YHM2_YEAST
ID YHM2_YEAST Reviewed; 314 AA.
AC Q04013; D6W067;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Citrate/oxoglutarate carrier protein {ECO:0000303|PubMed:20371607};
DE Short=Coc1p {ECO:0000303|PubMed:20371607};
DE AltName: Full=Mitochondrial DNA replication protein YHM2 {ECO:0000305};
GN Name=YHM2; OrderedLocusNames=YMR241W; ORFNames=YM9408.03;
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=9169872;
RA Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL Nature 387:90-93(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] {ECO:0000305}
RP SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 249-PRO--LYS-253.
RX PubMed=9742088; DOI=10.1128/mcb.18.10.5712;
RA Cho J.H., Ha S.J., Kao L.R., Megraw T.L., Chae C.-B.;
RT "A novel DNA-binding protein bound to the mitochondrial inner membrane
RT restores the null mutation of mitochondrial histone Abf2p in Saccharomyces
RT cerevisiae.";
RL Mol. Cell. Biol. 18:5712-5723(1998).
RN [4]
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 [5]
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 [6]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 76625 / YPH499;
RX PubMed=14576278; DOI=10.1073/pnas.2135385100;
RA Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E.,
RA Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P.,
RA Pfanner N., Meisinger C.;
RT "The proteome of Saccharomyces cerevisiae mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003).
RN [7]
RP FUNCTION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=20371607; DOI=10.1074/jbc.m109.097188;
RA Castegna A., Scarcia P., Agrimi G., Palmieri L., Rottensteiner H.,
RA Spera I., Germinario L., Palmieri F.;
RT "Identification and functional characterization of a novel mitochondrial
RT carrier for citrate and oxoglutarate in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 285:17359-17370(2010).
CC -!- FUNCTION: Mitochondrial antiporter which catalyzes the transport of
CC citrate and oxoglutarate across the membrane. Also shows specificity
CC for oxaloacetate, and to a lesser extent succinate and fumarate.
CC Transports isocitrate, cis-aconitate and L-malate with very low
CC efficiency. Does not show uniporter activity. Helps to maintain normal
CC citrate levels and NADPH/NADP(+) ratios under conditions of oxidative
CC stress. In addition, associates with the mitochondrial nucleoid and
CC binds DNA in vitro, although the relevance of these data in vivo is
CC unclear. {ECO:0000269|PubMed:20371607, ECO:0000269|PubMed:9742088}.
CC -!- ACTIVITY REGULATION: Strongly inhibited by mersalyl, p-
CC chloromercuribenzenesulfonate, mercuric chloride, N-ethylmaleimide,
CC pyridoxal 5'-phosphate, bathophenanthroline, and tannic acid. Partially
CC inhibited by alpha-cyanocinnamate and bromescol purple. Weakly
CC inhibited by butylmalonate and phenylsuccinate. Not inhibited by 1,2,3-
CC benzenetricarboxylate or carboxyatractyloside.
CC {ECO:0000269|PubMed:20371607}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.16 mM for citrate (with purified protein reconstituted into
CC proteoliposomes) {ECO:0000269|PubMed:20371607};
CC KM=1.2 mM for oxoglutarate (with purified protein reconstituted into
CC proteoliposomes) {ECO:0000269|PubMed:20371607};
CC Vmax=9.8 mmol/min/g enzyme for [14C]citrate/citrate and
CC [14C]citrate/oxoglutarate exchange (with purified protein
CC reconstituted into proteoliposomes) {ECO:0000269|PubMed:20371607};
CC Vmax=10.3 mmol/min/g enzyme for [14C]oxoglutarate/oxoglutarate and
CC [14C]oxoglutarate/citrate exchange (with purified protein
CC reconstituted into proteoliposomes) {ECO:0000269|PubMed:20371607};
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:14576278,
CC ECO:0000269|PubMed:20371607, ECO:0000269|PubMed:9742088}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:14576278, ECO:0000269|PubMed:20371607,
CC ECO:0000269|PubMed:9742088}. Mitochondrion matrix, mitochondrion
CC nucleoid {ECO:0000269|PubMed:9742088}.
CC -!- DISRUPTION PHENOTYPE: Shows slow growth and respiration defects in
CC minimal medium. Shows growth defects in acetate-supplemented medium;
CC the phenotype is enhanced by addition of hydrogen peroxide (increased
CC oxidative stress) and/or double knockout of YHM2 and ZWF1. The
CC cytosolic NADPH/NADP(+) ratio is decreased compared to wild type; this
CC effect is enhanced in the presence of hydrogen peroxide. The
CC mitochondrial NADPH/NADP(+) ratio is increased, but only in the
CC presence of hydrogen peroxide. Levels of cytosolic citrate are reduced,
CC but only in the presence of hydrogen peroxide. Levels of cytosolic
CC oxoglutarate are reduced, but only in the presence of hydrogen
CC peroxide; the effect is enhanced by double knockout of YHM2 and ZWF1.
