MBL2 encodes mannose-binding lectin (MBL; also mannan-binding lectin/protein, MBP-C, collectin-1), a secreted, liver-derived serum collectin of the innate immune system. It is a C-type lectin built from a structural subunit that combines an N-terminal cysteine-rich region, a collagen-like Gly-X-Y domain (with hydroxyproline modifications), an alpha-helical coiled-coil neck that drives trimerization, and a C-terminal C-type carbohydrate-recognition domain (CRD). Three subunits assemble into a homotrimer, and several homotrimers further oligomerize into higher-order bouquet-like structures. Through the CRD it binds, in a calcium-dependent manner, terminal mannose, N-acetylglucosamine and fucose residues arranged in the repetitive geometric patterns characteristic of microbial (bacterial, fungal, viral, protozoan) surfaces, while largely sparing the differently arranged sugars of host glycoproteins. MBL therefore acts as a soluble pattern-recognition molecule; upon binding a microbial surface it triggers the associated MBL-associated serine proteases (chiefly MASP-1, which activates MASP-2) to cleave complement C4 and C2, initiating the lectin pathway of complement and leading to opsonization, phagocytosis and membrane attack. MBL also binds altered-self and certain viral glycoproteins (e.g. influenza A haemagglutinin and SARS-CoV-2 spike) and can modulate inflammatory signaling. Common structural and promoter MBL2 variants lower circulating MBL and cause a common, usually subclinical, immunodeficiency that increases infection risk in the immunologically immature or compromised.
Definition: Recognition of a spatially repetitive, geometrically defined array of terminal monosaccharides (e.g. mannose, N-acetylglucosamine, fucose) on a microbial or altered-self surface by a multivalent oligomeric collectin, in which avidity arises from the simultaneous engagement of multiple low-affinity C-type lectin carbohydrate-recognition domains presented by the oligomer, thereby discriminating microbial macropatterns from host glycoproteins.
Justification: MBL specificity for non-self arises from the geometric spacing of multiple CRDs across a higher-order oligomer (the macropattern concept). Existing MF terms (carbohydrate binding, calcium-dependent carbohydrate binding, pattern recognition receptor activity) capture facets but none captures the multivalent, oligomer-dependent macropattern discrimination that distinguishes collectins/ficolins and that experimentally governs microbial binding and complement activation.
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: MBL is a secreted serum collectin synthesized in the liver and acting in plasma and tissue fluid; extracellular region is correct and is where its core function takes place. |
| GO:0050766 positive regulation of phagocytosis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: MBL is an opsonin and enhances phagocytosis of bound microbes, largely via complement deposition and collectin receptors. A genuine but downstream effector consequence of MBL recognition/complement-initiation activity rather than its core function. |
| GO:0005771 multivesicular body | IBA GO_REF:0000033 | REMOVE | Summary: An IBA-propagated localization that does not fit a secreted serum collectin. MBL acts extracellularly/at the cell surface, not in multivesicular bodies; likely over-propagation from surfactant-protein relatives (which traffic through lamellar/multivesicular bodies in pneumocytes). Reason: No experimental support for MBL function in multivesicular bodies; inconsistent with a liver-secreted plasma lectin. Likely IBA over-propagation from surfactant-protein paralogs. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN002771384 · PANTHER internal tree node NOT RELEVANT Internal PAINT node identifier for the asserted clade, not an independent evidence source. RGD:3665 · rat surfactant-collectin source gene (per GOA WITH field) SUPPORTS SOURCE BUT NOT TARGET Pulmonary surfactant collectins traffic through lamellar/multivesicular bodies in type II pneumocytes; that compartment biology is real for the source but does not transfer to liver-secreted serum MBL. RGD:3667 · rat surfactant-collectin source gene (per GOA WITH field) SUPPORTS SOURCE BUT NOT TARGET Same surfactant-branch compartment biology; no evidence places human MBL in multivesicular bodies. |
