hem1 (SPAC2F3.09; UniProt O14092) encodes mitochondrial 5-aminolevulinate synthase (ALAS, EC 2.3.1.37), a pyridoxal 5'-phosphate-dependent enzyme of the class-II aminotransferase family. In the mitochondrial matrix it condenses succinyl-CoA with glycine to 5-aminolevulinate, the first and committed step of heme biosynthesis. hem1 deletion is lethal unless ALA or hemin is supplied, so hem1 mutants are used to make S. pombe depend on heme uptake.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003870 5-aminolevulinate synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from ALAS node PTN000343737 (PTHR13693), whose IBD seeds include S. cerevisiae HEM1, mammalian ALAS1/2 and hem1 itself (PomBase:SPAC2F3.09). hem1 is in the ALAS-specific NCBIfam TIGR01821 family; sound. Supporting Evidence: file:SCHPO/hem1/hem1-uniprot.txt PANTHER; PTHR13693; CLASS II AMINOTRANSFERASE/8-AMINO-7-OXONONANOATE SYNTHASE; 1. file:SCHPO/hem1/hem1-uniprot.txt NCBIfam; TIGR01821; 5aminolev_synth; 1. file:SCHPO/hem1/hem1-uniprot.txt FUNCTION: Catalyzes the synthesis of 5-aminolevulinate (ALA) from succinyl-CoA and glycine, the first and rate-limiting step in heme biosynthesis. file:SCHPO/hem1/hem1-uniprot.txt Reaction=succinyl-CoA + glycine + H(+) = 5-aminolevulinate + CO2 + CoA; |
| GO:0003870 5-aminolevulinate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC 2.3.1.37 / RHEA:12921 InterPro mapping; consistent. Supporting Evidence: file:SCHPO/hem1/hem1-uniprot.txt Reaction=succinyl-CoA + glycine + H(+) = 5-aminolevulinate + CO2 + CoA; |
| GO:0003870 5-aminolevulinate synthase activity | IMP PMID:25733668 Shu1 is a cell-surface protein involved in iron acquisition ... | ACCEPT | Summary: hem1 deletion is lethal unless ALA is supplied: the auxotrophy is specific to the product of the ALAS reaction. Supporting Evidence: PMID:25733668 The hem1 Ξ deletion is lethal for S. pombe ( 9 ), unless exogenous ALA is provided, allowing heme biosynthesis from step 2 to proceed. PMID:25733668 Hem1 (or Ξ΄-aminolevulinate acid synthase) catalyzes the biosynthesis of Ξ΄-aminolevulinate (ALA) 2 from succinyl-CoA and glycine. |
| GO:0003870 5-aminolevulinate synthase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Curator transfer from S. cerevisiae HEM1 (P09950), whose ALAS activity was shown on the purified enzyme; consistent with the hem1 deletion phenotype. Supporting Evidence: file:SCHPO/hem1/hem1-uniprot.txt FUNCTION: Catalyzes the synthesis of 5-aminolevulinate (ALA) from succinyl-CoA and glycine, the first and rate-limiting step in heme biosynthesis. PMID:6381051 5-Aminolevulinate synthase from yeast mitochondria has been purified to homogeneity for the first time. |
| GO:0005739 mitochondrion | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome YFP screen placed hem1 in mitochondria. Whole-cell imaging cannot resolve the sub-compartment, so the root organelle row is accepted; the matrix is captured by the GO:0005759 rows. Supporting Evidence: file:SCHPO/hem1/hem1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:16823372}. PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA is_active_in mitochondrion from PTN000343737. Checked the IBD seeds: S. cerevisiae HEM1, mammalian ALAS1/2 and hem1 itself are mitochondrial matrix enzymes, and the S. pombe screen agrees. The organelle claim holds; the matrix is captured by the GO:0005759 rows. Supporting Evidence: file:SCHPO/hem1/hem1-uniprot.txt PANTHER; PTHR13693; CLASS II AMINOTRANSFERASE/8-AMINO-7-OXONONANOATE SYNTHASE; 1. file:SCHPO/hem1/hem1-uniprot.txt NCBIfam; TIGR01821; 5aminolev_synth; 1. PMID:16823372 we determined the localization of 4,431 proteins file:SCHPO/hem1/hem1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:16823372}. |
