Existing Annotations Review

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 ∆F508 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 α7 N...	MARK AS OVER ANNOTATED	Summary: This reflects calnexin's role in NACHO-dependent α7 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 α7 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.

Core Functions

Lectin that specifically recognizes and binds the monoglucosylated (Glc1Man9GlcNAc2) N-glycan on nascent glycoproteins in the ER - the glycan-dependent substrate-recognition step that initiates and sustains client engagement in the calnexin/calreticulin cycle.

Molecular Function:

carbohydrate binding

Cellular Locations:

endoplasmic reticulum membrane

Supporting Evidence:

file:human/CANX/CANX-uniprot.txt
monoglucosylated glycoproteins in the endoplasmic reticulum

Lectin chaperone that binds monoglucosylated N-glycans on nascent glycoproteins in the ER and, with ERp57 and PPIB recruited via its P domain, assists their folding and assembly as part of the calnexin/calreticulin cycle.

Molecular Function:

protein folding chaperone

Directly Involved In:

protein folding in endoplasmic reticulum

Cellular Locations:

endoplasmic reticulum membrane lumenal side of endoplasmic reticulum membrane

Supporting Evidence:

file:human/CANX/CANX-uniprot.txt
Calcium-binding protein that interacts with newly synthesized
PMID:22314232
calnexin, a major ER chaperone involved in glycoprotein folding

Quality-control retention factor that holds incompletely or incorrectly folded glycoproteins in the ER and triages terminally misfolded clients toward ER-associated degradation.

Molecular Function:

unfolded protein binding

Directly Involved In:

ERAD pathway

Cellular Locations:

endoplasmic reticulum quality control compartment

Supporting Evidence:

file:human/CANX/CANX-uniprot.txt
quality control apparatus of the ER

Calcium-binding ER protein contributing to ER calcium handling via conserved high-capacity Ca2+-binding repeats.

Molecular Function:

calcium ion binding

Cellular Locations:

endoplasmic reticulum membrane

Supporting Evidence:

PMID:8136357
A subdomain containing four internal repeats binds Ca2+ with the highest affinity.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:12643545

Proteomic analysis of early melanosomes: identification of novel melanosomal proteins.

PMID:14966132

A predominant role of acyl-CoA:monoacylglycerol acyltransferase-2 in dietary fat absorption implicated by tissue distribution, subcellular localization, and up-regulation by high fat diet.

PMID:16361248

Mechanisms of pharmacological rescue of trafficking-defective hERG mutant channels in human long QT syndrome.

PMID:16546175

Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the alpha-glucosidase inhibitor miglustat.

PMID:17081065

Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.

PMID:17110338

Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis.

PMID:17220478

Proteomics analysis of the interactome of N-myc downstream regulated gene 1 and its interactions with the androgen response program in prostate cancer cells.

PMID:17380188

Simultaneous induction of the four subunits of the TRAP complex by ER stress accelerates ER degradation.

PMID:18458083

Molecular identification of a novel mammalian brain isoform of acyl-CoA:lysophospholipid acyltransferase with prominent ethanolamine lysophospholipid acylating activity, LPEAT2.

PMID:19723497

Nogo-B receptor stabilizes Niemann-Pick type C2 protein and regulates intracellular cholesterol trafficking.

PMID:19946888

Defining the membrane proteome of NK cells.

PMID:20528919

Human delta opioid receptor biogenesis is regulated via interactions with SERCA2b and calnexin.

PMID:20531390

Suppression of the novel ER protein Maxer by mutant ataxin-1 in Bergman glia contributes to non-cell-autonomous toxicity.

PMID:21190736

The non-conventional MHC class I MR1 molecule controls infection by Klebsiella pneumoniae in mice.

PMID:21205830

A systematic search for endoplasmic reticulum (ER) membrane-associated RING finger proteins identifies Nixin/ZNRF4 as a regulator of calnexin stability and ER homeostasis.

PMID:21235781

Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages.

PMID:22013210

The unfolded protein response: integrating stress signals through the stress sensor IRE1α.

PMID:22190034

Global landscape of HIV-human protein complexes.

PMID:22314232

Palmitoylated calnexin is a key component of the ribosome-translocon complex.

Calnexin is a major ER glycoprotein-folding chaperone whose palmitoylation by DHHC6 couples it to the ribosome-translocon complex for co-translational client capture.

"calnexin, a major ER chaperone involved in glycoprotein folding"

PMID:22314232

Palmitoylated calnexin is a key component of the ribosome-translocon complex.

PMID:22572157

Sensitive detection of idiotypic platelet-reactive alloantibodies by an electrical protein chip.

PMID:22658674

Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.

PMID:22681889

The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.

PMID:22872700

Inherited genetic variants in autism-related CNTNAP2 show perturbed trafficking and ATF6 activation.

PMID:23455425

Autophagosomes form at ER-mitochondria contact sites.

PMID:23533145

In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.

PMID:23814182

Tracking a refined eIF4E-binding motif reveals Angel1 as a new partner of eIF4E.

PMID:23826168

SERPINA2 is a novel gene with a divergent function from SERPINA1.

PMID:24263861

HCV NS3 protease enhances liver fibrosis via binding to and activating TGF-β type I receptor.

PMID:24454821

Transmembrane and coiled-coil domain family 1 is a novel protein of the endoplasmic reticulum.

PMID:24764305

TMTC1 and TMTC2 are novel endoplasmic reticulum tetratricopeptide repeat-containing adapter proteins involved in calcium homeostasis.

PMID:25170080

HIV-1 protein Nef inhibits activity of ATP-binding cassette transporter A1 by targeting endoplasmic reticulum chaperone calnexin.

PMID:26496610

A human interactome in three quantitative dimensions organized by stoichiometries and abundances.

PMID:26618866

∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:29568061

An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations.

PMID:29765154

The cancer-associated microprotein CASIMO1 controls cell proliferation and interacts with squalene epoxidase modulating lipid droplet formation.

PMID:29924966

A Proteomic Variant Approach (ProVarA) for Personalized Medicine of Inherited and Somatic Disease.

PMID:30021884

Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.

PMID:30188326

Deletion of Tmtc4 activates the unfolded protein response and causes postnatal hearing loss.

PMID:31324722

Inhibition of calpain 1 restores plasma membrane stability to pharmacologically rescued Phe508del-CFTR variant.

PMID:31735293

TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities.

PMID:32783947

NACHO Engages N-Glycosylation ER Chaperone Pathways for α7 Nicotinic Receptor Assembly.

NACHO-mediated alpha7 nicotinic receptor assembly requires N-glycosylation and calnexin chaperone activity.

"NACHO-mediated effects on α7 assembly and channel function require N-glycosylation and calnexin chaperone activity."

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:36012204

Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

PMID:8055875

The molecular chaperones HSP28, GRP78, endoplasmin, and calnexin exhibit strikingly different levels in quiescent keratinocytes as compared to their proliferating normal and transformed counterparts: cDNA cloning and expression of calnexin.

