S2512_MOUSE
ID S2512_MOUSE Reviewed; 677 AA.
AC Q8BH59; A2BFG0;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Electrogenic aspartate/glutamate antiporter SLC25A12, mitochondrial {ECO:0000250|UniProtKB:O75746};
DE AltName: Full=Solute carrier family 25 member 12 {ECO:0000312|MGI:MGI:1926080};
GN Name=Slc25a12 {ECO:0000312|MGI:MGI:1926080};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Hippocampus, and Pituitary;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium;
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 [4]
RP PROTEIN SEQUENCE OF 18-68; 144-163; 174-190; 234-243; 245-259; 284-309;
RP 330-351; 359-370; 382-403; 407-414; 454-482; 491-543; 552-565; 570-578;
RP 587-622; 625-659 AND 662-671.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By
CC similarity). 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 (By similarity). {ECO:0000250|UniProtKB:F1LX07,
CC ECO:0000250|UniProtKB:O75746}.
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:0000250|UniProtKB:O75746};
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:0000250|UniProtKB:O75746};
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:0000250|UniProtKB:F1LX07};
CC -!- SUBUNIT: Homodimer (via N-terminus). {ECO:0000250|UniProtKB:O75746}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:O75746}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O75746}.
CC -!- DOMAIN: The EF-hand 2 domain within the regulatory N-terminal domain
CC binds one calcium in the mitochondrial intermembrane space. Calcium
CC triggers the binding of the regulatory N-terminal domain to the C-
CC terminal domain, opening a vestibule which allows the substrates to be
CC translocated through the carrier domain. In the absence of calcium, the
CC linker loop domain may close the vestibule and prevent substrates from
CC entering the carrier domain. {ECO:0000250|UniProtKB:O75746}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {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; AK030595; BAC27037.1; -; mRNA.
DR EMBL; AK083156; BAC38787.1; -; mRNA.
DR EMBL; BX284624; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC060505; AAH60505.1; -; mRNA.
DR CCDS; CCDS16113.1; -.
DR RefSeq; NP_766024.1; NM_172436.3.
DR AlphaFoldDB; Q8BH59; -.
DR SMR; Q8BH59; -.
DR BioGRID; 219664; 19.
DR IntAct; Q8BH59; 17.
DR MINT; Q8BH59; -.
DR STRING; 10090.ENSMUSP00000122103; -.
DR iPTMnet; Q8BH59; -.
DR PhosphoSitePlus; Q8BH59; -.
DR SwissPalm; Q8BH59; -.
DR EPD; Q8BH59; -.
DR jPOST; Q8BH59; -.
DR MaxQB; Q8BH59; -.
DR PaxDb; Q8BH59; -.
DR PeptideAtlas; Q8BH59; -.
DR PRIDE; Q8BH59; -.
DR ProteomicsDB; 283389; -.
DR Antibodypedia; 33855; 229 antibodies from 26 providers.
DR DNASU; 78830; -.
DR Ensembl; ENSMUST00000151937; ENSMUSP00000122103; ENSMUSG00000027010.
DR GeneID; 78830; -.
DR KEGG; mmu:78830; -.
DR UCSC; uc008kan.1; mouse.
DR CTD; 8604; -.
DR MGI; MGI:1926080; Slc25a12.
DR VEuPathDB; HostDB:ENSMUSG00000027010; -.
DR eggNOG; KOG0751; Eukaryota.
DR GeneTree; ENSGT00940000155963; -.
DR HOGENOM; CLU_014931_3_0_1; -.
DR InParanoid; Q8BH59; -.
DR OMA; DWDCEWA; -.
DR OrthoDB; 1007928at2759; -.
DR PhylomeDB; Q8BH59; -.
DR TreeFam; TF313209; -.
DR Reactome; R-MMU-70263; Gluconeogenesis.
DR Reactome; R-MMU-8963693; Aspartate and asparagine metabolism.
DR BioGRID-ORCS; 78830; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Slc25a12; mouse.
DR PRO; PR:Q8BH59; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8BH59; protein.
