SLC25A15

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) assignment placing ORNT1 activity in the mitochondrion. This is correct but general; the specific and experimentally supported location is the mitochondrial inner membrane. Reason: ORNT1 is a mitochondrial carrier that acts in the mitochondrion; the IBA call across the SLC25 ornithine-carrier clade is sound. It is a correct parent of the more specific mitochondrial inner membrane annotation, so it is retained as accurate though non-core. The precise location is captured by GO:0005743.
GO:0000064 L-ornithine transmembrane transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of L-ornithine transmembrane transporter activity, the core molecular function of ORNT1 and its fungal orthologs (N. crassa ARG13, S. cerevisiae ARG11/ORT1). Reason: This is the core molecular function, directly supported by reconstitution assays and by the disease mechanism, and is consistent across the ornithine-carrier phylogenetic clade. Supporting Evidence: PMID:10369256 Our results show that ORNT1 encodes the mitochondrial ornithine transporter involved in UC function and is defective in HHH syndrome.
GO:1990575 mitochondrial L-ornithine transmembrane transport	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of the biological process of transporting L-ornithine across the mitochondrial membrane, the process this carrier mediates. Reason: Correctly captures the core biological process (movement of L-ornithine across the inner mitochondrial membrane) that ORNT1 performs as part of urea-cycle function. Supporting Evidence: PMID:10369256 ORNT1 expression restores ornithine metabolism in fibroblasts from patients with hyperammonaemia-hyperornithinaemia-homocitrullinuria (HHH) syndrome.
GO:0000064 L-ornithine transmembrane transporter activity	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning electronic annotation of the core L-ornithine transmembrane transporter activity. Reason: Duplicates the well-supported core molecular function (also assigned by IBA, EXP, and TAS). The electronic mapping is at the correct level of specificity.
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (multi-method IEA) assignment of mitochondrial inner membrane location, from UniProt subcellular-location mapping (SL-0168). Reason: Correct core location for this multi-pass SLC25 inner-membrane carrier; concordant with the UniProt subcellular location and the ISS-from-ortholog call.
GO:0015297 antiporter activity	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic annotation of generic antiporter activity, reflecting the exchange (antiport) transport mechanism of ORNT1. Reason: ORNT1 is genuinely an antiporter (ornithine/citrulline exchange), so the term is correct although general. It is retained as a true parent of the more informative specific antiport function; the physiologically meaningful antiport is the arginine:ornithine / ornithine:citrulline exchange captured by GO:0043858 and by the ornithine-transporter terms.
GO:0031966 mitochondrial membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation (UniProt subcellular-location mapping, SL-0171) of mitochondrial membrane location. Reason: Correct but less specific than mitochondrial inner membrane. Retained as a true parent; the precise, experimentally consistent location is GO:0005743.
GO:0000050 urea cycle	TAS Reactome:R-HSA-70635	ACCEPT	Summary: Reactome-traceable assignment placing ORNT1 in the urea cycle, which it connects by shuttling ornithine and citrulline across the inner mitochondrial membrane. Reason: Core biological process. ORNT1 physically links the cytosolic and matrix halves of the urea cycle; its loss causes the urea-cycle disorder HHH syndrome. Supporting Evidence: PMID:10369256 ORNT1 encodes the mitochondrial ornithine transporter involved in UC function and is defective in HHH syndrome.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9956519	ACCEPT	Summary: Reactome-traceable assignment of mitochondrial inner membrane location (from the Reactome reaction describing ornithine/citrulline translocation). Reason: Correct core location. Although the source Reactome event concerns disease variants that fail to translocate, the localization to the inner membrane is a correct statement about the wild-type protein.
GO:0000064 L-ornithine transmembrane transporter activity	TAS Reactome:R-HSA-9956519	ACCEPT	Summary: Reactome-traceable assignment of the core L-ornithine transmembrane transporter activity. Reason: Duplicates the well-supported core molecular function. Correct level of specificity.
GO:0005743 mitochondrial inner membrane	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity (ISS) transfer of mitochondrial inner membrane location from the S. cerevisiae ortholog ORT1/Q12375. Reason: Correct core location; concordant with UniProt and electronic annotations and with the multi-pass SLC25 topology.
GO:0031966 mitochondrial membrane	EXP PMID:10369256 Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrom...	ACCEPT	Summary: Experimental localization of ORNT1 to the mitochondrial membrane in the original disease-gene study. Reason: Experimentally supported mitochondrial membrane localization. The term is correct though more general than the inner-membrane call; retained as a true and experimentally grounded parent. Supporting Evidence: PMID:10369256 mutations in a gene encoding a mitochondrial ornithine transporter
