MMSA_DROME
ID MMSA_DROME Reviewed; 520 AA.
AC Q7KW39; O46056; Q8T9I0; Q9V408;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Probable methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial;
DE Short=MMSDH;
DE Short=Malonate-semialdehyde dehydrogenase [acylating];
DE EC=1.2.1.18;
DE EC=1.2.1.27;
DE Flags: Precursor;
GN ORFNames=CG17896;
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] {ECO:0000312|EMBL:AAF45510.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
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] {ECO:0000305, ECO:0000312|EMBL:AAF45510.2}
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 [3] {ECO:0000305, ECO:0000312|EMBL:CAA15632.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Oregon-R {ECO:0000269|PubMed:10731137};
RX PubMed=10731137; DOI=10.1126/science.287.5461.2220;
RA Benos P.V., Gatt M.K., Ashburner M., Murphy L., Harris D., Barrell B.G.,
RA Ferraz C., Vidal S., Brun C., Demailles J., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Borkova D., Minana B., Kafatos F.C.,
RA Louis C., Siden-Kiamos I., Bolshakov S., Papagiannakis G., Spanos L.,
RA Cox S., Madueno E., de Pablos B., Modolell J., Peter A., Schoettler P.,
RA Werner M., Mourkioti F., Beinert N., Dowe G., Schaefer U., Jaeckle H.,
RA Bucheton A., Callister D.M., Campbell L.A., Darlamitsou A., Henderson N.S.,
RA McMillan P.J., Salles C., Tait E.A., Valenti P., Saunders R.D.C.,
RA Glover D.M.;
RT "From sequence to chromosome: the tip of the X chromosome of D.
RT melanogaster.";
RL Science 287:2220-2222(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 332-520.
RC STRAIN=Berkeley; TISSUE=Ovary;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Plays a role in valine and pyrimidine metabolism. Binds fatty
CC acyl-CoA (By similarity). {ECO:0000250|UniProtKB:Q02252}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methyl-3-oxopropanoate + CoA + H2O + NAD(+) = H(+) +
CC hydrogencarbonate + NADH + propanoyl-CoA; Xref=Rhea:RHEA:20804,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17544,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57392, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57700, ChEBI:CHEBI:57945; EC=1.2.1.27;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxopropanoate + CoA + NAD(+) = acetyl-CoA + CO2 + NADH;
CC Xref=Rhea:RHEA:22992, ChEBI:CHEBI:16526, ChEBI:CHEBI:33190,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.2.1.18;
CC Evidence={ECO:0000250|UniProtKB:Q02252};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxopropanoate + CoA + NADP(+) = acetyl-CoA + CO2 + NADPH;
CC Xref=Rhea:RHEA:22988, ChEBI:CHEBI:16526, ChEBI:CHEBI:33190,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.2.1.18;
CC Evidence={ECO:0000250|UniProtKB:Q02252};
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:Q02252}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q02252}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B {ECO:0000303|PubMed:10731132};
CC IsoId=Q7KW39-1; Sequence=Displayed;
CC Name=A {ECO:0000303|PubMed:10731132};
CC IsoId=Q7KW39-2; Sequence=VSP_051919;
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA15632.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AE014298; AAF45510.2; -; Genomic_DNA.
DR EMBL; AE014298; AAF45511.1; -; Genomic_DNA.
DR EMBL; AL009147; CAA15632.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL009147; CAB41309.1; -; Genomic_DNA.
DR EMBL; AY069284; AAL39429.2; -; mRNA.
DR PIR; T13418; T13418.
DR RefSeq; NP_569845.2; NM_130489.3. [Q7KW39-1]
DR RefSeq; NP_726672.1; NM_166844.1. [Q7KW39-2]
DR AlphaFoldDB; Q7KW39; -.
DR SMR; Q7KW39; -.
DR BioGRID; 57566; 3.
DR IntAct; Q7KW39; 2.
DR STRING; 7227.FBpp0070087; -.
DR MEROPS; M14.A20; -.
DR PaxDb; Q7KW39; -.
DR DNASU; 30995; -.
DR EnsemblMetazoa; FBtr0070092; FBpp0070087; FBgn0023537. [Q7KW39-1]
DR EnsemblMetazoa; FBtr0070093; FBpp0070088; FBgn0023537. [Q7KW39-2]
DR GeneID; 30995; -.
DR KEGG; dme:Dmel_CG17896; -.
