Mpo

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0001878 response to yeast	IMP PMID:10085024 Severe impairment in early host defense against Candida albi...	KEEP AS NON CORE	Summary: Mpo-/- mice challenged with Candida albicans showed delayed fungal clearance and death, so Mpo is required for the normal response to this yeast. Reason: The claim is correct but the stimulus-response framing is peripheral; the informative statements about the same experiment are GO:0050832 defense response to fungus and GO:0070947 neutrophil-mediated killing of fungus, both retained here. Kept rather than refined because neither of those terms is a descendant of GO:0001878, so replacing it would change the assertion rather than sharpen it. Supporting Evidence: PMID:10085024 However, they showed increased susceptibility to pneumonia and death following intratracheal infection with Candida albicans.
GO:0002252 immune effector process	IEA GO_REF:0000117	TOO GENERAL	Summary: Root-level immune effector grouping term from an ARBA model. Reason: True of Mpo but uninformative - the specific descendants GO:0070944 neutrophil-mediated killing of bacterium and GO:0070947 neutrophil-mediated killing of fungus are accepted in this review and entail it.
GO:0002679 respiratory burst involved in defense response	IMP PMID:10085024 Severe impairment in early host defense against Candida albi...	MARK AS OVER ANNOTATED	Summary: MGI IMP from the Mpo knockout paper. The respiratory burst itself is the NADPH-oxidase-driven step that generates superoxide and H2O2; Mpo acts downstream, consuming the H2O2 to make hypochlorous acid. Reason: GO:0002679 is defined as the production "by an NADH dependent system, of hydrogen peroxide (H2O2), superoxide anions and hydroxyl radicals" - that is NOX2, not Mpo. In the cited paper superoxide generation was if anything slightly higher in Mpo-/- neutrophils, so the burst does not require Mpo. Not wrong that Mpo works inside the burst-derived oxidant cascade, hence over-annotation rather than removal; the accurate statements are GO:0042744 hydrogen peroxide catabolic process and the peroxidase MF, both accepted here. Supporting Evidence: PMID:10085024 During the respiratory burst, neutrophils generate O 2 − via the NADPH oxidase system. O 2 − is then reduced to H 2 O 2 , from which HOCl is generated by the MPO reaction. PMID:10085024 The neutrophils of homozygous mutant mice generated a slightly higher level of O 2 −
GO:0004601 peroxidase activity	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBD/IBA for peroxidase activity placed on the animal heme-peroxidase clade; Mpo appears among the descendant evidences because it has its own experimental annotation for the term. Reason: Peroxidase activity is the core catalytic function of Mpo and is inherited across the animal heme peroxidase family (MPO, EPX, LPO, TPO, peroxidasins); the node placement is sound and the target retains the catalytic heme-peroxidase architecture, so GO:0004601 is the right term for a family-level inference. The UniProt quote below is the curated reaction for mouse Mpo itself, cited to show that the inherited activity is realised in this protein - the IBA row asserts peroxidase activity at family level, not the halide specificity. Supporting Evidence: UniProtKB:P11247 Reaction=chloride + H2O2 + H(+) = hypochlorous acid + H2O;
GO:0004601 peroxidase activity	IDA PMID:10085024 Severe impairment in early host defense against Candida albi...	ACCEPT	Summary: Peroxidase (TMB) activity was measured directly in neutrophils of wild-type, heterozygous and Mpo-/- mice and tracked gene dosage. Reason: Direct demonstration of the core catalytic activity in mouse cells, and specifically of the chloride-to-HOCl reaction: HOCl production, not just generic turnover, tracked Mpo gene dosage. GO:0004601 is the correct and most specific existing term for the activity, so ACCEPT. That GO has no term for the individual reaction (EC 1.11.2.2, RHEA:28218) is an ontology gap, raised in proposed_new_terms and suggested_questions rather than held against this row; a split of the twelve GO:0004601 rows by how specific each one's evidence is was tried and rejected, because rows sharing a term must take consistent actions. Supporting Evidence: PMID:10085024 Quantitative analysis by spectrophotometry demonstrated that the average MPO activity in wild-type mice was 1.7 nmol/min/10 6 cells
GO:0004601 peroxidase activity	IDA PMID:11792727 Absence of functional peroxisomes does not lead to deficienc...	ACCEPT	Summary: MGI IDA for peroxidase activity from a Pex5-knockout liver enzymology study. Reason: Peroxidase activity is not in doubt for Mpo. The cached record is abstract-only and does not mention the MPO assay, so the measurement cannot be re-read here; the curator read the full text, and the claim - generic peroxidase activity - is correct. GO:0004601 is the right level for what this row shows.