DR Bgee; ENSMUSG00000027010; Expressed in digastric muscle group and 224 other tissues.
DR ExpressionAtlas; Q8BH59; baseline and differential.
DR Genevisible; Q8BH59; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0000514; F:3-sulfino-L-alanine: proton, glutamate antiporter activity; ISS:UniProtKB.
DR GO; GO:0015297; F:antiporter activity; ISO:MGI.
DR GO; GO:0000515; F:aspartate:glutamate, proton antiporter activity; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0015183; F:L-aspartate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005313; F:L-glutamate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015810; P:aspartate transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006537; P:glutamate biosynthetic process; IEA:Ensembl.
DR GO; GO:0015813; P:L-glutamate transmembrane transport; ISS:UniProtKB.
DR GO; GO:0043490; P:malate-aspartate shuttle; IMP:MGI.
DR GO; GO:1904024; P:negative regulation of glucose catabolic process to lactate via pyruvate; IEA:Ensembl.
DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IEA:Ensembl.
DR GO; GO:0010907; P:positive regulation of glucose metabolic process; IEA:Ensembl.
DR GO; GO:0031643; P:positive regulation of myelination; IEA:Ensembl.
DR GO; GO:0051592; P:response to calcium ion; ISS:UniProtKB.
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 1: Evidence at protein level;
KW Acetylation; Calcium; Direct protein sequencing; Membrane; Metal-binding;
KW Mitochondrion; Mitochondrion inner membrane; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT CHAIN 2..677
FT /note="Electrogenic aspartate/glutamate antiporter
FT SLC25A12, mitochondrial"
FT /id="PRO_0000090599"
FT TOPO_DOM 2..329
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 330..347
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 348..390
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 391..410
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 411..433
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 434..447
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 448..482
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 483..502
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 503..521
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 522..539
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 540..578
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 579..598
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 599..677
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT DOMAIN 40..85
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 122..156
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 324..416
FT /note="Solcar 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 424..508
FT /note="Solcar 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 516..604
FT /note="Solcar 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REGION 2..294
FT /note="Regulatory N-terminal domain"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT REGION 295..310
FT /note="Linker loop domain"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT REGION 320..612
FT /note="Carrier domain"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT REGION 613..677
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 677 AA; 74570 MW; 488ABC7EB8227571 CRC64;
MAVKVHTTKR GDPHELRNIF LQYASTEVDG EHYMTPEDFV QRYLGLYNDP NSNPKIVQLL
AGVADQTKDG LISYQEFLAF ESVLCAPDSM FIVAFQLFDK SGNGEVTFEN VKEIFGQTII
HHHIPFNWDC EFIRLHFGHN RKKHLNYVEF TQFLQELQLE HARQAFALKD KSKSGMISGL
DFSDVMVTIR SHMLTPFVEE NLVSAAGGGT SHQVSFSYFN AFNSLLNNME LVRKIYSTLA
GTRKDIEVTK EEFAQSAIRY GQVTPLEIDI LYQLADLYNA SGRLTLADIE RIAPLAEGAL
PYNLAELQRQ QSPGLGRPIW LQIAESAYRF TLGSVAGAVG ATAVYPIDLV KTRMQNQRGT
GSVVGELMYK NSFDCFKKVL RYEGFFGLYR GLIPQLIGVA PEKAIKLTVN DFVRDKFTKR
DGSIPLPAEI LAGGCAGGSQ VIFTNPLEIV KIRLQVAGEI TTGPRVSALN VLQDLGLFGL
YKGAKACFLR DIPFSAIYFP VYAHCKLLLA DENGRVGGIN LLTAGALAGV PAASLVTPAD
VIKTRLQVAA RAGQTTYSGV VDCFRKILRE EGPSAFWKGT AARVFRSSPQ FGVTLVTYEL
LQRWFYIDFG GLKPSGSEPT PKSRIADLPP ANPDHIGGYR LATATFAGIE NKFGLYLPKF
KSPSVAVAQP KAAAAAQ