DR UCSC; CG17896-RA; d. melanogaster. [Q7KW39-1]
DR FlyBase; FBgn0023537; CG17896.
DR VEuPathDB; VectorBase:FBgn0023537; -.
DR eggNOG; KOG2449; Eukaryota.
DR GeneTree; ENSGT00940000156110; -.
DR InParanoid; Q7KW39; -.
DR OMA; HGKRAQC; -.
DR PhylomeDB; Q7KW39; -.
DR Reactome; R-DME-70895; Branched-chain amino acid catabolism.
DR BioGRID-ORCS; 30995; 0 hits in 1 CRISPR screen.
DR ChiTaRS; CG17896; fly.
DR GenomeRNAi; 30995; -.
DR PRO; PR:Q7KW39; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0023537; Expressed in adult Malpighian tubule (Drosophila) and 25 other tissues.
DR ExpressionAtlas; Q7KW39; baseline and differential.
DR Genevisible; Q7KW39; DM.
DR GO; GO:0005739; C:mitochondrion; ISS:FlyBase.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; ISS:UniProtKB.
DR GO; GO:0018478; F:malonate-semialdehyde dehydrogenase (acetylating) activity; ISS:UniProtKB.
DR GO; GO:0102662; F:malonate-semialdehyde dehydrogenase (acetylating, NAD+) activity; IEA:RHEA.
DR GO; GO:0004491; F:methylmalonate-semialdehyde dehydrogenase (acylating) activity; ISS:UniProtKB.
DR GO; GO:0006206; P:pyrimidine nucleobase metabolic process; ISS:FlyBase.
DR GO; GO:0006210; P:thymine catabolic process; IBA:GO_Central.
DR GO; GO:0019859; P:thymine metabolic process; ISS:UniProtKB.
DR GO; GO:0006574; P:valine catabolic process; IBA:GO_Central.
DR GO; GO:0006573; P:valine metabolic process; ISS:UniProtKB.
DR CDD; cd07085; ALDH_F6_MMSDH; 1.
DR Gene3D; 3.40.309.10; -; 1.
DR Gene3D; 3.40.605.10; -; 1.
DR InterPro; IPR016161; Ald_DH/histidinol_DH.
DR InterPro; IPR016163; Ald_DH_C.
DR InterPro; IPR016160; Ald_DH_CS_CYS.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR InterPro; IPR010061; MeMal-semiAld_DH.
DR PANTHER; PTHR43866; PTHR43866; 1.
DR Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR TIGRFAMs; TIGR01722; MMSDH; 1.
DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Mitochondrion; NAD; Oxidoreductase;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..520
FT /note="Probable methylmalonate-semialdehyde dehydrogenase
FT [acylating], mitochondrial"
FT /id="PRO_0000043373"
FT ACT_SITE 303
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q02252,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 195..199
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255"
FT BINDING 247..252
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255"
FT BINDING 403
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255"
FT VAR_SEQ 2..10
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:10731132"
FT /id="VSP_051919"
SQ SEQUENCE 520 AA; 55972 MW; 12AC03D9B9C3E41D CRC64;
MSLVRLIGAE ARHLAKRSYS SAAPTTKLFI DGKFVESKTN EWIDVHDPAT NQVVTRVPKA
TQAEMQAALE SNKKAFRSWS NQSILTRQQV MFKLQALIKE NMGELAKNIT KEQGKTLADA
EGDVLRGLQV VEHCCSIPSL QMGETVANVA RDMDTYSLVL PLGVTAGVAP FNFPAMIPLW
MFPVAITTGN TMLLKPSERV PGATMLLMEL LNEAGCPPGV VNVIHGQHDA VNFICDAPEI
KAVSFVGSDQ AGKYIYERAG KNGKRVQSNM GAKNHGIILG DANKENTLNQ LAGAAFGAAG
QRCMALSTAV FVGDAQAWIP DLVERAQKLK VNAGHVPGTD VGPVISAASR QRINDLIESG
VKEGAKLILD GRKITVPGYE DGYFVGPTIL SDVTPSMKCY TEEIFGPVLV ILKADTLDDA
IGIVNANPYG NGTAVFTTNG AAARKFVNEI DAGQVGVNVP IPVPLPMFSF TGTRGSFRGD
HHFYGKQGIK FYTQTKTVTQ LWRKTDVTHT QAAVAMPTMK