PMID:8136357

Human, mouse, and rat calnexin cDNA cloning: identification of potential calcium binding motifs and gene localization to human chromosome 5.

Calnexin is a 90-kDa integral ER membrane protein that binds Ca2+ via a conserved high-affinity repeat motif.

"A subdomain containing four internal repeats binds Ca2+ with the highest affinity."

Reactome:R-HSA-2130478

Interaction of invariant chain trimer and MHC II alpha beta dimer

Reactome:R-HSA-2213241

Formation of nonameric complex

Reactome:R-HSA-535717

Binding of calnexin/calreticulin to the unfolded protein

Reactome:R-HSA-548890

Removal of the third glucose by glucosidase II and release from the chaperone

Reactome:R-HSA-8950342

EBI3:CANX binds IL27

Reactome:R-HSA-8950362

EBI3:CANX binds IL12A

Reactome:R-HSA-8950387

CANX binds EBI3

Reactome:R-HSA-8950398

CANX dissociates from IL27:EBI3

Reactome:R-HSA-8950740

CANX dissociates from IL12A:EBI3

Reactome:R-HSA-8951500

Dissociation of CANX from nonameric complex

Reactome:R-HSA-901047

Binding of ERp57

Reactome:R-HSA-9683686

Maturation of spike protein

Reactome:R-HSA-9683772

Trimmed spike protein binds to calnexin

Reactome:R-HSA-983145

Binding of newly synthesized MHC class I heavy chain (HC) with calnexin

Reactome:R-HSA-983146

Interaction of beta-2-microglobulin (B2M) chain with class I HC

Reactome:R-HSA-9932913

Glucosidase II removes glucose residue from Glu1Man9GlucNAc2-CDH1

Reactome:R-HSA-9932988

CANX binds Glu1Man9GlcNAc2-CDH1

file:human/CANX/CANX-uniprot.txt

CANX UniProtKB record (P27824)

file:human/CANX/CANX-notes.md

Manual CANX curation notes

Suggested Experiments

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

📚 Additional Documentation

Notes

(CANX-notes.md)

CANX (Calnexin, P27824) curation notes

Overview

CANX is a type I single-pass ER membrane lectin chaperone, one of the two central
ER lectins of the calnexin/calreticulin cycle. It binds monoglucosylated N-glycans
(Glc1Man9GlcNAc2) on nascent glycoproteins, recruits ERp57 (PDIA3) for oxidative
folding, retains misfolded glycoproteins for ER quality control, and binds calcium.

Core function evidence

UniProt FUNCTION [file:human/CANX/CANX-uniprot.txt]:
"Calcium-binding protein that interacts with newly synthesized monoglucosylated
glycoproteins in the endoplasmic reticulum. It may act in assisting protein
assembly and/or in the retention within the ER of unassembled protein subunits.
It seems to play a major role in the quality control apparatus of the ER by the
retention of incorrectly folded proteins."
Topology: lumenal (21-481), transmembrane (482-502), cytoplasmic (503-592). The
lumenal globular lectin domain + extended P domain (276-409) recruit ERp57 and PPIB.
Ca2+ binding sites at residues 74, 117, 436; alpha-D-glucoside (glycan) binding at
164, 166, 185, 192, 425. [file:human/CANX/CANX-uniprot.txt]
Palmitoylation/translocon: PMID:22314232 and "palmitoylation mediates the association of calnexin
with the ribosome-translocon complex (RTC)". When supercomplex formation was disrupted,
"folding of glycoproteins was impaired." This is direct experimental support for ER
membrane localization and the glycoprotein-folding core function.
ERAD / quality control: calnexin retains misfolded glycoproteins; the IBA ERAD pathway
annotation reflects the well-established role of the CNX/CRT cycle feeding terminally
misfolded clients to ERAD.
Client-specific chaperone examples (all consistent with the core lectin-chaperone role,
but client-specific, not the generic function):
CHRNA7/α7 nicotinic receptor assembly via NACHO: PMID:32783947
hERG/KCNH2 PMID:16361248, CFTR [PMID:16546175, 26618866, 31324722, 36012204],
SERPINA1/SERPINA2 PMID:23826168, delta opioid receptor PMID:20528919, NPC2/Nogo-B
receptor PMID:19723497.

Localization

ER membrane is the core compartment (IDA, EXP PMID:22314232, multiple IDA).
Melanosome membrane (PMID:12643545, 17081065): mass-spec detection in melanosome
fractions; secondary localization of an ER protein, non-core.
Mitochondrial membrane / MAM contact site (PMID:23455425): MAM localization is real;
the bare "mitochondrial membrane" subcell mapping is an over-call (calnexin is at the
ER side of ER-mitochondria contact sites).
Extracellular exosome (HDA PMID:23533145): high-throughput proteomic; non-core. Note a
NEGATED exosome annotation from PMID:21235781.
Presynapse / synaptic vesicle endocytosis / clathrin-dependent endocytosis: derived from
ortholog (rodent) SGIP1-related receptor-mediated endocytosis role; UniProt notes "may
play a role in receptor-mediated endocytosis at the synapse." Speculative for human,
non-core.
Nuclear membrane (IEA Ensembl): over-call, the ER membrane is continuous with the nuclear
envelope so this is a propagated contiguity artifact.

Over-annotations / uninformative

The large block of GO:0005515 "protein binding" (IPI) annotations come from interactome
maps (PMID:26496610, 28514442, 29568061, 33961781, 35271311, 40205054, 30021884, 32296183
via BioPlex/OpenCell/etc.), virus host factor screens (HIV PMID:22190034, 25170080),
and individual client studies. Per curation guidelines, bare "protein binding" is
uninformative -> MARK_AS_OVER_ANNOTATED (a few that pinpoint the chaperone-client
relationship could in principle be MODIFY to unfolded protein binding, but most are
generic interactome hits).
RNA binding (HDA PMID:22658674, 22681889): from global mRNA-interactome capture; calnexin
is not a bona fide RNA-binding protein in a functional sense -> over-annotated.
Viral protein processing (TAS Reactome, SARS-CoV-2 spike): client-specific application of
the chaperone cycle; non-core.

Calcium

Ca2+ binding (IBA, IEA, TAS PMID:8136357): supported; calnexin contributes to ER Ca2+
via high-capacity Ca2+ binding in its acidic regions. Core ER property. [PMID:8136357
cDNA cloning "identification of potential calcium binding motifs"]

Summary of core functions

MF: carbohydrate (monoglucosylated N-glycan) binding lectin / unfolded protein binding
chaperone activity in the ER.
MF: calcium ion binding (ER Ca2+ buffering).
BP: protein folding in the ER / glycoprotein quality control (calnexin/calreticulin cycle).
BP: ERAD pathway (retention/triage of terminally misfolded clients).
CC: ER membrane (lumenal-facing lectin domain).

