CMC_DROME
ID CMC_DROME Reviewed; 695 AA.
AC Q9VA73; A4V3N6; Q95TN5; Q9U5V8; Q9VA72; Q9VA74;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Calcium-binding mitochondrial carrier protein Aralar1;
GN Name=aralar1 {ECO:0000303|PubMed:32200800,
GN ECO:0000312|FlyBase:FBgn0028646};
GN ORFNames=CG2139 {ECO:0000312|FlyBase:FBgn0028646};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Ovary;
RX PubMed=10642534; DOI=10.1042/0264-6021:3450725;
RA Del Arco A., Agudo M., Satrustegui J.;
RT "Characterization of a second member of the subfamily of calcium-binding
RT mitochondrial carriers expressed in human non-excitable tissues.";
RL Biochem. J. 345:725-732(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP FUNCTION.
RX PubMed=32200800; DOI=10.1016/j.cell.2020.02.044;
RA Kanellopoulos A.K., Mariano V., Spinazzi M., Woo Y.J., McLean C., Pech U.,
RA Li K.W., Armstrong J.D., Giangrande A., Callaerts P., Smit A.B.,
RA Abrahams B.S., Fiala A., Achsel T., Bagni C.;
RT "Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social
RT Behavior Deficits.";
RL Cell 180:1178-1197.e20(2020).
CC -!- FUNCTION: Mitochondrial and calcium-binding carrier that catalyzes the
CC calcium-dependent exchange of cytoplasmic glutamate with mitochondrial
CC aspartate across the mitochondrial inner membrane (By similarity).
CC Necessary for gamma-aminobutyric acid (GABA) uptake in brain
CC mitochondria in response to increased mitochondrial membrane
CC polarization (PubMed:32200800). {ECO:0000250|UniProtKB:O75746,
CC ECO:0000269|PubMed:32200800}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=C;
CC IsoId=Q9VA73-1; Sequence=Displayed;
CC Name=2; Synonyms=A, D;
CC IsoId=Q9VA73-2; Sequence=VSP_003266;
CC Name=3; Synonyms=B;
CC IsoId=Q9VA73-3; Sequence=VSP_003265;
CC -!- DOMAIN: Upon calcium binding, the EF-hand-containing regulatory N-
CC terminal domain binds to the C-terminal domain, opening a vestibule
CC which allows the substrates to be translocated through the carrier
CC domain. In the absence of calcium, the linker loop domain may close the
CC vestibule, which may prevent substrates from entering the carrier
CC domain. {ECO:0000250|UniProtKB:O75746}.
CC -!- MISCELLANEOUS: Binds to one calcium ion with high affinity.
CC {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; Y18197; CAB62169.1; -; mRNA.
DR EMBL; AE014297; AAF57048.1; -; Genomic_DNA.
DR EMBL; AE014297; AAF57049.1; -; Genomic_DNA.
DR EMBL; AE014297; AAF57050.3; -; Genomic_DNA.
DR EMBL; AE014297; AAN14230.1; -; Genomic_DNA.
DR EMBL; AY058654; AAL13883.1; -; mRNA.
DR RefSeq; NP_651795.2; NM_143538.3. [Q9VA73-2]
DR RefSeq; NP_733364.1; NM_170485.2. [Q9VA73-1]
DR RefSeq; NP_733365.1; NM_170486.2. [Q9VA73-2]
DR RefSeq; NP_733366.2; NM_170487.3. [Q9VA73-3]
DR AlphaFoldDB; Q9VA73; -.
DR SMR; Q9VA73; -.
DR BioGRID; 68470; 2.
DR DIP; DIP-17130N; -.
DR IntAct; Q9VA73; 5.
DR MINT; Q9VA73; -.
DR STRING; 7227.FBpp0297541; -.
DR PaxDb; Q9VA73; -.
DR PRIDE; Q9VA73; -.
DR DNASU; 43616; -.
DR EnsemblMetazoa; FBtr0085692; FBpp0085054; FBgn0028646. [Q9VA73-1]
DR EnsemblMetazoa; FBtr0085693; FBpp0085055; FBgn0028646. [Q9VA73-3]
DR EnsemblMetazoa; FBtr0085694; FBpp0085056; FBgn0028646. [Q9VA73-2]
DR EnsemblMetazoa; FBtr0085695; FBpp0085057; FBgn0028646. [Q9VA73-2]
DR GeneID; 43616; -.
DR KEGG; dme:Dmel_CG2139; -.
DR UCSC; CG2139-RA; d. melanogaster.
DR CTD; 43616; -.
DR FlyBase; FBgn0028646; aralar1.
DR VEuPathDB; VectorBase:FBgn0028646; -.
DR eggNOG; KOG0751; Eukaryota.
DR GeneTree; ENSGT00940000155963; -.
