MFTC_HUMAN
ID MFTC_HUMAN Reviewed; 315 AA.
AC Q9H2D1; A0A024R9D0; Q96JZ6; Q96SU7;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2003, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Mitochondrial folate transporter/carrier;
DE AltName: Full=Solute carrier family 25 member 32;
GN Name=SLC25A32; Synonyms=MFT, MFTC;
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], AND VARIANT HIS-117.
RX PubMed=10978331; DOI=10.1074/jbc.m005163200;
RA Titus S.A., Moran R.G.;
RT "Retrovirally mediated complementation of the glyB phenotype. Cloning of a
RT human gene encoding the carrier for entry of folates into mitochondria.";
RL J. Biol. Chem. 275:36811-36817(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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=15140890; DOI=10.1074/jbc.m403677200;
RA McCarthy E.A., Titus S.A., Taylor S.M., Jackson-Cook C., Moran R.G.;
RT "A mutation inactivating the mitochondrial inner membrane folate
RT transporter creates a glycine requirement for survival of chinese hamster
RT cells.";
RL J. Biol. Chem. 279:33829-33836(2004).
RN [7]
RP FUNCTION.
RX PubMed=16165386; DOI=10.1016/j.ymgme.2005.07.014;
RA Spaan A.N., Ijlst L., van Roermund C.W., Wijburg F.A., Wanders R.J.,
RA Waterham H.R.;
RT "Identification of the human mitochondrial FAD transporter and its
RT potential role in multiple acyl-CoA dehydrogenase deficiency.";
RL Mol. Genet. Metab. 86:441-447(2005).
RN [8]
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 [9]
RP INVOLVEMENT IN RREI, VARIANT RREI HIS-147, AND CHARACTERIZATION OF VARIANT
RP RREI HIS-147.
RX PubMed=26933868; DOI=10.1056/nejmc1513610;
RA Schiff M., Veauville-Merllie A., Su C.H., Tzagoloff A., Rak M.,
RA Ogier de Baulny H., Boutron A., Smedts-Walters H., Romero N.B., Rigal O.,
RA Rustin P., Vianey-Saban C., Acquaviva-Bourdain C.;
RT "SLC25A32 Mutations and Riboflavin-Responsive Exercise Intolerance.";
RL N. Engl. J. Med. 374:795-797(2016).
RN [10]
RP VARIANTS NTD VAL-55; ALA-71; THR-128; 131-GLY--LYS-315 DEL AND ASN-260,
RP CHARACTERIZATION OF VARIANT NTD 131-GLY--LYS-315 DEL, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=29666258; DOI=10.1073/pnas.1800138115;
RA Kim J., Lei Y., Guo J., Kim S.E., Wlodarczyk B.J., Cabrera R.M., Lin Y.L.,
RA Nilsson T.K., Zhang T., Ren A., Wang L., Yuan Z., Zheng Y.F., Wang H.Y.,
RA Finnell R.H.;
RT "Formate rescues neural tube defects caused by mutations in Slc25a32.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:4690-4695(2018).
CC -!- FUNCTION: Transports folate across the inner membranes of mitochondria
CC (PubMed:15140890, PubMed:29666258). Can also transport FAD across the
CC mitochondrial inner membrane (PubMed:16165386).
CC {ECO:0000269|PubMed:15140890, ECO:0000269|PubMed:16165386,
CC ECO:0000269|PubMed:29666258}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:29666258}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Exercise intolerance, riboflavin-responsive (RREI)
CC [MIM:616839]: A riboflavin-responsive form of exercise intolerance, a
CC condition characterized by failure to maintain an expected level of
CC force during sustained or repeated muscle contraction, resulting in an
CC overwhelming sense of tiredness, lack of energy and feeling of
CC exhaustion. RREI transmission pattern is consistent with autosomal
CC recessive inheritance. {ECO:0000269|PubMed:26933868}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Neural tube defects (NTD) [MIM:182940]: Congenital
CC malformations of the central nervous system and adjacent structures
CC related to defective neural tube closure during the first trimester of
CC pregnancy. Failure of neural tube closure can occur at any level of the
CC embryonic axis. Common NTD forms include anencephaly, myelomeningocele
CC and spina bifida, which result from the failure of fusion in the
CC cranial and spinal region of the neural tube. NTDs have a
CC multifactorial etiology encompassing both genetic and environmental
CC components. {ECO:0000269|PubMed:29666258}. Note=Disease susceptibility
CC is associated with variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; AF283645; AAG37834.1; -; mRNA.