Pn Notes

(CANX-pn-notes.md)

CANX PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: P27824
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-06
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/CANX/CANX-ai-review.yaml
AIGR review HTML: present - genes/human/CANX/CANX-ai-review.html
Gene notes: present - genes/human/CANX/CANX-notes.md
GOA TSV: present - genes/human/CANX/CANX-goa.tsv
UniProt record: present - genes/human/CANX/CANX-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/CANX.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/CANX.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

Description: 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).
Existing/core annotation action counts: ACCEPT: 42; KEEP_AS_NON_CORE: 5; MARK_AS_OVER_ANNOTATED: 42

PN Consistency Summary

Consistency: Internally consistent on biology — review, notes, and PN all describe calnexin as the membrane-bound lectin chaperone of the CNX/CRT cycle binding monoglucosylated N-glycans. BUT the PROJECTED GO term is inconsistent with calnexin's molecular role (see below).
PN story / NEW pressure: GO:0006487 is VERIFIED real but its definition is "a process in which a carbohydrate unit is ADDED to a protein via the N4 atom of asparagine" — i.e. the catalytic glycan-transfer step (OST machinery). Calnexin RECOGNIZES/BINDS the already-installed glycan; it does not perform N-glycosylation. The review correctly captures the true function as GO:0030246 carbohydrate binding, GO:0044183 protein folding chaperone, GO:0034975 protein folding in ER, GO:0036503 ERAD. GO:0006487 is absent from CANX GOA (confirmed). Conclude: OVER-REACHES — projecting GO:0006487 to a lectin chaperone is a category error from a mixed "N-glycosylation system" container node; do NOT add.
Evidence alignment: PN node carries no reference titles; review is heavily evidenced (PMID:22314232 palmitoyl-translocon, PMID:8136357 cloning/Ca2+, PMID:35948544/Reactome MHC-I, many IDA ER-localization). No citation conflict, but no shared evidence supports the N-glycosylation-process claim.
Verdict: OVER-REACHES — projected GO:0006487 mis-assigns an enzymatic process to a lectin chaperone; reject for CANX (true function already captured). Recommended edits: [MAP] do not propagate GO:0006487 to CANX; re-map the "Lectin chaperone" type node to a binding/chaperone term (e.g. GO:0030246 carbohydrate binding / GO:0036503 ERAD pathway).

Full Consistency Review

UniProt: P27824 · batch: proteostasis-batch-2026-06-06 · review status: COMPLETE (exhaustive; ~90 annotations reviewed, notes present)
PN placement: ER proteostasis|Glycoproteostasis|N-glycosylation system|Lectin chaperone ; PN-node mapping: type (Lectin chaperone)→no_mapping; group (N-glycosylation system)→GO:0006487 protein N-linked glycosylation (mapped/ok_for_propagation); class/branch→no_mapping.
Consistency: Internally consistent on biology — review, notes, and PN all describe calnexin as the membrane-bound lectin chaperone of the CNX/CRT cycle binding monoglucosylated N-glycans. BUT the PROJECTED GO term is inconsistent with calnexin's molecular role (see below).
PN story / NEW pressure: GO:0006487 is VERIFIED real but its definition is "a process in which a carbohydrate unit is ADDED to a protein via the N4 atom of asparagine" — i.e. the catalytic glycan-transfer step (OST machinery). Calnexin RECOGNIZES/BINDS the already-installed glycan; it does not perform N-glycosylation. The review correctly captures the true function as GO:0030246 carbohydrate binding, GO:0044183 protein folding chaperone, GO:0034975 protein folding in ER, GO:0036503 ERAD. GO:0006487 is absent from CANX GOA (confirmed). Conclude: OVER-REACHES — projecting GO:0006487 to a lectin chaperone is a category error from a mixed "N-glycosylation system" container node; do NOT add.
Mapping strategy: The group node "N-glycosylation system" lumps the OST/glycan-installing/processing enzymes with the lectin chaperones that read the glycan; a single GO:0006487 mapping over-annotates the lectin-chaperone members (CANX, CALR). Recommend the lectin-chaperone TYPE node carry a binding/chaperone mapping (e.g. GO:0030246 carbohydrate binding or GO:0006457/GO:0036503) rather than inheriting the enzymatic process term.
Evidence alignment: PN node carries no reference titles; review is heavily evidenced (PMID:22314232 palmitoyl-translocon, PMID:8136357 cloning/Ca2+, PMID:35948544/Reactome MHC-I, many IDA ER-localization). No citation conflict, but no shared evidence supports the N-glycosylation-process claim.
Verdict: OVER-REACHES — projected GO:0006487 mis-assigns an enzymatic process to a lectin chaperone; reject for CANX (true function already captured). Recommended edits: [MAP] do not propagate GO:0006487 to CANX; re-map the "Lectin chaperone" type node to a binding/chaperone term (e.g. GO:0030246 carbohydrate binding / GO:0036503 ERAD pathway).

PN Dossier Context

review_batch: proteostasis-batch-2026-06-06
review_yaml: genes/human/CANX/CANX-ai-review.yaml
PN workbook rows: 1

PN row 1: ER proteostasis | Glycoproteostasis | N-glycosylation system | Lectin chaperone

UniProt: P27824
In branches: ER
PN-node mapping records (path + ancestors):
- [type] ER proteostasis|Glycoproteostasis|N-glycosylation system|Lectin chaperone
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
- [group] ER proteostasis|Glycoproteostasis|N-glycosylation system
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0006487 protein N-linked glycosylation]
  rationale: This PN group captures the ER N-glycosylation machinery that installs and processes N-linked glycans during proteostasis. GO protein N-linked glycosylation is the best current propagation target in the local cache.
- [class] ER proteostasis|Glycoproteostasis
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
- [branch] ER proteostasis
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

Projected GO annotations (1)

GO:0006487 protein N-linked glycosylation | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=ER proteostasis|Glycoproteostasis|N-glycosylation system

