MMSA_RAT
ID MMSA_RAT Reviewed; 535 AA.
AC Q02253;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial {ECO:0000305};
DE Short=MMSDH;
DE Short=Malonate-semialdehyde dehydrogenase [acylating];
DE EC=1.2.1.18 {ECO:0000269|PubMed:2768248};
DE EC=1.2.1.27 {ECO:0000269|PubMed:2768248};
DE AltName: Full=Aldehyde dehydrogenase family 6 member A1;
DE Flags: Precursor;
GN Name=Aldh6a1; Synonyms=Mmsdh;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 33-50 AND 166-190.
RC TISSUE=Liver;
RX PubMed=1527093; DOI=10.1016/s0021-9258(18)41835-2;
RA Kedishvili N.Y., Popov K.M., Rougraff P.M., Zhao Y., Crabb D.W.,
RA Harris R.A.;
RT "CoA-dependent methylmalonate-semialdehyde dehydrogenase, a unique member
RT of the aldehyde dehydrogenase superfamily. cDNA cloning, evolutionary
RT relationships, and tissue distribution.";
RL J. Biol. Chem. 267:19724-19729(1992).
RN [2]
RP PROTEIN SEQUENCE OF 33-50, CHARACTERIZATION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=2768248; DOI=10.1016/s0021-9258(18)63797-4;
RA Goodwin G.W., Rougraff P.M., Davis E.J., Harris R.A.;
RT "Purification and characterization of methylmalonate-semialdehyde
RT dehydrogenase from rat liver. Identity to malonate-semialdehyde
RT dehydrogenase.";
RL J. Biol. Chem. 264:14965-14971(1989).
RN [3]
RP PROTEIN SEQUENCE OF N-TERMINUS.
RX PubMed=1898092; DOI=10.1016/0003-9861(91)90586-8;
RA Kedishvili N.Y., Popov K.M., Harris R.A.;
RT "The effect of ligand binding on the proteolytic pattern of methylmalonate
RT semialdehyde dehydrogenase.";
RL Arch. Biochem. Biophys. 290:21-26(1991).
RN [4]
RP PROTEIN SEQUENCE OF 56-70, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE SPECIFICITY.
RC STRAIN=Holtzman; TISSUE=Sperm;
RX PubMed=20966424; DOI=10.2164/jandrol.110.010967;
RA Suryawanshi A.R., Khan S.A., Gajbhiye R.K., Gurav M.Y., Khole V.V.;
RT "Differential proteomics leads to identification of domain specific
RT epididymal sperm proteins.";
RL J. Androl. 32:240-259(2011).
CC -!- FUNCTION: Plays a role in valine and pyrimidine metabolism. Binds fatty
CC acyl-CoA.
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 Evidence={ECO:0000269|PubMed:2768248};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20805;
CC Evidence={ECO:0000305|PubMed:2768248};
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:0000269|PubMed:2768248};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22993;
CC Evidence={ECO:0000305|PubMed:2768248};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.3 uM for 2-methyl-3-oxopropanoate {ECO:0000269|PubMed:2768248};
CC KM=9.4 uM for 3-oxopropanoate {ECO:0000269|PubMed:2768248};
CC KM=150 uM for NAD(+) {ECO:0000269|PubMed:2768248};
CC KM=30 uM for CoA {ECO:0000269|PubMed:2768248};
CC pH dependence:
CC Optimum pH is 8. {ECO:0000269|PubMed:2768248};
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- TISSUE SPECIFICITY: Expressed in the head and flagellum of epididymal
CC sperm but not in testicular sperm (at protein level). Kidney > liver >
CC heart > muscle > brain. {ECO:0000269|PubMed:20966424}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M93401; AAA41638.1; -; mRNA.
DR PIR; A44097; A44097.
DR RefSeq; NP_112319.2; NM_031057.2.
DR AlphaFoldDB; Q02253; -.
DR SMR; Q02253; -.
DR BioGRID; 249586; 1.
DR IntAct; Q02253; 2.
DR STRING; 10116.ENSRNOP00000015545; -.
