ALAD

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006783 heme biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred involvement in heme biosynthesis. ALAD catalyzes the second, committed pyrrole-forming step of the heme pathway, so this is a core biological process. Reason: Correct and well supported. ALAD is the second enzyme of the heme biosynthetic pathway, condensing two ALA molecules into porphobilinogen. This is a core process for the gene. Supporting Evidence: PMID:3463993 the second enzyme in the heme Reactome:R-HSA-189451 Two molecules of ALA are condensed to form the monopyrrole porphobilinogen (PBG).
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred cytosolic localization. The cytosolic steps of heme biosynthesis, including the ALAD reaction, occur in the cytosol. Reason: Consistent with the UniProt-curated subcellular location (Cytoplasm, cytosol) and with Reactome, which places the ALAD-catalyzed step among the cytosolic heme-synthesis steps. Supporting Evidence: file:human/ALAD/ALAD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol Reactome:R-HSA-189451 The next four steps take place in the cytosol.
GO:0004655 porphobilinogen synthase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred porphobilinogen synthase (5-aminolevulinate dehydratase) activity, the core molecular function of ALAD across the ALAD/PBGS family. Reason: This is the defining molecular function of the gene, congruent with abundant experimental evidence (EXP/IDA) and the EC 4.2.1.24 / RHEA:24064 assignment in UniProt. Supporting Evidence: file:human/ALAD/ALAD-uniprot.txt Binds two molecules of 5-aminolevulinate per subunit, each at a Reactome:R-HSA-189439 catalyzes the asymmetric condensation of two molecules of ALA to form porphobilinogen
GO:0004655 porphobilinogen synthase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (ARBA/InterPro/RHEA/EC) of the core porphobilinogen synthase activity. Reason: Correctly captures the core catalytic function via EC 4.2.1.24 / RHEA:24064 mapping; redundant with, and confirmed by, the experimental annotations. Supporting Evidence: file:human/ALAD/ALAD-uniprot.txt EC=4.2.1.24
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation from the UniProt subcellular-location vocabulary mapping (cytosol). Reason: Consistent with curated UniProt localization and Reactome; the enzyme acts in the cytosol. Supporting Evidence: file:human/ALAD/ALAD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0033014 tetrapyrrole biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based electronic annotation to the broader tetrapyrrole biosynthetic process. Reason: Correct parent process: porphobilinogen is the committed precursor of all tetrapyrroles. Slightly more general than the heme-specific terms but accurate. Supporting Evidence: PMID:19812033 catalyzes the first common step in tetrapyrrole Reactome:R-HSA-189439 the precursor to all tetrapyrrole pigments such as heme and chlorophyll
GO:0046872 metal ion binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro-based electronic annotation for metal ion binding. ALAD is a zinc metalloenzyme (binds up to 8 Zn2+ per octamer) and also binds inhibitory Pb2+. Reason: Correct but generic parent of the more specific zinc ion binding (IDA) annotation. Zinc binding underpins catalysis but is a supporting molecular feature rather than the core function; kept as non-core. Supporting Evidence: PMID:11032836 eight Zn(II) per homo-octamer
GO:0001666 response to hypoxia	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic (Ensembl Compara) projection from the rat ortholog of a broad stimulus-response profile. Reason: Part of a large block of ECO:0000265 "response to X" terms projected from rat P06214. These reflect transcriptional/physiological responses in the ortholog, not ALAD's molecular role, and over-annotate the gene. No evidence connects ALAD's function specifically to hypoxia.
GO:0005576 extracellular region	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic projection of an extracellular-region localization from the rat ortholog. Reason: ALAD is a cytosolic enzyme. Extracellular detection reflects bystander presence in secretomes/granule proteomes rather than a genuine extracellular function; kept as non-core to remain consistent with the Reactome extracellular-region annotations.
GO:0006783 heme biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (ARBA) annotation to the core heme biosynthetic process. Reason: Correctly captures the core biological process; redundant with the IBA/IDA/TAS annotations. Supporting Evidence: PMID:3758678 the second enzyme in the heme biosynthetic pathway
GO:0006979 response to oxidative stress	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a stress-response term from the rat ortholog. Reason: Part of the broad rat-projected stimulus-response block; not informative of ALAD's molecular function and likely over-propagated.
GO:0007584 response to nutrient	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a nutrient-response term from the rat ortholog. Reason: Generic stimulus-response term projected from rat P06214; over-annotation.