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: P27824
gene_symbol: CANX
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: '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).'
alternative_products:
- name: '1'
  id: P27824-1
- name: '2'
  id: P27824-2
  sequence_note: VSP_055516
- name: '3'
  id: P27824-3
  sequence_note: VSP_055515
existing_annotations:
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Protein folding is a core biological process for calnexin in the calnexin/calreticulin
      cycle.
    action: ACCEPT
    reason: Phylogenetic transfer agrees with extensive experimental evidence that
      calnexin assists folding of nascent glycoproteins in the ER.
    supported_by:
    - reference_id: file:human/CANX/CANX-uniprot.txt
      supporting_text: in assisting protein assembly
    - reference_id: PMID:22314232
      supporting_text: calnexin, a major ER chaperone involved in glycoprotein folding
- term:
    id: GO:0036503
    label: ERAD pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: The calnexin/calreticulin cycle triages terminally misfolded glycoproteins
      toward ER-associated degradation, so participation in the ERAD pathway is well
      supported.
    action: ACCEPT
    reason: Calnexin retains incorrectly folded proteins and the cycle delivers persistent
      non-native clients to ERAD; this is an established core role.
    supported_by:
    - reference_id: file:human/CANX/CANX-uniprot.txt
      supporting_text: quality control apparatus of the ER
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Calcium ion binding is a core, conserved molecular function of calnexin.
    action: ACCEPT
    reason: Calnexin binds Ca2+ via conserved high-capacity motifs and contributes
      to ER calcium handling.
    supported_by:
    - reference_id: PMID:8136357
      supporting_text: Calnexin binds Ca2+ and may function as a chaperone in the
        transition of proteins from the ER to the outer cellular membrane.
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Electronic InterPro-based calcium ion binding annotation is consistent
      with the conserved calreticulin-family Ca2+-binding motifs.
    action: ACCEPT
    reason: Same well-supported core molecular function as the IBA/TAS calcium annotations.
    supported_by:
    - reference_id: PMID:8136357
      supporting_text: A subdomain containing four internal repeats binds Ca2+ with
        the highest affinity.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: ER localization is the core compartment for calnexin.
    action: ACCEPT
    reason: Calnexin is a resident ER membrane protein; ER localization is supported
      by abundant experimental data.
    supported_by:
    - reference_id: PMID:8136357
      supporting_text: Calnexin is a 90-kDa integral membrane protein of the endoplasmic
        reticulum
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: ER membrane is the precise core localization of this single-pass type
      I membrane chaperone.
    action: ACCEPT
    reason: Topology (luminal lectin domain, single TM, cytoplasmic tail) and direct
      experimental localization place calnexin in the ER membrane.
    supported_by:
    - reference_id: file:human/CANX/CANX-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Electronic protein folding annotation duplicates the well-supported core
      folding role.
    action: ACCEPT
    reason: Consistent with experimental and phylogenetic evidence for chaperone-assisted
      glycoprotein folding.
    supported_by:
    - reference_id: PMID:22314232
      supporting_text: calnexin, a major ER chaperone involved in glycoprotein folding
- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: The supportable localization is the ER-mitochondria contact site (MAM);
      a generic mitochondrial membrane assignment for an ER chaperone is an over-call.
- term:
    id: GO:0033162
    label: melanosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Melanosome membrane localization derives from proteomic detection in
      melanosome fractions and is a secondary localization of an ER protein.
    action: KEEP_AS_NON_CORE
    reason: Detected by mass spectrometry in melanosomes but not part of the core
      ER chaperone function.
    supported_by:
    - reference_id: file:human/CANX/CANX-uniprot.txt
      supporting_text: spectrometry in melanosome fractions from stage I to stage IV
- term:
    id: GO:0098793
    label: presynapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: located_in
  review:
    summary: Presynapse localization is an inter-ontology inference tied to a speculative
      synaptic endocytosis role; not a core compartment for human calnexin.
    action: MARK_AS_OVER_ANNOTATED
    reason: Based on logical inference rather than direct evidence; the conserved function
      of calnexin is ER glycoprotein quality control.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16546175
  qualifier: enables
  review:
    summary: Bare protein binding is uninformative; this CFTR-rescue study reflects
      the chaperone-client relationship already captured by folding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Per curation guidelines, generic protein binding does not convey calnexin's
      molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17110338
  qualifier: enables
  review:
    summary: Generic protein binding from a CFTR/Aha1 study; uninformative for calnexin
      function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding should not be treated as a meaningful molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17220478
  qualifier: enables
  review:
    summary: Generic protein binding from an NDRG1 interactome study; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is not an informative molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17380188
  qualifier: enables
  review:
    summary: Generic protein binding from a TRAP-complex ER-stress study; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding does not capture a specific calnexin function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20528919
  qualifier: enables
  review:
    summary: This reflects calnexin chaperoning the delta opioid receptor (a glycoprotein
      client), but the bare protein binding term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: The underlying biology is client chaperoning, already represented by ER
      protein-folding terms; generic protein binding adds nothing.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22190034
  qualifier: enables
  review:
    summary: Generic protein binding from an HIV-host complex screen; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput host-virus interaction; bare protein binding is not informative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22314232
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding obscures the specific translocon-coupling biology
      reported here; the functional content is the folding/translocon role.
    supported_by:
    - reference_id: PMID:22314232
      supporting_text: palmitoylation mediates the association of calnexin with the
        ribosome-translocon complex (RTC)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22872700
  qualifier: enables
  review:
    summary: Generic protein binding from a CNTNAP2 trafficking/ATF6 study; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding does not convey a specific calnexin function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25170080
  qualifier: enables
  review:
    summary: Generic protein binding from an HIV-1 Nef/ABCA1/calnexin study; uninformative
      as a function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is not an informative molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  qualifier: enables
  review:
    summary: Generic protein binding from a quantitative interactome map; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput interactome hit; bare protein binding does not convey function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26618866
  qualifier: enables
  review:
    summary: Generic protein binding from a CFTR-interactome study; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is not informative for curation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Generic protein binding from a proteome-scale interactome; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput interaction; bare protein binding adds no functional information.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29568061
  qualifier: enables
  review:
    summary: Generic protein binding from a MAC-tag interaction/localization map; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is not an informative molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29924966
