GHC1_HUMAN
ID GHC1_HUMAN Reviewed; 323 AA.
AC Q9H936; A8K366; C9J1H6; E9PJD3; E9PKB2; E9PL68; E9PN26; E9PNQ3; E9PP01;
AC E9PR97; Q8TBU8;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Mitochondrial glutamate carrier 1;
DE Short=GC-1;
DE AltName: Full=Glutamate/H(+) symporter 1;
DE AltName: Full=Solute carrier family 25 member 22;
GN Name=SLC25A22 {ECO:0000312|HGNC:HGNC:19954}; Synonyms=GC1;
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, TISSUE SPECIFICITY, TRANSPORTER
RP ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, Muscle, and Skin;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP IDENTIFICATION BY 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).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [8]
RP VARIANT DEE3 LEU-206, AND CHARACTERIZATION OF VARIANT DEE3 LEU-206.
RX PubMed=15592994; DOI=10.1086/427564;
RA Molinari F., Raas-Rothschild A., Rio M., Fiermonte G., Encha-Razavi F.,
RA Palmieri L., Palmieri F., Ben-Neriah Z., Kadhom N., Vekemans M.,
RA Attie-Bitach T., Munnich A., Rustin P., Colleaux L.;
RT "Impaired mitochondrial glutamate transport in autosomal recessive neonatal
RT myoclonic epilepsy.";
RL Am. J. Hum. Genet. 76:334-339(2005).
CC -!- FUNCTION: Mitochondrial glutamate/H(+) symporter. Responsible for the
CC transport of glutamate from the cytosol into the mitochondrial matrix
CC with the concomitant import of a proton (PubMed:11897791). Plays a role
CC in the control of glucose-stimulated insulin secretion (By similarity).
CC {ECO:0000250|UniProtKB:A0A0G2K5L2, 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=4.85 mM for glutamate {ECO:0000269|PubMed:11897791};
CC Vmax=63.1 umol/min/g enzyme with glutamate as substrate
CC {ECO:0000269|PubMed:11897791};
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:A0A0G2K5L2}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in brain, liver, and
CC pancreas. {ECO:0000269|PubMed:11897791}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 3 (DEE3)
CC [MIM:609304]: A severe form of epilepsy characterized by frequent tonic
CC seizures or spasms beginning in infancy with a specific EEG finding of
CC suppression-burst patterns, characterized by high-voltage bursts
CC alternating with almost flat suppression phases. DEE3 is characterized
CC by a very early onset, erratic and fragmentary myoclonus, massive
CC myoclonus, partial motor seizures and late tonic spasms. The prognosis
CC is poor, with no effective treatment, and children with the condition
CC either die within 1 to 2 years after birth or survive in a persistent
CC vegetative state. {ECO:0000269|PubMed:15592994}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH24212.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ428202; CAD21007.1; -; mRNA.
DR EMBL; AK023106; BAB14407.1; -; mRNA.
DR EMBL; AK290481; BAF83170.1; -; mRNA.
DR EMBL; AP006621; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC019033; AAH19033.1; -; mRNA.
DR EMBL; BC023545; AAH23545.1; -; mRNA.
DR EMBL; BC024212; AAH24212.2; ALT_INIT; mRNA.
DR CCDS; CCDS7715.1; -.
DR RefSeq; NP_001177989.1; NM_001191060.1.
DR RefSeq; NP_001177990.1; NM_001191061.1.
DR RefSeq; NP_078974.1; NM_024698.5.
DR RefSeq; XP_011518671.1; XM_011520369.1.
DR RefSeq; XP_011518672.1; XM_011520370.1.
DR RefSeq; XP_011518673.1; XM_011520371.1.
DR AlphaFoldDB; Q9H936; -.
DR SMR; Q9H936; -.
DR BioGRID; 122862; 94.
DR IntAct; Q9H936; 67.
DR MINT; Q9H936; -.
DR STRING; 9606.ENSP00000322020; -.
DR DrugBank; DB00142; Glutamic acid.
DR TCDB; 2.A.29.14.3; the mitochondrial carrier (mc) family.
DR iPTMnet; Q9H936; -.
DR PhosphoSitePlus; Q9H936; -.
DR SwissPalm; Q9H936; -.
DR BioMuta; SLC25A22; -.
DR DMDM; 34222632; -.
DR EPD; Q9H936; -.
