SLC25A13

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005313 L-glutamate transmembrane transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of L-glutamate transporter activity. Citrin imports L-glutamate together with a proton as one half of its aspartate/glutamate antiport, so this is a correct component of the core function. Reason: Directly supported by experimental reconstitution showing electrogenic exchange of aspartate for glutamate and a proton. This activity is one arm of the aspartate/glutamate antiport; the more specific antiporter term (GO:0000515) is the primary/core molecular function, but this term is accurate. Supporting Evidence: PMID:11566871 shown to catalyze the electrogenic exchange of aspartate for glutamate and a H
GO:0015183 L-aspartate transmembrane transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of L-aspartate transporter activity. Citrin exports L-aspartate from the matrix as the other half of its antiport; a correct component of the core function. Reason: Experimentally demonstrated. Aspartate efflux is one arm of the electrogenic aspartate/glutamate antiport (the core activity, GO:0000515). This transporter-activity term is accurate. Supporting Evidence: PMID:11566871 shown to catalyze the electrogenic exchange of aspartate for glutamate and a H
GO:0043490 malate-aspartate shuttle	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment placing citrin in the malate-aspartate NADH shuttle, which it participates in as the inner-membrane aspartate/glutamate exchange step. Reason: Well supported: overexpression of citrin increases malate-aspartate shuttle activity in human cells, and the carrier is an integral component of the shuttle. Core biological process for citrin. Supporting Evidence: PMID:11566871 Overexpression of the carriers in transfected human cells increased the activity of the malate/aspartate NADH shuttle
GO:0005743 mitochondrial inner membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment to the mitochondrial inner membrane, where citrin is active as a multi-pass carrier. Correct and core subcellular location. Reason: Consistent with all experimental localization data and the multi-pass topology of the SLC25 carrier domain. Core location. Supporting Evidence: PMID:39419476 located in the mitochondrial inner membrane
GO:0015810 aspartate transmembrane transport	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) BP assignment for aspartate transmembrane transport, the process arm of citrin's aspartate efflux. Reason: Experimentally supported process term corresponding to the aspartate half of the antiport. Accurate. Supporting Evidence: PMID:11566871 shown to catalyze the electrogenic exchange of aspartate for glutamate and a H
GO:0015813 L-glutamate transmembrane transport	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) BP assignment for L-glutamate transmembrane transport, the process arm of citrin's glutamate import. Reason: Experimentally supported process term corresponding to the glutamate half of the antiport. Accurate. Supporting Evidence: PMID:11566871 shown to catalyze the electrogenic exchange of aspartate for glutamate and a H
GO:0000514 3-sulfino-L-alanine: proton, glutamate antiporter activity	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA electronic annotation for cysteinesulfinate (3-sulfino-L-alanine) / glutamate, proton antiport. Citrin exchanges cysteinesulfinate with glutamate and a proton experimentally; correct but a secondary (non-core) substrate. Reason: Experimentally demonstrated as a secondary substrate exchange, but aspartate/glutamate antiport (GO:0000515) is the physiologically central function. Real but ancillary. Supporting Evidence: PMID:11566871 AGC also transports cysteinesulfinate in exchange for either aspartate or glutamate
GO:0000515 aspartate:glutamate, proton antiporter activity	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic annotation for the aspartate:glutamate, proton antiporter activity, the primary catalytic function of citrin. Duplicated by an EXP and an IDA annotation. Reason: The primary/core molecular function of citrin, directly demonstrated by reconstitution and independently confirmed. The electronic annotation is correct. Supporting Evidence: PMID:11566871 shown to catalyze the electrogenic exchange of aspartate for glutamate and a H
GO:0005509 calcium ion binding	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (InterPro EF-hand) for calcium ion binding. Citrin has a regulatory N-terminal EF-hand domain; the structure confirms calcium binding at EF-hand 2. Reason: Supported by X-ray structure showing calcium bound at EF-hand 2. Calcium binding is a genuine molecular activity of the regulatory domain. Supporting Evidence: PMID:25410934 Only EF-hand 2 binds calcium