GO:0004601 peroxidase activity	IDA PMID:11980719 Spi-B can functionally replace PU.1 in myeloid but not lymph...	ACCEPT	Summary: MGI IDA for peroxidase activity from the Spi-B/PU.1 knock-in study, where MPO staining is the standard readout of myeloid differentiation. Reason: Only the abstract is cached, so the assay cannot be checked here, but the claim - that Mpo has peroxidase activity - is independently established in mouse by PMID:10085024. MPO staining reports peroxidase turnover, not the halide reaction, so GO:0004601 is the right level for this row.
GO:0004601 peroxidase activity	IDA PMID:15159534 Corticotropin-releasing hormone (CRH) requirement in Clostri...	ACCEPT	Summary: MPO enzymatic activity was assayed in mouse ileal tissue as a measure of neutrophil infiltration in the Clostridioides difficile toxin A model. Reason: A direct peroxidase activity measurement on mouse tissue (the Bradley o-dianisidine assay), used as a neutrophil-activation readout. It shows generic peroxidase turnover rather than the chloride-to-HOCl reaction, so GO:0004601 is the right level for this row. Supporting Evidence: PMID:15159534 MPO activity was determined by a modified method of Bradley et al.
GO:0004601 peroxidase activity	IDA PMID:23306200 Ceruloplasmin is an endogenous inhibitor of myeloperoxidase.	ACCEPT	Summary: Purified myeloperoxidase was shown to generate hypochlorous acid from H2O2 and chloride, and this activity was inhibited by ceruloplasmin. Reason: Direct enzymology on purified myeloperoxidase - HOCl production from chloride and H2O2, quantified through its inhibition by ceruloplasmin - so the core catalytic activity is demonstrated outside the knockout system as well. GO:0004601 is the correct existing term. Supporting Evidence: PMID:23306200 Ceruloplasmin was a potent inhibitor of purified myeloperoxidase, inhibiting production of hypochlorous acid by 50% at 25 nm. PMID:23306200 We found that myeloperoxidase oxidized 75% of the ascorbate in plasma from ceruloplasmin knock-out mice
GO:0004601 peroxidase activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined electronic inference of peroxidase activity (ARBA, ortholog and InterPro IPR010255 evidence). Reason: Combined electronic inference (ARBA, ortholog and InterPro IPR010255 evidence) of generic peroxidase activity. GO:0004601 is the right level for it, and the claim is independently established experimentally in mouse.
GO:0004601 peroxidase activity	IMP PMID:10085024 Severe impairment in early host defense against Candida albi...	ACCEPT	Summary: Mpo-/- neutrophils produced essentially no HOCl and no detectable MPO activity, establishing by loss of function that Mpo enables the peroxidase reaction. Reason: Loss of function for the same activity: HOCl generation was abolished in Mpo-null neutrophils. This is the row that most directly carries the chemistry the obsoleted BP term GO:0002149 restated, and GO:0004601 is the correct existing term for it. The missing term for the individual reaction is handled as an ontology request in proposed_new_terms. Supporting Evidence: PMID:10085024 the neutrophils of homozygous mutant mice produced HOCl at an almost undetectable level PMID:10085024 Myeloperoxidase (MPO) catalyzes the reaction of hydrogen peroxide with chloride ion to produce hypochlorous acid (HOCl), which is used for microbial killing by phagocytic cells.
GO:0004601 peroxidase activity	ISO GO_REF:0000008	ACCEPT	Summary: Curated orthology transfer of peroxidase activity from human MPO (P05164). Reason: Curated MGI orthology transfer from human MPO (P05164). Orthology is unambiguous and the claim - generic peroxidase activity - is independently established experimentally in mouse, so GO:0004601 is correct at this level.
GO:0004601 peroxidase activity	ISO GO_REF:0000096	ACCEPT	Summary: Automated mouse-rat orthology transfer of peroxidase activity. Reason: Automated mouse-rat orthology transfer. Same claim at the same level of generality, independently established experimentally in mouse.