DR jPOST; Q9H936; -.
DR MassIVE; Q9H936; -.
DR MaxQB; Q9H936; -.
DR PaxDb; Q9H936; -.
DR PeptideAtlas; Q9H936; -.
DR PRIDE; Q9H936; -.
DR ProteomicsDB; 81277; -.
DR TopDownProteomics; Q9H936; -.
DR Antibodypedia; 9992; 68 antibodies from 21 providers.
DR DNASU; 79751; -.
DR Ensembl; ENST00000320230.9; ENSP00000322020.5; ENSG00000177542.11.
DR Ensembl; ENST00000531214.5; ENSP00000437236.1; ENSG00000177542.11.
DR Ensembl; ENST00000628067.3; ENSP00000486058.1; ENSG00000177542.11.
DR GeneID; 79751; -.
DR KEGG; hsa:79751; -.
DR MANE-Select; ENST00000628067.3; ENSP00000486058.1; NM_001191061.2; NP_001177990.1.
DR UCSC; uc001lri.3; human.
DR CTD; 79751; -.
DR DisGeNET; 79751; -.
DR GeneCards; SLC25A22; -.
DR HGNC; HGNC:19954; SLC25A22.
DR HPA; ENSG00000177542; Tissue enhanced (brain, pancreas).
DR MalaCards; SLC25A22; -.
DR MIM; 609302; gene.
DR MIM; 609304; phenotype.
DR neXtProt; NX_Q9H936; -.
DR OpenTargets; ENSG00000177542; -.
DR Orphanet; 1934; Early infantile epileptic encephalopathy.
DR Orphanet; 1935; Early myoclonic encephalopathy.
DR Orphanet; 293181; Malignant migrating focal seizures of infancy.
DR PharmGKB; PA134955826; -.
DR VEuPathDB; HostDB:ENSG00000177542; -.
DR eggNOG; KOG0750; Eukaryota.
DR GeneTree; ENSGT00940000161196; -.
DR InParanoid; Q9H936; -.
DR OMA; WQREGPT; -.
DR OrthoDB; 945010at2759; -.
DR PhylomeDB; Q9H936; -.
DR TreeFam; TF313209; -.
DR PathwayCommons; Q9H936; -.
DR Reactome; R-HSA-428643; Organic anion transporters.
DR SignaLink; Q9H936; -.
DR BioGRID-ORCS; 79751; 43 hits in 1087 CRISPR screens.
DR GenomeRNAi; 79751; -.
DR Pharos; Q9H936; Tbio.
DR PRO; PR:Q9H936; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9H936; protein.
DR Bgee; ENSG00000177542; Expressed in right hemisphere of cerebellum and 153 other tissues.
DR ExpressionAtlas; Q9H936; baseline and differential.
DR Genevisible; Q9H936; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA: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; IDA:UniProtKB.
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 GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB.
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 Disease variant; Epilepsy; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Repeat; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..323
FT /note="Mitochondrial glutamate carrier 1"
FT /id="PRO_0000090619"
FT TRANSMEM 12..32
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 62..82
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 107..127
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 223..243
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 292..312
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 6..93
FT /note="Solcar 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 101..214
FT /note="Solcar 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 223..312
FT /note="Solcar 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT VARIANT 206
FT /note="P -> L (in DEE3; disrupts L-glutamate transporter
FT activity; dbSNP:rs121918334)"
FT /evidence="ECO:0000269|PubMed:15592994"
FT /id="VAR_022737"
SQ SEQUENCE 323 AA; 34470 MW; D0E06FD88E5A3198 CRC64;
MADKQISLPA KLINGGIAGL IGVTCVFPID LAKTRLQNQQ NGQRVYTSMS DCLIKTVRSE
GYFGMYRGAA VNLTLVTPEK AIKLAANDFF RHQLSKDGQK LTLLKEMLAG CGAGTCQVIV
TTPMEMLKIQ LQDAGRIAAQ RKILAAQGQL SAQGGAQPSV EAPAAPRPTA TQLTRDLLRS
RGIAGLYKGL GATLLRDVPF SVVYFPLFAN LNQLGRPASE EKSPFYVSFL AGCVAGSAAA
VAVNPCDVVK TRLQSLQRGV NEDTYSGILD CARKILRHEG PSAFLKGAYC RALVIAPLFG
IAQVVYFLGI AESLLGLLQD PQA
