M2OM_CAEEL
ID M2OM_CAEEL Reviewed; 306 AA.
AC P90992;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Mitochondrial 2-oxoglutarate/malate carrier protein {ECO:0000250|UniProtKB:Q02978};
DE Short=alpha-oxoglutarate carrier;
DE AltName: Full=Mitochondrial solute carrier 1 {ECO:0000303|PubMed:21448454};
DE Short=MISC-1 {ECO:0000303|PubMed:21448454};
GN Name=misc-1 {ECO:0000303|PubMed:21884719, ECO:0000312|WormBase:B0432.4};
GN ORFNames=B0432.4 {ECO:0000312|WormBase:B0432.4};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21884719; DOI=10.1016/j.mad.2011.08.004;
RA Gallo M., Park D., Riddle D.L.;
RT "Increased longevity of some C. elegans mitochondrial mutants explained by
RT activation of an alternative energy-producing pathway.";
RL Mech. Ageing Dev. 132:515-518(2011).
RN [3] {ECO:0000305}
RP FUNCTION, INTERACTION WITH ANT-1.1 AND CED-9, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=21448454; DOI=10.1371/journal.pone.0017827;
RA Gallo M., Park D., Luciani D.S., Kida K., Palmieri F., Blacque O.E.,
RA Johnson J.D., Riddle D.L.;
RT "MISC-1/OGC links mitochondrial metabolism, apoptosis and insulin
RT secretion.";
RL PLoS ONE 6:E17827-E17827(2011).
CC -!- FUNCTION: Catalyzes the transport of 2-oxoglutarate (alpha-
CC oxoglutarate) across the inner mitochondrial membrane in an
CC electroneutral exchange for malate. Can also exchange 2-oxoglutarate
CC for other dicarboxylic acids such as malonate, succinate, maleate and
CC oxaloacetate, although with lower affinity. Contributes to several
CC metabolic processes, including the malate-aspartate shuttle, the
CC oxoglutarate/isocitrate shuttle, in gluconeogenesis from lactate, and
CC in nitrogen metabolism (By similarity). Maintains mitochondrial fusion
CC and fission events, and the organization and morphology of cristae
CC (PubMed:21448454). Regulator of apoptosis, insulin secretion and
CC germline proliferation (PubMed:21448454). Furthermore, plays a role in
CC the oxidative stress response regulating endogenous levels of reactive
CC oxygen species (ROS) (PubMed:21884719). Involved in the regulation of
CC lin-35/Rb-mediated apoptosis in the germline (PubMed:21448454).
CC {ECO:0000250|UniProtKB:P22292, ECO:0000269|PubMed:21448454,
CC ECO:0000269|PubMed:21884719}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate(in) + 2-oxoglutarate(out) = (S)-malate(out) + 2-
CC oxoglutarate(in); Xref=Rhea:RHEA:71587, ChEBI:CHEBI:15589,
CC ChEBI:CHEBI:16810; Evidence={ECO:0000250|UniProtKB:P22292};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate(out) + malonate(in) = 2-oxoglutarate(in) +
CC malonate(out); Xref=Rhea:RHEA:71591, ChEBI:CHEBI:15792,
CC ChEBI:CHEBI:16810; Evidence={ECO:0000250|UniProtKB:P22292};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate(out) + succinate(in) = 2-oxoglutarate(in) +
CC succinate(out); Xref=Rhea:RHEA:71595, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031; Evidence={ECO:0000250|UniProtKB:P22292};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate(out) + maleate(in) = 2-oxoglutarate(in) +
CC maleate(out); Xref=Rhea:RHEA:71599, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30780; Evidence={ECO:0000250|UniProtKB:P22292};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate(out) + oxaloacetate(in) = 2-oxoglutarate(in) +
CC oxaloacetate(out); Xref=Rhea:RHEA:71603, ChEBI:CHEBI:16452,
CC ChEBI:CHEBI:16810; Evidence={ECO:0000250|UniProtKB:P22292};
CC -!- SUBUNIT: Interacts with ant-1.1 and ced-9.
CC {ECO:0000269|PubMed:21448454}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:21448454}.
CC Mitochondrion inner membrane {ECO:0000250|UniProtKB:P97700}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P97700}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, but highly expressed in the
CC anterior pharynx. {ECO:0000269|PubMed:21448454}.
CC -!- DEVELOPMENTAL STAGE: First expressed in intestinal precursor cells
CC during embryogenesis. Expressed in intestinal and neuronal cells in
CC newly hatched larvae at the L1 stage of development.