| GO:0005759 mitochondrial matrix | EXP PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: PomBase assigned mitochondrial matrix from the ORFeome screen, and UniProt records the matrix location with experimental evidence from that paper. The matrix assignment agrees with the S. cerevisiae ortholog, which is imported into the matrix and processed (PMID:3023841), and with the use of mitochondrial succinyl-CoA. Accepted. Supporting Evidence: file:SCHPO/hem1/hem1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:16823372}. PMID:3023841 The enzyme is synthesized as a precursor in the cytoplasm and imported into the matrix of the mitochondria, where it is processed to its mature form. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping. Supporting Evidence: file:SCHPO/hem1/hem1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:16823372}. |
| GO:0006783 heme biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: First committed step of heme biosynthesis. Supporting Evidence: file:SCHPO/hem1/hem1-uniprot.txt PANTHER; PTHR13693; CLASS II AMINOTRANSFERASE/8-AMINO-7-OXONONANOATE SYNTHASE; 1. file:SCHPO/hem1/hem1-uniprot.txt NCBIfam; TIGR01821; 5aminolev_synth; 1. file:SCHPO/hem1/hem1-uniprot.txt FUNCTION: Catalyzes the synthesis of 5-aminolevulinate (ALA) from succinyl-CoA and glycine, the first and rate-limiting step in heme biosynthesis. |
| GO:0006783 heme biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA mapping; consistent. Supporting Evidence: file:SCHPO/hem1/hem1-uniprot.txt FUNCTION: Catalyzes the synthesis of 5-aminolevulinate (ALA) from succinyl-CoA and glycine, the first and rate-limiting step in heme biosynthesis. |
| GO:0006783 heme biosynthetic process | IMP PMID:25733668 Shu1 is a cell-surface protein involved in iron acquisition ... | ACCEPT | Summary: hem1 deletion blocks heme biosynthesis and is rescued by ALA (or by hemin uptake). Supporting Evidence: PMID:25733668 The hem1 Ξ deletion is lethal for S. pombe ( 9 ), unless exogenous ALA is provided, allowing heme biosynthesis from step 2 to proceed. |
| GO:0016740 transferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic transferase InterPro mapping; the specific ALAS activity is annotated. Reason: Correct but too general: 5-aminolevulinate synthase activity (GO:0003870), an is_a descendant already carried by hem1, is the specific activity. Proposed replacements: 5-aminolevulinate synthase activity Supporting Evidence: file:SCHPO/hem1/hem1-uniprot.txt Reaction=succinyl-CoA + glycine + H(+) = 5-aminolevulinate + CO2 + CoA; |
| GO:0030170 pyridoxal phosphate binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: PLP is the ALAS cofactor (InterPro2GO from the PLP-dependent transferase signatures). True and as specific as warranted, but a cofactor-binding property subsidiary to the enzyme activity. Supporting Evidence: file:SCHPO/hem1/hem1-uniprot.txt Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; |
| GO:0033014 tetrapyrrole biosynthetic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO mapping (IPR010961). ALA is the first committed precursor of all tetrapyrroles, heme and siroheme alike. Reason: Correct and as precise as warranted for this step: the product of this enzyme is a common precursor of all tetrapyrroles (heme and siroheme), so tetrapyrrole biosynthesis is not a mere restatement of heme biosynthesis. Kept as non-core because the core function is assigned to the heme pathway. Supporting Evidence: file:SCHPO/hem1/hem1-uniprot.txt FUNCTION: Catalyzes the synthesis of 5-aminolevulinate (ALA) from succinyl-CoA and glycine, the first and rate-limiting step in heme biosynthesis. |
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