  qualifier: enables
  review:
    summary: Generic protein binding from a proteomic-variant study; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding does not convey a specific function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30021884
  qualifier: enables
  review:
    summary: Generic protein binding from a histone crosslinking-MS study; uninformative
      and likely incidental.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is not informative; an ER chaperone-histone crosslink
      is not a meaningful function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31324722
  qualifier: enables
  review:
    summary: Generic protein binding from a CFTR/calpain rescue study; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is not an informative molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Generic protein binding from a dual proteome-scale network; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput interactome hit; bare protein binding adds no function information.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Generic protein binding from OpenCell endogenous tagging; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is not informative for curation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36012204
  qualifier: enables
  review:
    summary: Generic protein binding from CFTR proximity-labeling; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding does not convey a specific function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Generic protein binding from a multimodal cell-map study; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is not an informative molecular function.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Generic membrane is correct but uninformatively broad; the specific compartment
      is the ER membrane.
    action: MARK_AS_OVER_ANNOTATED
    reason: A bare membrane term is subsumed by the more precise ER membrane annotation.
- term:
    id: GO:0031965
    label: nuclear membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Nuclear membrane localization most likely reflects continuity of the
      ER membrane with the nuclear envelope rather than a distinct functional pool.
    action: MARK_AS_OVER_ANNOTATED
    reason: Likely a contiguity artifact; the functional compartment is the ER membrane.
- term:
    id: GO:0044322
    label: endoplasmic reticulum quality control compartment
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Localization to the ER quality control compartment is consistent with
      calnexin's role in retaining and triaging misfolded glycoproteins.
    action: ACCEPT
    reason: Directly aligned with calnexin's core ER quality-control function.
    supported_by:
    - reference_id: file:human/CANX/CANX-uniprot.txt
      supporting_text: quality control apparatus of the ER
- term:
    id: GO:0048488
    label: synaptic vesicle endocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: A synaptic vesicle endocytosis role is a speculative, ortholog-derived
      inference (via SGIP1) noted as possible in UniProt, not an established human
      function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Only suggested ("may play a role") and not supported by direct human evidence;
      not the core ER function.
- term:
    id: GO:0072583
    label: clathrin-dependent endocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Clathrin-dependent endocytosis is the same speculative synaptic/endocytic
      inference and is not a core calnexin function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Ortholog-derived and speculative; not supported by direct evidence for
      human calnexin.
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9683772
  qualifier: enables
  review:
    summary: Protein folding chaperone is an accurate core molecular function for calnexin.
    action: ACCEPT
    reason: Calnexin is a bona fide molecular chaperone for nascent glycoproteins.
    supported_by:
    - reference_id: PMID:22314232
      supporting_text: calnexin, a major ER chaperone involved in glycoprotein folding
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Immunofluorescence-based ER localization is consistent with the established
      core compartment.
    action: ACCEPT
    reason: ER residence is a core property of calnexin.
    supported_by:
    - reference_id: PMID:8136357
      supporting_text: Calnexin is a 90-kDa integral membrane protein of the endoplasmic
        reticulum
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: EXP
  original_reference_id: PMID:22314232
  qualifier: located_in
  review:
    summary: Experimental evidence places calnexin in the ER membrane, with palmitoylation
      directing it to the perinuclear rough ER and the translocon.
    action: ACCEPT
    reason: Direct experimental support for the core ER membrane localization.
    supported_by:
    - reference_id: PMID:22314232
      supporting_text: This modification leads to the preferential localization of
        calnexin to the perinuclear rough ER, at the expense of ER tubules.
- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence/orthology transfer of mitochondrial membrane localization overstates
      a MAM (ER-mitochondria contact) association.
    action: MARK_AS_OVER_ANNOTATED
    reason: Calnexin localizes to the ER side of MAM contact sites; the generic mitochondrial
      membrane term is an over-call.
- term:
    id: GO:0033162
    label: melanosome membrane
  evidence_type: EXP
  original_reference_id: PMID:12643545
  qualifier: located_in
  review:
    summary: Melanosome proteomics detected calnexin; a secondary localization of
      an ER protein.
    action: KEEP_AS_NON_CORE
    reason: Real proteomic detection in melanosomes but not part of the core ER chaperone
      function.
    supported_by:
    - reference_id: file:human/CANX/CANX-uniprot.txt
      supporting_text: spectrometry in melanosome fractions from stage I to stage IV
- term:
    id: GO:0033162
    label: melanosome membrane
  evidence_type: EXP
  original_reference_id: PMID:17081065
  qualifier: located_in
  review:
    summary: Independent melanosome proteomics again detected calnexin; secondary
      localization.
    action: KEEP_AS_NON_CORE
    reason: Consistent secondary melanosomal detection; non-core relative to ER function.
    supported_by:
    - reference_id: file:human/CANX/CANX-uniprot.txt
      supporting_text: spectrometry in melanosome fractions from stage I to stage IV
- term:
    id: GO:0019082
    label: viral protein processing
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9683686
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Calnexin folds viral glycoproteins as it folds other clients; retain as
      a context-specific application rather than core function.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9932913
  qualifier: located_in
  review:
    summary: Reactome ER membrane localization is consistent with the core compartment.
    action: ACCEPT
    reason: Matches the well-supported ER membrane localization.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9932988
  qualifier: located_in
  review:
    summary: Reactome ER membrane localization (CDH1 processing pathway) is consistent
      with the core compartment.
    action: ACCEPT
    reason: Matches the well-supported ER membrane localization.
- term:
    id: GO:0098553
    label: lumenal side of endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-983145
  qualifier: located_in
  review:
    summary: The lectin/chaperone domain of calnexin faces the ER lumen, so luminal-side
      ER membrane localization is accurate.
    action: ACCEPT
    reason: Topology places the functional globular and P domains on the luminal side
      of the ER membrane.
    supported_by:
    - reference_id: file:human/CANX/CANX-uniprot.txt
      supporting_text: TOPO_DOM        21..481
- term:
    id: GO:0098553
    label: lumenal side of endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-983146
  qualifier: located_in
  review:
    summary: Luminal-side ER membrane localization (MHC I assembly pathway) matches
      calnexin topology.
    action: ACCEPT
    reason: The functional luminal lectin domain is on the luminal side of the ER
      membrane.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32783947
  qualifier: enables
  review:
    summary: This reflects calnexin's role in NACHO-dependent α7 nicotinic receptor
      assembly (a glycoprotein client), but bare protein binding is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: The functional content is client chaperoning that requires calnexin chaperone
      activity; generic protein binding does not capture it.
    supported_by:
    - reference_id: PMID:32783947
