GHC2_HUMAN
ID GHC2_HUMAN Reviewed; 315 AA.
AC Q9H1K4;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Mitochondrial glutamate carrier 2;
DE Short=GC-2;
DE AltName: Full=Glutamate/H(+) symporter 2;
DE AltName: Full=Solute carrier family 25 member 18;
GN Name=SLC25A18 {ECO:0000312|HGNC:HGNC:10988}; Synonyms=GC2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=11897791; DOI=10.1074/jbc.m201572200;
RA Fiermonte G., Palmieri L., Todisco S., Agrimi G., Palmieri F., Walker J.E.;
RT "Identification of the mitochondrial glutamate transporter. Bacterial
RT expression, reconstitution, functional characterization, and tissue
RT distribution of two human isoforms.";
RL J. Biol. Chem. 277:19289-19294(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11381032; DOI=10.1101/gr.154901;
RA Footz T.K., Brinkman-Mills P., Banting G.S., Maier S.A., Riazi M.A.,
RA Bridgland L.J., Hu S., Birren B., Minoshima S., Shimizu N., Pan H.,
RA Nguyen T., Fang F., Fu Y., Ray L., Wu H., Shaull S., Phan S., Yao Z.,
RA Chen F., Huan A., Hu P., Wang Q., Loh P., Qi S., Roe B.A., McDermid H.E.;
RT "Analysis of the cat eye syndrome critical region in humans and the region
RT of conserved synteny in mice: a search for candidate genes at or near the
RT human chromosome 22 pericentromere.";
RL Genome Res. 11:1053-1070(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Responsible for the transport of glutamate from the cytosol
CC into the mitochondrial matrix with the concomitant import of a proton
CC (symport system). {ECO:0000269|PubMed:11897791}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(in) + L-glutamate(in) = H(+)(out) + L-glutamate(out);
CC Xref=Rhea:RHEA:70955, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985;
CC Evidence={ECO:0000269|PubMed:11897791};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.26 mM for glutamate {ECO:0000269|PubMed:11897791};
CC Vmax=15.7 umol/min/g enzyme with glutamate as substrate
CC {ECO:0000269|PubMed:11897791};
CC -!- INTERACTION:
CC Q9H1K4; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-6269587, EBI-3867333;
CC Q9H1K4; Q9HD26: GOPC; NbExp=3; IntAct=EBI-6269587, EBI-349832;
CC Q9H1K4; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-6269587, EBI-11953846;
CC Q9H1K4; Q3LI70: KRTAP19-6; NbExp=3; IntAct=EBI-6269587, EBI-12805508;
CC Q9H1K4; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-6269587, EBI-1043191;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q505J6}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, to a lesser extent in testis,
CC and poorly in all the other tissues. {ECO:0000269|PubMed:11897791}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; AJ428203; CAD21008.1; -; mRNA.
DR EMBL; AY008285; AAG22855.1; -; mRNA.
DR EMBL; CR456578; CAG30464.1; -; mRNA.
DR EMBL; BC031644; AAH31644.1; -; mRNA.
DR CCDS; CCDS13744.1; -.
DR RefSeq; NP_001290413.1; NM_001303484.1.
DR RefSeq; NP_113669.1; NM_031481.2.
DR RefSeq; XP_011544453.1; XM_011546151.2.
DR RefSeq; XP_011544454.1; XM_011546152.1.
DR RefSeq; XP_011544455.1; XM_011546153.2.
DR RefSeq; XP_011544456.1; XM_011546154.2.
DR RefSeq; XP_016884457.1; XM_017028968.1.
DR AlphaFoldDB; Q9H1K4; -.
DR SMR; Q9H1K4; -.
DR BioGRID; 123744; 32.
DR IntAct; Q9H1K4; 13.
DR MINT; Q9H1K4; -.
DR STRING; 9606.ENSP00000329033; -.
DR DrugBank; DB00142; Glutamic acid.
DR TCDB; 2.A.29.14.5; the mitochondrial carrier (mc) family.
DR iPTMnet; Q9H1K4; -.
DR PhosphoSitePlus; Q9H1K4; -.
DR SwissPalm; Q9H1K4; -.
DR BioMuta; SLC25A18; -.