GO:0004601 peroxidase activity	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer of peroxidase activity. Reason: Automated mouse-human orthology transfer. Same claim at the same level of generality, independently established experimentally in mouse.
GO:0004601 peroxidase activity	ISS GO_REF:0000024	ACCEPT	Summary: Curator-judged sequence-similarity transfer of peroxidase activity from human MPO. Reason: Curator-judged sequence-similarity transfer from human MPO. Same claim at the same level of generality, independently established experimentally in mouse.
GO:0005576 extracellular region	IBA GO_REF:0000033	ACCEPT	Summary: Mature MPO is constitutively secreted by granulocyte precursors and is released extracellularly on degranulation and during NET formation, where it stays catalytically active. Reason: Extracellular MPO is a genuine site of action, not only a location - it is a core NET component and produces oxidants in the inflamed extracellular space. Supporting Evidence: PMID:23306200 Myeloperoxidase is also released into the extracellular space as a result of incomplete phagosome closure and during chronic inflammation when neutrophils are activated and degranulate in the absence of infection. UniProtKB:P11247 A substantial fraction is also constitutively secreted by normal bone marrow granulocyte precursors
GO:0005576 extracellular region	IEA GO_REF:0000120	ACCEPT	Summary: Electronic inference of extracellular localisation (UniProt SubCell SL-0243 plus ortholog evidence). Reason: Same claim as the IBA row; secretion of MPO is well established.
GO:0005576 extracellular region	ISO GO_REF:0000096	ACCEPT	Summary: Automated mouse-rat orthology transfer of extracellular localisation. Reason: Same claim; consistent with the curated UniProt subcellular location.
GO:0005576 extracellular region	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer, asserting MPO is active in the extracellular region. Reason: Secreted MPO is catalytically active; is_active_in is the appropriate relation.
GO:0005576 extracellular region	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer of extracellular localisation. Reason: Same claim as the other extracellular rows.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: During NET formation MPO translocates into the nucleus and binds chromatin. Reason: Nuclear localisation is mechanistically required for the chromatin-decondensing arm of MPO function, which this review keeps as a core function. Supporting Evidence: UniProtKB:P11247 During formation of neutrophil extracellular traps (NETs), translocates into the nucleus and associates to chromatin, leading to chromatin dislocation and its transformation into NETs
GO:0005634 nucleus	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer asserting MPO is active in the nucleus. Reason: Consistent with the nucleosome-destabilising activity retained as a core function here.
GO:0005654 nucleoplasm	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer of nucleoplasm localisation. Reason: A sub-compartment refinement of the accepted nuclear localisation during NET formation; no reason to doubt it.
GO:0005694 chromosome	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt SubCell-derived chromosome localisation, reflecting MPO binding to nucleosomes/chromatin during NET formation. Reason: Correct but a by-product of the chromatin-binding step during NET formation, and less informative than the nuclear localisations accepted here (GO:0005634 nucleus, GO:0005654 nucleoplasm). The activities behind it - GO:0031491 nucleosome binding, GO:0140776 and GO:0006337 - are retained as core, so nothing is lost by holding this CC row as non-core. Supporting Evidence: UniProtKB:P11247 Promotes NET formation by mediating chromatin disassembly: translocates to the nucleus and specifically binds to nucleosomes, both as monomer and homodimer, leading to nucleosome unstacking and initial chromatin decondensation
GO:0005739 mitochondrion	HDA PMID:14651853 Integrated analysis of protein composition, tissue diversity...	REMOVE	Summary: Single high-throughput mass-spectrometry hit in a mouse mitochondrial proteome survey of brain, heart, kidney and liver. Reason: Mpo is a myeloid granule protein whose curated locations are azurophil granule/lysosome, phagosome, secreted, and nucleus during NETosis; it has no mitochondrial targeting and no mitochondrial function is known. A lone HDA hit in an organelle-enrichment survey of highly vascularised tissues is best explained by co-purifying leukocyte material, so this is an electronic/high-throughput artefact rather than a localisation claim. Supporting Evidence: UniProtKB:P11247 Localizes to azurophil granules, a type of primary lysosome found in neutrophils and monocytes that contains antimicrobial proteins
GO:0005764 lysosome	IEA GO_REF:0000044	MODIFY	Summary: UniProt SubCell-derived lysosome localisation. Reason: Correct but less specific than the evidence supports - the azurophil granule is the primary lysosome of neutrophils and monocytes, is an is_a descendant of lysosome, and is already annotated to Mpo in this same GOA set. Proposed replacements: azurophil granule Supporting Evidence: UniProtKB:P11247 Localizes to azurophil granules, a type of primary lysosome found in neutrophils and monocytes that contains antimicrobial proteins
GO:0006337 nucleosome disassembly	IEA GO_REF:0000107	ACCEPT	Summary: MPO drives nucleosome unstacking and complete nucleosome disassembly during NET formation. Reason: Core to the chromatin-decondensation arm of MPO function; mechanistically characterised for the orthologous human protein and transferred here. Supporting Evidence: UniProtKB:P11247 Homodimers clash with one end of the nucleosomal DNA, leading to DNA unwrapping, initiating complete disassembly of nucleosomes and chromatin transformation into NETs in an ATP-independent manner
GO:0006337 nucleosome disassembly	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer of nucleosome disassembly. Reason: Same claim as the Ensembl-Compara row; reinforcing evidence.