| GO:0043129 surfactant homeostasis | IBA GO_REF:0000033 | REMOVE | Summary: Surfactant homeostasis is a function of the pulmonary surfactant collectins (SFTPA/SP-A, SFTPD/SP-D) in the same PANTHER family, not of serum MBL. IBA over-propagation across the collectin family. Reason: No evidence MBL participates in surfactant homeostasis; the role belongs to the surfactant-protein paralogs. OpenScientist confirmed this as an IBA-only collectin-family carry-over from pulmonary surfactant collectins onto liver-derived serum MBL2. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN001523874 · collectin PANTHER source node SUPPORTS SOURCE BUT NOT TARGET The source node captures surfactant collectin biology in the pulmonary SP-A/SP-D branch, but MBL2 is a liver-derived serum lectin. UniProtKB:P35247 · surfactant protein D / pulmonary collectin source SUPPORTS SOURCE BUT NOT TARGET Surfactant protein D supports surfactant homeostasis in lung, not serum MBL2 complement biology. RGD:3667 · rodent surfactant collectin source SUPPORTS SOURCE BUT NOT TARGET Rodent surfactant-collectin biology should not transfer the alveolar surfactant-homeostasis process to human MBL2. Supporting Evidence: file:human/MBL2/MBL2-goa.tsv UniProtKB P11226 MBL2 involved_in GO:0043129 surfactant homeostasis biological_process ECO:0000318 IBA GO_REF:0000033 PANTHER:PTN001523874|RGD:3667|UniProtKB:P35247 9606 Homo sapiens GO_Central Mannose-binding protein C 20170613 file:human/MBL2/MBL2-hypotheses/function-hypothesis-go-0043129/openscientist.md The seed hypothesis that **MBL2 has surfactant homeostasis (GO:0043129)** is **over-annotated / refuted as a direct function.** |
| GO:0001867 complement activation, lectin pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Correct and central - MBL is the eponymous initiator of the lectin pathway. Redundant with the strongly supported IDA annotations to the same term. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Correct secreted location; redundant with experimentally supported extracellular-region annotations. |
| GO:0009986 cell surface | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: MBL is found at the cell surface (it binds carbohydrate on pathogen and altered-self cell surfaces and is detected on host cells). Acceptable as a location, though the functionally meaningful surface is the microbial/symbiont surface (GO:0106139), which is separately annotated and treated as core; host cell surface is kept as a genuine but non-core location. Reason: Correct but non-core; the core locations of MBL action are the extracellular region and the symbiont (microbial) cell surface, captured by the GO:0106139 annotations. |
| GO:0005515 protein binding | IPI PMID:11290788 Interaction properties of human mannan-binding lectin (MBL)-... | MARK AS OVER ANNOTATED | Summary: MBL-MASP1/MASP2/MAp19 interaction (the lectin-protease initiating complex). The interaction is real and important, but protein binding is an uninformative MF; the MBL-MASP relationship is better represented as membership in the MBL-MASP serine-type endopeptidase complex (see core_functions), and the informative MF of MBL is carbohydrate binding. |
| GO:0005515 protein binding | IPI PMID:15117939 The X-ray structure of human mannan-binding lectin-associate... | MARK AS OVER ANNOTATED | Summary: MBL-MAp19 interaction within the lectin-protease complex; a real partner interaction but uninformative as a generic protein-binding MF. |
| GO:0005515 protein binding | IPI PMID:18177377 The chaperone and potential mannan-binding lectin (MBL) co-r... | MARK AS OVER ANNOTATED | Summary: MBL-calreticulin interaction (via the MASP-binding site). Specific but uninformative as a generic protein-binding MF. |
| GO:0005515 protein binding | IPI PMID:19939495 MBL-associated serine protease-3 circulates in high serum co... | MARK AS OVER ANNOTATED | Summary: Derived from a MASP-3/Ficolin-3 study; weak/peripheral support for MBL and uninformative as an MF. |
| GO:0005515 protein binding | IPI PMID:20956340 Collectin 11 (CL-11, CL-K1) is a MASP-1/3-associated plasma ... | MARK AS OVER ANNOTATED | Summary: From a collectin-11 study; MBL is peripheral. Uninformative generic MF. |
