SUOX encodes sulfite oxidase, the terminal enzyme of oxidative sulfur amino acid (cysteine and methionine) catabolism. It is a homodimeric molybdenum-cofactor (Mo-molybdopterin) and heme b (cytochrome b5-type) dependent oxidoreductase that catalyses the oxidation of sulfite to sulfate (EC 1.8.3.1), transferring electrons ultimately to cytochrome c. Each subunit is organized into an N-terminal cytochrome b5 heme-binding domain, a central molybdopterin/oxidoreductase (Moco) domain, and a C-terminal dimerization domain. The mature protein is imported into the mitochondrial intermembrane space via a cleavable N-terminal transit peptide. Under hypoxic or ischemic conditions the enzyme can additionally run in reverse and reduce nitrite to nitric oxide. Loss-of-function variants cause isolated sulfite oxidase deficiency, a severe autosomal recessive neurometabolic disorder with neonatal encephalopathy, intractable seizures, and ectopia lentis that phenotypically resembles molybdenum cofactor deficiency.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Correct organelle but less specific than the authoritative UniProt localization, which places the mature enzyme in the mitochondrial intermembrane space (GO:0005758). Kept as non-core in favour of the more precise IMS term. Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Mitochondrion intermembrane space |
| GO:0006790 sulfur compound metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Correct but overly general. SUOX carries out the terminal reaction in the oxidative degradation of sulfur-containing (cysteine/methionine) amino acids, so a more specific catabolic process term is warranted. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN008570343 · sulfite oxidase family node SUPPORTS TRANSFER Family-level IBA term is biologically true but uninformative; the terminal role in sulfur amino acid catabolism warrants the more specific child term. Proposed replacements: sulfur amino acid catabolic process Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt reaction in the oxidative degradation of sulfur-containing amino acids |
| GO:0008482 sulfite oxidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function of SUOX, correctly assigned. Consistent with the experimental IDA (PMID:23163752) and UniProt catalytic activity (EC 1.8.3.1). Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Catalyzes the oxidation of sulfite to sulfate, the terminal |
| GO:0020037 heme binding | IBA GO_REF:0000033 | ACCEPT | Summary: Core cofactor-binding function. Each subunit binds one heme b non-covalently in its N-terminal cytochrome b5 domain, resolved crystallographically (PDB 1MJ4). Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Binds 1 heme b (iron(II)-protoporphyrin IX) group non-covalently |
| GO:0043546 molybdopterin cofactor binding | IBA GO_REF:0000033 | ACCEPT | Summary: Core cofactor-binding function. Each subunit binds one Mo-molybdopterin (Mo-MPT) cofactor essential for sulfite oxidase catalysis. Supported experimentally (IDA, PMID:23163752). Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit |
| GO:0005758 mitochondrial intermembrane space | IEA GO_REF:0000044 | ACCEPT | Summary: Correct and authoritative subcellular location. SUOX is a soluble enzyme of the mitochondrial intermembrane space, consistent with the UniProt subcellular location. Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Mitochondrion intermembrane space |
| GO:0008482 sulfite oxidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Correct core molecular function, electronically inferred from the EC 1.8.3.1 / Rhea mapping. Redundant with the experimental IDA and IBA annotations to the same term. Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt EC=1.8.3.1 |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Not wrong but far too general: this is a high-level parent of the specific sulfite oxidase activity (GO:0008482) already annotated. Over-annotation. |
| GO:0020037 heme binding | IEA GO_REF:0000002 | ACCEPT | Summary: Correct heme-binding function inferred electronically from the InterPro cytochrome b5 heme-binding signature. Redundant with the IBA annotation to the same term. Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Cytochrome b5 heme-binding |
| GO:0030151 molybdenum ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Technically correct (the Mo-MPT cofactor contains a molybdenum ion coordinated at the active site), but this is subsumed by the more informative molybdopterin cofactor binding (GO:0043546) already annotated. Kept as non-core. Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit |
| GO:0043546 molybdopterin cofactor binding | IEA GO_REF:0000002 | ACCEPT | Summary: Correct core cofactor-binding function inferred electronically from InterPro. Redundant with the experimental IDA and IBA annotations to the same term. Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a high-throughput edgotyping/interactome screen of Mendelian-disease alleles. Uninformative about SUOX molecular function and not part of its evolved role; retained (IPI) but flagged as over-annotation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from the HuRI systematic human binary interactome map. The reported partners (transcription factors, keratins, etc.) are not biologically coherent for a mitochondrial intermembrane-space metabolic enzyme. Uninformative; retained (IPI) but flagged as over-annotation. |
