ID S2512_PONAB Reviewed; 678 AA.
AC Q5RBC8;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 22-FEB-2023, entry version 95.
DE RecName: Full=Electrogenic aspartate/glutamate antiporter SLC25A12, mitochondrial {ECO:0000250|UniProtKB:O75746};
DE AltName: Full=Solute carrier family 25 member 12 {ECO:0000250|UniProtKB:O75746};
GN Name=SLC25A12 {ECO:0000250|UniProtKB:O75746};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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}.
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DR EMBL; CR858723; CAH90932.1; -; mRNA.
DR RefSeq; NP_001125534.1; NM_001132062.1.
DR AlphaFoldDB; Q5RBC8; -.
DR SMR; Q5RBC8; -.
DR STRING; 9601.ENSPPYP00000014435; -.
DR GeneID; 100172446; -.
DR KEGG; pon:100172446; -.
DR CTD; 8604; -.
DR eggNOG; KOG0751; Eukaryota.
DR InParanoid; Q5RBC8; -.
DR OrthoDB; 1220009at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0015810; P:aspartate transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006754; P:ATP biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045333; P:cellular respiration; ISS:UniProtKB.
DR GO; GO:0015813; P:L-glutamate transmembrane transport; ISS:UniProtKB.
DR GO; GO:0043490; P:malate-aspartate shuttle; ISS:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; ISS:UniProtKB.
DR Gene3D; 1.10.238.10; EF-hand; 2.
DR Gene3D; 1.50.40.10; Mitochondrial carrier domain; 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 PANTHER; PTHR45678:SF7; CALCIUM-BINDING MITOCHONDRIAL CARRIER PROTEIN ARALAR1; 1.
DR PANTHER; PTHR45678; MITOCHONDRIAL 2-OXODICARBOXYLATE CARRIER 1-RELATED; 1.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00926; MITOCARRIER.
DR SMART; SM00054; EFh; 3.
DR SUPFAM; SSF47473; EF-hand; 2.
DR SUPFAM; SSF103506; Mitochondrial carrier; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
DR PROSITE; PS50920; SOLCAR; 3.
PE 2: Evidence at transcript level;
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..678
FT /note="Electrogenic aspartate/glutamate antiporter
FT SLC25A12, mitochondrial"
FT /id="PRO_0000231652"
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..678
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 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..678
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 678 AA; 74711 MW; F43DC50F47EF8FBC CRC64;
MAVKVQTTKR GDPHELRNIF LQYASTEVDG EHYMTPEDFV QRYLGLYNDP NSNPKIVQLL
AGVADQTKDG LISYQEFLAF ESVLCAPDSM FIVAFQLFDK SGNGEVTFEN VKEIFGQTII
HHHIPFNWDC EFIRLHFGHN RKKHLNYTEF TQFLQELQLE HARQAFALKD KSKSGVISGL
DFSDIMVTIR SHMLTPFVEE NLVSAAGGSI SHQVSFSYFN AFNSLLNNME LVRKIYSTLA
GTRKDVEVTK EEFAQSAIRY GQVTPLEIDI LYQLADLYNA SGRLTLADIE RIAPLAEGAL
PYNLAELQRQ QSPGLGRPIW LQIAESAYRF TLGSVAGAVG ATAVYPIDLV KTRMQNQRGS
GSVVGELMYK NSFDCFKKVL RYEGFFGLYR GLIPQLIGVA PEKAIKLTVN DFVRDKFTRR
DGSVPLPAEV LAGGCAGGSQ VIFTNPLEIV KIRLQVAGEI TTGPRVSALN VLRDLGIFGL
YKGAKACFLR DIPFSAIYFP VYAHCKLLLA DENGHVGGLN LLAAGAMAGV PAASLVTPAD
VIKTRLQVAA RAGQTTYSGV IDCFRKILRE EGPSAFWKGT AARVFRSSPQ FGVTLVTYEL
LQRWFYIDFG GLKPAGSEPT PKSRIADLPP ANPDHIGGYR LATATFAGIE NKFGLYLPKF
KSPSVAVVQP KAAVAATQ
//
