ID S2539_HUMAN Reviewed; 359 AA. AC Q9BZJ4; A8JZZ2; D3DX51; D3DX54; Q4V9M1; Q9P182; Q9UF66; Q9Y379; DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 2. DT 27-MAR-2024, entry version 192. DE RecName: Full=Probable mitochondrial glutathione transporter SLC25A39 {ECO:0000305}; DE AltName: Full=Solute carrier family 25 member 39 {ECO:0000305}; GN Name=SLC25A39 {ECO:0000303|PubMed:34707288, GN ECO:0000312|HGNC:HGNC:24279}; GN ORFNames=CGI-69 {ECO:0000303|PubMed:11139402}, PRO2163 GN {ECO:0000303|Ref.7}; 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] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND VARIANT LEU-247. RC TISSUE=Liver; RX PubMed=11139402; DOI=10.1042/bj3530369; RA Yu X.X., Lewin D.A., Zhong A., Brush J., Schow P.W., Sherwood S.W., Pan G., RA Adams S.H.; RT "Overexpression of the human 2-oxoglutarate carrier lowers mitochondrial RT membrane potential in HEK-293 cells: contrast with the unique cold-induced RT mitochondrial carrier CGI-69."; RL Biochem. J. 353:369-375(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=10810093; DOI=10.1101/gr.10.5.703; RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.; RT "Identification of novel human genes evolutionarily conserved in RT Caenorhabditis elegans by comparative proteomics."; RL Genome Res. 10:703-713(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT LEU-247. RC TISSUE=Testis; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LEU-247. 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP LEU-247. RC TISSUE=Brain, Cervix, and Colon; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-359 (ISOFORM 2), AND VARIANT RP LEU-247. RC TISSUE=Fetal liver; RA Zhang C., Yu Y., Zhang S., Wei H., Zhang Y., Zhou G., Bi J., Liu M., He F.; RT "Functional prediction of the coding sequences of 79 new genes deduced by RT analysis of cDNA clones from human fetal liver."; RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases. RN [8] RP SUBCELLULAR LOCATION. RX PubMed=11256614; DOI=10.1093/embo-reports/kvd058; RA Simpson J.C., Wellenreuther R., Poustka A., Pepperkok R., Wiemann S.; RT "Systematic subcellular localization of novel proteins identified by large- RT scale cDNA sequencing."; RL EMBO Rep. 1:287-292(2000). RN [9] RP FUNCTION, TRANSPORTER ACTIVITY, AND MUTAGENESIS OF ASP-226 AND LYS-329. 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 [10] RP FUNCTION, TRANSPORTER ACTIVITY, AND MUTAGENESIS OF ASP-226. RX PubMed=35513392; DOI=10.1038/s41467-022-30126-9; RA Shi X., Reinstadler B., Shah H., To T.L., Byrne K., Summer L., Calvo S.E., RA Goldberger O., Doench J.G., Mootha V.K., Shen H.; RT "Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial RT glutathione transport linking iron homeostasis to OXPHOS."; RL Nat. Commun. 13:2483-2483(2022). CC -!- FUNCTION: Mitochondrial transporter required for glutathione import CC into mitochondria (PubMed:34707288, PubMed:35513392). Glutathione, CC which plays key roles in oxidative metabolism, is produced exclusively CC in the 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 CC (PubMed:34707288). {ECO:0000269|PubMed:34707288, CC ECO:0000269|PubMed:35513392}. CC -!