CC {ECO:0000269|PubMed:21448454}.
CC -!- DISRUPTION PHENOTYPE: Viable, with no visible phenotype
CC (PubMed:21884719). Animals have increased levels of reactive oxygen
CC species along with increased sensitivity to the reactive oxygen species
CC (ROS) generator Jugalone (5-hydroxy-1,4-naphtoquinone)
CC (PubMed:21884719). Conversely, display increased resistance to sodium
CC azide, which is a mitochondrial poison that inhibits cytochrome c
CC (PubMed:21884719). Animals also have morphological defects in their
CC mitochondondria, whereby mitochondria are smaller in size, abnormally
CC shaped, and contain fewer cristae which are irregular and disorganized
CC (PubMed:21448454). Increased germline apoptosis characterized by an
CC increased number of apoptotic corpses in the gonadal arms
CC (PubMed:21448454). RNAi-mediated knockdown results in increased
CC secretion of a beta-type insulin, daf-28 by coelomocytes and longer
CC distal tip processes (PubMed:21448454). {ECO:0000269|PubMed:21448454,
CC ECO:0000269|PubMed:21884719}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000255|RuleBase:RU000488}.
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DR EMBL; BX284602; CCD61938.1; -; Genomic_DNA.
DR PIR; T25459; T25459.
DR RefSeq; NP_493694.2; NM_061293.6.
DR AlphaFoldDB; P90992; -.
DR STRING; 6239.B0432.4.1; -.
DR EPD; P90992; -.
DR PaxDb; P90992; -.
DR PeptideAtlas; P90992; -.
DR EnsemblMetazoa; B0432.4.1; B0432.4.1; WBGene00015186.
DR GeneID; 173414; -.
DR KEGG; cel:CELE_B0432.4; -.
DR UCSC; B0432.4; c. elegans.
DR CTD; 173414; -.
DR WormBase; B0432.4; CE32102; WBGene00015186; misc-1.
DR eggNOG; KOG0759; Eukaryota.
DR GeneTree; ENSGT00940000158465; -.
DR HOGENOM; CLU_015166_14_1_1; -.
DR InParanoid; P90992; -.
DR OMA; FLHTPFM; -.
DR OrthoDB; 892773at2759; -.
DR PhylomeDB; P90992; -.
DR Reactome; R-CEL-70263; Gluconeogenesis.
DR PRO; PR:P90992; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00015186; Expressed in larva and 4 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:WormBase.
DR GO; GO:0015297; F:antiporter activity; IBA:GO_Central.
DR GO; GO:0015140; F:malate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015131; F:oxaloacetate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015141; F:succinate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015116; F:sulfate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015117; F:thiosulfate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0071423; P:malate transmembrane transport; IBA:GO_Central.
DR GO; GO:0015729; P:oxaloacetate transport; IBA:GO_Central.
DR GO; GO:0035435; P:phosphate ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0071422; P:succinate transmembrane transport; IBA:GO_Central.
DR GO; GO:0008272; P:sulfate transport; IBA:GO_Central.
DR GO; GO:0015709; P:thiosulfate transport; IBA:GO_Central.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR Pfam; PF00153; Mito_carr; 3.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW Antiport; Lipid transport; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..306
FT /note="Mitochondrial 2-oxoglutarate/malate carrier protein"
FT /evidence="ECO:0000305"
FT /id="PRO_0000443420"
FT TRANSMEM 9..38
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TRANSMEM 72..93
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TRANSMEM 108..122
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TRANSMEM 172..192
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TRANSMEM 205..226
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TRANSMEM 268..286
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT REPEAT 7..95
FT /note="Solcar 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 103..194
FT /note="Solcar 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 203..292
FT /note="Solcar 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
SQ SEQUENCE 306 AA; 33308 MW; CA6DEE146A6D10C9 CRC64;
MSNEGGVPNV VKFAFGGTAG MGATLVVQPL DLVKNRMQLS GTTGKKEYRS SMHALTSIMK
NEGVFAVYNG LSAGLLRQAT YTTTRLGTYA FLLERFTEKD KPLSFGMKAV LGMTAGGIGS
FVGTPAEIAL IRMTGDGRLP VEQRRNYTGV VNALTRITKE EGVLTLWRGC TPTVLRAMVV
NAAQLATYSQ AKQALLASGK VQDGIFCHFL ASMISGLATT IASMPVDIAK TRIQSMKVID
GKPEYKNAFD VWGKVIKNEG IFALWKGFTP YYMRLGPHTV LTFIILEQMN AAYFQYVLKR
DVTSAL
