SLC25A38 is a mitochondrial glycine carrier of the SLC25 (mitochondrial carrier, TC 2.A.29) family. It is a multi-pass inner-membrane transport protein with the canonical mitochondrial-carrier architecture of three tandem Solcar repeats and six transmembrane helices. Its molecular function is to import glycine from the cytosol across the inner membrane into the mitochondrial matrix. The imported glycine supplies the substrate for the first, committed step of heme biosynthesis, in which 5-aminolevulinate synthase condenses glycine with succinyl-CoA to form 5-aminolevulinate; it also feeds mitochondrial glycine/one-carbon metabolism. SLC25A38 is preferentially expressed in erythroid cells and is required during erythropoiesis, where heme production is high. The yeast orthologue is Hem25p. Loss-of-function variants cause autosomal recessive, pyridoxine-refractory congenital sideroblastic anemia (SIDBA2), reflecting impaired mitochondrial glycine supply for heme synthesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: SLC25A38 is a mitochondrial protein; the phylogenetic (IBA) mitochondrion annotation is correct but general. The specific, better-supported location is the mitochondrial inner membrane (GO:0005743), where this multi-pass carrier resides. Keep as non-core context. Supporting Evidence: file:human/SLC25A38/SLC25A38-uniprot.txt Mitochondrion inner membrane |
| GO:0015187 glycine transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Correct and specific molecular function. SLC25A38 (and its yeast orthologue Hem25p) was experimentally shown to be a mitochondrial glycine carrier; this phylogenetic annotation is consistent with the direct biochemical evidence. Core function. Supporting Evidence: PMID:27476175 are the main mitochondrial glycine transporters |
| GO:1904983 glycine import into mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Correct directional transport process, matching the demonstrated import of glycine into the matrix. Consistent with the direct experimental evidence (IMP). Core process. Supporting Evidence: file:human/SLC25A38/SLC25A38-uniprot.txt Mitochondrial glycine transporter that imports glycine into |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Correct core cellular location. UniProt places SLC25A38 in the mitochondrial inner membrane as a multi-pass membrane protein, consistent with its six transmembrane helices and mitochondrial-carrier architecture. Supporting Evidence: file:human/SLC25A38/SLC25A38-uniprot.txt Mitochondrion inner membrane |
| GO:0015187 glycine transmembrane transporter activity | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of the core glycine transmembrane transporter activity annotation, here by electronic inference (InterPro/UniRule). Correct and consistent with the experimental evidence. Core function. Supporting Evidence: PMID:27476175 are the main mitochondrial glycine transporters |
| GO:0016020 membrane | IEA GO_REF:0000104 | MARK AS OVER ANNOTATED | Summary: True but uninformative. The specific location is the mitochondrial inner membrane (GO:0005743); the bare "membrane" term is a generic over-annotation that adds no information beyond the more specific inner-membrane annotation. Supporting Evidence: file:human/SLC25A38/SLC25A38-uniprot.txt Mitochondrion inner membrane |
| GO:0030218 erythrocyte differentiation | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: SLC25A38 is erythroid-specific and required during erythropoiesis; its loss causes ineffective erythropoiesis and sideroblastic anemia. This is a downstream physiological role that follows from supplying heme precursor for hemoglobinization, not the gene's molecular function. Keep as non-core process context. Supporting Evidence: file:human/SLC25A38/SLC25A38-uniprot.txt Required during erythropoiesis |
| GO:1904983 glycine import into mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of the core glycine-import process annotation, here by electronic inference. Correct and consistent with the direct experimental evidence. Core process. Supporting Evidence: file:human/SLC25A38/SLC25A38-uniprot.txt Mitochondrial glycine transporter that imports glycine into |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | KEEP AS NON CORE | Summary: High-throughput proteomic localization of SLC25A38 to mitochondria, corroborating its mitochondrial residence. Correct but general; the specific location is the inner membrane (GO:0005743). Keep as non-core context. Supporting Evidence: file:human/SLC25A38/SLC25A38-uniprot.txt Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Core cellular location, transferred by sequence similarity from the mouse orthologue (Q91XD8). Consistent with UniProt's inner-membrane, multi-pass assignment and the protein's transmembrane topology. Core location. Supporting Evidence: file:human/SLC25A38/SLC25A38-uniprot.txt Mitochondrion inner membrane |
| GO:0015187 glycine transmembrane transporter activity | IMP PMID:27476175 Characterization of Human and Yeast Mitochondrial Glycine Ca... | ACCEPT | Summary: Direct experimental basis for the core molecular function. Reconstituted human SLC25A38 (and yeast Hem25p) was characterized as a mitochondrial glycine carrier, providing definitive evidence of glycine transport. This is the primary, most specific, well-supported MF. Core function. Supporting Evidence: PMID:27476175 Hem25p and its human orthologue SLC25A38 are the main mitochondrial glycine transporters required for heme synthesis, providing definitive evidence of their previously proposed glycine transport function. |
| GO:1904983 glycine import into mitochondrion | IMP PMID:27476175 Characterization of Human and Yeast Mitochondrial Glycine Ca... | ACCEPT | Summary: Direct experimental basis for the core transport process: SLC25A38 imports glycine into the mitochondrial matrix. Consistent with the demonstrated glycine carrier activity and heme-synthesis dependence in the complementation assays. Core process. Supporting Evidence: PMID:27476175 Hem25p and its human orthologue SLC25A38 are the main mitochondrial glycine transporters required for heme synthesis |
| GO:0006783 heme biosynthetic process | TAS PMID:19412178 Mutations in mitochondrial carrier family gene SLC25A38 caus... | ACCEPT | Summary: SLC25A38 supplies glycine for the first committed step of heme biosynthesis (ALA synthase: glycine + succinyl-CoA -> 5-aminolevulinate). Loss of function impairs heme synthesis and causes sideroblastic anemia. Core biological process. Supporting Evidence: PMID:19412178 SLC25A38 is important for the biosynthesis of heme in |
| GO:0030218 erythrocyte differentiation | IMP PMID:19412178 Mutations in mitochondrial carrier family gene SLC25A38 caus... | KEEP AS NON CORE | Summary: SLC25A38 is preferentially expressed in erythroid cells and required during erythropoiesis; loss-of-function variants cause congenital sideroblastic anemia from defective heme supply. A physiological/erythroid-context role downstream of the core glycine-import-for-heme function, rather than the gene's molecular activity. Keep as non-core. Supporting Evidence: file:human/SLC25A38/SLC25A38-uniprot.txt Preferentially expressed in erythroid cells |
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