- CATALYTIC ACTIVITY: CC Reaction=glutathione(in) = glutathione(out); Xref=Rhea:RHEA:74819, CC ChEBI:CHEBI:57925; Evidence={ECO:0000269|PubMed:34707288, CC ECO:0000269|PubMed:35513392}; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:11139402, ECO:0000269|PubMed:11256614}; Multi-pass CC membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=CGI-69L {ECO:0000303|PubMed:11139402}; CC IsoId=Q9BZJ4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BZJ4-2; Sequence=VSP_003264; CC -!- TISSUE SPECIFICITY: Expressed in many tissues (PubMed:11139402). CC Abundant in testis and kidney (PubMed:11139402). CC {ECO:0000269|PubMed:11139402}. CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF69618.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF317711; AAG60687.1; -; mRNA. DR EMBL; AF151827; AAD34064.1; -; mRNA. DR EMBL; AL133584; CAB63728.1; -; mRNA. DR EMBL; AK026060; BAB15341.1; -; mRNA. DR EMBL; AK289357; BAF82046.1; -; mRNA. DR EMBL; CH471178; EAW51602.1; -; Genomic_DNA. DR EMBL; CH471178; EAW51603.1; -; Genomic_DNA. DR EMBL; CH471178; EAW51604.1; -; Genomic_DNA. DR EMBL; CH471178; EAW51605.1; -; Genomic_DNA. DR EMBL; CH471178; EAW51606.1; -; Genomic_DNA. DR EMBL; CH471178; EAW51607.1; -; Genomic_DNA. DR EMBL; BC001398; AAH01398.1; -; mRNA. DR EMBL; BC009330; AAH09330.1; -; mRNA. DR EMBL; BC096819; AAH96819.1; -; mRNA. DR EMBL; AF119864; AAF69618.1; ALT_INIT; mRNA. DR CCDS; CCDS11482.1; -. [Q9BZJ4-2] DR CCDS; CCDS45700.1; -. [Q9BZJ4-1] DR PIR; T43493; T43493. DR RefSeq; NP_001137252.1; NM_001143780.2. [Q9BZJ4-1] DR RefSeq; NP_057100.1; NM_016016.3. [Q9BZJ4-2] DR AlphaFoldDB; Q9BZJ4; -. DR SMR; Q9BZJ4; -. DR BioGRID; 119645; 9. DR IntAct; Q9BZJ4; 3. DR MINT; Q9BZJ4; -. DR STRING; 9606.ENSP00000366299; -. DR TCDB; 2.A.29.14.8; the mitochondrial carrier (mc) family. DR iPTMnet; Q9BZJ4; -. DR PhosphoSitePlus; Q9BZJ4; -. DR BioMuta; SLC25A39; -. DR DMDM; 317373277; -. DR jPOST; Q9BZJ4; -. DR MassIVE; Q9BZJ4; -. DR MaxQB; Q9BZJ4; -. DR PaxDb; 9606-ENSP00000366299; -. DR PeptideAtlas; Q9BZJ4; -. DR ProteomicsDB; 79858; -. [Q9BZJ4-1] DR ProteomicsDB; 79859; -. [Q9BZJ4-2] DR Pumba; Q9BZJ4; -. DR Antibodypedia; 17434; 59 antibodies from 16 providers. DR DNASU; 51629; -. DR Ensembl; ENST00000225308.12; ENSP00000225308.8; ENSG00000013306.16. [Q9BZJ4-2] DR Ensembl; ENST00000377095.10; ENSP00000366299.4; ENSG00000013306.16. [Q9BZJ4-1] DR Ensembl; ENST00000590194.5; ENSP00000467681.1; ENSG00000013306.16. [Q9BZJ4-2] DR GeneID; 51629; -. DR KEGG; hsa:51629; -. DR MANE-Select; ENST00000377095.10; ENSP00000366299.4; NM_001143780.3; NP_001137252.1. DR UCSC; uc002igm.3; human. [Q9BZJ4-1] DR AGR; HGNC:24279; -. DR CTD; 51629; -. DR DisGeNET; 51629; -. DR GeneCards; SLC25A39; -. DR HGNC; HGNC:24279; SLC25A39. DR HPA; ENSG00000013306; Low tissue specificity. DR MIM; 610820; gene. DR neXtProt; NX_Q9BZJ4; -. DR OpenTargets; ENSG00000013306; -. DR PharmGKB; PA162403626; -. DR VEuPathDB; HostDB:ENSG00000013306; -. DR eggNOG; KOG0761; Eukaryota. DR GeneTree; ENSGT00940000156382; -. DR HOGENOM; CLU_015166_0_0_1; -. DR InParanoid; Q9BZJ4; -. DR OMA; DQTSVGA; -. DR OrthoDB; 3490716at2759; -. DR PhylomeDB; Q9BZJ4; -. DR TreeFam; TF314720; -. DR PathwayCommons; Q9BZJ4; -. DR SignaLink; Q9BZJ4; -. DR BioGRID-ORCS; 51629; 18 