| GO:0005515 protein binding | IPI PMID:21035894 Serum concentration and interaction properties of MBL/ficoli... | MARK AS OVER ANNOTATED | Summary: MBL-MAP-1/MAp44 interaction in the lectin-protease complex; uninformative generic MF. |
| GO:0005515 protein binding | IPI PMID:21054788 CD91 interacts with mannan-binding lectin (MBL) through the ... | MARK AS OVER ANNOTATED | Summary: MBL-CD91/LRP1 interaction (via the MASP-binding site). Specific but uninformative as generic protein binding. |
| GO:0005515 protein binding | IPI PMID:21106539 Heterocomplexes of mannose-binding lectin and the pentraxins... | MARK AS OVER ANNOTATED | Summary: MBL-pentraxin (PTX3/SAP) heterocomplexes; a real interaction modulating complement, but uninformative as a generic MF. |
| GO:0005515 protein binding | IPI PMID:21203938 Specific interaction of hepatitis C virus glycoproteins with... | MARK AS OVER ANNOTATED | Summary: MBL-HCV glycoprotein interaction; this is actually carbohydrate-mediated recognition of a viral glycoprotein and is better captured by the carbohydrate-binding/PRR MF than by generic protein binding. |
| GO:0005515 protein binding | IPI PMID:21268013 Serglycin inhibits the classical and lectin pathways of comp... | MARK AS OVER ANNOTATED | Summary: From a serglycin study (GAG-mediated lectin-pathway inhibition); MBL is a target. Uninformative generic MF. |
| GO:0005515 protein binding | IPI PMID:21383675 Mannan-binding lectin directly interacts with Toll-like rece... | MARK AS OVER ANNOTATED | Summary: MBL-TLR4 ectodomain interaction (immunomodulatory, dampens LPS signaling). A specific regulatory interaction but uninformative as a generic protein-binding MF. |
| GO:0005515 protein binding | IPI PMID:22607836 MASP interactions with plasma-derived MBL. | MARK AS OVER ANNOTATED | Summary: MASP-MBL interaction study; supports complex assembly but uninformative as a generic MF. |
| GO:0005515 protein binding | IPI PMID:22811680 The salivary scavenger and agglutinin binds MBL and regulate... | MARK AS OVER ANNOTATED | Summary: MBL-DMBT1/SALSA interaction regulating the lectin pathway; specific but uninformative as a generic MF. |
| GO:0005515 protein binding | IPI PMID:22854970 Crystal structure and functional characterization of the com... | MARK AS OVER ANNOTATED | Summary: MBL-MAP-1 interaction (competitive complement regulator); uninformative generic MF. |
| GO:0005515 protein binding | IPI PMID:23460739 Deciphering complement receptor type 1 interactions with rec... | MARK AS OVER ANNOTATED | Summary: MBL-CR1 interaction; a specific receptor interaction but uninformative as a generic MF. |
| GO:0005515 protein binding | IPI PMID:25579818 Structural insights into the initiating complex of the lecti... | MARK AS OVER ANNOTATED | Summary: MBL-MASP-1 interaction in the initiating complex; best captured as complex membership. Uninformative as a generic MF. |
| GO:0005515 protein binding | IPI PMID:27104295 Oligomerization of Mannan-binding Lectin Dictates Binding Pr... | MARK AS OVER ANNOTATED | Summary: MBL oligomerization / MASP interaction; this is largely MBL self-association (identical protein binding) and MASP binding, uninformative as a generic protein-binding MF. |
| GO:0005515 protein binding | IPI PMID:29563915 C1q and Mannose-Binding Lectin Interact with CR1 in the Same... | MARK AS OVER ANNOTATED | Summary: MBL-CR1 (CCP24-25) interaction; specific but uninformative as a generic MF. |
| GO:0005515 protein binding | IPI PMID:32041782 C1q/TNF-Related Protein 6 Is a Pattern Recognition Molecule ... | MARK AS OVER ANNOTATED | Summary: From a CTRP6/collectin-11 study; MBL peripheral. Uninformative generic MF. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: High-throughput binary interactome (HuRI); a generic, low-specificity protein-binding IPI with no informative value for MBL molecular function. |
| GO:0005515 protein binding | IPI PMID:32759297 Complement Activation and Thrombin Generation by MBL Bound t... | MARK AS OVER ANNOTATED | Summary: MBL-beta2-glycoprotein I interaction (complement/thrombin crosstalk); specific but uninformative as a generic MF. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: High-throughput AP-MS interactome (BioPlex); a generic protein-binding IPI, uninformative for MBL molecular function. |