DR EMBL; AK027531; BAB55180.1; -; mRNA.
DR EMBL; AK027787; BAB55368.1; -; mRNA.
DR EMBL; AC012213; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471060; EAW91877.1; -; Genomic_DNA.
DR EMBL; CH471060; EAW91878.1; -; Genomic_DNA.
DR EMBL; BC021893; AAH21893.1; -; mRNA.
DR CCDS; CCDS6300.1; -.
DR RefSeq; NP_110407.2; NM_030780.4.
DR AlphaFoldDB; Q9H2D1; -.
DR SMR; Q9H2D1; -.
DR BioGRID; 123352; 34.
DR IntAct; Q9H2D1; 13.
DR STRING; 9606.ENSP00000297578; -.
DR DrugBank; DB00158; Folic acid.
DR TCDB; 2.A.29.10.2; the mitochondrial carrier (mc) family.
DR iPTMnet; Q9H2D1; -.
DR PhosphoSitePlus; Q9H2D1; -.
DR SwissPalm; Q9H2D1; -.
DR BioMuta; SLC25A32; -.
DR DMDM; 34223740; -.
DR EPD; Q9H2D1; -.
DR jPOST; Q9H2D1; -.
DR MassIVE; Q9H2D1; -.
DR MaxQB; Q9H2D1; -.
DR PaxDb; Q9H2D1; -.
DR PeptideAtlas; Q9H2D1; -.
DR PRIDE; Q9H2D1; -.
DR ProteomicsDB; 80530; -.
DR Antibodypedia; 13342; 79 antibodies from 16 providers.
DR DNASU; 81034; -.
DR Ensembl; ENST00000297578.9; ENSP00000297578.4; ENSG00000164933.12.
DR GeneID; 81034; -.
DR KEGG; hsa:81034; -.
DR MANE-Select; ENST00000297578.9; ENSP00000297578.4; NM_030780.5; NP_110407.2.
DR UCSC; uc003yll.5; human.
DR CTD; 81034; -.
DR DisGeNET; 81034; -.
DR GeneCards; SLC25A32; -.
DR HGNC; HGNC:29683; SLC25A32.
DR HPA; ENSG00000164933; Low tissue specificity.
DR MalaCards; SLC25A32; -.
DR MIM; 138480; gene.
DR MIM; 182940; phenotype.
DR MIM; 616839; phenotype.
DR neXtProt; NX_Q9H2D1; -.
DR OpenTargets; ENSG00000164933; -.
DR Orphanet; 394532; Multiple acyl-CoA dehydrogenase deficiency, mild type.
DR PharmGKB; PA142670905; -.
DR VEuPathDB; HostDB:ENSG00000164933; -.
DR eggNOG; KOG0764; Eukaryota.
DR GeneTree; ENSGT00920000149145; -.
DR HOGENOM; CLU_015166_6_4_1; -.
DR InParanoid; Q9H2D1; -.
DR OMA; GLYFLWY; -.
DR OrthoDB; 1080385at2759; -.
DR PhylomeDB; Q9H2D1; -.
DR TreeFam; TF314217; -.
DR PathwayCommons; Q9H2D1; -.
DR Reactome; R-HSA-196757; Metabolism of folate and pterines.
DR SignaLink; Q9H2D1; -.
DR BioGRID-ORCS; 81034; 14 hits in 1078 CRISPR screens.
DR ChiTaRS; SLC25A32; human.
DR GenomeRNAi; 81034; -.
DR Pharos; Q9H2D1; Tbio.
DR PRO; PR:Q9H2D1; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9H2D1; protein.
DR Bgee; ENSG00000164933; Expressed in calcaneal tendon and 103 other tissues.