hits in 1162 CRISPR screens. DR ChiTaRS; SLC25A39; human. DR GeneWiki; SLC25A39; -. DR GenomeRNAi; 51629; -. DR Pharos; Q9BZJ4; Tdark. DR PRO; PR:Q9BZJ4; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q9BZJ4; Protein. DR Bgee; ENSG00000013306; Expressed in lower esophagus mucosa and 173 other cell types or tissues. DR ExpressionAtlas; Q9BZJ4; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0160007; P:glutathione import into mitochondrion; IDA:UniProtKB. DR GO; GO:0006783; P:heme biosynthetic process; IEA:UniProtKB-KW. DR Gene3D; 1.50.40.10; Mitochondrial carrier domain; 2. DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier. DR InterPro; IPR023395; Mt_carrier_dom_sf. DR InterPro; IPR045315; Mtm1-like. DR PANTHER; PTHR45760; FI19922P1-RELATED; 1. DR PANTHER; PTHR45760:SF1; MITOCHONDRIAL GLUTATHIONE TRANSPORTER SLC25A39-RELATED; 1. DR Pfam; PF00153; Mito_carr; 4. DR SUPFAM; SSF103506; Mitochondrial carrier; 1. DR PROSITE; PS50920; SOLCAR; 3. DR Genevisible; Q9BZJ4; HS. PE 1: Evidence at protein level; KW Alternative splicing; Heme biosynthesis; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Reference proteome; Repeat; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..359 FT /note="Probable mitochondrial glutathione transporter FT SLC25A39" FT /id="PRO_0000090596" FT TRANSMEM 15..35 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TRANSMEM 122..142 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TRANSMEM 161..181 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TRANSMEM 215..235 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TRANSMEM 259..279 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TRANSMEM 318..338 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT REPEAT 9..151 FT /note="Solcar 1" FT REPEAT 159..243 FT /note="Solcar 2" FT REPEAT 253..347 FT /note="Solcar 3" FT VAR_SEQ 64..72 FT /note="LPSSLQSTG -> W (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10810093, FT ECO:0000303|PubMed:11139402, ECO:0000303|PubMed:11230166, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.7" FT /id="VSP_003264" FT VARIANT 247 FT /note="F -> L (in dbSNP:rs2011951)" FT /evidence="ECO:0000269|PubMed:11139402, FT ECO:0000269|PubMed:11230166, ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.5, ECO:0000269|Ref.7" FT /id="VAR_012756" FT MUTAGEN 226 FT /note="D->A: Abolished glutathione import into mitochondria FT without affecting the levels of NAD." FT /evidence="ECO:0000269|PubMed:34707288, FT ECO:0000269|PubMed:35513392" FT MUTAGEN 329 FT /note="K->A: Abolished glutathione import into mitochondria FT without affecting the levels of NAD." FT /evidence="ECO:0000269|PubMed:34707288" FT CONFLICT 266 FT /note="G -> R (in Ref. 7; AAF69618)" FT /evidence="ECO:0000305" SQ SEQUENCE 359 AA; 39249 MW; C29C750032E94D0A CRC64; MADQDPAGIS PLQQMVASGT GAVVTSLFMT PLDVVKVRLQ SQRPSMASEL MPSSRLWSLS YTKLPSSLQS TGKCLLYCNG VLEPLYLCPN GARCATWFQD PTRFTGTMDA FVKIVRHEGT RTLWSGLPAT LVMTVPATAI YFTAYDQLKA FLCGRALTSD LYAPMVAGAL ARLGTVTVIS PLELMRTKLQ AQHVSYRELG ACVRTAVAQG GWRSLWLGWG PTALRDVPFS ALYWFNYELV KSWLNGFRPK DQTSVGMSFV AGGISGTVAA VLTLPFDVVK TQRQVALGAM EAVRVNPLHV DSTWLLLRRI RAESGTKGLF AGFLPRIIKA APSCAIMIST YEFGKSFFQR LNQDRLLGG //