MMSA_MOUSE
ID MMSA_MOUSE Reviewed; 535 AA.
AC Q9EQ20; Q3TDA2; Q8CIB4;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=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 AltName: Full=Aldehyde dehydrogenase family 6 member A1;
DE Flags: Precursor;
GN Name=Aldh6a1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Yang B.-Z., Zhang L.-F., Roe C.R., Ding J.-H.;
RT "Mouse methylmalonate-semialdehyde dehydrogenase (MMSDH) cDNA and gene
RT map.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Cecum, Kidney, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-47; LYS-52; LYS-55; LYS-76;
RP LYS-117; LYS-129; LYS-364; LYS-376; LYS-391 AND LYS-517, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-47; LYS-52; LYS-55; LYS-76;
RP LYS-87; LYS-117; LYS-129; LYS-298; LYS-330; LYS-331; LYS-364; LYS-376 AND
RP LYS-500, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Plays a role in valine and pyrimidine metabolism. Binds fatty
CC acyl-CoA (By similarity). {ECO:0000250}.
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 -!- 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 -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}.
CC -!- PTM: Acetylation of Lys-55; Lys-117 and Lys-331 is observed in liver
CC mitochondria from fasted mice but not from fed mice.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AF297860; AAG44988.1; -; mRNA.
DR EMBL; AK033587; BAC28375.1; -; mRNA.
DR EMBL; AK147146; BAE27715.1; -; mRNA.
DR EMBL; AK155814; BAE33445.1; -; mRNA.
DR EMBL; AK169915; BAE41455.1; -; mRNA.
DR EMBL; AK170305; BAE41702.1; -; mRNA.
DR EMBL; AK171581; BAE42539.1; -; mRNA.
DR EMBL; AK171896; BAE42726.1; -; mRNA.
DR EMBL; BC033440; AAH33440.1; -; mRNA.
DR CCDS; CCDS26046.1; -.
DR RefSeq; NP_598803.1; NM_134042.3.
DR AlphaFoldDB; Q9EQ20; -.
DR SMR; Q9EQ20; -.
DR BioGRID; 222701; 16.
DR IntAct; Q9EQ20; 2.
DR MINT; Q9EQ20; -.
DR STRING; 10090.ENSMUSP00000082288; -.
DR iPTMnet; Q9EQ20; -.
DR PhosphoSitePlus; Q9EQ20; -.
DR SwissPalm; Q9EQ20; -.
DR REPRODUCTION-2DPAGE; Q8CIB4; -.
DR REPRODUCTION-2DPAGE; Q9EQ20; -.
DR EPD; Q9EQ20; -.
DR jPOST; Q9EQ20; -.
DR MaxQB; Q9EQ20; -.
DR PaxDb; Q9EQ20; -.
DR PeptideAtlas; Q9EQ20; -.
DR PRIDE; Q9EQ20; -.
DR ProteomicsDB; 291478; -.
DR Antibodypedia; 25547; 513 antibodies from 31 providers.
DR DNASU; 104776; -.
DR Ensembl; ENSMUST00000085192; ENSMUSP00000082288; ENSMUSG00000021238.
DR GeneID; 104776; -.
DR KEGG; mmu:104776; -.
DR UCSC; uc007ofk.2; mouse.
DR CTD; 4329; -.
DR MGI; MGI:1915077; Aldh6a1.
DR VEuPathDB; HostDB:ENSMUSG00000021238; -.
DR eggNOG; KOG2449; Eukaryota.
DR GeneTree; ENSGT00940000156110; -.
DR HOGENOM; CLU_005391_1_10_1; -.
DR InParanoid; Q9EQ20; -.
DR OMA; HGKRAQC; -.
DR OrthoDB; 608999at2759; -.
DR PhylomeDB; Q9EQ20; -.
DR TreeFam; TF105651; -.
DR BRENDA; 1.2.1.18; 3474.
DR Reactome; R-MMU-70895; Branched-chain amino acid catabolism.
DR BioGRID-ORCS; 104776; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Aldh6a1; mouse.
DR PRO; PR:Q9EQ20; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q9EQ20; protein.
DR Bgee; ENSMUSG00000021238; Expressed in right kidney and 251 other tissues.
DR ExpressionAtlas; Q9EQ20; baseline and differential.
DR Genevisible; Q9EQ20; MM.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0018478; F:malonate-semialdehyde dehydrogenase (acetylating) activity; ISO:MGI.
DR GO; GO:0102662; F:malonate-semialdehyde dehydrogenase (acetylating, NAD+) activity; IEA:RHEA.
DR GO; GO:0004491; F:methylmalonate-semialdehyde dehydrogenase (acylating) activity; ISO:MGI.
DR GO; GO:0016790; F:thiolester hydrolase activity; ISO:MGI.
DR GO; GO:0019484; P:beta-alanine catabolic process; ISO:MGI.
DR GO; GO:0050873; P:brown fat cell differentiation; IDA:MGI.
DR GO; GO:0006210; P:thymine catabolic process; ISO:MGI.
DR GO; GO:0019859; P:thymine metabolic process; ISO:MGI.
DR GO; GO:0006574; P:valine catabolic process; ISO:MGI.
DR GO; GO:0006573; P:valine metabolic process; ISO:MGI.
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 1: Evidence at protein level;
KW Acetylation; Mitochondrion; NAD; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..32
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 33..535
FT /note="Methylmalonate-semialdehyde dehydrogenase
FT [acylating], mitochondrial"
FT /id="PRO_0000320299"
FT ACT_SITE 317
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 209..213
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255"
FT BINDING 261..266
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255"
FT BINDING 417
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255"
FT MOD_RES 47
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 47
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 52
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 52
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 55
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 55
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 76
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 76
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 87
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 117
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 117
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 129
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 129
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02252"
FT MOD_RES 298
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 330
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 331
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 364
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 364
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 376
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 376
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 380
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02252"
FT MOD_RES 391
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 500
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 517
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 55
FT /note="K -> R (in Ref. 2; BAE41702)"
FT /evidence="ECO:0000305"
FT CONFLICT 141
FT /note="G -> C (in Ref. 3; AAH33440)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="S -> P (in Ref. 2; BAE41702)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 535 AA; 57916 MW; 1EF4ED4C4FE2284D CRC64;
MAAAVAAAAA MRSRILQVSS KVNATWYPAS SFSSSSVPTV KLFIDGKFVE SKSDKWIDIH
NPATNEVVGR VPQSTKAEMD AAVESCKRAF PAWADTSILS RQQVLLRYQQ LIKENLKEIA
RLITLEQGKT LADAEGDVFR GLQVVEHACS VTSLMLGETM PSITKDMDLY SYRLPLGVCA
GIAPFNFPAM IPLWMFPMAM VCGNTFLMKP SERVPGATML LAKLLQDSGA PDGTLNIIHG
QHDAVNFICD HPDIKAISFV GSNQAGEYIF ERGSRNGKRV QANMGAKNHG VVMPDANKEN
TLNQLVGAAF GAAGQRCMAL STAILVGEAK KWLPELVDRA KNLRVNAGDQ PGADLGPLIT
PQAKERVCNL IDSGTKEGAS ILLDGRRIKV KGYENGNFVG PTIISNVKPS MTCYKEEIFG
PVLVVLETET LDEAIKIVND NPYGNGTAIF TTNGATARKY AHMVDVGQVG VNVPIPVPLP
MFSFTGSRSS FRGDTNFYGK QGIQFYTQLK TITSQWKEED ATLSSPAVVM PTMGR