| GO:0042802 identical protein binding | IPI PMID:21106539 Heterocomplexes of mannose-binding lectin and the pentraxins... | KEEP AS NON CORE | Summary: MBL self-association/oligomerization (the structural subunit is a homotrimer that further oligomerizes; higher-order assembly is required for avid binding and complement activation). Identical protein binding is more informative than generic protein binding; retain as a non-core structural/assembly property. |
| GO:0042802 identical protein binding | IPI PMID:21383675 Mannan-binding lectin directly interacts with Toll-like rece... | KEEP AS NON CORE | Summary: MBL self-association/oligomerization (the structural subunit is a homotrimer that further oligomerizes; higher-order assembly is required for avid binding and complement activation). Identical protein binding is more informative than generic protein binding; retain as a non-core structural/assembly property. |
| GO:0042802 identical protein binding | IPI PMID:22607836 MASP interactions with plasma-derived MBL. | KEEP AS NON CORE | Summary: MBL self-association/oligomerization (the structural subunit is a homotrimer that further oligomerizes; higher-order assembly is required for avid binding and complement activation). Identical protein binding is more informative than generic protein binding; retain as a non-core structural/assembly property. |
| GO:0042802 identical protein binding | IPI PMID:25579818 Structural insights into the initiating complex of the lecti... | KEEP AS NON CORE | Summary: MBL self-association/oligomerization (the structural subunit is a homotrimer that further oligomerizes; higher-order assembly is required for avid binding and complement activation). Identical protein binding is more informative than generic protein binding; retain as a non-core structural/assembly property. |
| GO:0042802 identical protein binding | IPI PMID:27104295 Oligomerization of Mannan-binding Lectin Dictates Binding Pr... | KEEP AS NON CORE | Summary: Oligomerization of the MBL homotrimer is directly studied here and shown to dictate binding and complement activation - the best-supported identical-protein-binding annotation. Retain as a non-core structural/assembly property underpinning function. |
| GO:0005576 extracellular region | EXP PMID:7982896 Structure and function of mannan-binding proteins isolated f... | ACCEPT | Summary: Direct evidence that MBP is secreted (purified from serum; secreted by transfected cells). Correct core location. |
| GO:0009986 cell surface | EXP PMID:22966085 Mannan-binding lectin-associated serine protease (MASP)-1 is... | KEEP AS NON CORE | Summary: MBL associates with cell surfaces in the context of lectin-pathway activation. Genuine location, but the functionally meaningful surface of action is the symbiont cell surface (GO:0106139, separately annotated from this same paper and treated as core). Reason: Correct but non-core; core location-of-action is captured by the GO:0106139 symbiont cell surface annotation from the same reference. |
| GO:0009986 cell surface | EXP PMID:2573758 Association of low levels of mannan-binding protein with a c... | KEEP AS NON CORE | Summary: MBP deposits complement on mannan-coated surfaces and corrects an opsonic defect; consistent with action at the (microbial) cell surface, which is separately and more precisely annotated as GO:0106139 symbiont cell surface from this same paper. Reason: Correct but non-core; the surface where MBL acts in this evidence is the microbial surface, captured by the core GO:0106139 annotation. |
| GO:0009986 cell surface | EXP PMID:8082295 Binding of mannan-binding protein to various bacterial patho... | KEEP AS NON CORE | Summary: MBP binds bacterial surfaces in a sugar-/Ca2+-dependent manner. Supports cell-surface (pathogen surface) localization; the same evidence is more precisely captured by the GO:0106139 symbiont cell surface annotation from this paper. Reason: Correct but non-core; the pathogen-surface location of action is captured by the core GO:0106139 annotation. |
| GO:0001867 complement activation, lectin pathway | IDA PMID:22691502 Revised mechanism of complement lectin-pathway activation re... | ACCEPT | Summary: MBL nucleates the initiating complex whose MASP-1/MASP-2 cleave C4/C2 to activate the lectin pathway. Core process role, well supported. |
