TPC_HUMAN
ID TPC_HUMAN Reviewed; 320 AA.
AC Q9HC21; E9PF74; Q6V9R7;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Mitochondrial thiamine pyrophosphate carrier;
DE AltName: Full=Mitochondrial uncoupling protein 1;
DE AltName: Full=Solute carrier family 25 member 19;
GN Name=SLC25A19; Synonyms=DNC, MUP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=11226231; DOI=10.1073/pnas.031430998;
RA Dolce V., Fiermonte G., Runswick M.J., Palmieri F., Walker J.E.;
RT "The human mitochondrial deoxynucleotide carrier and its role in the
RT toxicity of nucleoside antivirals.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2284-2288(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Renard S., Mondesert G., Besnard F.;
RT "MUP 1, a mitochondrial uncoupling protein.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Li H., Yu R., Zhou G., Ke R., Shen C., Lin L., Yang S.;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION.
RX PubMed=18280798; DOI=10.1016/j.mito.2008.01.001;
RA Kang J., Samuels D.C.;
RT "The evidence that the DNC (SLC25A19) is not the mitochondrial
RT deoxyribonucleotide carrier.";
RL Mitochondrion 8:103-108(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [10]
RP VARIANT MCPHA ALA-177.
RX PubMed=12185364; DOI=10.1038/ng948;
RA Rosenberg M.J., Agarwala R., Bouffard G., Davis J., Fiermonte G.,
RA Hilliard M.S., Koch T., Kalikin L.M., Makalowska I., Morton D.H.,
RA Petty E.M., Weber J.L., Palmieri F., Kelley R.I., Schaeffer A.A.,
RA Biesecker L.G.;
RT "Mutant deoxynucleotide carrier is associated with congenital
RT microcephaly.";
RL Nat. Genet. 32:175-179(2002).
RN [11]
RP VARIANT THMD4 SER-125, AND CHARACTERIZATION OF VARIANT THMD4 SER-125.
RX PubMed=19798730; DOI=10.1002/ana.21752;
RA Spiegel R., Shaag A., Edvardson S., Mandel H., Stepensky P., Shalev S.A.,
RA Horovitz Y., Pines O., Elpeleg O.;
RT "SLC25A19 mutation as a cause of neuropathy and bilateral striatal
RT necrosis.";
RL Ann. Neurol. 66:419-424(2009).
CC -!- FUNCTION: Mitochondrial transporter mediating uptake of thiamine
CC pyrophosphate (ThPP) into mitochondria. {ECO:0000269|PubMed:18280798}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9HC21-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HC21-2; Sequence=VSP_053908;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined except for
CC placenta. Highest levels in colon, kidney, lung, testis, spleen, and
CC brain. {ECO:0000269|PubMed:11226231}.
CC -!- DISEASE: Microcephaly, Amish type (MCPHA) [MIM:607196]: A disorder
CC characterized by severe congenital microcephaly and severe 2-
CC ketoglutaric aciduria leading to death within the first year.
CC {ECO:0000269|PubMed:12185364}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Thiamine metabolism dysfunction syndrome 4, bilateral striatal
CC degeneration and progressive polyneuropathy type (THMD4) [MIM:613710]:
CC A disease characterized by recurrent episodes of flaccid paralysis and
CC encephalopathy associated with bilateral striatal necrosis and chronic
CC progressive polyneuropathy. {ECO:0000269|PubMed:19798730}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: The transmembrane helices are not perpendicular to the
CC plane of the membrane, but cross the membrane at an angle. Odd-numbered
CC transmembrane helices exhibit a sharp kink, due to the presence of a
CC conserved proline residue (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; AJ251857; CAC27560.1; -; mRNA.
DR EMBL; AJ301616; CAC37793.1; -; Genomic_DNA.
DR EMBL; AF182404; AAG16903.1; -; mRNA.
DR EMBL; AY346372; AAQ54327.1; -; mRNA.
DR EMBL; AC022211; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001075; AAH01075.1; -; mRNA.
DR EMBL; BC005120; AAH05120.1; -; mRNA.
DR CCDS; CCDS11720.1; -. [Q9HC21-1]
DR RefSeq; NP_001119593.1; NM_001126121.1. [Q9HC21-1]
DR RefSeq; NP_001119594.1; NM_001126122.1. [Q9HC21-1]
DR RefSeq; NP_068380.3; NM_021734.4. [Q9HC21-1]
DR RefSeq; XP_005257616.1; XM_005257559.3. [Q9HC21-1]
DR RefSeq; XP_005257617.1; XM_005257560.2. [Q9HC21-1]
DR RefSeq; XP_005257618.1; XM_005257561.3. [Q9HC21-1]
DR RefSeq; XP_005257619.1; XM_005257562.2. [Q9HC21-1]
DR RefSeq; XP_006722070.1; XM_006722007.2. [Q9HC21-1]
DR RefSeq; XP_016880415.1; XM_017024926.1. [Q9HC21-1]
DR AlphaFoldDB; Q9HC21; -.
DR SMR; Q9HC21; -.
DR BioGRID; 121903; 105.
DR IntAct; Q9HC21; 21.
DR MINT; Q9HC21; -.
DR STRING; 9606.ENSP00000385312; -.
DR TCDB; 2.A.29.16.1; the mitochondrial carrier (mc) family.
DR iPTMnet; Q9HC21; -.
DR PhosphoSitePlus; Q9HC21; -.
DR SwissPalm; Q9HC21; -.
DR BioMuta; SLC25A19; -.
DR DMDM; 20137652; -.
DR EPD; Q9HC21; -.
DR jPOST; Q9HC21; -.
DR MassIVE; Q9HC21; -.
DR MaxQB; Q9HC21; -.