GO:0006337 nucleosome disassembly	ISS GO_REF:0000024	ACCEPT	Summary: Curator-judged sequence-similarity transfer of nucleosome disassembly from human MPO. Reason: Same claim; the NET-related chromatin activity is conserved.
GO:0006979 response to oxidative stress	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: ARBA/InterPro-driven assertion that Mpo is involved in the response to oxidative stress. Reason: Mpo generates oxidants rather than responding to them; it consumes H2O2 to make hypochlorous acid and other hypohalous acids. The claim inverts the relationship and comes from a family-level association rule, not from evidence that Mpo acts downstream of an oxidative-stress stimulus. The accurate statements kept here are GO:0042744 hydrogen peroxide catabolic process and the peroxidase MF. Supporting Evidence: UniProtKB:P11247 Mediates the formation of hypohalous acids, mainly hypochlorous acid (HOCl) in physiologic situations, that greatly enhance polymorphonuclear leukocyte microbicidal activity
GO:0006979 response to oxidative stress	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: Mouse-rat orthology transfer of the same response-to-oxidative-stress claim. Reason: Same over-annotation as the IEA row; Mpo is a source of oxidants, not a stress responder. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: RGD:1592081 · rat Mpo SUPPORTS SOURCE BUT NOT TARGET Rat row rests on the same family-level/response-to-stimulus framing; the transfer is faithful but the claim casts an oxidant-generating enzyme as a stress responder.
GO:0008201 heparin binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: MPO is strongly cationic and binds glycosaminoglycans; heparin binding is transferred from human MPO. Reason: Plausible and probably correct, but a binding property peripheral to the catalytic and NET functions; no mouse evidence and no downstream function is asserted on it.
GO:0008201 heparin binding	ISO GO_REF:0000008	KEEP AS NON CORE	Summary: Curated mouse-human orthology transfer of heparin binding. Reason: Same peripheral claim as the Ensembl-Compara row.
GO:0009612 response to mechanical stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Rat-derived electronic transfer of "response to mechanical stimulus". Reason: Rows of this type rest on changes in Mpo expression or in tissue MPO activity after a treatment, which mostly report neutrophil recruitment rather than a cell-autonomous Mpo response. The term is not false but adds nothing about Mpo function.
GO:0018969 thiocyanate metabolic process	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: Inter-ontology inference from GO:0036393 thiocyanate peroxidase activity. Reason: Follows logically from the thiocyanate-oxidising side activity, which is retained as non-core; chloride remains the physiologically dominant substrate. Supporting Evidence: UniProtKB:P11247 Reaction=thiocyanate + H2O2 + H(+) = hypothiocyanous acid + H2O;
GO:0019430 removal of superoxide radicals	IMP PMID:10085024 Severe impairment in early host defense against Candida albi...	MARK AS OVER ANNOTATED	Summary: MGI IMP from the knockout paper, where superoxide production by Mpo-/- neutrophils was measured. Reason: The measured effect was in the opposite direction to a removal function - Mpo-/- neutrophils made slightly more superoxide, which reflects loss of downstream H2O2 consumption rather than Mpo removing superoxide radicals. Mpo does interact with superoxide (compound III formation), so the term is not plainly false, but the cited phenotype does not support it; GO:0042744 hydrogen peroxide catabolic process is the claim the data support and it is accepted here. REMOVE was considered and not chosen: myeloperoxidase does react with superoxide (compound III formation, and UniProt records superoxide-driven chemistry for the enzyme), so the claim is not demonstrably false - only unsupported by the cited phenotype. Over-annotation records that distinction, and the row should be revisited if direct evidence either way appears. Supporting Evidence: PMID:10085024 O 2 − generation was slightly increased in our MPO-deficient mice, consistent with the deficiency in humans
GO:0020037 heme binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-derived heme binding, matching the curated covalent heme b cofactor. Reason: The covalently bound heme b is required for the peroxidase chemistry, so this is a core supporting function. Supporting Evidence: UniProtKB:P11247 Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per monomer.
