitochondria association. Reason: A real but specialized localization; the MAM pool is distinct from the bulk ER chaperone activity and is non-core. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: Generic membrane from an NK-cell membrane proteome; uninformatively broad. Reason: Subsumed by the precise ER membrane localization. |
| GO:0005783 endoplasmic reticulum | IDA PMID:24263861 HCV NS3 protease enhances liver fibrosis via binding to and ... | ACCEPT | Summary: Direct ER localization consistent with the core compartment. Reason: Reinforces the established ER localization. |
| GO:0005783 endoplasmic reticulum | IDA PMID:18458083 Molecular identification of a novel mammalian brain isoform ... | ACCEPT | Summary: Direct ER localization consistent with the core compartment. Reason: Reinforces the established ER localization. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | MARK AS OVER ANNOTATED | Summary: RNA binding is from global mRNA-interactome capture; calnexin is not a bona fide functional RNA-binding protein. Reason: High-throughput RNA-interactome capture; not a credible molecular function for an ER lectin chaperone. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MARK AS OVER ANNOTATED | Summary: RNA binding from a second mRNA-interactome capture dataset; same caveat. Reason: High-throughput capture artifact; not a genuine calnexin function. |
| GO:0005515 protein binding | IPI PMID:23826168 SERPINA2 is a novel gene with a divergent function from SERP... | MARK AS OVER ANNOTATED | Summary: This reflects calnexin chaperoning SERPINA1/SERPINA2 variants, but bare protein binding is uninformative. Reason: The functional content is serpin client chaperoning, captured by folding terms; generic protein binding adds nothing. |
| GO:0005783 endoplasmic reticulum | IDA PMID:23826168 SERPINA2 is a novel gene with a divergent function from SERP... | ACCEPT | Summary: Direct ER localization consistent with the core compartment. Reason: Reinforces the established ER localization. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2130478 | ACCEPT | Summary: The functional lectin/chaperone domains of calnexin reside in the ER lumen. Reason: Consistent with calnexin topology (large luminal domain). |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2213241 | ACCEPT | Summary: ER lumen localization of the functional domain; accurate. Reason: Consistent with calnexin topology. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-535717 | ACCEPT | Summary: ER lumen localization for the chaperone-client binding step; accurate. Reason: Consistent with calnexin topology and function. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-548890 | ACCEPT | Summary: ER lumen localization for the glucosidase II/release step; accurate. Reason: Consistent with calnexin topology and the CNX/CRT cycle. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8950342 | ACCEPT | Summary: ER lumen localization (EBI3/IL27 assembly pathway); accurate. Reason: Consistent with calnexin topology. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8950362 | ACCEPT | Summary: ER lumen localization (EBI3/IL12A assembly pathway); accurate. Reason: Consistent with calnexin topology. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8950387 | ACCEPT | Summary: ER lumen localization (CANX binds EBI3); accurate. Reason: Consistent with calnexin topology. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8950398 | ACCEPT | Summary: ER lumen localization (CANX dissociates from IL27:EBI3); accurate. Reason: Consistent with calnexin topology. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8950740 | ACCEPT | Summary: ER lumen localization (CANX dissociates from IL12A:EBI3); accurate. Reason: Consistent with calnexin topology. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8951500 | ACCEPT | Summary: ER lumen localization (dissociation from nonameric complex); accurate. Reason: Consistent with calnexin topology. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-901047 | ACCEPT | Summary: ER lumen localization for ERp57 binding; accurate and functionally central (P domain recruits ERp57). Reason: Consistent with calnexin topology and its ERp57-recruiting role. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-9683772 | ACCEPT | Summary: ER lumen localization (trimmed spike binds calnexin); accurate. Reason: Consistent with calnexin topology. |
| GO:0005783 endoplasmic reticulum | IDA PMID:21190736 The non-conventional MHC class I MR1 molecule controls infec... | ACCEPT | Summary: Direct ER localization consistent with the core compartment. Reason: Reinforces the established ER localization. |
| GO:0005515 protein binding | IPI PMID:16361248 Mechanisms of pharmacological rescue of trafficking-defectiv... | MARK AS OVER ANNOTATED | Summary: This reflects calnexin chaperoning the hERG/KCNH2 channel (a glycoprotein client), but bare protein binding is uninformative. Reason: The functional content is client chaperoning, captured by folding terms; generic protein binding adds nothing. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:19723497 Nogo-B receptor stabilizes Niemann-Pick type C2 protein and ... | ACCEPT | Summary: Direct ER membrane localization consistent with the core compartment. Reason: Matches the established ER membrane localization. |
| GO:0048488 synaptic vesicle endocytosis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Sequence/orthology-transferred synaptic vesicle endocytosis role is speculative for human calnexin. Reason: Based on ortholog inference only; not the conserved core ER function. |
| GO:0072583 clathrin-dependent endocytosis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Sequence/orthology-transferred clathrin-dependent endocytosis role is speculative for human calnexin. Reason: Ortholog inference only; not supported by direct human evidence. |
| GO:0005783 endoplasmic reticulum | IDA PMID:14966132 A predominant role of acyl-CoA:monoacylglycerol acyltransfer... | ACCEPT | Summary: Direct ER localization consistent with the core compartment. Reason: Reinforces the established ER localization. |
| GO:0005783 endoplasmic reticulum | NAS PMID:8136357 Human, mouse, and rat calnexin cDNA cloning: identification ... | ACCEPT | Summary: ER localization asserted in the original cloning paper; consistent with the core compartment. Reason: Matches the established ER localization. Supporting Evidence: PMID:8136357 Calnexin is a 90-kDa integral membrane protein of the endoplasmic reticulum |
| GO:0005509 calcium ion binding | TAS PMID:8136357 Human, mouse, and rat calnexin cDNA cloning: identification ... | ACCEPT | Summary: Calcium ion binding established biochemically in the cloning paper; core molecular function. Reason: Direct biochemical demonstration of Ca2+ binding by conserved calnexin motifs. Supporting Evidence: PMID:8136357 A subdomain containing four internal repeats binds Ca2+ with the highest affinity. |
| GO:0009306 protein secretion | TAS PMID:8055875 The molecular chaperones HSP28, GRP78, endoplasmin, and caln... | MARK AS OVER ANNOTATED | Summary: Protein secretion is a broad downstream consequence of chaperone-assisted folding; the precise function is ER glycoprotein folding/quality control. Reason: Calnexin enables secretion of correctly folded clients but is not a secretion factor per se; the BP is better captured by ER protein folding. |
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Download this section (compressed HTML)Q: To what extent does calnexin's palmitoylation-dependent coupling to the ribosome-translocon complex define a distinct co-translational chaperone function separable from the post-translational lectin cycle?
Suggested experts: van der Goot FG, Lakkaraju AK
Experiment: Compare glycoprotein folding kinetics and client maturation in cells expressing wild-type versus palmitoylation-site (C502/C503) mutant calnexin, using pulse-chase and proximity labeling at the translocon.
Hypothesis: Calnexin's palmitoylation-dependent translocon association is required for efficient co-translational capture and folding of a defined set of glycoprotein clients.
Type: cell-based mutant rescue with pulse-chase folding assay
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