GO:0009410 response to xenobiotic stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a xenobiotic-response term from the rat ortholog. Reason: Generic stimulus-response term; over-annotation not reflecting ALAD's molecular role.
GO:0009635 response to herbicide	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a herbicide-response term from the rat ortholog. Reason: Highly specific stimulus-response term projected electronically; over-annotation.
GO:0009636 response to toxic substance	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a toxic-substance-response term from the rat ortholog. Reason: Generic stimulus-response term; over-annotation.
GO:0009725 response to hormone	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a hormone-response term from the rat ortholog. Reason: Generic stimulus-response term; over-annotation.
GO:0010038 response to metal ion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic projection of a metal-ion-response term from the rat ortholog. ALAD activity is strongly modulated by metals (Zn2+ cofactor; Pb2+ inhibition). Reason: Unlike most terms in the projected block, this one is biologically defensible: ALAD is a zinc metalloenzyme whose activity is displaced by lead and other divalent metals. Retained as non-core biology rather than removed. Supporting Evidence: file:human/ALAD/ALAD-uniprot.txt Inhibited by divalent lead ions.
GO:0010039 response to iron ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of an iron-ion-response term from the rat ortholog. Reason: Iron is incorporated downstream (ferrochelatase), not by ALAD; this projected term is not informative of ALAD's molecular role and is over-annotated.
GO:0010043 response to zinc ion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic projection of a zinc-ion-response term from the rat ortholog. ALAD requires Zn2+ as its catalytic cofactor. Reason: Defensible given ALAD's obligate zinc-cofactor dependence; kept as non-core rather than removed. Supporting Evidence: PMID:11032836 eight Zn(II) per homo-octamer
GO:0010044 response to aluminum ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of an aluminum-ion-response term from the rat ortholog. Reason: Specific stimulus-response term projected electronically; over-annotation.
GO:0010212 response to ionizing radiation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a radiation-response term from the rat ortholog. Reason: Generic stimulus-response term; over-annotation.
GO:0010266 response to vitamin B1	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a vitamin B1-response term from the rat ortholog. Reason: Specific stimulus-response term projected electronically; over-annotation.
GO:0010269 response to selenium ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a selenium-ion-response term from the rat ortholog. Reason: Specific stimulus-response term projected electronically; over-annotation.
GO:0010288 response to lead ion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic projection of a lead-ion-response term from the rat ortholog. ALAD is the classic molecular target of lead poisoning. Reason: Biologically well supported: divalent lead inhibits ALAD by displacing the catalytic zinc, and ALAD is a principal target of lead. Retained as non-core toxicology-relevant biology. Supporting Evidence: PMID:11032836 is a main target in lead poisoning Reactome:R-HSA-190141 Lead binds to ALAD enzyme displacing half the zinc ions essential for its catalytic activity
GO:0014823 response to activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a "response to activity" term from the rat ortholog. Reason: Generic stimulus-response term; over-annotation.
GO:0031667 response to nutrient levels	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a nutrient-levels-response term from the rat ortholog. Reason: Generic stimulus-response term; over-annotation.
GO:0032025 response to cobalt ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a cobalt-ion-response term from the rat ortholog. Reason: Specific stimulus-response term projected electronically; over-annotation.
GO:0032496 response to lipopolysaccharide	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of an LPS-response term from the rat ortholog. Reason: Generic stimulus-response term; over-annotation.
GO:0033197 response to vitamin E	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a vitamin E-response term from the rat ortholog. Reason: Specific stimulus-response term projected electronically; over-annotation.
GO:0033273 response to vitamin	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a vitamin-response term from the rat ortholog. Reason: Generic stimulus-response term; over-annotation.
GO:0043200 response to amino acid	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of an amino-acid-response term from the rat ortholog. Reason: Generic stimulus-response term; over-annotation.
GO:0045471 response to ethanol	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of an ethanol-response term from the rat ortholog. Reason: Generic stimulus-response term; over-annotation.
GO:0046685 response to arsenic-containing substance	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of an arsenic-response term from the rat ortholog. Reason: Specific stimulus-response term projected electronically; over-annotation.
GO:0046686 response to cadmium ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a cadmium-ion-response term from the rat ortholog. Reason: Specific stimulus-response term projected electronically; over-annotation.
GO:0046689 response to mercury ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a mercury-ion-response term from the rat ortholog. Reason: Specific stimulus-response term projected electronically; over-annotation.
GO:0051384 response to glucocorticoid	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a glucocorticoid-response term from the rat ortholog. Reason: Generic stimulus-response term; over-annotation.
