S2540_HUMAN
ID S2540_HUMAN Reviewed; 338 AA.
AC Q8TBP6; A8K483; D6W5P6; Q53GB1; Q9UHR1;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Probable mitochondrial glutathione transporter SLC25A40 {ECO:0000305};
DE AltName: Full=Mitochondrial carrier family protein {ECO:0000303|Ref.1};
DE AltName: Full=Solute carrier family 25 member 40;
GN Name=SLC25A40 {ECO:0000303|PubMed:16949250, ECO:0000312|HGNC:HGNC:29680};
GN Synonyms=MCFP {ECO:0000303|Ref.1};
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 [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
RA Fu S., Shi J., Ren S., Gu J., Jin W., Huang Q., Dong H., Yu Y., Fu G.,
RA Wang Y., Chen Z., Han Z.;
RT "A novel gene expressed in the human adrenal gland.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 MRNA].
RC TISSUE=Small intestine;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [6]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal cortex;
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 [8]
RP IDENTIFICATION.
RX PubMed=16949250; DOI=10.1016/j.ygeno.2006.06.016;
RA Haitina T., Lindblom J., Renstroem T., Fredriksson R.;
RT "Fourteen novel human members of mitochondrial solute carrier family 25
RT (SLC25) widely expressed in the central nervous system.";
RL Genomics 88:779-790(2006).
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 FUNCTION.
RX PubMed=34707288; DOI=10.1038/s41586-021-04025-w;
RA Wang Y., Yen F.S., Zhu X.G., Timson R.C., Weber R., Xing C., Liu Y.,
RA Allwein B., Luo H., Yeh H.W., Heissel S., Unlu G., Gamazon E.R.,
RA Kharas M.G., Hite R., Birsoy K.;
RT "SLC25A39 is necessary for mitochondrial glutathione import in mammalian
RT cells.";
RL Nature 599:136-140(2021).
RN [11]
RP VARIANT ASN-105.
RX PubMed=28294470; DOI=10.1111/cas.13233;
RA Tode N., Kikuchi T., Sakakibara T., Hirano T., Inoue A., Ohkouchi S.,
RA Tamada T., Okazaki T., Koarai A., Sugiura H., Niihori T., Aoki Y.,
RA Nakayama K., Matsumoto K., Matsubara Y., Yamamoto M., Watanabe A.,
RA Nukiwa T., Ichinose M.;
RT "Exome sequencing deciphers a germline MET mutation in familial epidermal
RT growth factor receptor-mutant lung cancer.";
RL Cancer Sci. 108:1263-1270(2017).
CC -!- FUNCTION: Probable mitochondrial transporter required for glutathione
CC import into mitochondria (PubMed:34707288). Glutathione, which plays
CC key roles in oxidative metabolism, is produced exclusively in the
CC cytosol and is imported in many organelles (PubMed:34707288).
CC Mitochondrial glutathione is required for the activity and stability of
CC proteins containing iron-sulfur clusters, as well as erythropoiesis (By
CC similarity). {ECO:0000250|UniProtKB:Q8BGP6,
CC ECO:0000269|PubMed:34707288}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q9BZJ4}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; AF125531; AAF17225.1; -; mRNA.
DR EMBL; AK223020; BAD96740.1; -; mRNA.
DR EMBL; AK290848; BAF83537.1; -; mRNA.
DR EMBL; AC003083; AAS07443.1; -; Genomic_DNA.
DR EMBL; CH236949; EAL24171.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76933.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76935.1; -; Genomic_DNA.
DR EMBL; BC027322; AAH27322.1; -; mRNA.
DR CCDS; CCDS5610.1; -.
DR RefSeq; NP_061331.2; NM_018843.3.
DR AlphaFoldDB; Q8TBP6; -.
DR SMR; Q8TBP6; -.
DR BioGRID; 121018; 92.
DR IntAct; Q8TBP6; 3.
DR STRING; 9606.ENSP00000344831; -.
DR TCDB; 2.A.29.14.6; the mitochondrial carrier (mc) family.
DR iPTMnet; Q8TBP6; -.
DR PhosphoSitePlus; Q8TBP6; -.
DR BioMuta; SLC25A40; -.
DR DMDM; 74751387; -.
DR EPD; Q8TBP6; -.
DR jPOST; Q8TBP6; -.
DR MassIVE; Q8TBP6; -.
DR MaxQB; Q8TBP6; -.
DR PaxDb; Q8TBP6; -.
