MICU1_DROME
ID MICU1_DROME Reviewed; 525 AA.
AC A2VEI2; Q9VM38;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Calcium uptake protein 1 homolog, mitochondrial {ECO:0000305};
DE AltName: Full=Mitochondrial calcium uptake 1 {ECO:0000303|PubMed:27568554, ECO:0000303|PubMed:28198506, ECO:0000312|FlyBase:FBgn0031893};
DE Flags: Precursor;
GN Name=MICU1 {ECO:0000303|PubMed:27568554, ECO:0000303|PubMed:28198506,
GN ECO:0000312|FlyBase:FBgn0031893};
GN ORFNames=CG4495 {ECO:0000312|FlyBase:FBgn0031893};
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 [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 [2]
RP GENOME REANNOTATION.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J., Frise E., Kapadia B., Park S., Wan K., Yu C.,
RA Celniker S.;
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27568554; DOI=10.1016/j.celrep.2016.08.017;
RA Drago I., Davis R.L.;
RT "Inhibiting the Mitochondrial Calcium Uniporter during Development Impairs
RT Memory in Adult Drosophila.";
RL Cell Rep. 16:2763-2776(2016).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=28198506; DOI=10.4238/gmr16019436;
RA M'Angale P.G., Staveley B.E.;
RT "Inhibition of mitochondrial calcium uptake 1 in Drosophila neurons.";
RL Genet. Mol. Res. 16:0-0(2017).
CC -!- FUNCTION: Key regulator of mitochondrial calcium uniporter (MCU) that
CC senses calcium level via its EF-hand domains (Probable). During
CC development, required in alpha/beta or gamma mushroom body neurons to
CC support olfactory intermediate-term memory in the adult
CC (PubMed:27568554). {ECO:0000269|PubMed:27568554,
CC ECO:0000305|PubMed:27568554}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q9BPX6}; Single-pass membrane protein
CC {ECO:0000255}. Mitochondrion intermembrane space
CC {ECO:0000250|UniProtKB:Q9BPX6}. Note=The topology is subject to debate.
CC {ECO:0000250|UniProtKB:Q9BPX6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B;
CC IsoId=A2VEI2-1; Sequence=Displayed;
CC Name=A;
CC IsoId=A2VEI2-2; Sequence=VSP_039911;
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in lethality
CC (PubMed:27568554). RNAi-mediated knockdown in neurons shortens lifespan
CC and severely impairs climbing ability (PubMed:28198506). RNAi-mediated
CC knockdown in the developing eye decreases ommatidia number and disrupts
CC ommatidial array (PubMed:28198506). RNAi-mediated knockdown in neurons
CC and, more specifically, in alpha/beta or gamma mushroom body neurons,
CC impairs mitochondrial calcium entry and decreases intermediate-term
CC memory after conditioning (PubMed:27568554). Does not affect olfactory
CC learning (PubMed:27568554). {ECO:0000269|PubMed:27568554,
CC ECO:0000269|PubMed:28198506}.
CC -!- SIMILARITY: Belongs to the MICU1 family. MICU1 subfamily.
CC {ECO:0000305}.
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DR EMBL; AE014134; AAF52489.1; -; Genomic_DNA.
DR EMBL; AE014134; ABV53641.1; -; Genomic_DNA.
DR EMBL; AY051995; AAK93419.1; -; mRNA.
DR EMBL; BT030151; ABN49290.1; -; mRNA.
DR RefSeq; NP_001097110.1; NM_001103640.2. [A2VEI2-1]
DR RefSeq; NP_609100.1; NM_135256.3. [A2VEI2-2]
DR AlphaFoldDB; A2VEI2; -.
DR SMR; A2VEI2; -.
DR BioGRID; 60145; 1.
DR STRING; 7227.FBpp0111941; -.
DR PaxDb; A2VEI2; -.
DR PRIDE; A2VEI2; -.
DR EnsemblMetazoa; FBtr0079405; FBpp0079033; FBgn0031893. [A2VEI2-2]
DR EnsemblMetazoa; FBtr0113028; FBpp0111941; FBgn0031893. [A2VEI2-1]
DR GeneID; 33999; -.