GO:0051597 response to methylmercury	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a methylmercury-response term from the rat ortholog. Reason: Specific stimulus-response term projected electronically; over-annotation.
GO:0070541 response to platinum ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a platinum-ion-response term from the rat ortholog. Reason: Specific stimulus-response term projected electronically; over-annotation.
GO:0070542 response to fatty acid	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic projection of a fatty-acid-response term from the rat ortholog. Reason: Generic stimulus-response term; over-annotation.
GO:0071284 cellular response to lead ion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic projection of a cellular-lead-response term from the rat ortholog. ALAD is directly inhibited by lead. Reason: Biologically defensible: lead directly targets and inhibits ALAD by displacing its catalytic zinc. Retained as non-core toxicology-relevant biology. Supporting Evidence: Reactome:R-HSA-190141 Lead is a major environmental toxin and this enzyme is one of its principal molecular targets
GO:1904854 proteasome core complex binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic projection of a proteasome-core-complex-binding term from the rat ortholog, matching ALAD's characterized moonlighting role as the proteasome inhibitor CF-2. Reason: Corroborates the experimentally documented CF-2/proteasome-inhibitor moonlighting activity (PMID:8175643). This is a genuine secondary/moonlighting function, not the core catalytic role; kept as non-core. Supporting Evidence: PMID:8175643 inhibitory factor is indistinguishable from
GO:0006785 heme B biosynthetic process	IDA PMID:11032836 The molecular mechanism of lead inhibition of human porphobi...	ACCEPT	Summary: Direct-assay involvement in heme B (protoheme) biosynthesis, the specific end-product of the pathway ALAD initiates at the pyrrole-forming step. Reason: A valid, more specific child of heme biosynthetic process. ALAD's condensation of ALA to porphobilinogen is an essential early step toward heme B. Consistent with the experimental characterization of human PBGS. Supporting Evidence: PMID:11032836 porphobilinogen synthase
GO:0006783 heme biosynthetic process	TAS Reactome:R-HSA-189451	ACCEPT	Summary: Traceable (Reactome) involvement in heme biosynthesis; ALAD catalyzes the cytosolic condensation of two ALA into porphobilinogen within the eight-enzyme heme pathway. Reason: Core biological process, supported by the curated Reactome heme-biosynthesis pathway. Supporting Evidence: Reactome:R-HSA-189451 Eight enzymes are involved in heme biosynthesis
GO:0032791 lead ion binding	EXP PMID:11032836 The molecular mechanism of lead inhibition of human porphobi...	KEEP AS NON CORE	Summary: Experimentally demonstrated lead binding. Pb2+ binds ALAD at a hybrid of the ZnA and ZnB metal sites, partially displacing the catalytic zinc and inhibiting activity. Reason: Well supported experimentally and mechanistically important for lead toxicology, but it represents inhibitory metal binding rather than the enzyme's core catalytic function; kept as non-core. Supporting Evidence: PMID:11032836 ligands to both ZnA and ZnB interact with Pb(II) Reactome:R-HSA-190141 Lead binds to ALAD enzyme displacing half the zinc ions essential for its catalytic activity
GO:0004655 porphobilinogen synthase activity	EXP PMID:12897770 Control of tetrapyrrole biosynthesis by alternate quaternary...	ACCEPT	Summary: Experimental (crystallographic/biochemical) confirmation of human porphobilinogen synthase activity and its octamer/hexamer quaternary regulation. Reason: Directly supports the core molecular function with experimental evidence on the human enzyme. Supporting Evidence: PMID:12897770 catalyzes the first common step in the
GO:0004655 porphobilinogen synthase activity	EXP PMID:19812033 Allosteric inhibition of human porphobilinogen synthase.	ACCEPT	Summary: Experimental confirmation of human porphobilinogen synthase activity as an allosterically regulated enzyme (octamer/hexamer/dimer equilibrium). Reason: Directly supports the core molecular function with experimental evidence on the human enzyme. Supporting Evidence: PMID:19812033 catalyzes the first common step in tetrapyrrole
