SSDH_RAT
ID SSDH_RAT Reviewed; 523 AA.
AC P51650;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Succinate-semialdehyde dehydrogenase, mitochondrial;
DE Short=SSADH {ECO:0000303|PubMed:7814412};
DE EC=1.2.1.24 {ECO:0000269|PubMed:7814412};
DE AltName: Full=Aldehyde dehydrogenase family 5 member A1;
DE AltName: Full=NAD(+)-dependent succinic semialdehyde dehydrogenase;
DE Flags: Precursor;
GN Name=Aldh5a1; Synonyms=Ssadh;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), PROTEIN SEQUENCE OF
RP 36-84; 92-101; 129-153; 162-172; 303-311; 419-425 AND 503-526, CATALYTIC
RP ACTIVITY, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=7814412; DOI=10.1074/jbc.270.1.461;
RA Chambliss K.L., Caudle D.L., Hinson D.D., Moomaw C.R., Slaughter C.A.,
RA Jakobs C., Gibson K.M.;
RT "Molecular cloning of the mature NAD(+)-dependent succinic semialdehyde
RT dehydrogenase from rat and human. cDNA isolation, evolutionary homology,
RT and tissue expression.";
RL J. Biol. Chem. 270:461-467(1995).
RN [3]
RP PROTEIN SEQUENCE OF 36-48; 161-172 AND 401-418, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
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 Evidence={ECO:0000269|PubMed:7814412};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13218;
CC Evidence={ECO:0000305|PubMed:7814412};
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long {ECO:0000303|PubMed:7814412};
CC IsoId=P51650-1; Sequence=Displayed;
CC Name=Short {ECO:0000303|PubMed:7814412};
CC IsoId=P51650-2; Sequence=VSP_001284;
CC -!- TISSUE SPECIFICITY: Brain, pancreas, heart, liver, skeletal muscle,
CC kidney. Lower in spleen, lung, kidney and testis.
CC {ECO:0000269|PubMed:7814412}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AABR03105019; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L34821; AAA67058.1; -; mRNA.
DR PIR; I61704; I61704.
DR AlphaFoldDB; P51650; -.
DR SMR; P51650; -.
DR STRING; 10116.ENSRNOP00000035601; -.
DR iPTMnet; P51650; -.
DR PhosphoSitePlus; P51650; -.
DR World-2DPAGE; 0004:P51650; -.
DR jPOST; P51650; -.
DR PaxDb; P51650; -.
DR PeptideAtlas; P51650; -.
DR PRIDE; P51650; -.
DR UCSC; RGD:621422; rat. [P51650-1]
DR RGD; 621422; Aldh5a1.
DR eggNOG; KOG2451; Eukaryota.
DR InParanoid; P51650; -.
DR PhylomeDB; P51650; -.
DR BRENDA; 1.2.1.3; 5301.
DR Reactome; R-RNO-916853; Degradation of GABA.
DR SABIO-RK; P51650; -.
DR UniPathway; UPA00733; -.
DR PRO; PR:P51650; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0031406; F:carboxylic acid binding; IPI:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0051287; F:NAD binding; IDA:RGD.
DR GO; GO:0004777; F:succinate-semialdehyde dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; ISS:UniProtKB.
DR GO; GO:0009450; P:gamma-aminobutyric acid catabolic process; ISS:UniProtKB.
DR GO; GO:0009448; P:gamma-aminobutyric acid metabolic process; ISO:RGD.
DR GO; GO:0006536; P:glutamate metabolic process; ISO:RGD.
DR GO; GO:0042135; P:neurotransmitter catabolic process; ISO:RGD.
DR GO; GO:0006807; P:nitrogen compound metabolic process; IBA:GO_Central.
DR GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR GO; GO:0006105; P:succinate metabolic process; IDA:UniProtKB.
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; Alternative splicing; Direct protein sequencing;
KW Disulfide bond; Mitochondrion; NAD; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:7814412, ECO:0000269|Ref.3"
FT CHAIN 36..523
FT /note="Succinate-semialdehyde dehydrogenase, mitochondrial"
FT /id="PRO_0000056567"
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 114
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51649"
FT MOD_RES 114
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 123
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 172
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 253
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 253
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 353
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 390
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 399
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
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"
FT VAR_SEQ 107..134
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:7814412"
FT /id="VSP_001284"
SQ SEQUENCE 523 AA; 56131 MW; 4CA521139C9FA98F CRC64;
MATCFLLRNF CAARPALRPP GRLLREPAGA QRRSYVGGPA DLHADLLRGD SFVGGRWLPT
PATFPVYDPA SGAKLGTVAD CGVPEARAAV RAAYDAFSSW KEISVKERSS LLRKWYDLMI
QNKDELAKII TAESGKPLKE AQGEILYSAF FLEWFSEEAR RVYGDIIYTS AKDKRGLVLK
QPVGVASIIT PWNFPSAMIT RKVGAALAAG CTVVVKPAED TPYSALALAQ LANQAGIPPG
VYNVIPCSRT KAKEVGEVLC TDPLVSKISF TGSTATGKIL LHHAANSVKR VSMELGGLAP
FIVFDSANVD QAVAGAMASK FRNAGQTCVC SNRFLVQRGI HDSFVTKFAE AMKKSLRVGN
GFEEGTTQGP LINEKAVEKV EKHVNDAVAK GATVVTGGKR HQSGGNFFEP TLLSNVTRDM
LCITEETFGP VAPVIKFDKE EEAVAIANAA DVGLAGYFYS QDPAQIWRVA EQLEVGMVGV
NEGLISSVEC PFGGVKQSGL GREGSKYGID EYLEVKYVCY GGL