DR KEGG; dme:Dmel_CG4495; -.
DR UCSC; CG4495-RA; d. melanogaster.
DR UCSC; CG4495-RB; d. melanogaster. [A2VEI2-1]
DR CTD; 10367; -.
DR FlyBase; FBgn0031893; MICU1.
DR VEuPathDB; VectorBase:FBgn0031893; -.
DR eggNOG; KOG2643; Eukaryota.
DR GeneTree; ENSGT00950000183079; -.
DR HOGENOM; CLU_027103_3_0_1; -.
DR InParanoid; A2VEI2; -.
DR OMA; ALGNIRQ; -.
DR PhylomeDB; A2VEI2; -.
DR Reactome; R-DME-8949215; Mitochondrial calcium ion transport.
DR BioGRID-ORCS; 33999; 0 hits in 1 CRISPR screen.
DR ChiTaRS; CG4495; fly.
DR GenomeRNAi; 33999; -.
DR PRO; PR:A2VEI2; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0031893; Expressed in brain and 32 other tissues.
DR Genevisible; A2VEI2; DM.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:UniProtKB-SubCell.
DR GO; GO:1990246; C:uniplex complex; ISS:FlyBase.
DR GO; GO:0005509; F:calcium ion binding; ISS:FlyBase.
DR GO; GO:0007615; P:anesthesia-resistant memory; IMP:FlyBase.
DR GO; GO:0036444; P:calcium import into the mitochondrion; IMP:FlyBase.
DR GO; GO:0072375; P:medium-term memory; IMP:FlyBase.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0051561; P:positive regulation of mitochondrial calcium ion concentration; ISS:UniProtKB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR039800; MICU1/2/3.
DR PANTHER; PTHR12294; PTHR12294; 1.
DR Pfam; PF13202; EF-hand_5; 1.
DR Pfam; PF13833; EF-hand_8; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 2.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 2: Evidence at transcript level;
KW Alternative splicing; Calcium; Calcium transport; Ion transport; Membrane;
KW Metal-binding; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Repeat; Transit peptide; Transmembrane;
KW Transmembrane helix; Transport.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..525
FT /note="Calcium uptake protein 1 homolog, mitochondrial"
FT /id="PRO_0000399812"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 98..525
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT DOMAIN 268..303
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 459..494
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 109..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 281
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 283
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 285
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 287
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 292
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 472
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 474
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 476
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 478
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 483
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT VAR_SEQ 179..212
FT /note="VFRYFATIQVPVADDRHEVYMTPTDFLTSMTPGM -> IFRYFATVRLQDAT
FT QTIVCMTPEDFLRSIYPGI (in isoform A)"
FT /evidence="ECO:0000303|PubMed:12537569"
FT /id="VSP_039911"
SQ SEQUENCE 525 AA; 60344 MW; EB00098E8C9C1D23 CRC64;
MSVLRFLVTR QALAALTRPR TLNIIQNPAQ IAYASTLCNQ NSNHNAKDLT KSSANLSLMQ
TRGHKRFGHQ EEKTPSVTKY FHMFILSLFL ISVMDWGKVK RMLTPKVDAD AGQRPSSAAD
VNGEDKSSES ESEDSEDEEA GSDLHLHEGK KIREKVGFRE RKIIEYENRI RQFSTPDKVF
RYFATIQVPV ADDRHEVYMT PTDFLTSMTP GMKQPDGLGL DQYRRYDPKS VGEQLNLHLE
KNSIFYKLGS YGLITFSDYI FLLTVLSISR RHFEIAFRMF DLNGDGDVDC EEFEMVATLV
RQQTSMGTRH RDHANTGNTF KGVNSALITY FFGPNMDEKL TIEKFLDFQE QLQREILSLE
FERKEPNDEG NITEADFAEL LLAYAGYPLK KKQKKLKRVK RRFRDHGKGI SKQDYLDFFH
FLNNINDVDT ALTFYHIAGA SIDQQTLQHV AKTVAMVNLS DHVVDVVFTI FDENNDNQLS
NKEFISVMKN RVQRGLEKPK DTGFLKMMRS VFKCAKETKP VLLDI