GO:0030141 secretory granule	IEA GO_REF:0000107	MODIFY	Summary: Electronic transfer of secretory granule localisation from human MPO. Reason: Correct but less specific than the evidence supports - azurophil granule is an is_a descendant of secretory granule and is already annotated to Mpo in this same GOA set. Proposed replacements: azurophil granule
GO:0030141 secretory granule	ISO GO_REF:0000008	MODIFY	Summary: Curated mouse-human orthology transfer of secretory granule localisation. Reason: Same refinement as the Ensembl-Compara row; the specific compartment is the azurophil granule. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P05164 · human MPO SUPPORTS TRANSFER Human MPO is correctly annotated to the granule compartment; only the granularity is at issue, since azurophil granule is the specific descendant and is annotated to mouse Mpo in the same GOA set. Proposed replacements: azurophil granule
GO:0031491 nucleosome binding	IEA GO_REF:0000107	ACCEPT	Summary: MPO binds nucleosomes as monomer and homodimer, the first step of its chromatin-decondensing activity. Reason: A specific, informative binding function that underpins the NET-formation core function; not generic protein binding. Supporting Evidence: UniProtKB:P11247 Promotes NET formation by mediating chromatin disassembly: translocates to the nucleus and specifically binds to nucleosomes, both as monomer and homodimer, leading to nucleosome unstacking and initial chromatin decondensation
GO:0031491 nucleosome binding	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer of nucleosome binding. Reason: Same claim as the Ensembl-Compara row.
GO:0031491 nucleosome binding	ISS GO_REF:0000024	ACCEPT	Summary: Curator-judged sequence-similarity transfer of nucleosome binding. Reason: Same claim; reinforcing evidence.
GO:0032094 response to food	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Rat-derived electronic transfer of "response to food". Reason: An expression- or tissue-activity-based response annotation that says nothing about Mpo molecular function and is dominated by changes in neutrophil numbers.
GO:0032496 response to lipopolysaccharide	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Rat-derived electronic transfer of "response to lipopolysaccharide". Reason: LPS raises tissue MPO activity mainly by recruiting and activating neutrophils; this is a readout of inflammation rather than evidence that Mpo itself responds to LPS.
GO:0034374 low-density lipoprotein particle remodeling	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: MPO-derived oxidants chlorinate and nitrate apolipoprotein A-I and oxidise LDL lipids and protein, modifying lipoprotein particles. Reason: A real but downstream consequence of extracellular MPO oxidant chemistry in the vasculature, peripheral to the host-defence core functions. Supporting Evidence: UniProtKB:P11247 Chlorination and nitration of the lipid-free form of APOA1 impairs cholesterol transport
GO:0034374 low-density lipoprotein particle remodeling	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Automated mouse-human orthology transfer of LDL particle remodeling. Reason: Same peripheral claim as the Ensembl-Compara row.
GO:0036393 thiocyanate peroxidase activity	IEA GO_REF:0000116	KEEP AS NON CORE	Summary: Rhea-based mapping of the thiocyanate-oxidising side reaction (RHEA:69416), curated in UniProt by similarity to human MPO. Reason: A genuine alternative-substrate activity (HOSCN formation), but chloride is the physiologically dominant substrate; kept as a non-core catalytic activity. Supporting Evidence: UniProtKB:P11247 Reaction=thiocyanate + H2O2 + H(+) = hypothiocyanous acid + H2O;
GO:0042582 azurophil granule	IEA GO_REF:0000107	ACCEPT	Summary: MPO is the defining constituent of neutrophil azurophil (primary) granules. Reason: The core storage and action compartment; granule MPO is discharged into the phagosome on ingestion of microbes. Supporting Evidence: PMID:10085024 is a cationic heme-containing enzyme found in primary azurophilic granules of neutrophils and primary lysosomes of monocytes PMID:23306200 It is packaged in the azurophilic granules of neutrophils and released into phagosomes when they ingest and kill bacteria
GO:0042582 azurophil granule	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer asserting MPO is active in the azurophil granule. Reason: Same compartment claim; is_active_in is appropriate because granule MPO is catalytically competent.
