S2538_YEAST
ID S2538_YEAST Reviewed; 307 AA.
AC Q07534; D6VRN1;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Mitochondrial glycine transporter {ECO:0000255|HAMAP-Rule:MF_03064, ECO:0000303|PubMed:27476175};
DE AltName: Full=Heme biosynthesis protein of SLC25 family {ECO:0000303|PubMed:25957689};
DE AltName: Full=Solute carrier family 25 member 38 homolog {ECO:0000255|HAMAP-Rule:MF_03064};
GN Name=HEM25 {ECO:0000303|PubMed:25957689};
GN OrderedLocusNames=YDL119C {ECO:0000312|SGD:S000002277};
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [4]
RP CLASSIFICATION.
RX PubMed=9178508;
RX DOI=10.1002/(sici)1097-0061(199705)13:6<573::aid-yea107>3.0.co;2-i;
RA el Moualij B., Duyckaerts C., Lamotte-Brasseur J., Sluse F.E.;
RT "Phylogenetic classification of the mitochondrial carrier family of
RT Saccharomyces cerevisiae.";
RL Yeast 13:573-581(1997).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=10930523; DOI=10.1016/s0005-2736(00)00222-4;
RA Belenkiy R., Haefele A., Eisen M.B., Wohlrab H.;
RT "The yeast mitochondrial transport proteins: new sequences and consensus
RT residues, lack of direct relation between consensus residues and
RT transmembrane helices, expression patterns of the transport protein genes,
RT and protein-protein interactions with other proteins.";
RL Biochim. Biophys. Acta 1467:207-218(2000).
RN [6]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [7]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [8]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=16823961; DOI=10.1021/pr050477f;
RA Reinders J., Zahedi R.P., Pfanner N., Meisinger C., Sickmann A.;
RT "Toward the complete yeast mitochondrial proteome: multidimensional
RT separation techniques for mitochondrial proteomics.";
RL J. Proteome Res. 5:1543-1554(2006).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19412178; DOI=10.1038/ng.359;
RA Guernsey D.L., Jiang H., Campagna D.R., Evans S.C., Ferguson M.,
RA Kellogg M.D., Lachance M., Matsuoka M., Nightingale M., Rideout A.,
RA Saint-Amant L., Schmidt P.J., Orr A., Bottomley S.S., Fleming M.D.,
RA Ludman M., Dyack S., Fernandez C.V., Samuels M.E.;
RT "Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic
RT autosomal recessive congenital sideroblastic anemia.";
RL Nat. Genet. 41:651-653(2009).
RN [10]
RP DISRUPTION PHENOTYPE.
RX PubMed=25957689; DOI=10.1016/j.cell.2015.04.017;
RA Kardon J.R., Yien Y.Y., Huston N.C., Branco D.S., Hildick-Smith G.J.,
RA Rhee K.Y., Paw B.H., Baker T.A.;
RT "Mitochondrial ClpX activates a key enzyme for heme biosynthesis and
RT erythropoiesis.";
RL Cell 161:858-867(2015).
RN [11]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RX PubMed=27476175; DOI=10.1074/jbc.m116.736876;
RA Lunetti P., Damiano F., De Benedetto G., Siculella L., Pennetta A.,
RA Muto L., Paradies E., Marobbio C.M., Dolce V., Capobianco L.;
RT "Characterization of human and yeast mitochondrial glycine carriers with
RT implications for heme biosynthesis and anemia.";
RL J. Biol. Chem. 291:19746-19759(2016).
RN [12]
RP FUNCTION.
RX PubMed=26821380; DOI=10.1371/journal.pgen.1005783;
RA Fernandez-Murray J.P., Prykhozhij S.V., Dufay J.N., Steele S.L., Gaston D.,
RA Nasrallah G.K., Coombs A.J., Liwski R.S., Fernandez C.V., Berman J.N.,
RA McMaster C.R.;
RT "Glycine and folate ameliorate models of congenital sideroblastic anemia.";
RL PLoS Genet. 12:E1005783-E1005783(2016).
CC -!- FUNCTION: Mitochondrial glycine transporter that imports glycine into
CC the mitochondrial matrix. Plays an important role in providing glycine
CC for the first enzymatic step in heme biosynthesis, the condensation of
CC glycine with succinyl-CoA to produce 5-aminolevulinate (ALA) in the
CC mitochondrial matrix. {ECO:0000255|HAMAP-Rule:MF_03064,
CC ECO:0000269|PubMed:19412178, ECO:0000269|PubMed:26821380,
CC ECO:0000269|PubMed:27476175}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycine(in) = glycine(out); Xref=Rhea:RHEA:70715,
CC ChEBI:CHEBI:57305; Evidence={ECO:0000250|UniProtKB:Q96DW6};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.75 mM for glycine {ECO:0000269|PubMed:27476175};
CC Vmax=169.8 nmol/min/mg enzyme for glycine uptake
CC {ECO:0000269|PubMed:27476175};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:16823961, ECO:0000269|PubMed:27476175}.
