S2512_RAT
ID S2512_RAT Reviewed; 676 AA.
AC F1LX07;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-AUG-2022, sequence version 5.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Electrogenic aspartate/glutamate antiporter SLC25A12, mitochondrial {ECO:0000305|PubMed:4436323, ECO:0000305|PubMed:486467};
DE AltName: Full=Solute carrier family 25 member 12 {ECO:0000312|RGD:1305181};
GN Name=Slc25a12 {ECO:0000312|RGD:1305181};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=4436323; DOI=10.1016/s0021-9258(19)81269-3;
RA LaNoue K.F., Tischler M.E.;
RT "Electrogenic characteristics of the mitochondrial glutamate-aspartate
RT antiporter.";
RL J. Biol. Chem. 249:7522-7528(1974).
RN [3]
RP FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=486467; DOI=10.1016/0005-2736(79)90407-3;
RA Palmieri F., Stipani I., Iacobazzi V.;
RT "The transport of L-cysteinesulfinate in rat liver mitochondria.";
RL Biochim. Biophys. Acta 555:531-546(1979).
CC -!- FUNCTION: Mitochondrial electrogenic aspartate/glutamate antiporter
CC that favors efflux of aspartate and entry of glutamate and proton
CC within the mitochondria as part of the malate-aspartate shuttle
CC (PubMed:4436323). Also mediates the uptake of L-cysteinesulfinate by
CC mitochondria in exchange of L-glutamate and proton. Can also exchange
CC L-cysteinesulfinate with aspartate in their anionic form without any
CC proton translocation (PubMed:486467). {ECO:0000269|PubMed:4436323,
CC ECO:0000269|PubMed:486467}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(out) + L-aspartate(in) + L-glutamate(out) = H(+)(in) + L-
CC aspartate(out) + L-glutamate(in); Xref=Rhea:RHEA:70783,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:29991;
CC Evidence={ECO:0000269|PubMed:4436323};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-sulfino-L-alanine(out) + H(+)(in) + L-glutamate(in) = 3-
CC sulfino-L-alanine(in) + H(+)(out) + L-glutamate(out);
CC Xref=Rhea:RHEA:70967, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:61085; Evidence={ECO:0000269|PubMed:486467};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-sulfino-L-alanine(out) + L-aspartate(in) = 3-sulfino-L-
CC alanine(in) + L-aspartate(out); Xref=Rhea:RHEA:70975,
CC ChEBI:CHEBI:29991, ChEBI:CHEBI:61085;
CC Evidence={ECO:0000269|PubMed:486467};
CC -!- ACTIVITY REGULATION: L-aspartate and 3-sulfino-L-alanine uptake are
CC both inhibited by glisoxepide. {ECO:0000269|PubMed:486467}.
CC -!- SUBUNIT: Homodimer (via N-terminus). {ECO:0000250|UniProtKB:O75746}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:4436323, ECO:0000305|PubMed:486467}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- DOMAIN: Upon calcium binding, the EF-hand-containing regulatory N-
CC terminal domain binds to the C-terminal domain, opening a vestibule
CC which allows the substrates to be translocated through the carrier
CC domain. In the absence of calcium, the linker loop domain may close the
CC vestibule, which may prevent substrates from entering the carrier
CC domain. {ECO:0000250|UniProtKB:O75746}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; AABR07052490; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07052491; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07052492; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07052493; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07052494; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07052495; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07072871; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC107446; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR SMR; F1LX07; -.
DR STRING; 10116.ENSRNOP00000032909; -.
DR PhosphoSitePlus; F1LX07; -.
DR jPOST; F1LX07; -.
DR PaxDb; F1LX07; -.
DR PeptideAtlas; F1LX07; -.
DR PRIDE; F1LX07; -.
DR Ensembl; ENSRNOT00000036728.7; ENSRNOP00000032909.7; ENSRNOG00000022922.7.
DR RGD; 1305181; Slc25a12.
DR VEuPathDB; HostDB:ENSRNOG00000022922; -.
DR eggNOG; KOG0751; Eukaryota.
DR GeneTree; ENSGT00940000155963; -.
DR HOGENOM; CLU_014931_3_0_1; -.
DR InParanoid; F1LX07; -.
DR OMA; KKDFFGE; -.
DR Reactome; R-RNO-70263; Gluconeogenesis.
DR Reactome; R-RNO-8963693; Aspartate and asparagine metabolism.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000022922; Expressed in skeletal muscle tissue and 19 other tissues.
