SSDH_MOUSE
ID SSDH_MOUSE Reviewed; 523 AA.
AC Q8BWF0; Q5SZW1;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Succinate-semialdehyde dehydrogenase, mitochondrial;
DE EC=1.2.1.24;
DE AltName: Full=Aldehyde dehydrogenase family 5 member A1;
DE AltName: Full=NAD(+)-dependent succinic semialdehyde dehydrogenase;
DE Flags: Precursor;
GN Name=Aldh5a1;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP PROTEIN SEQUENCE OF 57-87; 115-123; 129-160; 162-172; 181-201; 254-289;
RP 291-320; 323-333; 339-347; 358-375; 401-436; 469-496 AND 507-516, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J, and OF1; TISSUE=Brain, and Hippocampus;
RA Lubec G., Klug S., Kang S.U., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-403, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC 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-114; LYS-123; LYS-172; LYS-253;
RP LYS-347 AND LYS-390, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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-74; LYS-114; LYS-128; LYS-253;
RP LYS-347; LYS-353 AND LYS-399, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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: Catalyzes one step in the degradation of the inhibitory
CC neurotransmitter gamma-aminobutyric acid (GABA). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) + succinate semialdehyde = 2 H(+) + NADH +
CC succinate; Xref=Rhea:RHEA:13217, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30031, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57706, ChEBI:CHEBI:57945; EC=1.2.1.24;
CC -!- ACTIVITY REGULATION: Redox-regulated. Inhibited under oxydizing
CC conditions (By similarity). {ECO:0000250}.
CC -!- PATHWAY: Amino-acid degradation; 4-aminobutanoate degradation.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AK052703; BAC35105.1; -; mRNA.
DR EMBL; AK144030; BAE25663.1; -; mRNA.
DR EMBL; AL589699; CAI26086.1; -; Genomic_DNA.
DR CCDS; CCDS26383.1; -.
DR RefSeq; NP_766120.1; NM_172532.3.
DR AlphaFoldDB; Q8BWF0; -.
DR SMR; Q8BWF0; -.
DR BioGRID; 229542; 11.
DR IntAct; Q8BWF0; 2.
DR MINT; Q8BWF0; -.
DR STRING; 10090.ENSMUSP00000040591; -.
DR iPTMnet; Q8BWF0; -.
DR PhosphoSitePlus; Q8BWF0; -.
DR SwissPalm; Q8BWF0; -.
DR jPOST; Q8BWF0; -.
DR MaxQB; Q8BWF0; -.
DR PaxDb; Q8BWF0; -.
DR PeptideAtlas; Q8BWF0; -.
DR PRIDE; Q8BWF0; -.
DR ProteomicsDB; 257075; -.
DR Antibodypedia; 25307; 453 antibodies from 34 providers.
DR DNASU; 214579; -.
DR Ensembl; ENSMUST00000037615; ENSMUSP00000040591; ENSMUSG00000035936.
DR GeneID; 214579; -.
DR KEGG; mmu:214579; -.
DR UCSC; uc007pwp.2; mouse.
DR CTD; 7915; -.
DR MGI; MGI:2441982; Aldh5a1.
DR VEuPathDB; HostDB:ENSMUSG00000035936; -.
DR eggNOG; KOG2451; Eukaryota.
DR GeneTree; ENSGT00930000151038; -.
DR HOGENOM; CLU_005391_5_3_1; -.
DR InParanoid; Q8BWF0; -.
DR OMA; WHKLIEQ; -.
DR OrthoDB; 899961at2759; -.
DR PhylomeDB; Q8BWF0; -.
DR TreeFam; TF352906; -.
DR BRENDA; 1.2.1.24; 3474.
DR Reactome; R-MMU-916853; Degradation of GABA.
DR UniPathway; UPA00733; -.
DR BioGRID-ORCS; 214579; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Aldh5a1; mouse.
DR PRO; PR:Q8BWF0; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q8BWF0; protein.
DR Bgee; ENSMUSG00000035936; Expressed in dorsal tegmental nucleus and 209 other tissues.
DR ExpressionAtlas; Q8BWF0; baseline and differential.
DR Genevisible; Q8BWF0; MM.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0031406; F:carboxylic acid binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0051287; F:NAD binding; ISO:MGI.
DR GO; GO:0004777; F:succinate-semialdehyde dehydrogenase (NAD+) activity; ISS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; ISS:UniProtKB.
DR GO; GO:0009450; P:gamma-aminobutyric acid catabolic process; IMP:MGI.
DR GO; GO:0009448; P:gamma-aminobutyric acid metabolic process; IMP:MGI.
DR GO; GO:0006536; P:glutamate metabolic process; IMP:MGI.
DR GO; GO:0042135; P:neurotransmitter catabolic process; IMP:MGI.
DR GO; GO:0006807; P:nitrogen compound metabolic process; IBA:GO_Central.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0006105; P:succinate metabolic process; IMP:MGI.
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; IPR029510; Ald_DH_CS_GLU.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR InterPro; IPR010102; Succ_semiAld_DH.
DR Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR TIGRFAMs; TIGR01780; SSADH; 1.
DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Disulfide bond; Mitochondrion; NAD;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 36..523
FT /note="Succinate-semialdehyde dehydrogenase, mitochondrial"
FT /id="PRO_0000007185"
FT ACT_SITE 294
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT ACT_SITE 328
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 201
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 201
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 216..219
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 272..277
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 322
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 486
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 193
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT MOD_RES 74
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 114
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 114
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 123
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 128
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 172
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 253
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 253
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 347
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 347
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 353
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 390
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 399
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 487
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51649"
FT DISULFID 328..330
FT /note="In inhibited form"
FT /evidence="ECO:0000250"
SQ SEQUENCE 523 AA; 55968 MW; E0CF82E4F4FAE9D0 CRC64;
MATCFLLRSF WAARPALPPP GRFRPEPAGT PRRSYASGPG GLHADLLRGD SFVGGRWLPA
PATFPVYDPA SGAKLGTVAD CGVPEARAAV RAAYDAFNSW KGVSVKERSL LLRKWYDLMI
QNKDDLAKII TAESGKPLKE AQGEILYSAL FLEWFSEEAR RIYGDIIYTS AKDKRGLVLK
QPVGVAAIIT PWNFPSAMIT RKVGAALAAG CTVVVKPAED TPYSALALAQ LANQAGIPAG
VYNVIPCSRN KAKEVGEVLC TDPLVSKISF TGSTATGKIL LHHAANSVKR VSMELGGLAP
FIVFDSANVD QAVAGAMASK FRNAGQTCVC SNRFLVQRGI HDSFVTKFAE AMKKSLRVGN
GFEEGTTQGP LINEKAVEKV EKQVNDAVAK GATVVTGGKR HQSGGNFFEP TLLSNVTRDM
LCITEETFGP LAPVIKFDKE EEAVAIANAA EVGLAGYFYS QDPAQIWRVA EQLEVGMVGV
NEGLISSVEC PFGGVKQSGL GREGSKYGID EYLEVKYVCY GGL