CC Cells show a very small increase in levels of reactive oxygen species
CC (ROS) following hydrogen peroxide treatment; in double knockouts of
CC YHM2 and ZWF1 there is a large increase in ROS. Overexpression
CC suppresses the temperature-sensitive growth defect of ABF2 in glucose-
CC rich medium. {ECO:0000269|PubMed:20371607, ECO:0000269|PubMed:9742088}.
CC -!- MISCELLANEOUS: Present with 2930 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 {ECO:0000305}.
CC -!- CAUTION: Was originally proposed to function in mitochondrial DNA
CC replication and maintenance. {ECO:0000303|PubMed:9742088}.
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DR EMBL; Z48756; CAA88651.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA10141.1; -; Genomic_DNA.
DR PIR; S56055; S56055.
DR RefSeq; NP_013968.1; NM_001182748.1.
DR AlphaFoldDB; Q04013; -.
DR BioGRID; 35420; 178.
DR DIP; DIP-6370N; -.
DR IntAct; Q04013; 13.
DR MINT; Q04013; -.
DR STRING; 4932.YMR241W; -.
DR TCDB; 2.A.29.29.1; the mitochondrial carrier (mc) family.
DR MaxQB; Q04013; -.
DR PaxDb; Q04013; -.
DR PRIDE; Q04013; -.
DR EnsemblFungi; YMR241W_mRNA; YMR241W; YMR241W.
DR GeneID; 855282; -.
DR KEGG; sce:YMR241W; -.
DR SGD; S000004854; YHM2.
DR VEuPathDB; FungiDB:YMR241W; -.
DR eggNOG; KOG0756; Eukaryota.
DR HOGENOM; CLU_052717_0_0_1; -.
DR InParanoid; Q04013; -.
DR OMA; AEYYAKT; -.
DR BioCyc; YEAST:G3O-32921-MON; -.
DR PRO; PR:Q04013; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; Q04013; protein.
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:0042645; C:mitochondrial nucleoid; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0003677; F:DNA binding; IDA:SGD.
DR GO; GO:0005371; F:tricarboxylate secondary active transmembrane transporter activity; IDA:SGD.
DR GO; GO:0015742; P:alpha-ketoglutarate transport; IDA:SGD.
DR GO; GO:0006843; P:mitochondrial citrate transmembrane transport; IDA:SGD.
DR GO; GO:0000002; P:mitochondrial genome maintenance; IMP:SGD.
DR GO; GO:0006842; P:tricarboxylic acid transport; IDA:SGD.
DR Gene3D; 1.50.40.10; -; 2.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR Pfam; PF00153; Mito_carr; 2.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW DNA-binding; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Mitochondrion nucleoid; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..314
FT /note="Citrate/oxoglutarate carrier protein"
FT /id="PRO_0000090688"
FT TRANSMEM 23..44
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..127
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..238
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 273..294
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 18..100
FT /note="Solcar 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 107..199
FT /note="Solcar 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 217..301
FT /note="Solcar 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT DNA_BIND 246..259
FT /evidence="ECO:0000269|PubMed:9742088"
FT MUTAGEN 249..253
FT /note="PNRPK->GGGGG: Fails to bind DNA in vitro."
FT /evidence="ECO:0000269|PubMed:9742088"
SQ SEQUENCE 314 AA; 34185 MW; EB483C715D195BED CRC64;
MPSTTNTAAA NVIEKKPVSF SNILLGACLN LSEVTTLGQP LEVVKTTMAA NRNFTFLESV
KHVWSRGGIL GYYQGLIPWA WIEASTKGAV LLFVSAEAEY RFKSLGLNNF ASGILGGVTG
GVTQAYLTMG FCTCMKTVEI TRHKSASAGG VPQSSWSVFK NIYKKEGIRG INKGVNAVAI
RQMTNWGSRF GLSRLVEDGI RKITGKTNKD DKLNPFEKIG ASALGGGLSA WNQPIEVIRV
EMQSKKEDPN RPKNLTVGKT FKYIYQSNGL KGLYRGVTPR IGLGIWQTVF MVGFGDMAKE
FVARMTGETP VAKH