DR InParanoid; Q9VA73; -.
DR OMA; DWDCEWA; -.
DR PhylomeDB; Q9VA73; -.
DR Reactome; R-DME-70263; Gluconeogenesis.
DR Reactome; R-DME-8963693; Aspartate and asparagine metabolism.
DR BioGRID-ORCS; 43616; 0 hits in 3 CRISPR screens.
DR ChiTaRS; aralar1; fly.
DR GenomeRNAi; 43616; -.
DR PRO; PR:Q9VA73; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0028646; Expressed in adult Malpighian tubule (Drosophila) and 31 other tissues.
DR ExpressionAtlas; Q9VA73; baseline and differential.
DR Genevisible; Q9VA73; DM.
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; HDA:FlyBase.
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; IBA:GO_Central.
DR GO; GO:0015813; P:L-glutamate transmembrane transport; IBA:GO_Central.
DR GO; GO:0043490; P:malate-aspartate shuttle; IBA:GO_Central.
DR GO; GO:0042060; P:wound healing; HMP:FlyBase.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
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; PF13833; EF-hand_8; 2.
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; 3.
DR PROSITE; PS50920; SOLCAR; 3.
PE 2: Evidence at transcript level;
KW Alternative splicing; Calcium; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..695
FT /note="Calcium-binding mitochondrial carrier protein
FT Aralar1"
FT /id="PRO_0000090606"
FT TRANSMEM 346..363
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TRANSMEM 406..425
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TRANSMEM 449..462
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TRANSMEM 498..517
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TRANSMEM 537..554
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TRANSMEM 594..613
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT DOMAIN 71..104
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 105..140
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 142..175
FT /note="EF-hand 3"
FT /evidence="ECO:0000305"
FT DOMAIN 176..211
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REPEAT 340..431
FT /note="Solcar 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 439..523
FT /note="Solcar 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 531..619
FT /note="Solcar 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REGION 1..310
FT /note="N-terminal domain"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT REGION 311..327
FT /note="Linker loop domain"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT REGION 336..627
FT /note="Carrier domain"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT REGION 628..695
FT /note="C-terminal domain"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT BINDING 84
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 86
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 88
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 90
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 95
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 118
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 122
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 124
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 129
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 189
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT VAR_SEQ 1..22
FT /note="MPMHIPFPFNWIPTLPVARCQE -> MPLTKSLPN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10642534,
FT ECO:0000303|PubMed:12537569"
FT /id="VSP_003266"
FT VAR_SEQ 1..21
FT /note="MPMHIPFPFNWIPTLPVARCQ -> MHDKD (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_003265"
FT CONFLICT 356..357
FT /note="GA -> AP (in Ref. 1; CAB62169)"
FT /evidence="ECO:0000305"
FT CONFLICT 556
FT /note="V -> A (in Ref. 1; CAB62169)"
FT /evidence="ECO:0000305"
FT CONFLICT 653
FT /note="V -> L (in Ref. 1; CAB62169)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 695 AA; 76754 MW; 8EC93D92031F5B77 CRC64;
MPMHIPFPFN WIPTLPVARC QESPSLLKRA GTEKLREVFL KYASIQKNGE HYMTSEDFVR
KFLGLFSESA FNDESVRLLA NIADTSKDGL ISFSEFQAFE GLLCTPDALY RTAFQLFDRK
GNGTVSYADF ADVVQKTELH SKIPFSLDGP FIKRYFGDKK QRLINYAEFT QLLHDFHEEH
AMEAFRSKDP AGTGFISPLD FQDIIVNVKR HLLTPGVRDN LVSVTEGHKV SFPYFIAFTS
LLNNMELIKQ VYLHATEGSR TDMITKDQIL LAAQTMSQIT PLEIDILFHL AGAVHQAGRI
DYSDLSNIAP EHYTKHMTHR LAEIKAVESP ADRSAFIQVL ESSYRFTLGS FAGAVGATVV
YPIDLVKTRM QNQRAGSYIG EVAYRNSWDC FKKVVRHEGF MGLYRGLLPQ LMGVAPEKAI
KLTVNDLVRD KLTDKKGNIP TWAEVLAGGC AGASQVVFTN PLEIVKIRLQ VAGEIASGSK
IRAWSVVREL GLFGLYKGAR ACLLRDVPFS AIYFPTYAHT KAMMADKDGY NHPLTLLAAG
AIAGVPAASL VTPADVIKTR LQVVARSGQT TYTGVWDATK KIMAEEGPRA FWKGTAARVF
RSSPQFGVTL VTYELLQRLF YVDFGGTQPK GSEAHKITTP LEQAAASVTT ENVDHIGGYR
AAVPLLAGVE SKFGLYLPRF GRGVTAASPS TATGS