DR PaxDb; Q9HC21; -.
DR PeptideAtlas; Q9HC21; -.
DR PRIDE; Q9HC21; -.
DR ProteomicsDB; 20044; -.
DR ProteomicsDB; 81625; -. [Q9HC21-1]
DR Antibodypedia; 46024; 104 antibodies from 18 providers.
DR DNASU; 60386; -.
DR Ensembl; ENST00000320362.7; ENSP00000319574.3; ENSG00000125454.12. [Q9HC21-1]
DR Ensembl; ENST00000375261.8; ENSP00000364410.4; ENSG00000125454.12. [Q9HC21-2]
DR Ensembl; ENST00000402418.7; ENSP00000385312.3; ENSG00000125454.12. [Q9HC21-1]
DR Ensembl; ENST00000416858.7; ENSP00000397818.2; ENSG00000125454.12. [Q9HC21-1]
DR Ensembl; ENST00000442286.6; ENSP00000402202.2; ENSG00000125454.12. [Q9HC21-1]
DR Ensembl; ENST00000580994.5; ENSP00000463795.1; ENSG00000125454.12. [Q9HC21-1]
DR GeneID; 60386; -.
DR KEGG; hsa:60386; -.
DR MANE-Select; ENST00000416858.7; ENSP00000397818.2; NM_001126121.2; NP_001119593.1.
DR UCSC; uc002jns.5; human. [Q9HC21-1]
DR CTD; 60386; -.
DR DisGeNET; 60386; -.
DR GeneCards; SLC25A19; -.
DR GeneReviews; SLC25A19; -.
DR HGNC; HGNC:14409; SLC25A19.
DR HPA; ENSG00000125454; Low tissue specificity.
DR MalaCards; SLC25A19; -.
DR MIM; 606521; gene.
DR MIM; 607196; phenotype.
DR MIM; 613710; phenotype.
DR neXtProt; NX_Q9HC21; -.
DR OpenTargets; ENSG00000125454; -.
DR Orphanet; 99742; Amish lethal microcephaly.
DR Orphanet; 217396; Progressive polyneuropathy with bilateral striatal necrosis.
DR PharmGKB; PA37879; -.
DR VEuPathDB; HostDB:ENSG00000125454; -.
DR eggNOG; KOG0752; Eukaryota.
DR GeneTree; ENSGT00550000074902; -.
DR HOGENOM; CLU_015166_10_3_1; -.
DR InParanoid; Q9HC21; -.
DR OMA; MYVCYGA; -.
DR PhylomeDB; Q9HC21; -.
DR TreeFam; TF313047; -.
DR PathwayCommons; Q9HC21; -.
DR Reactome; R-HSA-196819; Vitamin B1 (thiamin) metabolism.
DR SignaLink; Q9HC21; -.
DR BioGRID-ORCS; 60386; 115 hits in 1085 CRISPR screens.
DR GeneWiki; SLC25A19; -.
DR GenomeRNAi; 60386; -.
DR Pharos; Q9HC21; Tbio.
DR PRO; PR:Q9HC21; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9HC21; protein.
DR Bgee; ENSG00000125454; Expressed in left testis and 161 other tissues.
DR ExpressionAtlas; Q9HC21; baseline and differential.
DR Genevisible; Q9HC21; HS.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0030233; F:deoxynucleotide transmembrane transporter activity; TAS:UniProtKB.
DR GO; GO:0090422; F:thiamine pyrophosphate transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0015234; F:thiamine transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0030302; P:deoxynucleotide transport; NAS:UniProtKB.
DR GO; GO:0030974; P:thiamine pyrophosphate transmembrane transport; IBA:GO_Central.
DR GO; GO:0042723; P:thiamine-containing compound metabolic process; TAS:Reactome.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR002067; Mit_carrier.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00926; MITOCARRIER.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Neuropathy; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..320
FT /note="Mitochondrial thiamine pyrophosphate carrier"
FT /id="PRO_0000090611"
FT TRANSMEM 19..39
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 87..107
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 220..240
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 293..313
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 13..106
FT /note="Solcar 1"
FT REPEAT 116..202
FT /note="Solcar 2"
FT REPEAT 214..309
FT /note="Solcar 3"
FT MOTIF 241..246
FT /note="Substrate recognition"
FT /evidence="ECO:0000250"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 97..153
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_053908"
FT VARIANT 125
FT /note="G -> S (in THMD4; affects function as shown by
FT complementation studies in yeast; dbSNP:rs387906944)"
FT /evidence="ECO:0000269|PubMed:19798730"
FT /id="VAR_065125"
FT VARIANT 177
FT /note="G -> A (in MCPHA; dbSNP:rs119473030)"
FT /evidence="ECO:0000269|PubMed:12185364"
FT /id="VAR_014103"
FT CONFLICT 186
FT /note="F -> L (in Ref. 3; AAQ54327)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 320 AA; 35511 MW; 57CE0F01D538B1BE CRC64;
MVGYDPKPDG RNNTKFQVAV AGSVSGLVTR ALISPFDVIK IRFQLQHERL SRSDPSAKYH
GILQASRQIL QEEGPTAFWK GHVPAQILSI GYGAVQFLSF EMLTELVHRG SVYDAREFSV
HFVCGGLAAC MATLTVHPVD VLRTRFAAQG EPKVYNTLRH AVGTMYRSEG PQVFYKGLAP
TLIAIFPYAG LQFSCYSSLK HLYKWAIPAE GKKNENLQNL LCGSGAGVIS KTLTYPLDLF
KKRLQVGGFE HARAAFGQVR RYKGLMDCAK QVLQKEGALG FFKGLSPSLL KAALSTGFMF
FSYEFFCNVF HCMNRTASQR
