Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Electronic Gene Ontology annotations created by ARBA machine learning models
The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals.
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Original characterization of SLC25A19/DNC: recombinant reconstituted protein transported dNDPs (and less efficiently dNTPs) in exchange for dNDPs, ADP or ATP. This deoxynucleotide-carrier interpretation was later superseded by identification of TPP as the physiological substrate.
"catalyzed the transport of all four deoxy (d) NDPs, and, less efficiently, the corresponding dNTPs, in exchange for dNDPs, ADP, or ATP"
Expression of deoxynucleotide carrier is not associated with the mitochondrial DNA depletion caused by anti-HIV dideoxynucleoside analogs and mitochondrial dNTP uptake.
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DNC/SLC25A19 does not play a physiological role in deoxynucleotide transport: reconstituted dNTP uptake had millimolar Km (~1000x above physiological), and DNC over-expression/knockdown did not affect mtDNA depletion or mitochondrial dNTP uptake.
"DNC does not play an important role in the delayed cytotoxicity (mtDNA depletion) of anti-HIV dideoxynucleoside analogs and dNTPs uptake into mitochondria"
Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia.
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Slc25a19 knockout mice have normal mitochondrial dNTP/rNTP pools and no mtDNA depletion, but undetectable mitochondrial ThPP; reconstituted recombinant SLC25A19 transports ThPP. Establishes TPP transport as the physiological function, with loss causing OGDH dysfunction and 2-oxoglutaric aciduria.
"We identified thiamine pyrophosphate (ThPP) transport as a candidate function of SLC25A19 through homology searching and confirmed it by using transport assays of the recombinant reconstituted protein"
Proteomic characterization of the human sperm nucleus.
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Large-scale proteomic catalogue of the human sperm nucleus in which SLC25A19 was detected. As a mitochondrial inner-membrane carrier, its presence in this nuclear preparation most likely reflects a proteomic contaminant rather than functional nuclear localization.
"403 different proteins have been identified from the isolated sperm nuclei"
Structure-function characterization of the human mitochondrial thiamin pyrophosphate transporter (hMTPPT; SLC25A19): Important roles for Ile(33), Ser(34), Asp(37), His(137) and Lys(291).
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Site-directed mutagenesis with TPP uptake assays on isolated mitochondria identified Ile33, Ser34, Asp37, His137 and Lys291 as important for hMTPPT function, confirming SLC25A19 as the mitochondrial TPP uptake carrier.
"an important role for Ile33, Ser34, Asp37, His137 and Lys291 residues in function of the hMTPPT"
Functional analysis of the third identified SLC25A19 mutation causative for the thiamine metabolism dysfunction syndrome 4.
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Functional analysis of the THMD4-causing Q192H variant: it reduces 3H-TPP uptake by isolated mitochondria and lowers hMTPPT protein expression/mitochondrial delivery without affecting mRNA, supporting TPP transport as the disease-relevant function.
"mitochondrial TPP transporter (hMTPPT)"
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
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SLC25A19 is included in the high-confidence human mitochondrial proteome (MitoCoP), corroborating its mitochondrial localization.
"mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)"
Vitamin B1 (thiamin) metabolism
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Reactome pathway placing SLC25A19 within vitamin B1 (thiamin) metabolism; thiamin is pyrophosphorylated to the coenzyme thiamin pyrophosphate.
"thiamin is converted into the coenzyme thiamin pyrophosphate"
SLC25A19 transports ThDP from cytosol to mitochondrial matrix
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Reactome reaction describing SLC25A19-mediated transport of thiamine pyrophosphate (ThDP) from cytosol into the mitochondrial matrix, where it serves as a cofactor for PDH, alpha-ketoglutarate dehydrogenase and branched-chain amino acid dehydrogenase.
"transporter of thiamine pyrophosphate (ThDP) into mitochondria"
UniProtKB Q9HC21 (TPC_HUMAN) record
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UniProt describes SLC25A19 as the mitochondrial thiamine pyrophosphate carrier mediating uptake of thiamine diphosphate into mitochondria, a multi-pass inner-membrane protein of the mitochondrial carrier family, and documents its historical mis-identification as a deoxyribonucleotide carrier.
"Mitochondrial transporter mediating uptake of thiamine"