GO:0005829 cytosol	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity-based transfer of cytosolic localization from the mouse ortholog. Reason: Consistent with the curated cytosolic location and the cytosolic phase of heme synthesis. Supporting Evidence: file:human/ALAD/ALAD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798748	KEEP AS NON CORE	Summary: Reactome annotation placing ALAD in the extracellular region via neutrophil secretory-granule exocytosis. Reason: ALAD is a cytosolic enzyme detected as cargo in neutrophil granule/secretome datasets. This is a bystander localization, not a core function; kept as non-core rather than removed. Supporting Evidence: Reactome:R-HSA-6798748 Secretory vesicles provide a reservoir of secreted proteins
GO:0005576 extracellular region	TAS Reactome:R-HSA-6800434	KEEP AS NON CORE	Summary: Reactome annotation placing ALAD in the extracellular region via ficolin-1-rich granule exocytosis. Reason: Bystander granule/secretome localization of a cytosolic enzyme; not a core function. Supporting Evidence: Reactome:R-HSA-6800434 rapid release of pattern recognition molecules
GO:0034774 secretory granule lumen	TAS Reactome:R-HSA-6798748	KEEP AS NON CORE	Summary: Reactome annotation to the secretory granule lumen (neutrophil degranulation). Reason: Reflects detection of the abundant cytosolic protein in neutrophil granule proteomes; a bystander localization, not the core cytosolic catalytic compartment. Supporting Evidence: Reactome:R-HSA-6798748 Secretory vesicles provide a reservoir of secreted proteins
GO:1904813 ficolin-1-rich granule lumen	TAS Reactome:R-HSA-6800434	KEEP AS NON CORE	Summary: Reactome annotation to the ficolin-1-rich granule lumen (neutrophil degranulation). Reason: Bystander granule-proteome localization of a cytosolic enzyme; not a core function. Supporting Evidence: Reactome:R-HSA-6800434 ficolin-1 rich granules
GO:0004655 porphobilinogen synthase activity	IDA PMID:8175643 240-kDa proteasome inhibitor (CF-2) is identical to delta-am...	ACCEPT	Summary: Direct-assay porphobilinogen synthase (dehydratase) activity; the CF-2/proteasome-inhibitor protein retained ALA-dehydratase activity, confirming its identity as ALAD. Reason: Supports the core catalytic function; the study showed similar dehydratase specific activities in CF-2 and ALAD and dehydratase activity in recombinant ALAD. Supporting Evidence: PMID:8175643 similar dehydratase and proteasome
GO:1901799 negative regulation of proteasomal protein catabolic process	IDA PMID:8175643 240-kDa proteasome inhibitor (CF-2) is identical to delta-am...	KEEP AS NON CORE	Summary: Direct-assay evidence that ALAD (as CF-2) inhibits the proteasome, a moonlighting function distinct from its heme-synthesis role. Reason: Genuine gene-sharing/moonlighting activity: the 240-kDa proteasome inhibitor CF-2 is identical to ALAD and inhibits the ATP/ubiquitin-dependent proteasome pathway. Not the core catalytic function; retained as non-core. Supporting Evidence: PMID:8175643 The dual role of this protein as CF-2 in the
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: High-throughput proteomic detection of ALAD in urinary/prostatic exosome preparations. Reason: Bystander localization of an abundant cytosolic protein in exosome proteomes; not a core function. Retained per curation policy for experimental HDA localizations. Supporting Evidence: PMID:23533145 exosome preparations were characterized by a shotgun proteomics procedure
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	KEEP AS NON CORE	Summary: High-throughput proteomic detection of ALAD in isolated human sperm nuclei. Reason: Bystander localization of an abundant cytosolic protein in a sperm-nucleus proteome; there is no functional evidence for a nuclear role. Retained (not removed) per policy for experimental HDA localizations. Supporting Evidence: PMID:21630459 403 different proteins have been identified from the isolated sperm nuclei
GO:0005829 cytosol	TAS Reactome:R-HSA-189439	ACCEPT	Summary: Reactome traceable annotation placing the ALAD-catalyzed ALA-condensation reaction in the cytosol. Reason: Core localization; the enzyme acts in the cytosol. Supporting Evidence: Reactome:R-HSA-189439 catalyzes the asymmetric condensation of two molecules of ALA to form porphobilinogen
GO:0005829 cytosol	TAS Reactome:R-HSA-190141	ACCEPT	Summary: Reactome traceable annotation of cytosolic localization (ALAD-Pb2+ binding reaction). Reason: Core localization; consistent with UniProt and the other cytosol annotations. Supporting Evidence: file:human/ALAD/ALAD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0004655 porphobilinogen synthase activity	IDA PMID:11032836 The molecular mechanism of lead inhibition of human porphobi...	ACCEPT	Summary: Direct-assay porphobilinogen synthase activity of purified/recombinant human PBGS, with kinetic characterization and cysteine mutagenesis defining the catalytic zinc site. Reason: Strong experimental support for the core molecular function on the human enzyme. Supporting Evidence: PMID:11032836 is a main target in lead poisoning