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (multiple IEA methods / UniProt SubCell) for mitochondrial inner membrane localization. Correct and duplicated by EXP/IDA annotations. Reason: Consistent with experimental subcellular localization. Core location. Supporting Evidence: PMID:39419476 located in the mitochondrial inner membrane
GO:0015804 neutral amino acid transport	IEA GO_REF:0000108	MODIFY	Summary: Inter-ontology (GO_REF:0000108) inference from the cysteinesulfinate antiport term GO:0000514, classifying cysteinesulfinate transport as neutral amino acid transport. Reason: Citrin's physiological substrates aspartate and glutamate are acidic (anionic) amino acids, not neutral amino acids. This term is a logical by-product of the secondary cysteinesulfinate activity and mischaracterizes the core function; better captured by the aspartate/glutamate transport terms. Proposed replacements: aspartate transmembrane transport L-glutamate transmembrane transport
GO:0043490 malate-aspartate shuttle	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic annotation to the malate-aspartate shuttle, duplicating the IBA and IDA annotations to this term. Reason: Correct; the malate-aspartate shuttle is a core biological process for citrin, independently supported by experimental data. Supporting Evidence: PMID:11566871 Overexpression of the carriers in transfected human cells increased the activity of the malate/aspartate NADH shuttle
GO:0051592 response to calcium ion	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA electronic annotation for response to calcium ion, reflecting calcium stimulation of citrin transport activity via its EF-hand domain. Reason: Citrin transport is stimulated by calcium binding at the intermembrane-space EF-hand domain, so a response-to-calcium annotation has an experimental basis. However this is a regulatory/response process rather than citrin's core transport function. Retain as non-core. Supporting Evidence: PMID:11566871 stimulated by Ca
GO:0055085 transmembrane transport	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO electronic annotation to the generic transmembrane transport process from the mitochondrial carrier domain signature. Reason: Correct but very general parent term. The specific aspartate/glutamate transport processes and the malate-aspartate shuttle capture the core function; this broad term is a valid, non-core ancestor.
GO:0070778 L-aspartate transmembrane transport	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (from the aspartate transporter/antiporter MF terms) for L-aspartate transmembrane transport, the process arm of citrin's aspartate efflux. Reason: Accurate specific process term for aspartate transport, consistent with the experimentally demonstrated aspartate efflux activity. Supporting Evidence: PMID:11566871 shown to catalyze the electrogenic exchange of aspartate for glutamate and a H
GO:1902600 proton transmembrane transport	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: Inter-ontology inference (from GO:0000514) that citrin is involved in proton transmembrane transport, reflecting co-transport of a proton with glutamate. Reason: Citrin co-transports a proton with glutamate, so proton translocation is part of its electrogenic mechanism; not wrong, but a mechanistic by-product rather than the primary amino-acid antiport function. Retain as non-core. Supporting Evidence: PMID:11566871 shown to catalyze the electrogenic exchange of aspartate for glutamate and a H
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: High-throughput interactome (IPI) annotation with the paralog SLC25A12 / aralar (O75746) as the recorded partner. Uninformative bare protein-binding term. Reason: Per curation guidelines, bare protein binding conveys no specific function. The recorded partner is the paralog SLC25A12, consistent with the mitochondrial-carrier context, but this generic term does not describe citrin's molecular function. The informative interaction (homodimerization) is captured by GO:0042802.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: High-throughput interactome (IPI) annotation with the paralog SLC25A12 (O75746). Uninformative bare protein-binding term. Reason: Bare protein binding is uninformative and is discouraged. Duplicate large-scale interactome hit against the paralog SLC25A12; does not add functional specificity.
GO:0005515 protein binding	IPI PMID:40355756 The solute carrier superfamily interactome.	MARK AS OVER ANNOTATED	Summary: Solute carrier interactome (IPI) annotation with the paralog SLC25A12 (O75746). Uninformative bare protein-binding term. Reason: Bare protein binding is uninformative. Large-scale SLC interactome hit against the paralog SLC25A12; no specific molecular function conveyed.