GO:0043858 arginine:ornithine antiporter activity	EXP PMID:12807890 The mitochondrial ornithine transporter. Bacterial expressio...	ACCEPT	Summary: Experimentally demonstrated arginine/ornithine antiport by reconstituted, purified ORNT1 (ORC1). This is a specific antiport activity of the carrier and corresponds to the UniProt/Rhea reaction L-arginine(out) + L-ornithine(in) = L-arginine(in) + L-ornithine(out) (RHEA:34991). Reason: Directly measured for reconstituted ORNT1 and matches the GO term direction (arginine(out) + ornithine(in) = arginine(in) + ornithine(out)). It represents a real, specific antiport function of the carrier. The physiologically dominant exchange is ornithine/citrulline, but arginine:ornithine antiport is a genuine biochemical activity and captures the carrier antiport mechanism more precisely than generic antiporter activity. Supporting Evidence: PMID:12807890 Both transport L-isomers of ornithine, lysine, arginine, and citrulline by exchange and by unidirectional mechanisms, and they are inactivated by the same inhibitors.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	KEEP AS NON CORE	Summary: High-throughput mitochondrial-proteome study detecting ORNT1 in the mitochondrion. Reason: Consistent with the well-established mitochondrial localization, though less specific than the experimentally supported inner-membrane location and derived from a high-throughput proteomic dataset. Retained as a correct but corroborative, non-core localization annotation.
GO:0015189 L-lysine transmembrane transporter activity	IDA PMID:12807890 The mitochondrial ornithine transporter. Bacterial expressio...	KEEP AS NON CORE	Summary: Direct assay of reconstituted ORNT1 showed transport of L-lysine, reflecting the carrier broad basic-amino-acid specificity (UniProt Rhea reaction L-ornithine(out) + L-lysine(in) = L-ornithine(in) + L-lysine(out), RHEA:70799). Reason: Experimentally demonstrated in the reconstituted system (do not remove an IDA activity). However, lysine is a lower-affinity substrate than ornithine (Km 0.8 vs 0.22 mM) and lysine transport is not the physiological role of the carrier; the urea-cycle-relevant function is ornithine/citrulline exchange. Marked non-core to reflect the broad in vitro specificity rather than the primary biological function. Supporting Evidence: PMID:12807890 Both transport L-isomers of ornithine, lysine, arginine, and citrulline by exchange and by unidirectional mechanisms, and they are inactivated by the same inhibitors.
GO:0015297 antiporter activity	IDA PMID:12807890 The mitochondrial ornithine transporter. Bacterial expressio...	ACCEPT	Summary: Direct demonstration that ORNT1 transports basic amino acids by an exchange (antiport) mechanism in reconstituted proteoliposomes. Reason: Correct, experimentally grounded description of the antiport mechanism, although general. Retained as a true parent of the specific antiport activities; the more informative specific term is GO:0043858 (arginine:ornithine antiporter). Supporting Evidence: PMID:12807890 Both transport L-isomers of ornithine, lysine, arginine, and citrulline by exchange and by unidirectional mechanisms, and they are inactivated by the same inhibitors.
GO:0061459 L-arginine transmembrane transporter activity	IDA PMID:12807890 The mitochondrial ornithine transporter. Bacterial expressio...	KEEP AS NON CORE	Summary: Direct assay of reconstituted ORNT1 showed transport of L-arginine, reflecting the carrier broad basic-amino-acid specificity (UniProt Rhea reaction RHEA:34991). Reason: Experimentally demonstrated (do not remove an IDA activity). Arginine is a lower-affinity substrate than ornithine (Km 1.58 vs 0.22 mM) and arginine transport is not the carrier principal physiological role, which is ornithine/citrulline exchange in the urea cycle. Marked non-core to reflect the broad in vitro specificity. Supporting Evidence: PMID:12807890 Both transport L-isomers of ornithine, lysine, arginine, and citrulline by exchange and by unidirectional mechanisms, and they are inactivated by the same inhibitors.
GO:1903401 L-lysine transmembrane transport	IDA PMID:12807890 The mitochondrial ornithine transporter. Bacterial expressio...	KEEP AS NON CORE	Summary: Biological-process counterpart of the demonstrated L-lysine transport activity by reconstituted ORNT1. Reason: Experimentally supported but non-core; a manifestation of the carrier broad basic-amino-acid specificity rather than its urea-cycle role. Supporting Evidence: PMID:12807890 Both transport L-isomers of ornithine, lysine, arginine, and citrulline by exchange and by unidirectional mechanisms, and they are inactivated by the same inhibitors.
GO:1903826 L-arginine transmembrane transport	IDA PMID:12807890 The mitochondrial ornithine transporter. Bacterial expressio...	KEEP AS NON CORE	Summary: Biological-process counterpart of the demonstrated L-arginine transport activity by reconstituted ORNT1. Reason: Experimentally supported but non-core; reflects broad basic-amino-acid specificity, not the primary urea-cycle function. Supporting Evidence: PMID:12807890 Both transport L-isomers of ornithine, lysine, arginine, and citrulline by exchange and by unidirectional mechanisms, and they are inactivated by the same inhibitors.