| GO:0002752 cell surface pattern recognition receptor signaling pathway | IDA PMID:22966085 Mannan-binding lectin-associated serine protease (MASP)-1 is... | ACCEPT | Summary: MBL recognizes microbial carbohydrate patterns and triggers the MASP proteolytic cascade - a soluble pattern-recognition-receptor signaling event. Closely related to the lectin-pathway and PRR-activity annotations. Retain. |
| GO:0006508 proteolysis | IDA PMID:22691502 Revised mechanism of complement lectin-pathway activation re... | REMOVE | Summary: The proteolysis (C4/C2 cleavage) is carried out by the MASP serine proteases, not by MBL itself - MBL has no protease activity. Annotating MBL with proteolysis attributes an activity of its associated MASP serine proteases to MBL; this is closer to a wrong-gene attribution than an over-annotation. MBL membership in the proteolytic complex is already captured by GO:1905370 (serine-type endopeptidase complex) and its role by the lectin-pathway process annotations. Reason: MBL is not a protease; proteolysis is the activity of the associated MASP serine proteases. Attributing it to MBL is effectively a wrong-gene attribution, so the annotation is removed; MBL involvement is correctly represented by complex membership (GO:1905370) and the lectin-pathway process. |
| GO:0009897 external side of plasma membrane | NAS PMID:22966085 Mannan-binding lectin-associated serine protease (MASP)-1 is... | KEEP AS NON CORE | Summary: MBL is a soluble secreted protein that binds surfaces; external side of plasma membrane (a membrane-component location) is a marginal NAS assignment. Acceptable as a non-core location where MBL transiently associates with the outer leaflet of host/microbial membranes. |
| GO:1903028 positive regulation of opsonization | IDA PMID:22966085 Mannan-binding lectin-associated serine protease (MASP)-1 is... | KEEP AS NON CORE | Summary: By depositing complement opsonins on bound microbes, MBL promotes opsonization. A genuine but downstream effector role rather than the core recognition function. |
| GO:1905370 serine-type endopeptidase complex | IPI PMID:25579818 Structural insights into the initiating complex of the lecti... | ACCEPT | Summary: MBL is the recognition subunit of the MBL-MASP initiating complex (ComplexPortal CPX-6170/CPX-6203), which contains the MASP serine proteases. Correct, informative complex membership; this is how the otherwise-generic MBL-MASP protein-binding annotations should be represented. |
| GO:0001867 complement activation, lectin pathway | IDA PMID:9087411 A second serine protease associated with mannan-binding lect... | ACCEPT | Summary: Foundational evidence (MASP-2 discovery) that MBL binds microbial carbohydrate and activates complement via associated serine proteases. Core process role. |
| GO:0005537 D-mannose binding | IDA PMID:6643429 Isolation and characterization of a mannan-binding protein f... | ACCEPT | Summary: Direct biochemical demonstration of Ca2+-dependent, saturable, high-affinity mannan/mannose binding by serum MBP, specific for mannose and N-acetylglucosamine. This is the defining core molecular function of MBL. |
| GO:0038187 pattern recognition receptor activity | IDA PMID:9087411 A second serine protease associated with mannan-binding lect... | ACCEPT | Summary: MBL is a prototypic soluble pattern-recognition molecule recognizing microbial carbohydrate PAMPs and triggering complement. Core molecular function (alongside carbohydrate binding). |
| GO:0106139 symbiont cell surface | IDA PMID:22966085 Mannan-binding lectin-associated serine protease (MASP)-1 is... | ACCEPT | Summary: MBL is functionally active at the microbial (symbiont/pathogen) cell surface, where it binds carbohydrate and assembles the lectin-pathway complex. Correct, meaningful location of action. |
| GO:0106139 symbiont cell surface | IDA PMID:2573758 Association of low levels of mannan-binding protein with a c... | ACCEPT | Summary: MBL is functionally active at the microbial (symbiont/pathogen) cell surface, where it binds carbohydrate and assembles the lectin-pathway complex. Correct, meaningful location of action. |
| GO:0106139 symbiont cell surface | IDA PMID:8082295 Binding of mannan-binding protein to various bacterial patho... | ACCEPT | Summary: MBL is functionally active at the microbial (symbiont/pathogen) cell surface, where it binds carbohydrate and assembles the lectin-pathway complex. Correct, meaningful location of action. |