GO:0005313 L-glutamate transmembrane transporter activity	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl-Compara (GO_REF:0000107) orthology transfer from mouse Slc25a13 (Q9QXX4) of L-glutamate transporter activity. Duplicates the IBA annotation to this term. Reason: Correct: glutamate import is one arm of citrin's antiport, well supported experimentally. The orthology transfer is appropriate. Supporting Evidence: PMID:11566871 shown to catalyze the electrogenic exchange of aspartate for glutamate and a H
GO:0005739 mitochondrion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-Compara orthology transfer of mitochondrion localization. Correct but less specific than the mitochondrial inner membrane annotations. Reason: Accurate but a broad parent of the specific mitochondrial inner membrane location that is the core annotation. Retain as non-core. Supporting Evidence: PMID:39419476 located in the mitochondrial inner membrane
GO:0006094 gluconeogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-Compara orthology transfer for involvement in gluconeogenesis, reflecting the requirement for cytosolic aspartate (supplied by citrin) in gluconeogenesis from lactate. Reason: Citrin-supplied cytosolic aspartate is needed for the conversion of oxoglutarate to oxaloacetate in gluconeogenesis from lactate/alanine, so the process link is physiologically valid but downstream and tissue-context dependent rather than a core molecular function. Retain as non-core. Supporting Evidence: PMID:25410934 Cytosolic aspartate is also required for the conversion of oxoglutarate to oxaloacetate, a crucial step in gluconeogenesis from lactate and alanine
GO:0015172 acidic amino acid transmembrane transporter activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-Compara orthology transfer of acidic amino acid transmembrane transporter activity, a parent term covering the transport of the acidic amino acids aspartate and glutamate. Reason: Correct as a broader (parent) molecular function: aspartate and glutamate are acidic amino acids. The specific aspartate:glutamate antiporter activity (GO:0000515) and the individual aspartate/glutamate transporter terms are the core annotations; this generalization is a valid non-core ancestor.
GO:0005739 mitochondrion	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: Immunofluorescence-based (HPA, IDA) mitochondrial localization. Consistent with the established mitochondrial inner-membrane location. Reason: Correct but less specific than mitochondrial inner membrane; retain as non-core. Human Protein Atlas reports SLC25A13 as tissue-enriched in liver with mitochondrial staining.
GO:0000515 aspartate:glutamate, proton antiporter activity	EXP PMID:38945283 The mitochondrial aspartate/glutamate carrier does not trans...	ACCEPT	Summary: Experimental (EXP) confirmation of aspartate:glutamate, proton antiporter activity. Reconfirmed the canonical antiport and showed citrin does NOT transport GABA, sharpening substrate specificity. Reason: Directly supports the primary/core molecular function; additionally excludes GABA as a substrate, refining specificity of the antiport. Supporting Evidence: PMID:38945283 the human AGC isoforms (AGC1/aralar1 and AGC2/citrin) are unable to transport GABA both in homo- and in hetero-exchange with either glutamate or aspartate, i.e. the canonical substrates of AGC
GO:0005743 mitochondrial inner membrane	EXP PMID:10642534 Characterization of a second member of the subfamily of calc...	ACCEPT	Summary: Experimental localization of citrin (Aralar2) to mitochondria in human cell lines. Core location, duplicated by other EXP/IDA/IBA annotations. Reason: The mitochondrial localization of citrin was experimentally established in this characterization study; it is the core subcellular location. Supporting Evidence: PMID:10642534 The localization of Aralar2/citrin expressed in human cell lines is mitochondrial
GO:0005743 mitochondrial inner membrane	EXP PMID:39419476 Distinct roles for the domains of the mitochondrial aspartat...	ACCEPT	Summary: Experimental localization to the mitochondrial inner membrane, from the domain-dissection study of citrin (which also showed N-terminal mutations cause a mitochondrial import defect). Core location. Reason: Directly supported experimental annotation of the core inner-membrane location. Supporting Evidence: PMID:39419476 located in the mitochondrial inner membrane
GO:0043490 malate-aspartate shuttle	IGI PMID:37647199 The malate-aspartate shuttle is important for de novo serine...	ACCEPT	Summary: Genetic-interaction (IGI) annotation from a panel of malate-aspartate-shuttle-deficient cell lines showing the shuttle (including its AGC component) is important for de novo serine biosynthesis. Places citrin in the malate-aspartate shuttle. Reason: The malate-aspartate shuttle is a core biological process for citrin. This genetic study of MAS components (full text assessed by the curator) supports the shuttle involvement; the abstract confirms the MAS focus. Consistent with the IBA/IDA annotations to the same term. Supporting Evidence: PMID:37647199 we show that the MAS is important for de novo serine biosynthesis
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	KEEP AS NON CORE	Summary: High-throughput proteomics (HTP) placement of SLC25A13 in the mitochondrion (high-confidence mitochondrial proteome). Consistent with the established mitochondrial inner-membrane location. Reason: Correct but broader than the specific mitochondrial inner-membrane location; a proteome-scale mitochondrial call. Retain as non-core.