GO:0042582 azurophil granule	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer of azurophil granule localisation. Reason: Same claim as the other azurophil granule rows.
GO:0042582 azurophil granule	ISS GO_REF:0000024	ACCEPT	Summary: Curator-judged sequence-similarity transfer of azurophil granule localisation. Reason: Same claim; reinforcing evidence.
GO:0042742 defense response to bacterium	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA for defense response to bacterium across the animal heme peroxidase clade. Reason: Directly supported in mouse - Mpo-deficient mice were more likely to die of polymicrobial sepsis and failed to accumulate the MPO-specific oxidation product 3-chlorotyrosine. Supporting Evidence: PMID:11593004 In a mouse model of polymicrobial sepsis, we observed that mice deficient in myeloperoxidase were more likely than wild-type mice to die from infection. PMID:11593004 Thus, myeloperoxidase plays an important role in host defense against bacterial pathogens
GO:0042744 hydrogen peroxide catabolic process	IDA PMID:10085024 Severe impairment in early host defense against Candida albi...	ACCEPT	Summary: Mpo consumes the H2O2 generated by the NADPH oxidase, converting it to hypochlorous acid. Reason: This is the mechanistically correct process home for the chemistry that the obsoleted GO:0002149 hypochlorous acid biosynthetic process used to carry, and it is supported directly in mouse neutrophils. Supporting Evidence: PMID:10085024 During the respiratory burst, neutrophils generate O 2 − via the NADPH oxidase system. O 2 − is then reduced to H 2 O 2 , from which HOCl is generated by the MPO reaction.
GO:0042744 hydrogen peroxide catabolic process	IEA GO_REF:0000120	ACCEPT	Summary: Combined electronic inference of hydrogen peroxide catabolic process. Reason: Same claim as the mouse IDA/IMP rows.
GO:0042744 hydrogen peroxide catabolic process	IMP PMID:10085024 Severe impairment in early host defense against Candida albi...	ACCEPT	Summary: Loss of Mpo abolished HOCl generation from neutrophil-derived H2O2. Reason: Loss-of-function support for the same process claim. Supporting Evidence: PMID:10085024 the neutrophils of homozygous mutant mice produced HOCl at an almost undetectable level
GO:0042744 hydrogen peroxide catabolic process	ISO GO_REF:0000008	ACCEPT	Summary: Curated mouse-human orthology transfer of hydrogen peroxide catabolic process. Reason: Same claim, experimentally grounded in mouse.
GO:0042744 hydrogen peroxide catabolic process	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer of hydrogen peroxide catabolic process. Reason: Same claim, experimentally grounded in mouse.
GO:0044194 cytolytic granule	IEA GO_REF:0000044	MODIFY	Summary: UniProt SubCell-derived "cytolytic granule" localisation (SL-0543). Reason: GO:0044194 is defined as "A specialized secretory lysosome that is present in cells with cytolytic capability such as cytotoxic T lymphocytes and natural killer cells" - that is not where Mpo sits. Mpo is stored in the azurophil (primary) granule of neutrophils and monocytes, which is not a descendant of cytolytic granule, so this is a lateral correction to the right compartment. Proposed replacements: azurophil granule Supporting Evidence: UniProtKB:P11247 Localizes to azurophil granules, a type of primary lysosome found in neutrophils and monocytes that contains antimicrobial proteins
GO:0045335 phagocytic vesicle	IEA GO_REF:0000120	ACCEPT	Summary: Granule MPO is discharged into the phagosome, where it generates microbicidal oxidants. Reason: The phagosome is a principal site of action for the core peroxidase function. Supporting Evidence: PMID:23306200 It is packaged in the azurophilic granules of neutrophils and released into phagosomes when they ingest and kill bacteria
GO:0045335 phagocytic vesicle	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer asserting MPO is active in the phagocytic vesicle. Reason: Same claim; the phagosome is where phagocytosed pathogens meet MPO-derived HOCl.