| GO:0001867 complement activation, lectin pathway | IDA PMID:35102342 Recognition and inhibition of SARS-CoV-2 by humoral innate i... | ACCEPT | Summary: After binding SARS-CoV-2 spike, MBL activates the lectin pathway. Supports the core lectin-pathway process in an antiviral context. |
| GO:0048306 calcium-dependent protein binding | IPI PMID:35102342 Recognition and inhibition of SARS-CoV-2 by humoral innate i... | MODIFY | Summary: The Ca2+-dependent binding of MBL to SARS-CoV-2 spike is glycan-dependent, i.e. it is calcium-dependent carbohydrate binding of a viral glycoprotein rather than protein-protein binding; better captured by calcium-dependent carbohydrate binding (GO:0120153). The curator's original choice of calcium-dependent protein binding was reasonable - the assay measured Ca2+-dependent binding of MBL to a specific protein (the SARS-CoV-2 spike glycoprotein), so at the level of the observed partner it is a protein. This MODIFY refines the mechanism (the binding is glycan-mediated via the C-type lectin CRD) rather than correcting a curator error. Reason: The interaction is mediated by the spike glycan via the C-type lectin CRD in a calcium-dependent manner; calcium-dependent carbohydrate binding is the accurate, informative MF. The original calcium-dependent protein binding was a defensible choice (the measured partner is the spike protein); the MODIFY refines mechanism, not a curator mistake. Proposed replacements: calcium-dependent carbohydrate binding |
| GO:0140374 antiviral innate immune response | IDA PMID:35102342 Recognition and inhibition of SARS-CoV-2 by humoral innate i... | KEEP AS NON CORE | Summary: MBL binds SARS-CoV-2 spike, inhibits the virus in vitro and activates complement - an antiviral innate-immune effector role. A (virus-specific) facet of MBL innate defense; non-core relative to the general carbohydrate-recognition MF. |
| GO:0050830 defense response to Gram-positive bacterium | IDA PMID:15148336 Mannose-binding lectin-deficient mice are susceptible to inf... | KEEP AS NON CORE | Summary: MBL-null mice are highly susceptible to S. aureus, directly demonstrating defense against Gram-positive bacteria (via the rodent orthologs). A specific, well-supported facet of MBL antibacterial innate defense; non-core relative to the general carbohydrate-recognition MF. |
| GO:0005537 D-mannose binding | IDA PMID:23544079 Serum amyloid P is a sialylated glycoprotein inhibitor of in... | ACCEPT | Summary: MBL is described as a beta-type (Ca2+-dependent C-type-lectin) inhibitor of influenza A that binds mannose-rich glycans on viral haemagglutinin; this paper is primarily about SAP and the MBL data are comparative, but the mannose-binding MF is correct and far better supported by PMID:6643429. |
| GO:0048525 negative regulation of viral process | IDA PMID:23544079 Serum amyloid P is a sialylated glycoprotein inhibitor of in... | KEEP AS NON CORE | Summary: MBL acts as a beta-inhibitor of influenza A (CRD binding to viral HA glycans), restraining infection. A genuine antiviral facet but supported here only comparatively; downstream/process-level and virus-specific, hence non-core. |
| GO:0005576 extracellular region | IDA PMID:23544079 Serum amyloid P is a sialylated glycoprotein inhibitor of in... | ACCEPT | Summary: Consistent with MBL being a secreted serum/airway lectin. Correct location. |
| GO:0045087 innate immune response | IDA PMID:23544079 Serum amyloid P is a sialylated glycoprotein inhibitor of in... | ACCEPT | Summary: MBL is a core innate-immune effector (pattern recognition plus complement). The high-level process assignment is well established; this particular reference is a comparative antiviral study. Core innate-immune role. |
| GO:0009986 cell surface | TAS PMID:2477488 Lipopolysaccharide (LPS) binding protein opsonizes LPS-beari... | KEEP AS NON CORE | Summary: Cell-surface location is correct for MBL and is supported by EXP annotations elsewhere; the function/location is sound and only this specific reference (PMID:2477488) is a miscitation (an LBP paper - see reference_review on PMID:2477488). Reason: Location correct and supported elsewhere by EXP evidence; only the cited reference is miscited (LBP paper). |
