S2539_HUMAN
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 03-AUG-2022, entry version 183.
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, ECO:0000312|HGNC:HGNC:24279};
GN ORFNames=CGI-69 {ECO:0000303|PubMed:11139402}, PRO2163 {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, 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).
CC -!- FUNCTION: Mitochondrial transporter required for glutathione import
CC into mitochondria (PubMed:34707288). Glutathione, which plays key roles
CC in oxidative metabolism, is produced exclusively in the cytosol and is
CC imported in many organelles (PubMed:34707288). Mitochondrial
CC glutathione is required for the activity and stability of proteins
CC containing iron-sulfur clusters, as well as erythropoiesis
CC (PubMed:34707288). {ECO:0000269|PubMed:34707288}.
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};
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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; 8.
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; Q9BZJ4; -.
DR PeptideAtlas; Q9BZJ4; -.
DR PRIDE; Q9BZJ4; -.
DR ProteomicsDB; 79858; -. [Q9BZJ4-1]
DR ProteomicsDB; 79859; -. [Q9BZJ4-2]
DR Antibodypedia; 17434; 42 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 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; 1007936at2759; -.
DR PhylomeDB; Q9BZJ4; -.
DR TreeFam; TF314720; -.
DR PathwayCommons; Q9BZJ4; -.
DR SignaLink; Q9BZJ4; -.
DR BioGRID-ORCS; 51629; 18 hits in 1081 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 171 other tissues.
DR ExpressionAtlas; Q9BZJ4; baseline and differential.
DR Genevisible; Q9BZJ4; 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: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; -; 2.
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 SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
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 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