GO:0000514 3-sulfino-L-alanine: proton, glutamate antiporter activity	IDA PMID:11566871 Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate...	KEEP AS NON CORE	Summary: Direct experimental (IDA) demonstration that citrin exchanges cysteinesulfinate (3-sulfino-L-alanine) for glutamate and a proton. A genuine but secondary substrate activity. Reason: Experimentally demonstrated secondary substrate exchange. Physiologically the aspartate/glutamate antiport (GO:0000515) is central; cysteinesulfinate exchange is ancillary. Retain as accurate but non-core. Supporting Evidence: PMID:11566871 AGC also transports cysteinesulfinate in exchange for either aspartate or glutamate
GO:0000515 aspartate:glutamate, proton antiporter activity	IDA PMID:11566871 Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate...	ACCEPT	Summary: Direct experimental (IDA) demonstration of the electrogenic aspartate:glutamate, proton antiport by reconstituted citrin. The defining, core molecular function. Reason: The foundational experimental evidence for citrin's core function: reconstituted protein catalyzes electrogenic exchange of aspartate for glutamate and a proton. Primary molecular function. Supporting Evidence: PMID:11566871 shown to catalyze the electrogenic exchange of aspartate for glutamate and a H
GO:0005743 mitochondrial inner membrane	IDA PMID:11566871 Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate...	ACCEPT	Summary: Direct experimental (IDA) inner-membrane localization with defined multi-pass topology (N- and C-terminal domains in the intermembrane space; six-TM carrier domain). Core location. Reason: Directly supported experimental annotation of the core inner-membrane location and topology. Supporting Evidence: PMID:11566871 Ca(2+)-stimulated aspartate/glutamate transporters
GO:0005509 calcium ion binding	IDA PMID:25410934 Calcium-induced conformational changes of the regulatory dom...	ACCEPT	Summary: Direct experimental (IDA) calcium binding, from the X-ray structure of the citrin N-terminal domain showing calcium bound at EF-hand 2. Core molecular activity of the regulatory domain. Reason: Crystallographic demonstration of calcium binding at EF-hand 2. Calcium binding by the regulatory EF-hand domain is a genuine, core molecular function of citrin. Supporting Evidence: PMID:25410934 Only EF-hand 2 binds calcium
GO:0042802 identical protein binding	IDA PMID:25410934 Calcium-induced conformational changes of the regulatory dom...	KEEP AS NON CORE	Summary: Direct experimental (IDA) identical protein binding, reflecting the demonstrated homodimerization of citrin via its N-terminal domain (SEC-MALLS and the dimeric crystal structure). Reason: Citrin forms a homodimer via the N-terminal domain, so identical protein binding is experimentally supported and more informative than bare protein binding. However dimerization is a structural property rather than the core transport function (the carrier transports substrate as a functional monomer). Retain as non-core. Supporting Evidence: PMID:25410934 demonstrating that the full-length carrier was dimeric
GO:0006839 mitochondrial transport	NAS PMID:10642534 Characterization of a second member of the subfamily of calc...	KEEP AS NON CORE	Summary: Non-traceable author statement (NAS) that citrin functions in mitochondrial transport, from the initial characterization describing it as a calcium-regulated mitochondrial metabolite carrier. Reason: Correct but very general. The specific aspartate/glutamate antiport and its downstream processes (malate-aspartate shuttle, aspartate/glutamate transport) capture the core function; this broad process term is a valid non-core ancestor. Supporting Evidence: PMID:10642534 function as calcium-regulated metabolite (possibly anionic) carriers
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-372448	ACCEPT	Summary: Traceable author statement (Reactome) for mitochondrial inner-membrane localization, from the Reactome reaction in which SLC25A12/13 exchange L-Glu and L-Asp. Core location. Reason: Reactome curation consistent with all experimental localization data. Core inner-membrane location.