GO:0005739 mitochondrion	IDA PMID:10369256 Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrom...	KEEP AS NON CORE	Summary: Direct experimental localization of ORNT1 to the mitochondrion in the original disease-gene identification study. Reason: Experimentally supported mitochondrial localization, consistent with the more specific inner-membrane location. Retained as a correct parent, non-core relative to the specific mitochondrial inner membrane location. Supporting Evidence: PMID:10369256 mutations in a gene encoding a mitochondrial ornithine transporter
GO:0000064 L-ornithine transmembrane transporter activity	EXP PMID:12807890 The mitochondrial ornithine transporter. Bacterial expressio...	ACCEPT	Summary: Experimental demonstration (reconstituted, purified ORNT1) of L-ornithine transport, establishing the core molecular function. Reason: Directly measured core molecular function; ornithine is the highest-affinity substrate (Km 0.22 mM). This is the defining activity of the carrier. Supporting Evidence: PMID:12807890 Both transport L-isomers of ornithine, lysine, arginine, and citrulline by exchange and by unidirectional mechanisms, and they are inactivated by the same inhibitors.
GO:0000064 L-ornithine transmembrane transporter activity	EXP PMID:12948741 Cloning and characterization of human ORNT2: a second mitoch...	ACCEPT	Summary: Experimental support for L-ornithine transporter activity in the study characterizing ORNT2 and confirming the ornithine-transport function shared with ORNT1 (functional rescue of ornithine metabolism in HHH patient fibroblasts). Reason: Reinforces the core molecular function of the ORNT ornithine carriers. The paper demonstrates the ornithine-transport function that ORNT1 provides in the urea cycle and that ORNT2 can partially replace. Supporting Evidence: PMID:12948741 When ORNT2 is overexpressed transiently in cultured fibroblasts from HHH patients, it rescues the deficient ornithine metabolism in these cells.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-70634	ACCEPT	Summary: Reactome-traceable assignment of mitochondrial inner membrane location, from the reaction describing cytosolic/mitochondrial ornithine-citrulline exchange. Reason: Correct core location, concordant with all other localization annotations.
GO:0000050 urea cycle	TAS PMID:10369256 Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrom...	ACCEPT	Summary: Author-stated (TAS) involvement of ORNT1 in the urea cycle, from the disease-gene identification study. Reason: Core biological process. ORNT1 connects the cytosolic and matrix reactions of the urea cycle; its deficiency causes the urea-cycle disorder HHH syndrome. Supporting Evidence: PMID:10369256 ORNT1 encodes the mitochondrial ornithine transporter involved in UC function and is defective in HHH syndrome.
GO:0000064 L-ornithine transmembrane transporter activity	TAS PMID:10369256 Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrom...	ACCEPT	Summary: Author-stated (TAS) L-ornithine transporter activity for ORNT1 in the disease-gene study. Reason: Duplicates the well-supported core molecular function. Supporting Evidence: PMID:10369256 mutations in a gene encoding a mitochondrial ornithine transporter
GO:0005743 mitochondrial inner membrane	TAS PMID:10369256 Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrom...	ACCEPT	Summary: Author-stated (TAS) mitochondrial inner membrane location for ORNT1. Reason: Correct core location, consistent with experimental and electronic annotations. Supporting Evidence: PMID:10369256 transport ornithine across the mitochondrial inner membrane
GO:0016020 membrane	TAS PMID:10369256 Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrom...	MARK AS OVER ANNOTATED	Summary: Author-stated (TAS) generic membrane location, superseded by the specific mitochondrial inner membrane annotations. Reason: Not incorrect (ORNT1 is a multi-pass membrane protein), but GO:0016020 is uninformative given the well-established mitochondrial inner membrane localization. It is a legacy general term that adds no biological information beyond the specific inner-membrane annotations.
GO:1990575 mitochondrial L-ornithine transmembrane transport	TAS PMID:10369256 Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrom...	ACCEPT	Summary: Author-stated (TAS) biological process of L-ornithine transport across the mitochondrial membrane. Reason: Core biological process, concordant with the IBA assignment and the urea-cycle role. Supporting Evidence: PMID:10369256 transport ornithine across the mitochondrial inner membrane

Gene Description

Existing Annotations Review

Core Functions

Ornithine/citrulline antiport across the inner mitochondrial membrane that couples the cytosolic and matrix halves of the urea cycle, importing cytosolic L-ornithine into the matrix in exchange for exporting matrix L-citrulline.

Transmembrane movement of L-ornithine across the mitochondrial inner membrane, the transport process that ORNT1 mediates.

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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