      supporting_text: NACHO-mediated effects on α7 assembly and channel function require
        N-glycosylation and calnexin chaperone activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31735293
  qualifier: enables
  review:
    summary: Generic protein binding from a TMX2 redox study; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding does not convey a specific calnexin function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30188326
  qualifier: enables
  review:
    summary: Generic protein binding from a TMTC4/UPR study; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is not an informative molecular function.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:30188326
  qualifier: located_in
  review:
    summary: Direct ER localization consistent with the core compartment.
    action: ACCEPT
    reason: Reinforces the established ER localization of calnexin.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29765154
  qualifier: enables
  review:
    summary: Generic protein binding from a CASIMO1/squalene epoxidase study; uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding does not convey a specific function.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:24454821
  qualifier: located_in
  review:
    summary: Direct ER localization consistent with the core compartment.
    action: ACCEPT
    reason: Reinforces the established ER localization.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21205830
  qualifier: enables
  review:
    summary: This reflects the ZNRF4-calnexin interaction regulating calnexin stability,
      but bare protein binding is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: The biology is regulation of calnexin stability/ubiquitination by ZNRF4;
      generic protein binding does not capture it.
    supported_by:
    - reference_id: PMID:21205830
      supporting_text: Nixin/ZNRF4 as a regulator of calnexin stability and ER homeostasis
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:23814182
  qualifier: located_in
  review:
    summary: Direct ER membrane localization consistent with the core compartment.
    action: ACCEPT
    reason: Matches the established ER membrane localization.
- term:
    id: GO:0034975
    label: protein folding in endoplasmic reticulum
  evidence_type: TAS
  original_reference_id: PMID:22013210
  qualifier: involved_in
  review:
    summary: Protein folding in the ER is the precise core biological process for
      calnexin.
    action: ACCEPT
    reason: This is the most accurate BP term for calnexin's chaperone activity in
      the ER.
    supported_by:
    - reference_id: PMID:22314232
      supporting_text: calnexin, a major ER chaperone involved in glycoprotein folding
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:20531390
  qualifier: located_in
  review:
    summary: Direct ER membrane localization consistent with the core compartment.
    action: ACCEPT
    reason: Matches the established ER membrane localization.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:22572157
  qualifier: located_in
  review:
    summary: Direct ER localization consistent with the core compartment.
    action: ACCEPT
    reason: Reinforces the established ER localization.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24764305
  qualifier: enables
  review:
    summary: Generic protein binding from a TMTC1/TMTC2 calcium-homeostasis study;
      uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is not an informative molecular function.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    summary: High-throughput exosome proteomics detected calnexin; an incidental/non-core
      localization for an ER membrane protein.
    action: MARK_AS_OVER_ANNOTATED
    reason: Calnexin is commonly used as a negative (non-exosomal) marker; HDA exosome
      detection is likely contamination and not a genuine functional location.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: IDA
  original_reference_id: PMID:21235781
  qualifier: located_in
  negated: true
  review:
    summary: This NOT annotation states calnexin is absent from these exosomes, consistent
      with its use as a non-exosomal ER marker.
    action: ACCEPT
    reason: The negation is biologically appropriate; calnexin is an ER-resident protein
      typically excluded from exosomes.
- term:
    id: GO:0044233
    label: mitochondria-associated endoplasmic reticulum membrane contact site
  evidence_type: IDA
  original_reference_id: PMID:23455425
  qualifier: located_in
  review:
    summary: Calnexin localizes to MAM contact sites, the accurate description of
      its ER-mitochondria association.
    action: KEEP_AS_NON_CORE
    reason: A real but specialized localization; the MAM pool is distinct from the
      bulk ER chaperone activity and is non-core.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: Generic membrane from an NK-cell membrane proteome; uninformatively broad.
    action: MARK_AS_OVER_ANNOTATED
    reason: Subsumed by the precise ER membrane localization.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:24263861
  qualifier: located_in
  review:
    summary: Direct ER localization consistent with the core compartment.
    action: ACCEPT
    reason: Reinforces the established ER localization.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:18458083
  qualifier: located_in
  review:
    summary: Direct ER localization consistent with the core compartment.
    action: ACCEPT
    reason: Reinforces the established ER localization.
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    summary: RNA binding is from global mRNA-interactome capture; calnexin is not
      a bona fide functional RNA-binding protein.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput RNA-interactome capture; not a credible molecular function
      for an ER lectin chaperone.
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22681889
  qualifier: enables
  review:
    summary: RNA binding from a second mRNA-interactome capture dataset; same caveat.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput capture artifact; not a genuine calnexin function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23826168
  qualifier: enables
  review:
    summary: This reflects calnexin chaperoning SERPINA1/SERPINA2 variants, but bare
      protein binding is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: The functional content is serpin client chaperoning, captured by folding
      terms; generic protein binding adds nothing.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:23826168
  qualifier: located_in
  review:
    summary: Direct ER localization consistent with the core compartment.
    action: ACCEPT
    reason: Reinforces the established ER localization.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2130478
  qualifier: located_in
  review:
    summary: The functional lectin/chaperone domains of calnexin reside in the ER
      lumen.
    action: ACCEPT
    reason: Consistent with calnexin topology (large luminal domain).
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2213241
  qualifier: located_in
  review:
    summary: ER lumen localization of the functional domain; accurate.
    action: ACCEPT
    reason: Consistent with calnexin topology.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-535717
  qualifier: located_in
  review:
    summary: ER lumen localization for the chaperone-client binding step; accurate.
    action: ACCEPT
    reason: Consistent with calnexin topology and function.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-548890
  qualifier: located_in
  review:
    summary: ER lumen localization for the glucosidase II/release step; accurate.
    action: ACCEPT
    reason: Consistent with calnexin topology and the CNX/CRT cycle.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950342
  qualifier: located_in
  review:
    summary: ER lumen localization (EBI3/IL27 assembly pathway); accurate.
    action: ACCEPT
    reason: Consistent with calnexin topology.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950362
  qualifier: located_in
  review:
    summary: ER lumen localization (EBI3/IL12A assembly pathway); accurate.
    action: ACCEPT
    reason: Consistent with calnexin topology.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950387
  qualifier: located_in
  review:
    summary: ER lumen localization (CANX binds EBI3); accurate.
    action: ACCEPT
    reason: Consistent with calnexin topology.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950398
  qualifier: located_in
  review:
    summary: ER lumen localization (CANX dissociates from IL27:EBI3); accurate.
    action: ACCEPT
    reason: Consistent with calnexin topology.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950740
  qualifier: located_in
  review:
    summary: ER lumen localization (CANX dissociates from IL12A:EBI3); accurate.
    action: ACCEPT
    reason: Consistent with calnexin topology.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8951500
  qualifier: located_in
  review:
    summary: ER lumen localization (dissociation from nonameric complex); accurate.
    action: ACCEPT
    reason: Consistent with calnexin topology.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-901047
  qualifier: located_in
  review:
    summary: ER lumen localization for ERp57 binding; accurate and functionally central
      (P domain recruits ERp57).
    action: ACCEPT
    reason: Consistent with calnexin topology and its ERp57-recruiting role.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9683772
  qualifier: located_in
  review:
    summary: ER lumen localization (trimmed spike binds calnexin); accurate.
    action: ACCEPT
    reason: Consistent with calnexin topology.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:21190736
  qualifier: located_in
  review:
    summary: Direct ER localization consistent with the core compartment.
    action: ACCEPT
    reason: Reinforces the established ER localization.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16361248
  qualifier: enables
  review:
    summary: This reflects calnexin chaperoning the hERG/KCNH2 channel (a glycoprotein
      client), but bare protein binding is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: The functional content is client chaperoning, captured by folding terms;
      generic protein binding adds nothing.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:19723497
  qualifier: located_in
  review:
    summary: Direct ER membrane localization consistent with the core compartment.
    action: ACCEPT
    reason: Matches the established ER membrane localization.
- term:
    id: GO:0048488
    label: synaptic vesicle endocytosis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence/orthology-transferred synaptic vesicle endocytosis role is speculative
      for human calnexin.
    action: MARK_AS_OVER_ANNOTATED
    reason: Based on ortholog inference only; not the conserved core ER function.
- term:
    id: GO:0072583
    label: clathrin-dependent endocytosis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence/orthology-transferred clathrin-dependent endocytosis role is
      speculative for human calnexin.
    action: MARK_AS_OVER_ANNOTATED
    reason: Ortholog inference only; not supported by direct human evidence.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:14966132
  qualifier: located_in
  review:
    summary: Direct ER localization consistent with the core compartment.
    action: ACCEPT
    reason: Reinforces the established ER localization.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: NAS
  original_reference_id: PMID:8136357
  qualifier: located_in
  review:
    summary: ER localization asserted in the original cloning paper; consistent with
      the core compartment.
    action: ACCEPT
    reason: Matches the established ER localization.
    supported_by:
    - reference_id: PMID:8136357
      supporting_text: Calnexin is a 90-kDa integral membrane protein of the endoplasmic
        reticulum
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: TAS
  original_reference_id: PMID:8136357
  qualifier: enables
  review:
    summary: Calcium ion binding established biochemically in the cloning paper; core
      molecular function.
    action: ACCEPT
    reason: Direct biochemical demonstration of Ca2+ binding by conserved calnexin
      motifs.
    supported_by:
    - reference_id: PMID:8136357
      supporting_text: A subdomain containing four internal repeats binds Ca2+ with
        the highest affinity.
- term:
    id: GO:0009306
    label: protein secretion
  evidence_type: TAS
  original_reference_id: PMID:8055875
  qualifier: involved_in
  review:
    summary: Protein secretion is a broad downstream consequence of chaperone-assisted
      folding; the precise function is ER glycoprotein folding/quality control.
    action: MARK_AS_OVER_ANNOTATED
    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.
core_functions:
- description: Lectin that specifically recognizes and binds the monoglucosylated
    (Glc1Man9GlcNAc2) N-glycan on nascent glycoproteins in the ER - the glycan-dependent
    substrate-recognition step that initiates and sustains client engagement in the
    calnexin/calreticulin cycle.
  molecular_function:
    id: GO:0030246
    label: carbohydrate binding
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/CANX/CANX-uniprot.txt
    supporting_text: monoglucosylated glycoproteins in the endoplasmic reticulum
    reference_section_type: DATABASE_ENTRY
- description: Lectin chaperone that binds monoglucosylated N-glycans on nascent glycoproteins
    in the ER and, with ERp57 and PPIB recruited via its P domain, assists their folding
    and assembly as part of the calnexin/calreticulin cycle.
  molecular_function:
    id: GO:0044183
    label: protein folding chaperone
  directly_involved_in:
  - id: GO:0034975
    label: protein folding in endoplasmic reticulum
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  - id: GO:0098553
    label: lumenal side of endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/CANX/CANX-uniprot.txt
    supporting_text: Calcium-binding protein that interacts with newly synthesized
  - reference_id: PMID:22314232
    supporting_text: calnexin, a major ER chaperone involved in glycoprotein folding
- description: Quality-control retention factor that holds incompletely or incorrectly
    folded glycoproteins in the ER and triages terminally misfolded clients toward
    ER-associated degradation.
  molecular_function:
    id: GO:0051082
    label: unfolded protein binding
  directly_involved_in:
  - id: GO:0036503
    label: ERAD pathway
  locations:
  - id: GO:0044322
    label: endoplasmic reticulum quality control compartment
  supported_by:
  - reference_id: file:human/CANX/CANX-uniprot.txt
    supporting_text: quality control apparatus of the ER
- description: Calcium-binding ER protein contributing to ER calcium handling via conserved
    high-capacity Ca2+-binding repeats.
  molecular_function:
    id: GO:0005509
    label: calcium ion binding
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: PMID:8136357
    supporting_text: A subdomain containing four internal repeats binds Ca2+ with
      the highest affinity.
proposed_new_terms: []
suggested_questions:
- question: 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?
  experts:
  - van der Goot FG
  - Lakkaraju AK
suggested_experiments:
- hypothesis: Calnexin's palmitoylation-dependent translocon association is required
    for efficient co-translational capture and folding of a defined set of glycoprotein
    clients.
  description: 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.
  experiment_type: cell-based mutant rescue with pulse-chase folding assay
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology
    links
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:12643545
  title: 'Proteomic analysis of early melanosomes: identification of novel melanosomal
    proteins.'
  findings: []
- id: PMID:14966132
  title: A predominant role of acyl-CoA:monoacylglycerol acyltransferase-2 in dietary
    fat absorption implicated by tissue distribution, subcellular localization, and
    up-regulation by high fat diet.
  findings: []
- id: PMID:16361248
  title: Mechanisms of pharmacological rescue of trafficking-defective hERG mutant
    channels in human long QT syndrome.
  findings: []
- id: PMID:16546175
  title: Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial
    cells by the alpha-glucosidase inhibitor miglustat.
  findings: []
- id: PMID:17081065
  title: Proteomic and bioinformatic characterization of the biogenesis and function
    of melanosomes.
  findings: []
- id: PMID:17110338
  title: Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic
    fibrosis.
  findings: []
- id: PMID:17220478
  title: Proteomics analysis of the interactome of N-myc downstream regulated gene
    1 and its interactions with the androgen response program in prostate cancer cells.
  findings: []
- id: PMID:17380188
  title: Simultaneous induction of the four subunits of the TRAP complex by ER stress
    accelerates ER degradation.
  findings: []
- id: PMID:18458083
  title: Molecular identification of a novel mammalian brain isoform of acyl-CoA:lysophospholipid
    acyltransferase with prominent ethanolamine lysophospholipid acylating activity,
    LPEAT2.
  findings: []
- id: PMID:19723497
  title: Nogo-B receptor stabilizes Niemann-Pick type C2 protein and regulates intracellular
    cholesterol trafficking.
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:20528919