GO:0045335 phagocytic vesicle	ISS GO_REF:0000024	ACCEPT	Summary: Curator-judged sequence-similarity transfer of phagosomal activity. Reason: Same claim as the other phagocytic vesicle rows.
GO:0050830 defense response to Gram-positive bacterium	IMP NOT PMID:10085024 Severe impairment in early host defense against Candida albi...	ACCEPT	Summary: NOT annotation - Mpo-/- mice cleared intraperitoneal Staphylococcus aureus as efficiently as wild-type, so Mpo is not required for defence against this Gram-positive bacterium. Reason: The negative claim is exactly what the cited experiment shows, and the authors attribute the compensation to other reactive oxygen species. Retaining the NOT is compatible with the general GO:0042742 defense response to bacterium annotation, which rests on the polymicrobial sepsis model. Supporting Evidence: PMID:10085024 Homozygous mutant mice did not exhibit a remarkable difference from wild-type mice in the rate of clearance of S. aureus from the peritoneal cavity PMID:10085024 It is thus likely that reactive oxygen species other than HOCl, such as O 2 − , are sufficient for neutrophils to kill S. aureus .
GO:0050832 defense response to fungus	IEA GO_REF:0000117	ACCEPT	Summary: ARBA-derived defense response to fungus. Reason: Independently established in mouse by the knockout phenotype, so the electronic row states a correct and core claim.
GO:0050832 defense response to fungus	IMP PMID:10085024 Severe impairment in early host defense against Candida albi...	ACCEPT	Summary: Mpo-/- mice developed lethal Candida albicans pneumonia and disseminated infection, with clearance delayed several hundred-fold. Reason: Core host-defence role, demonstrated by loss of function in mouse. Supporting Evidence: PMID:10085024 Thus, MPO is important for early host defense against fungal infection, and the inability to generate HOCl cannot be compensated for by other oxygen-dependent systems in vivo in mice.
GO:0070943 neutrophil-mediated killing of symbiont cell	IEA GO_REF:0000107	TOO GENERAL	Summary: Parent grouping term covering neutrophil killing of any symbiont cell. Reason: True, but entailed by the two specific descendants retained here, GO:0070944 neutrophil-mediated killing of bacterium and GO:0070947 neutrophil-mediated killing of fungus.
GO:0070943 neutrophil-mediated killing of symbiont cell	ISO GO_REF:0000119	TOO GENERAL	Summary: Mouse-human orthology transfer of the same grouping term. Reason: Same uninformative grouping; the specific descendants are kept.
GO:0070944 neutrophil-mediated killing of bacterium	IEA GO_REF:0000107	ACCEPT	Summary: Neutrophil MPO-derived hypohalous acids kill phagocytosed bacteria. Reason: Supported in mouse by the sepsis model, where Mpo-deficient mice died more often and the MPO-specific chlorination marker 3-chlorotyrosine failed to rise. Supporting Evidence: PMID:11593004 Levels of 3-chlorotyrosine did not rise in the septic myeloperoxidase-deficient mice.
GO:0070944 neutrophil-mediated killing of bacterium	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer of neutrophil-mediated killing of bacterium. Reason: Same claim as the Ensembl-Compara row.
GO:0070944 neutrophil-mediated killing of bacterium	ISS GO_REF:0000024	ACCEPT	Summary: Curator-judged sequence-similarity transfer of neutrophil-mediated killing of bacterium. Reason: Same claim; reinforcing evidence.
GO:0070947 neutrophil-mediated killing of fungus	IEA GO_REF:0000107	ACCEPT	Summary: Neutrophil MPO is required for effective killing of Candida albicans. Reason: The most specific accurate process statement about the mouse knockout phenotype, in which fungal killing - not fungal recognition - was impaired. Supporting Evidence: PMID:10085024 It is well known that MPO plus H 2 O 2 plus Cl − forms a cytotoxic triad in vitro which is toxic for fungi
GO:0070947 neutrophil-mediated killing of fungus	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer of neutrophil-mediated killing of fungus. Reason: Same claim as the Ensembl-Compara row, and directly supported in mouse.
GO:0070947 neutrophil-mediated killing of fungus	ISS GO_REF:0000024	ACCEPT	Summary: Curator-judged sequence-similarity transfer of neutrophil-mediated killing of fungus. Reason: Same claim; reinforcing evidence.