GO:0005509 calcium ion binding	IDA PMID:10642534 Characterization of a second member of the subfamily of calc...	ACCEPT	Summary: Direct experimental (IDA) calcium binding from the initial characterization, where the N-terminal half of citrin was shown to bind calcium (requiring the two most distal EF-hands). Core molecular activity of the regulatory domain. Reason: Experimentally demonstrated calcium binding by the N-terminal EF-hand domain. Duplicates the structurally-supported IDA calcium-binding annotation. Supporting Evidence: PMID:10642534 The N-terminal half of Aralar2/citrin is able to bind calcium and this requires the presence of the two most distal EF-hands
GO:0005739 mitochondrion	IDA PMID:10642534 Characterization of a second member of the subfamily of calc...	KEEP AS NON CORE	Summary: Direct experimental (IDA) mitochondrial localization of citrin expressed in human cell lines. Consistent with the inner-membrane location; broader term. Reason: Accurate but a broad parent of the specific mitochondrial inner membrane location. Retain as non-core. Supporting Evidence: PMID:10642534 The localization of Aralar2/citrin expressed in human cell lines is mitochondrial
GO:0005743 mitochondrial inner membrane	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity (ISS) transfer from mouse Slc25a13 (Q9QXX4) of inner-membrane localization. Correct and duplicated by EXP/IDA/IBA annotations. Reason: Consistent with all experimental localization data. Core location. Supporting Evidence: PMID:39419476 located in the mitochondrial inner membrane
GO:0005886 plasma membrane	NAS PMID:10642534 Characterization of a second member of the subfamily of calc...	REMOVE	Summary: Non-traceable author statement (NAS) placing citrin at the plasma membrane. Contradicts the extensive experimental evidence for a mitochondrial inner-membrane localization, including the conclusion of the same cited paper. Reason: Citrin is an integral protein of the mitochondrial inner membrane; there is no experimental support for a plasma-membrane location, and the cited characterization study itself concludes the localization is mitochondrial. This NAS annotation is inconsistent with established biology and should be removed. Supporting Evidence: PMID:10642534 The localization of Aralar2/citrin expressed in human cell lines is mitochondrial
GO:0006754 ATP biosynthetic process	IDA PMID:12851387 Recombinant expression of the Ca(2+)-sensitive aspartate/glu...	KEEP AS NON CORE	Summary: Direct experimental (IDA) annotation that recombinant citrin increases mitochondrial ATP production in agonist-stimulated cells, linking its calcium-sensitive transport activity to mitochondrial energy metabolism. Reason: Experimentally supported: citrin overexpression raises mitochondrial ATP upon calcium-mobilizing agonist stimulation, via its role in the malate-aspartate shuttle feeding reducing equivalents to oxidative phosphorylation. This is a downstream physiological consequence rather than citrin's direct molecular function; retain as non-core. Supporting Evidence: PMID:12851387 larger in cells expressing aralar and citrin
GO:0045333 cellular respiration	IDA PMID:12851387 Recombinant expression of the Ca(2+)-sensitive aspartate/glu...	KEEP AS NON CORE	Summary: Direct experimental (IDA) annotation linking citrin to cellular respiration through its calcium-stimulated enhancement of mitochondrial ATP production and aerobic metabolism. Reason: Citrin contributes to aerobic/oxidative metabolism by feeding cytosolic reducing equivalents into mitochondria via the malate-aspartate shuttle, and its overexpression stimulates mitochondrial ATP on agonist stimulation. Downstream physiological role rather than a core molecular function; retain as non-core. Supporting Evidence: PMID:12851387 the stimulation of aerobic metabolism