DR ExpressionAtlas; F1LX07; baseline and differential.
DR Genevisible; F1LX07; RN.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0000514; F:3-sulfino-L-alanine: proton, glutamate antiporter activity; ISS:UniProtKB.
DR GO; GO:0000515; F:aspartate:glutamate, proton antiporter activity; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0015183; F:L-aspartate transmembrane transporter activity; ISO:RGD.
DR GO; GO:0005313; F:L-glutamate transmembrane transporter activity; ISO:RGD.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015810; P:aspartate transmembrane transport; ISO:RGD.
DR GO; GO:0006537; P:glutamate biosynthetic process; IMP:RGD.
DR GO; GO:0015813; P:L-glutamate transmembrane transport; ISO:RGD.
DR GO; GO:0043490; P:malate-aspartate shuttle; IMP:RGD.
DR GO; GO:1904024; P:negative regulation of glucose catabolic process to lactate via pyruvate; IMP:RGD.
DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IMP:RGD.
DR GO; GO:0010907; P:positive regulation of glucose metabolic process; IMP:RGD.
DR GO; GO:0031643; P:positive regulation of myelination; IMP:RGD.
DR GO; GO:0051592; P:response to calcium ion; ISO:RGD.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
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 SMART; SM00054; EFh; 3.
DR SUPFAM; SSF103506; SSF103506; 1.
DR SUPFAM; SSF47473; SSF47473; 2.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
DR PROSITE; PS50920; SOLCAR; 3.
PE 3: Inferred from homology;
KW Acetylation; Calcium; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT CHAIN 2..676
FT /note="Electrogenic aspartate/glutamate antiporter
FT SLC25A12, mitochondrial"
FT /id="PRO_0000455803"
FT TOPO_DOM 2..328
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 329..346
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 347..389
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 390..409
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 410..432
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 433..446
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 447..481
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 482..501
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 502..520
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 521..538
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 539..577
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 578..597
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 598..676
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT DOMAIN 65..76
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
FT DOMAIN 86..121
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 125..155
FT /note="EF-hand 3"
FT /evidence="ECO:0000305"
FT DOMAIN 157..192
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REPEAT 323..415
FT /note="Solcar 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 423..507
FT /note="Solcar 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 515..603
FT /note="Solcar 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REGION 2..293
FT /note="Regulatory N-terminal domain"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT REGION 294..309
FT /note="Linker loop domain"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT REGION 319..611
FT /note="Carrier domain"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT REGION 612..674
FT /note="C-terminal domain"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT BINDING 65
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT BINDING 67
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT BINDING 69
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT BINDING 71
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT BINDING 76
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O75746"
SQ SEQUENCE 676 AA; 74361 MW; 95457012E889517F CRC64;
MAVKVHTTKR GDPHELRNIF LQYASTEVDG EHYMTPEDFV QRYLGLYNDP NSNPKIVQLL
AGVADQTKDG LISYQEFLAF ESVLCAPDSM FIVAFQLFDK SGNGEVTFEN VKEIFGQTII
HHHIPFNWDC EFIRLHFGHN RKKHLNYVEF TQFLQELQLE HARQAFALKD KSKSGMISGL
DFSDVMVTIR SHMLTPFVEE NLVSAAGGST SHQVSFSYFN AFNSLLNNME LVRKIYSTLA
GTRKDIEVTK EEFASAITYG VVTPINVGIL YFINNVHIST GRLTLADIER IAPLAEGALP
YNLAELQRQQ SPGLGRPIWL QIAESAYRFT LGSVAGAVGA TAVYPIDLVK TRMQNQRGTG
SVVGELMYKN SFDCFKKVLR YEGFFGLYRG LIPQLIGVAP EKAIKLTVND FVRDKFTRRD
GSIPLPAEIL AGGCAGGSQV IFTNPLEIVK IRLQVAGEIT TGPRVSALNV LQDLGLFGLY
KGAKACFLRD IPFSAIYFPV YAHCKLLLAD ENGHVGGINL LTAGAMAGVP AASLVTPADV
IKTRLQVAAR AGQTTYSGVI DCFRKILREE GPSAFWKGTA ARVFRSSPQF GVTLVTYELL
QRWFYIDFGG LKPSGSEPTP KSRIADLPPA NPDHIGGYRL ATATFAGIEN KFGLYLPKFK
SPGVAAAQPK VAAAAQ