DR ExpressionAtlas; Q9H2D1; baseline and differential.
DR Genevisible; Q9H2D1; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0015230; F:FAD transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0008517; F:folic acid transmembrane transporter activity; IGI:BHF-UCL.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:1904947; P:folate import into mitochondrion; IMP:UniProtKB.
DR GO; GO:0046655; P:folic acid metabolic process; TAS:Reactome.
DR GO; GO:0015884; P:folic acid transport; NAS:UniProtKB.
DR GO; GO:1990548; P:mitochondrial FAD transmembrane transport; IMP:UniProtKB.
DR GO; GO:0006839; P:mitochondrial transport; IEA:InterPro.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR002030; Mit_uncoupling_UCP-like.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR InterPro; IPR044712; SLC25A32-like.
DR PANTHER; PTHR45683; PTHR45683; 1.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00784; MTUNCOUPLING.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW Disease variant; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..315
FT /note="Mitochondrial folate transporter/carrier"
FT /id="PRO_0000090641"
FT TRANSMEM 26..43
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 89..106
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 123..143
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 186..203
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 227..243
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 281..300
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 20..109
FT /note="Solcar 1"
FT REPEAT 118..209
FT /note="Solcar 2"
FT REPEAT 222..306
FT /note="Solcar 3"
FT SITE 91
FT /note="Important for substrate recognition"
FT /evidence="ECO:0000250|UniProtKB:Q6IZB5"
FT SITE 142
FT /note="Important for substrate recognition"
FT /evidence="ECO:0000250|UniProtKB:Q6IZB5"
FT SITE 249
FT /note="Important for substrate recognition"
FT /evidence="ECO:0000250|UniProtKB:Q6IZB5"
FT VARIANT 55
FT /note="G -> V (in NTD; uncertain pathological significance;
FT dbSNP:rs1332049392)"
FT /evidence="ECO:0000269|PubMed:29666258"
FT /id="VAR_082961"
FT VARIANT 71
FT /note="T -> A (in NTD; uncertain pathological significance;
FT dbSNP:rs564720045)"
FT /evidence="ECO:0000269|PubMed:29666258"
FT /id="VAR_082962"
FT VARIANT 117
FT /note="R -> H (in dbSNP:rs17803441)"
FT /evidence="ECO:0000269|PubMed:10978331"
FT /id="VAR_050130"
FT VARIANT 128
FT /note="A -> T (in NTD; uncertain pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29666258"
FT /id="VAR_082963"
FT VARIANT 131..315
FT /note="Missing (in NTD; uncertain pathological
FT significance; loss of function; no effect on mitochondrial
FT localization)"
FT /evidence="ECO:0000269|PubMed:29666258"
FT /id="VAR_082964"
FT VARIANT 147
FT /note="R -> H (in RREI; decreases succinate dehydrogenase
FT activity and glycerol-3-phosphate dehydrogenase activity;
FT dbSNP:rs142329098)"
FT /evidence="ECO:0000269|PubMed:26933868"
FT /id="VAR_076364"
FT VARIANT 260
FT /note="S -> N (in NTD; uncertain pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29666258"
FT /id="VAR_082965"
FT CONFLICT 306
FT /note="F -> L (in Ref. 2; BAB55368)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 315 AA; 35407 MW; EED376828B4D1069 CRC64;
MTGQGQSASG SSAWSTVFRH VRYENLIAGV SGGVLSNLAL HPLDLVKIRF AVSDGLELRP
KYNGILHCLT TIWKLDGLRG LYQGVTPNIW GAGLSWGLYF FFYNAIKSYK TEGRAERLEA
TEYLVSAAEA GAMTLCITNP LWVTKTRLML QYDAVVNSPH RQYKGMFDTL VKIYKYEGVR
GLYKGFVPGL FGTSHGALQF MAYELLKLKY NQHINRLPEA QLSTVEYISV AALSKIFAVA
ATYPYQVVRA RLQDQHMFYS GVIDVITKTW RKEGVGGFYK GIAPNLIRVT PACCITFVVY
ENVSHFLLDL REKRK