  title: Human delta opioid receptor biogenesis is regulated via interactions with
    SERCA2b and calnexin.
  findings: []
- id: PMID:20531390
  title: Suppression of the novel ER protein Maxer by mutant ataxin-1 in Bergman glia
    contributes to non-cell-autonomous toxicity.
  findings: []
- id: PMID:21190736
  title: The non-conventional MHC class I MR1 molecule controls infection by Klebsiella
    pneumoniae in mice.
  findings: []
- id: PMID:21205830
  title: A systematic search for endoplasmic reticulum (ER) membrane-associated RING
    finger proteins identifies Nixin/ZNRF4 as a regulator of calnexin stability and
    ER homeostasis.
  findings: []
- id: PMID:21235781
  title: 'Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages.'
  findings: []
- id: PMID:22013210
  title: 'The unfolded protein response: integrating stress signals through the stress
    sensor IRE1α.'
  findings: []
- id: PMID:22190034
  title: Global landscape of HIV-human protein complexes.
  findings: []
- id: PMID:22314232
  title: Palmitoylated calnexin is a key component of the ribosome-translocon complex.
  findings:
  - statement: Calnexin is a major ER glycoprotein-folding chaperone whose palmitoylation
      by DHHC6 couples it to the ribosome-translocon complex for co-translational
      client capture.
    supporting_text: calnexin, a major ER chaperone involved in glycoprotein folding
    reference_section_type: ABSTRACT
- id: PMID:22314232
  title: Palmitoylated calnexin is a key component of the ribosome-translocon complex.
  findings: []
- id: PMID:22572157
  title: Sensitive detection of idiotypic platelet-reactive alloantibodies by an electrical
    protein chip.
  findings: []
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
- id: PMID:22681889
  title: The mRNA-bound proteome and its global occupancy profile on protein-coding
    transcripts.
  findings: []
- id: PMID:22872700
  title: Inherited genetic variants in autism-related CNTNAP2 show perturbed trafficking
    and ATF6 activation.
  findings: []
- id: PMID:23455425
  title: Autophagosomes form at ER-mitochondria contact sites.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
    secretions in urine.
  findings: []
- id: PMID:23814182
  title: Tracking a refined eIF4E-binding motif reveals Angel1 as a new partner of
    eIF4E.
  findings: []
- id: PMID:23826168
  title: SERPINA2 is a novel gene with a divergent function from SERPINA1.
  findings: []
- id: PMID:24263861
  title: HCV NS3 protease enhances liver fibrosis via binding to and activating TGF-β
    type I receptor.
  findings: []
- id: PMID:24454821
  title: Transmembrane and coiled-coil domain family 1 is a novel protein of the endoplasmic
    reticulum.
  findings: []
- id: PMID:24764305
  title: TMTC1 and TMTC2 are novel endoplasmic reticulum tetratricopeptide repeat-containing
    adapter proteins involved in calcium homeostasis.
  findings: []
- id: PMID:25170080
  title: HIV-1 protein Nef inhibits activity of ATP-binding cassette transporter A1
    by targeting endoplasmic reticulum chaperone calnexin.
  findings: []
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by stoichiometries
    and abundances.
  findings: []
- id: PMID:26618866
  title: ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
- id: PMID:29568061
  title: An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein
    interactions and subcellular localizations.
  findings: []
- id: PMID:29765154
  title: The cancer-associated microprotein CASIMO1 controls cell proliferation and
    interacts with squalene epoxidase modulating lipid droplet formation.
  findings: []
- id: PMID:29924966
  title: A Proteomic Variant Approach (ProVarA) for Personalized Medicine of Inherited
    and Somatic Disease.
  findings: []
- id: PMID:30021884
  title: Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry
    in Intact Cell Nuclei.
  findings: []
- id: PMID:30188326
  title: Deletion of Tmtc4 activates the unfolded protein response and causes postnatal
    hearing loss.
  findings: []
- id: PMID:31324722
  title: Inhibition of calpain 1 restores plasma membrane stability to pharmacologically
    rescued Phe508del-CFTR variant.
  findings: []
- id: PMID:31735293
  title: TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction
    Causes Severe Brain Developmental Abnormalities.
  findings: []
- id: PMID:32783947
  title: NACHO Engages N-Glycosylation ER Chaperone Pathways for α7 Nicotinic Receptor
    Assembly.
  findings:
  - statement: NACHO-mediated alpha7 nicotinic receptor assembly requires N-glycosylation
      and calnexin chaperone activity.
    supporting_text: NACHO-mediated effects on α7 assembly and channel function require
      N-glycosylation and calnexin chaperone activity.
    reference_section_type: ABSTRACT
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:36012204
  title: Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment
    in Multiple SLC Transporters.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:8055875
  title: 'The molecular chaperones HSP28, GRP78, endoplasmin, and calnexin exhibit
    strikingly different levels in quiescent keratinocytes as compared to their proliferating
    normal and transformed counterparts: cDNA cloning and expression of calnexin.'
  findings: []
- id: PMID:8136357
  title: 'Human, mouse, and rat calnexin cDNA cloning: identification of potential
    calcium binding motifs and gene localization to human chromosome 5.'
  findings:
  - statement: Calnexin is a 90-kDa integral ER membrane protein that binds Ca2+ via
      a conserved high-affinity repeat motif.
    supporting_text: A subdomain containing four internal repeats binds Ca2+ with
      the highest affinity.
    reference_section_type: ABSTRACT
- id: Reactome:R-HSA-2130478
  title: Interaction of invariant chain trimer and MHC II alpha beta dimer
  findings: []
- id: Reactome:R-HSA-2213241
  title: Formation of nonameric complex
  findings: []
- id: Reactome:R-HSA-535717
  title: Binding of calnexin/calreticulin to the unfolded protein
  findings: []
- id: Reactome:R-HSA-548890
  title: Removal of the third glucose by glucosidase II and release from the chaperone
  findings: []
- id: Reactome:R-HSA-8950342
  title: EBI3:CANX binds IL27
  findings: []
- id: Reactome:R-HSA-8950362
  title: EBI3:CANX binds IL12A
  findings: []
- id: Reactome:R-HSA-8950387
  title: CANX binds EBI3
  findings: []
- id: Reactome:R-HSA-8950398
  title: CANX dissociates from IL27:EBI3
  findings: []
- id: Reactome:R-HSA-8950740
  title: CANX dissociates from IL12A:EBI3
  findings: []
- id: Reactome:R-HSA-8951500
  title: Dissociation of CANX from nonameric complex
  findings: []
- id: Reactome:R-HSA-901047
  title: Binding of ERp57
  findings: []
- id: Reactome:R-HSA-9683686
  title: Maturation of spike protein
  findings: []
- id: Reactome:R-HSA-9683772
  title: Trimmed spike protein binds to calnexin
  findings: []
- id: Reactome:R-HSA-983145
  title: Binding of newly synthesized MHC class I heavy chain (HC) with calnexin
  findings: []
- id: Reactome:R-HSA-983146
  title: Interaction of beta-2-microglobulin (B2M) chain with  class I HC
  findings: []
- id: Reactome:R-HSA-9932913
  title: Glucosidase II removes glucose residue from Glu1Man9GlucNAc2-CDH1
  findings: []
- id: Reactome:R-HSA-9932988
  title: CANX binds Glu1Man9GlcNAc2-CDH1
  findings: []
- id: file:human/CANX/CANX-uniprot.txt
  title: CANX UniProtKB record (P27824)
  findings: []
- id: file:human/CANX/CANX-notes.md
  title: Manual CANX curation notes
  findings: []

CANX

Gene Description

Existing Annotations Review

Core Functions

Lectin that specifically recognizes and binds the monoglucosylated (Glc1Man9GlcNAc2) N-glycan on nascent glycoproteins in the ER - the glycan-dependent substrate-recognition step that initiates and sustains client engagement in the calnexin/calreticulin cycle.

Lectin chaperone that binds monoglucosylated N-glycans on nascent glycoproteins in the ER and, with ERp57 and PPIB recruited via its P domain, assists their folding and assembly as part of the calnexin/calreticulin cycle.

Quality-control retention factor that holds incompletely or incorrectly folded glycoproteins in the ER and triages terminally misfolded clients toward ER-associated degradation.

Calcium-binding ER protein contributing to ER calcium handling via conserved high-capacity Ca2+-binding repeats.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

CANX (Calnexin, P27824) curation notes

Overview

Core function evidence

Localization

Over-annotations / uninformative

Calcium

Summary of core functions

Pn Notes

CANX PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: ER proteostasis | Glycoproteostasis | N-glycosylation system | Lectin chaperone

Projected GO annotations (1)

Note

📄 View Raw YAML