CC Mitochondrion inner membrane {ECO:0000255|HAMAP-Rule:MF_03064,
CC ECO:0000305|PubMed:10930523, ECO:0000305|PubMed:27476175}; Multi-pass
CC membrane protein {ECO:0000255|HAMAP-Rule:MF_03064,
CC ECO:0000305|PubMed:10930523}.
CC -!- DISRUPTION PHENOTYPE: Yeasts grow well on the fermentable carbon source
CC dextrose, but only poorly aerobically on glycerol, indicating a defect
CC in respiration. Furthermore, the deletion strain is unable to reduce
CC sodium nitroprusside, indicating that the defect is likely in heme
CC biosynthesis. Nitroprusside reduction can be rescued by supplementation
CC of the medium with either glycine or 5-aminolevulinate (ALA)
CC (PubMed:19412178). In combination with a disruption of MCX1, abrogates
CC mitochondrial respiration (PubMed:25957689).
CC {ECO:0000269|PubMed:19412178, ECO:0000269|PubMed:25957689}.
CC -!- MISCELLANEOUS: Present with 1550 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC SLC25A38 subfamily. {ECO:0000255|HAMAP-Rule:MF_03064}.
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DR EMBL; Z74167; CAA98686.1; -; Genomic_DNA.
DR EMBL; AY692648; AAT92667.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA11741.1; -; Genomic_DNA.
DR PIR; S67662; S67662.
DR RefSeq; NP_010164.1; NM_001180178.1.
DR AlphaFoldDB; Q07534; -.
DR SMR; Q07534; -.
DR BioGRID; 31944; 154.
DR MINT; Q07534; -.
DR STRING; 4932.YDL119C; -.
DR MaxQB; Q07534; -.
DR PaxDb; Q07534; -.
DR PRIDE; Q07534; -.
DR EnsemblFungi; YDL119C_mRNA; YDL119C; YDL119C.
DR GeneID; 851439; -.
DR KEGG; sce:YDL119C; -.
DR SGD; S000002277; HEM25.
DR VEuPathDB; FungiDB:YDL119C; -.
DR eggNOG; KOG0766; Eukaryota.
DR GeneTree; ENSGT00550000075117; -.
DR HOGENOM; CLU_015166_0_3_1; -.
DR InParanoid; Q07534; -.
DR OMA; IRDAPYA; -.
DR BioCyc; YEAST:G3O-29518-MON; -.
DR PRO; PR:Q07534; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; Q07534; protein.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0015187; F:glycine transmembrane transporter activity; IDA:SGD.
DR GO; GO:1904983; P:glycine import into mitochondrion; IMP:SGD.
DR GO; GO:0006783; P:heme biosynthetic process; IMP:UniProtKB.
DR Gene3D; 1.50.40.10; -; 1.
DR HAMAP; MF_03064; SLC25A38; 1.
DR InterPro; IPR030847; Hem25/SLC25A38.
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 Membrane; Mitochondrion; Mitochondrion inner membrane; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..307
FT /note="Mitochondrial glycine transporter"
FT /id="PRO_0000240707"
FT TRANSMEM 14..39
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT TRANSMEM 62..88
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT TRANSMEM 121..146
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT TRANSMEM 174..197
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT TRANSMEM 225..251
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT TRANSMEM 280..298
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT REPEAT 8..87
FT /note="Solcar 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT REPEAT 115..199
FT /note="Solcar 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT REPEAT 221..305
FT /note="Solcar 3"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
SQ SEQUENCE 307 AA; 34204 MW; 7448D1559E157C17 CRC64;
MTEQATKPRN SSHLIGGFFG GLTSAVALQP LDLLKTRIQQ DKKATLWKNL KEIDSPLQLW
RGTLPSALRT SIGSALYLSC LNLMRSSLAK RRNAVPSLTN DSNIVYNKSS SLPRLTMYEN
LLTGAFARGL VGYITMPITV IKVRYESTLY NYSSLKEAIT HIYTKEGLFG FFRGFGATCL
RDAPYAGLYV LLYEKSKQLL PMVLPSRFIH YNPEGGFTTY TSTTVNTTSA VLSASLATTV
TAPFDTIKTR MQLEPSKFTN SFNTFTSIVK NENVLKLFSG LSMRLARKAF SAGIAWGIYE
ELVKRFM