GO:0140644 neutrophil extracellular trap	IEA GO_REF:0000107	ACCEPT	Summary: MPO is a core protein constituent of neutrophil extracellular traps. Reason: Structural membership of the NET is well curated for the orthologous human protein and is the compartment in which extracellular MPO acts. Supporting Evidence: UniProtKB:P11247 Core component of NETs
GO:0140644 neutrophil extracellular trap	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer asserting MPO is active in the NET. Reason: Same claim; NET-bound MPO remains catalytically active.
GO:0140644 neutrophil extracellular trap	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer of NET localisation. Reason: Same claim as the other NET rows.
GO:0140644 neutrophil extracellular trap	ISS GO_REF:0000024	ACCEPT	Summary: Curator-judged sequence-similarity transfer of NET membership. Reason: Same claim; reinforcing evidence.
GO:0140645 neutrophil extracellular trap formation	IEA GO_REF:0000107	ACCEPT	Summary: MPO promotes NET formation by decondensing chromatin, independently of its peroxidase chemistry. Reason: A core, mechanistically distinct second function of the protein, retained as a separate core function in this review. Supporting Evidence: UniProtKB:P11247 Homodimers clash with one end of the nucleosomal DNA, leading to DNA unwrapping, initiating complete disassembly of nucleosomes and chromatin transformation into NETs in an ATP-independent manner
GO:0140645 neutrophil extracellular trap formation	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer of involvement in NET formation. Reason: Same claim as the Ensembl-Compara row.
GO:0140776 protein-containing complex destabilizing activity	IEA GO_REF:0000107	ACCEPT	Summary: MPO destabilises the nucleosome, promoting dissociation of its components - the molecular function behind chromatin decondensation in NET formation. Reason: An informative, non-catalytic molecular function of MPO; it is also the MF used for human MPO in the cached NET GO-CAM gomodel:68fac5ed00000028. Supporting Evidence: UniProtKB:P11247 Promotes NET formation by mediating chromatin disassembly: translocates to the nucleus and specifically binds to nucleosomes, both as monomer and homodimer, leading to nucleosome unstacking and initial chromatin decondensation
GO:0140776 protein-containing complex destabilizing activity	ISO GO_REF:0000119	ACCEPT	Summary: Automated mouse-human orthology transfer of complex-destabilising activity. Reason: Same claim as the Ensembl-Compara row.
GO:0140776 protein-containing complex destabilizing activity	ISS GO_REF:0000024	ACCEPT	Summary: Curator-judged sequence-similarity transfer of complex-destabilising activity. Reason: Same claim; reinforcing evidence.
GO:1904109 positive regulation of cholesterol import	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic transfer from human MPO of positive regulation of cholesterol import. Reason: The underlying chemistry is MPO-mediated chlorination and nitration of apolipoprotein A-I, which impairs cholesterol transport; casting this as a regulatory role of Mpo in cholesterol import turns a downstream oxidative modification of a substrate protein into a regulatory function, and there is no mouse evidence for it. The lipoprotein-modification claim is retained non-core as GO:0034374. Supporting Evidence: UniProtKB:P11247 Chlorination and nitration of the lipid-free form of APOA1 impairs cholesterol transport
GO:1904109 positive regulation of cholesterol import	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Automated mouse-human orthology transfer of the same regulatory claim. Reason: Same over-annotation as the Ensembl-Compara row. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P05164 · human MPO SUPPORTS SOURCE BUT NOT TARGET The human evidence concerns MPO-mediated chlorination/nitration of APOA1 and oxidation of lipoproteins; recasting that chemistry as regulation of cholesterol import overstates it, and no mouse evidence exists.
GO:1990268 response to gold nanoparticle	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Rat-derived electronic transfer of "response to gold nanoparticle". Reason: A treatment-response annotation that reports tissue MPO activity or expression change as an inflammation readout; it carries no information about Mpo function.

Gene Description

Proposed New Ontology Terms

hypochlorous acid synthase activity

Existing Annotations Review

Core Functions

Non-catalytic nucleosome-destabilising activity - myeloperoxidase translocates into the nucleus, binds nucleosomes as monomer and homodimer and unstacks and disassembles them in an ATP-independent manner, decondensing chromatin so that it can be extruded as a neutrophil extracellular trap.

References

Suggested Questions for Experts

Suggested Experiments

Knowledge Gaps

📚 Additional Documentation

Notes

📄 View Raw YAML