| GO:0042742 defense response to bacterium | TAS PMID:2477488 Lipopolysaccharide (LPS) binding protein opsonizes LPS-beari... | ACCEPT | Summary: Defense against bacteria is a genuine core process for MBL (recognition plus complement plus opsonization; MBL-null mice die from S. aureus). The function is correct; only this specific reference (PMID:2477488) is a miscitation (an LBP paper - see reference_review on PMID:2477488). Reason: Function well supported (PMID:8082295, PMID:15148336, PMID:2573758); only the cited reference is miscited (LBP paper). |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166721 | ACCEPT | Summary: Correct secreted extracellular location (Reactome lectin-pathway/recognition reaction). |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166726 | ACCEPT | Summary: Correct secreted extracellular location (Reactome lectin-pathway/recognition reaction). |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166753 | ACCEPT | Summary: Correct secreted extracellular location (Reactome lectin-pathway/recognition reaction). |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166792 | ACCEPT | Summary: Correct secreted extracellular location (Reactome lectin-pathway/recognition reaction). |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9758529 | ACCEPT | Summary: Correct secreted extracellular location (Reactome lectin-pathway/recognition reaction). |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9921544 | ACCEPT | Summary: Correct secreted extracellular location (Reactome lectin-pathway/recognition reaction). |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9957161 | ACCEPT | Summary: Correct secreted extracellular location (Reactome lectin-pathway/recognition reaction). |
| GO:0001867 complement activation, lectin pathway | IDA PMID:15148336 Mannose-binding lectin-deficient mice are susceptible to inf... | ACCEPT | Summary: MBL-null mice lack the MBL complement pathway; supports MBL upstream role in lectin-pathway complement activation. Core process role. |
| GO:0005515 protein binding | IPI PMID:11485744 MASP-3 and its association with distinct complexes of the ma... | MARK AS OVER ANNOTATED | Summary: MBL-MASP-3 complex association; a real interaction within the lectin-protease system but uninformative as a generic protein-binding MF. |
| GO:0048306 calcium-dependent protein binding | IPI PMID:12421953 Characterization of the interaction between L-ficolin/p35 an... | KEEP AS NON CORE | Summary: Calcium-dependent association within the MBL/ficolin-MASP system (binding to the MASP proteases). The Ca2+ dependence reflects MBL C-type-lectin biology, but the partner here is a protein, so calcium-dependent protein binding is defensible. Non-core; the informative core MF is calcium-dependent carbohydrate binding. |
| GO:0048306 calcium-dependent protein binding | IPI PMID:18596036 Crystal structure of the CUB1-EGF-CUB2 domain of human MASP-... | KEEP AS NON CORE | Summary: Calcium-dependent association within the MBL/ficolin-MASP system (binding to the MASP proteases). The Ca2+ dependence reflects MBL C-type-lectin biology, but the partner here is a protein, so calcium-dependent protein binding is defensible. Non-core; the informative core MF is calcium-dependent carbohydrate binding. |
| GO:0005537 D-mannose binding | TAS PMID:2477488 Lipopolysaccharide (LPS) binding protein opsonizes LPS-beari... | ACCEPT | Summary: D-mannose binding is the defining core molecular function of MBL and is well supported by the IDA annotations (PMID:6643429). The function is correct; the issue is solely that this specific reference (PMID:2477488) is the LBP paper and is a miscitation (see reference_review on PMID:2477488). The annotation is accepted on the basis of the function, not the citation. Reason: Mannose binding is the core MBL MF (PMID:6643429); only the cited reference is miscited (LBP paper). |
| GO:0006953 acute-phase response | TAS PMID:2477488 Lipopolysaccharide (LPS) binding protein opsonizes LPS-beari... | KEEP AS NON CORE | Summary: MBL is a (modest) acute-phase reactant (its founding cDNA paper titled it an acute-phase reactant). The function is plausibly correct and kept as a non-core process; only this specific reference (PMID:2477488) is a miscitation (an LBP paper - see reference_review on PMID:2477488). Reason: Acute-phase behavior of MBL is real but modest; only the cited reference is miscited (LBP paper). |