DR CarbonylDB; Q02253; -.
DR iPTMnet; Q02253; -.
DR PhosphoSitePlus; Q02253; -.
DR jPOST; Q02253; -.
DR PaxDb; Q02253; -.
DR PRIDE; Q02253; -.
DR GeneID; 81708; -.
DR KEGG; rno:81708; -.
DR UCSC; RGD:621556; rat.
DR CTD; 4329; -.
DR RGD; 621556; Aldh6a1.
DR eggNOG; KOG2449; Eukaryota.
DR InParanoid; Q02253; -.
DR OrthoDB; 608999at2759; -.
DR PhylomeDB; Q02253; -.
DR Reactome; R-RNO-70895; Branched-chain amino acid catabolism.
DR SABIO-RK; Q02253; -.
DR PRO; PR:Q02253; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; ISS:UniProtKB.
DR GO; GO:0018478; F:malonate-semialdehyde dehydrogenase (acetylating) activity; IDA:UniProtKB.
DR GO; GO:0102662; F:malonate-semialdehyde dehydrogenase (acetylating, NAD+) activity; IEA:RHEA.
DR GO; GO:0004491; F:methylmalonate-semialdehyde dehydrogenase (acylating) activity; IDA:UniProtKB.
DR GO; GO:0016790; F:thiolester hydrolase activity; IDA:RGD.
DR GO; GO:0019484; P:beta-alanine catabolic process; IDA:RGD.
DR GO; GO:0050873; P:brown fat cell differentiation; ISO:RGD.
DR GO; GO:0006210; P:thymine catabolic process; IDA:RGD.
DR GO; GO:0019859; P:thymine metabolic process; IDA:UniProtKB.
DR GO; GO:0006574; P:valine catabolic process; IDA:RGD.
DR GO; GO:0006573; P:valine metabolic process; IDA: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 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Mitochondrion; NAD; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..32
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1527093,
FT ECO:0000269|PubMed:1898092, ECO:0000269|PubMed:2768248"
FT CHAIN 33..535
FT /note="Methylmalonate-semialdehyde dehydrogenase
FT [acylating], mitochondrial"
FT /id="PRO_0000007190"
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:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 47
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 52
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 52
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 55
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 55
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 76
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 76
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 87
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 117
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 117
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 129
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 129
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02252"
FT MOD_RES 298
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 330
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 331
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 364
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 364
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 376
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 376
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 380
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02252"
FT MOD_RES 391
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 500
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT MOD_RES 517
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ20"
FT CONFLICT 45
FT /note="D -> N (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="E -> Q (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="D -> N (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="D -> N (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 184
FT /note="P -> T (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="M -> G (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 535 AA; 57808 MW; D914CE0311AA466A CRC64;
MAAAVAAAAA VRSRILQVSS KVNSTWYPAS SFSSSSVPTV KLFIDGKFVE SKSDKWIDIH
NPATNEVVGR VPQSTKAEME AAVAACKRAF PAWADTSILS RQQVLLRYQQ LIKENLKEIA
RLITLEQGKT LADAEGDVFR GLQVVEHACS VTSLMLGETM PSITKDMDLY SYRLPLGVCA
GIAPFNFPAM IPLWMFPMAM VCGNTFLMKP SERVPGATML LAKLLQDSGA PDGTLNIIHG
QHEAVNFICD HPDIKAISFV GSNQAGEYIF ERGSRNGKRV QANMGAKNHG VVMPDANKEN
TLNQLVGAAF GAAGQRCMAL STAVLVGEAK KWLPELVERA KNLRVNAGDQ PGADLGPLIT
PQAKERVCNL IDSGAKEGAS ILLDGRKIKV KGYENGNFVG PTIISNVKPS MTCYKEEIFG
PVLVVLETET LDEAIKIVND NPYGNGTAIF TTNGAIARKY AHMVDVGQVG VNVPIPVPLP
MFSFTGSRSS FRGDTNFYGK QGIQFYTQLK TITSQWKEED ATLSSPAVVM PTMGR