DR DMDM; 20140247; -.
DR EPD; Q9H1K4; -.
DR jPOST; Q9H1K4; -.
DR MassIVE; Q9H1K4; -.
DR MaxQB; Q9H1K4; -.
DR PaxDb; Q9H1K4; -.
DR PeptideAtlas; Q9H1K4; -.
DR PRIDE; Q9H1K4; -.
DR ProteomicsDB; 80424; -.
DR Antibodypedia; 22673; 76 antibodies from 16 providers.
DR DNASU; 83733; -.
DR Ensembl; ENST00000327451.11; ENSP00000329033.5; ENSG00000182902.14.
DR Ensembl; ENST00000399813.1; ENSP00000382710.1; ENSG00000182902.14.
DR GeneID; 83733; -.
DR KEGG; hsa:83733; -.
DR MANE-Select; ENST00000327451.11; ENSP00000329033.5; NM_031481.3; NP_113669.1.
DR UCSC; uc002zmp.2; human.
DR CTD; 83733; -.
DR DisGeNET; 83733; -.
DR GeneCards; SLC25A18; -.
DR HGNC; HGNC:10988; SLC25A18.
DR HPA; ENSG00000182902; Group enriched (brain, choroid plexus, liver).
DR MIM; 609303; gene.
DR neXtProt; NX_Q9H1K4; -.
DR OpenTargets; ENSG00000182902; -.
DR PharmGKB; PA35864; -.
DR VEuPathDB; HostDB:ENSG00000182902; -.
DR eggNOG; KOG0750; Eukaryota.
DR GeneTree; ENSGT00940000162050; -.
DR HOGENOM; CLU_015166_3_4_1; -.
DR InParanoid; Q9H1K4; -.
DR OMA; HRTCASA; -.
DR OrthoDB; 945010at2759; -.
DR PhylomeDB; Q9H1K4; -.
DR TreeFam; TF313209; -.
DR PathwayCommons; Q9H1K4; -.
DR Reactome; R-HSA-428643; Organic anion transporters.
DR SignaLink; Q9H1K4; -.
DR BioGRID-ORCS; 83733; 14 hits in 1072 CRISPR screens.
DR ChiTaRS; SLC25A18; human.
DR GenomeRNAi; 83733; -.
DR Pharos; Q9H1K4; Tbio.
DR PRO; PR:Q9H1K4; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q9H1K4; protein.
DR Bgee; ENSG00000182902; Expressed in medial globus pallidus and 117 other tissues.
DR ExpressionAtlas; Q9H1K4; baseline and differential.
DR Genevisible; Q9H1K4; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005280; F:amino acid:proton symporter activity; IDA: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; IBA:GO_Central.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0015813; P:L-glutamate transmembrane transport; IDA:UniProtKB.
DR GO; GO:0043490; P:malate-aspartate shuttle; IBA:GO_Central.
DR Gene3D; 1.50.40.10; -; 1.
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; Phosphoprotein;
KW Reference proteome; Repeat; Symport; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..315
FT /note="Mitochondrial glutamate carrier 2"
FT /id="PRO_0000090621"
FT TRANSMEM 12..32
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 61..81
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 106..126
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..205
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..245
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 288..308
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 6..92
FT /note="Solcar 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 100..210
FT /note="Solcar 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 219..308
FT /note="Solcar 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REGION 141..160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 142..160
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
SQ SEQUENCE 315 AA; 33849 MW; B23A9E5036671634 CRC64;
MTHQDLSITA KLINGGVAGL VGVTCVFPID LAKTRLQNQH GKAMYKGMID CLMKTARAEG
FFGMYRGAAV NLTLVTPEKA IKLAANDFFR RLLMEDGMQR NLKMEMLAGC GAGMCQVVVT
CPMEMLKIQL QDAGRLAVHH QGSASAPSTS RSYTTGSAST HRRPSATLIA WELLRTQGLA
GLYRGLGATL LRDIPFSIIY FPLFANLNNL GFNELAGKAS FAHSFVSGCV AGSIAAVAVT
PLDVLKTRIQ TLKKGLGEDM YSGITDCARK LWIQEGPSAF MKGAGCRALV IAPLFGIAQG
VYFIGIGERI LKCFD