| GO:0006790 sulfur compound metabolic process | IEA GO_REF:0000041 | MODIFY | Summary: Correct but overly general UniPathway-derived annotation, duplicating the IBA annotation to the same term. A more specific sulfur amino acid catabolic process term is preferable. Proposed replacements: sulfur amino acid catabolic process Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt reaction in the oxidative degradation of sulfur-containing amino acids |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Contradicts the authoritative UniProt localization, which places SUOX in the mitochondrial intermembrane space (GO:0005758) as a soluble enzyme, not anchored in the inner membrane. This ISS transfer from the chicken orthologue (Q07116) is an over-annotation of location. Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Mitochondrion intermembrane space |
| GO:0098809 nitrite reductase activity | IDA PMID:41337830 An electrochemical perspective on human sulfite oxidase as a... | KEEP AS NON CORE | Summary: Experimentally demonstrated secondary activity: human sulfite oxidase can act as a nitrite reductase (KM 3.5 mM at pH 7), proposed to generate nitric oxide from nitrite under hypoxic/ischemic conditions. This is a real but non-core, proposed physiological role; sulfite is the only established physiological substrate. Kept as non-core. Supporting Evidence: PMID:41337830 HSO can act as an effective nitrite reductase with a KM file:human/SUOX/SUOX-uniprot.txt Can run in reverse direction and reduce nitrite to |
| GO:0005758 mitochondrial intermembrane space | ISS GO_REF:0000024 | ACCEPT | Summary: Correct core location, transferred by sequence similarity from the chicken orthologue (Q07116). Consistent with the UniProt subcellular location and the IEA-SubCell annotation to the same term. Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Mitochondrion intermembrane space |
| GO:0008482 sulfite oxidase activity | IDA PMID:23163752 Metal insertion into the molybdenum cofactor: product-substr... | ACCEPT | Summary: Direct experimental support for the core sulfite oxidase activity. UniProt cites this paper for the human SUOX catalytic activity (EC 1.8.3.1); the full text (not in the abstract-only cache) contains the enzymatic assay read by the curator. This is the defining molecular function of the gene. Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Catalyzes the oxidation of sulfite to sulfate, the terminal |
| GO:0043546 molybdopterin cofactor binding | IDA PMID:23163752 Metal insertion into the molybdenum cofactor: product-substr... | ACCEPT | Summary: Direct experimental support for binding of the Mo-molybdopterin cofactor, cited by UniProt for the human SUOX cofactor. Core cofactor-binding function. Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | KEEP AS NON CORE | Summary: Correct organelle from a high-confidence mitochondrial proteome study, but less specific than the mitochondrial intermembrane space localization. Kept as non-core. Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Mitochondrion intermembrane space |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-1614544 | MARK AS OVER ANNOTATED | Summary: Conflicts with the authoritative UniProt localization. SUOX resides in the mitochondrial intermembrane space (GO:0005758), not the matrix; the Reactome placement is an over-annotation of location. Supporting Evidence: file:human/SUOX/SUOX-uniprot.txt Mitochondrion intermembrane space |
| GO:0008482 sulfite oxidase activity | TAS PMID:9428520 Molecular basis of sulfite oxidase deficiency from the struc... | ACCEPT | Summary: Author-traceable statement of the core sulfite oxidase activity from the structural study of sulfite oxidase. Correct and core. Supporting Evidence: PMID:9428520 sulfite oxidase catalyzes the conversion of sulfite to sulfate |
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Download this section (compressed HTML)Q: Is the nitrite reductase / nitric-oxide-generating activity of SUOX physiologically significant in vivo under hypoxia, and does it contribute measurably to NO homeostasis?
Q: What is the electron acceptor and electron-transfer path in the human enzyme, and how does the intermembrane-space localization relate to cytochrome c as physiological acceptor?
Experiment: Genetic or pharmacological perturbation of SUOX in a hypoxia model to test whether the nitrite reductase activity affects cellular NO levels and downstream signaling.
Experiment: Structural determination of the full-length human holoenzyme (heme + Mo-MPT domains) to clarify inter-domain electron transfer and the basis of disease-associated variants.
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