DR PeptideAtlas; Q8TBP6; -.
DR PRIDE; Q8TBP6; -.
DR ProteomicsDB; 74037; -.
DR Antibodypedia; 29759; 42 antibodies from 11 providers.
DR DNASU; 55972; -.
DR Ensembl; ENST00000341119.10; ENSP00000344831.5; ENSG00000075303.13.
DR GeneID; 55972; -.
DR KEGG; hsa:55972; -.
DR MANE-Select; ENST00000341119.10; ENSP00000344831.5; NM_018843.4; NP_061331.2.
DR UCSC; uc003uje.4; human.
DR CTD; 55972; -.
DR DisGeNET; 55972; -.
DR GeneCards; SLC25A40; -.
DR HGNC; HGNC:29680; SLC25A40.
DR HPA; ENSG00000075303; Low tissue specificity.
DR MIM; 610821; gene.
DR neXtProt; NX_Q8TBP6; -.
DR OpenTargets; ENSG00000075303; -.
DR PharmGKB; PA162403655; -.
DR VEuPathDB; HostDB:ENSG00000075303; -.
DR eggNOG; KOG0761; Eukaryota.
DR GeneTree; ENSGT00940000160249; -.
DR HOGENOM; CLU_015166_0_0_1; -.
DR InParanoid; Q8TBP6; -.
DR OMA; YWWGYES; -.
DR OrthoDB; 1007936at2759; -.
DR PhylomeDB; Q8TBP6; -.
DR TreeFam; TF314720; -.
DR PathwayCommons; Q8TBP6; -.
DR SignaLink; Q8TBP6; -.
DR BioGRID-ORCS; 55972; 39 hits in 1081 CRISPR screens.
DR ChiTaRS; SLC25A40; human.
DR GenomeRNAi; 55972; -.
DR Pharos; Q8TBP6; Tdark.
DR PRO; PR:Q8TBP6; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q8TBP6; protein.
DR Bgee; ENSG00000075303; Expressed in adrenal tissue and 170 other tissues.
DR ExpressionAtlas; Q8TBP6; baseline and differential.
DR Genevisible; Q8TBP6; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0048821; P:erythrocyte development; IEA:Ensembl.
DR GO; GO:1990542; P:mitochondrial transmembrane transport; IEA:InterPro.
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 InterPro; IPR045315; Mtm1-like.
DR PANTHER; PTHR45760; PTHR45760; 1.
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 Membrane; Mitochondrion; Mitochondrion inner membrane; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..338
FT /note="Probable mitochondrial glutathione transporter
FT SLC25A40"
FT /id="PRO_0000291809"
FT TRANSMEM 19..39
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..123
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 142..162
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 199..220
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..259
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..318
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 13..131
FT /note="Solcar 1"
FT REPEAT 139..223
FT /note="Solcar 2"
FT REPEAT 233..327
FT /note="Solcar 3"
FT VARIANT 105
FT /note="S -> N (in dbSNP:rs200954020)"
FT /evidence="ECO:0000269|PubMed:28294470"
FT /id="VAR_079372"
FT VARIANT 123
FT /note="T -> I (in dbSNP:rs724665)"
FT /id="VAR_032863"
FT VARIANT 186
FT /note="K -> Q (in dbSNP:rs3213633)"
FT /id="VAR_032864"
FT CONFLICT 71
FT /note="E -> K (in Ref. 3; BAD96740)"
FT /evidence="ECO:0000305"
FT CONFLICT 161
FT /note="P -> Q (in Ref. 1; AAF17225)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 338 AA; 38125 MW; 19F3AC921F5A6961 CRC64;
MDPETRGQEI IKVTPLQQML ASCTGAILTS VIVTPLDVVK IRLQAQNNPL PKGKCFVYSN
GLMDHLCVCE EGGNKLWYKK PGNFQGTLDA FFKIIRNEGI KSLWSGLPPT LVMAVPATVI
YFTCYDQLSA LLRSKLGENE TCIPIVAGIV ARFGAVTVIS PLELIRTKMQ SKKFSYVELH
RFVSKKVSED GWISLWRGWA PTVLRDVPFS AMYWYNYEIL KKWLCEKSGL YEPTFMINFT
SGALSGSFAA VATLPFDVVK TQKQTQLWTY ESHKISMPLH MSTWIIMKNI VAKNGFSGLF
SGLIPRLIKI APACAIMIST YEFGKAFFQK QNVRRQQY