GO:0005739 mitochondrion	IDA PMID:11566871 Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate...	KEEP AS NON CORE	Summary: Direct experimental (IDA) mitochondrial localization from the functional reconstitution study. Consistent with the inner-membrane location; broader term. Reason: Accurate but a broad parent of the specific mitochondrial inner membrane location. Retain as non-core. Supporting Evidence: PMID:11566871 Ca(2+)-stimulated aspartate/glutamate transporters
GO:0015810 aspartate transmembrane transport	IDA PMID:11566871 Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate...	ACCEPT	Summary: Direct experimental (IDA) aspartate transmembrane transport, the process arm of citrin's aspartate efflux, demonstrated by reconstitution. Reason: Experimentally supported specific process term for aspartate transport (the aspartate half of the antiport). Accurate. Supporting Evidence: PMID:11566871 shown to catalyze the electrogenic exchange of aspartate for glutamate and a H
GO:0015813 L-glutamate transmembrane transport	IDA PMID:11566871 Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate...	ACCEPT	Summary: Direct experimental (IDA) L-glutamate transmembrane transport, the process arm of citrin's glutamate import, demonstrated by reconstitution. Reason: Experimentally supported specific process term for glutamate transport (the glutamate half of the antiport). Accurate. Supporting Evidence: PMID:11566871 shown to catalyze the electrogenic exchange of aspartate for glutamate and a H
GO:0043490 malate-aspartate shuttle	IDA PMID:11566871 Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate...	ACCEPT	Summary: Direct experimental (IDA) annotation to the malate-aspartate shuttle: citrin overexpression increased malate-aspartate shuttle activity in human cells. Core biological process. Reason: Foundational experimental evidence that citrin is a component of the malate-aspartate NADH shuttle. Core biological process. Supporting Evidence: PMID:11566871 Overexpression of the carriers in transfected human cells increased the activity of the malate/aspartate NADH shuttle
GO:0051592 response to calcium ion	IDA PMID:11566871 Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate...	KEEP AS NON CORE	Summary: Direct experimental (IDA) annotation for response to calcium ion: citrin transport activity is stimulated by calcium on the external face of the inner membrane, where its EF-hand domains reside. Reason: Experimentally supported calcium stimulation of transport, a genuine regulatory response. However it is a regulatory process rather than citrin's core transport function, and the physiological significance of the calcium regulation has since been debated. Retain as non-core. Supporting Evidence: PMID:11566871 stimulated by Ca
GO:0000050 urea cycle	TAS PMID:11566871 Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate...	NEW	Summary: Proposed new annotation. Citrin supplies the cytosolic aspartate consumed by argininosuccinate synthetase (ASS1) in the hepatic urea cycle; loss of this supply underlies the argininosuccinate synthetase deficiency and citrullinemia of citrin deficiency. Central role documented but not currently in the GOA for SLC25A13. Reason: The urea cycle role is a defining, textbook function of citrin and mechanistically explains citrullinemia type II, yet no urea cycle (GO:0000050) annotation exists in the current GOA. Adding it captures a core biological process. Supported by the primary functional paper and the structural review. Supporting Evidence: PMID:11566871 urea cycle and the aspartate/malate NADH shuttle PMID:25410934 In liver, cytosolic aspartate is required for the urea cycle

Gene Description

Existing Annotations Review

Core Functions

Electrogenic mitochondrial-inner-membrane aspartate/glutamate antiporter: exports L-aspartate from the matrix to the cytosol in exchange for cytosolic L-glutamate plus a proton.

Calcium binding by the regulatory N-terminal EF-hand domain (EF-hand 2) in the mitochondrial intermembrane space, which modulates the carrier.

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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