GO:0006783 heme biosynthetic process	IDA PMID:11032836 The molecular mechanism of lead inhibition of human porphobi...	ACCEPT	Summary: Direct-assay involvement in heme biosynthesis via characterization of human PBGS as the pyrrole-forming enzyme of the heme pathway. Reason: Core biological process, experimentally supported on the human enzyme. Supporting Evidence: PMID:11032836 porphobilinogen synthase
GO:0008270 zinc ion binding	IDA PMID:11032836 The molecular mechanism of lead inhibition of human porphobi...	KEEP AS NON CORE	Summary: Direct-assay zinc binding: human PBGS purifies with eight Zn2+ per homo-octamer, four of which are required for activity; cysteine mutagenesis maps the catalytic ZnB site. Reason: Well-supported and mechanistically essential (the catalytic metal), but it is a supporting molecular feature underpinning the porphobilinogen synthase activity rather than the core function term itself; kept as non-core. Supporting Evidence: PMID:11032836 eight Zn(II) per homo-octamer PMID:11032836 are required for activity
GO:0042802 identical protein binding	IPI PMID:11032836 The molecular mechanism of lead inhibition of human porphobi...	MARK AS OVER ANNOTATED	Summary: Self-interaction (ALAD binds ALAD), reflecting its assembly into a homo-octamer/homohexamer. Reason: "Identical protein binding" is an uninformative binding term; the biologically meaningful fact (self-assembly into the active octamer) is better captured by protein homooligomerization. Per curation policy this bare protein-binding IPI is marked as over-annotated rather than removed. Supporting Evidence: file:human/ALAD/ALAD-uniprot.txt Homooctamer; active form. Homohexamer; low activity form.
GO:0051260 protein homooligomerization	IPI PMID:11032836 The molecular mechanism of lead inhibition of human porphobi...	KEEP AS NON CORE	Summary: Homo-oligomerization into the catalytically active octamer (and low-activity hexamer), central to ALAD's morpheein-type allosteric regulation. Reason: Functionally meaningful: the octamer is the active oligomeric form and the octamer/hexamer equilibrium governs activity and disease. Retained as non-core biology that supports, but is not itself, the catalytic function. Supporting Evidence: file:human/ALAD/ALAD-uniprot.txt Homooctamer; active form. Homohexamer; low activity form.
GO:0003824 catalytic activity	TAS PMID:2063868 delta-Aminolevulinate dehydratase deficient porphyria: ident...	MODIFY	Summary: Traceable annotation to generic catalytic activity; ALAD's specific catalytic function is porphobilinogen synthase activity. Reason: The root-level "catalytic activity" term is uninformative for a well-characterized enzyme. It should be replaced by the specific molecular function porphobilinogen synthase activity (GO:0004655). Proposed replacements: porphobilinogen synthase activity Supporting Evidence: PMID:2063868 the heme biosynthetic enzyme, delta-aminolevulinate dehydratase
GO:0004655 porphobilinogen synthase activity	TAS PMID:3463993 Human delta-aminolevulinate dehydratase: nucleotide sequence...	ACCEPT	Summary: Traceable annotation of porphobilinogen synthase activity from the cDNA-cloning paper that identified ALA-D (PBGS, EC 4.2.1.24). Reason: Supports the core molecular function; consistent with all other MF evidence. Supporting Evidence: PMID:3463993 porphobilinogen synthase; EC 4.2.1.24
GO:0006783 heme biosynthetic process	TAS PMID:3758678 Molecular cloning of a cDNA for human delta-aminolevulinate ...	ACCEPT	Summary: Traceable annotation of involvement in heme biosynthesis from the cDNA-cloning paper that identified ALA-D as the second enzyme of the heme pathway. Reason: Supports the core biological process. Supporting Evidence: PMID:3758678 the second enzyme in the heme biosynthetic pathway

Gene Description

Existing Annotations Review

Core Functions

Porphobilinogen synthase (5-aminolevulinate dehydratase, EC 4.2.1.24): catalyzes the second step of heme biosynthesis, the zinc-dependent asymmetric condensation of two molecules of 5-aminolevulinate into the monopyrrole porphobilinogen, acting as a cytosolic homo-octamer.

Zinc-dependent metallo-catalysis: ALAD binds zinc ions (up to eight per octamer, four required for activity) at its catalytic site; this metal-ion binding is essential for the porphobilinogen synthase reaction and is the site displaced by inhibitory lead.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

📄 View Raw YAML