| GO:0008228 opsonization | TAS PMID:2477488 Lipopolysaccharide (LPS) binding protein opsonizes LPS-beari... | KEEP AS NON CORE | Summary: MBL is an opsonin (its deficiency causes a common opsonic defect, PMID:2573758). The process is correct though downstream and kept as non-core; only this specific reference (PMID:2477488) is a miscitation (an LBP paper - see reference_review on PMID:2477488). Reason: Opsonization role well established (PMID:2573758) but a downstream effector consequence; only the cited reference is miscited (LBP paper). |
| GO:0001867 complement activation, lectin pathway | IPI PMID:11549596 Endothelial oxidative stress activates the lectin complement... | ACCEPT | Summary: MBL binding to oxidative-stress-induced endothelial cytokeratin-1 activates the lectin pathway (altered-self recognition). Supports the lectin-pathway process. Core process role. |
| GO:0005102 signaling receptor binding | IPI PMID:11549596 Endothelial oxidative stress activates the lectin complement... | MARK AS OVER ANNOTATED | Summary: This annotation derives from MBL binding endothelial cytokeratin-1 (CK1) after oxidative stress. CK1 is not a canonical signaling receptor, and the interaction is recognition of an altered-self surface ligand by the lectin. Signaling receptor binding misclassifies this; the informative MF remains carbohydrate/altered-self ligand binding via the CRD. Reason: The CK1 interaction is altered-self ligand recognition by the lectin, not binding of a bona fide signaling receptor; the term is a poor fit. |
| GO:0005537 D-mannose binding | NAS PMID:11549596 Endothelial oxidative stress activates the lectin complement... | ACCEPT | Summary: D-mannose binding is the core MF of MBL and is correct; supported far more directly by the IDA annotations (PMID:6643429). This NAS entry is redundant but accurate. |
| GO:0006979 response to oxidative stress | NAS PMID:11549596 Endothelial oxidative stress activates the lectin complement... | REMOVE | Summary: MBL does not respond to oxidative stress; rather, oxidative stress on endothelium exposes a ligand (cytokeratin-1) that MBL then binds. Annotating MBL with response to oxidative stress misattributes the host cell stress response to MBL. Reason: The oxidative stress is experienced by the endothelial cell (inducing CK1); MBL merely recognizes the resulting altered-self ligand. MBL itself has no role in the oxidative-stress response. |
| GO:0005576 extracellular region | TAS PMID:1304173 High frequencies in African and non-African populations of i... | ACCEPT | Summary: Correct secreted location (MBL2 population-genetics paper noting low serum MBP). |
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Download this section (compressed HTML)Q: Beyond binding, does MBL contribute any conformational/allosteric signal that activates the bound MASP zymogens, or is its role purely to cluster and co-localize MASPs on the target surface?
Q: How quantitatively important is the antibody-independent MBL lectin pathway in healthy human adults (most MBL-deficient adults are healthy), versus in specific windows such as infancy, neutropenia, or immunosuppression?
Experiment: Compare wild-type recombinant MBL with CRD point mutants that abolish Ca2+/sugar binding (mutations of the Ca2+/glycosyl-coordinating residues around 212-233) for binding to mannan, S. aureus, influenza A and SARS-CoV-2 spike, and for MASP-dependent C4/C2 cleavage and opsonophagocytosis, using EDTA and competing mannose/GlcNAc as controls.
Hypothesis: The calcium-dependent carbohydrate-recognition activity of the CRD is strictly required for all MBL effector functions (complement activation, opsonization, antiviral inhibition).
Type: structure-function / CRD mutagenesis with binding and complement-activation assays
Experiment: Produce defined recombinant MBL oligomers, quantify avidity for panels of microbial vs host glycans (SPR / glycan arrays) and MASP recruitment, correlate with C4 deposition and bacterial opsonophagocytosis, and relate to oligomer distributions produced by common MBL2 structural variants.
Hypothesis: MBL oligomerization state (trimer vs tetramer-and-higher) sets the threshold for microbial discrimination and complement activation in a physiologically meaningful way.
Type: biophysical oligomer fractionation with glycan-array and complement assays
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