SSDH_HUMAN
ID SSDH_HUMAN Reviewed; 535 AA.
AC P51649; B2RD26; G5E949; Q546H9; Q8N3W6;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Succinate-semialdehyde dehydrogenase, mitochondrial {ECO:0000305};
DE EC=1.2.1.24 {ECO:0000269|PubMed:12208142, ECO:0000269|PubMed:14635103, ECO:0000269|PubMed:19300440, ECO:0000269|PubMed:9683595};
DE AltName: Full=Aldehyde dehydrogenase family 5 member A1;
DE AltName: Full=NAD(+)-dependent succinic semialdehyde dehydrogenase;
DE Flags: Precursor;
GN Name=ALDH5A1 {ECO:0000312|HGNC:HGNC:408}; Synonyms=SSADH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CATALYTIC ACTIVITY.
RC TISSUE=Lymphocyte;
RX PubMed=9683595; DOI=10.1086/301964;
RA Chambliss K.L., Hinson D.D., Trettel F., Malaspina P., Novelletto A.,
RA Jakobs C., Gibson K.M.;
RT "Two exon-skipping mutations as the molecular basis of succinic
RT semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria).";
RL Am. J. Hum. Genet. 63:399-408(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 69-535 (ISOFORM 2), ALTERNATIVE SPLICING, VARIANTS ARG-36; TYR-180;
RP LEU-182; SER-237; SER-372 AND ILE-406, CATALYTIC ACTIVITY, AND
RP CHARACTERIZATION OF VARIANTS ARG-36; TYR-180; LEU-182 AND SER-237.
RC TISSUE=B-cell;
RX PubMed=12208142; DOI=10.1016/s1096-7192(02)00105-1;
RA Blasi P., Boyl P.P., Ledda M., Novelletto A., Gibson K.M., Jakobs C.,
RA Hogema B., Akaboshi S., Loreni F., Malaspina P.;
RT "Structure of human succinic semialdehyde dehydrogenase gene:
RT identification of promoter region and alternatively processed isoforms.";
RL Mol. Genet. Metab. 76:348-362(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT TYR-180.
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 213-535 (ISOFORM 1).
RC TISSUE=Liver;
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 [8]
RP SUBUNIT.
RC TISSUE=Brain;
RX PubMed=9059628;
RA Trettel F., Malaspina P., Jodice C., Novelletto A., Slaughter C.A.,
RA Caudle D.L., Hinson D.D., Chambliss K.L., Gibson K.M.;
RT "Human succinic semialdehyde dehydrogenase. Molecular cloning and
RT chromosomal localization.";
RL Adv. Exp. Med. Biol. 414:253-260(1997).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-126, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-499, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 49-535 IN COMPLEX WITH PRODUCT AND
RP ADP, FUNCTION, ACTIVITY REGULATION, DISULFIDE BOND, MUTAGENESIS OF ARG-213;
RP ARG-334; CYS-342 AND SER-498, AND CATALYTIC ACTIVITY.
RX PubMed=19300440; DOI=10.1038/emboj.2009.40;
RA Kim Y.-G., Lee S., Kwon O.-S., Park S.-Y., Lee S.-J., Park B.-J.,
RA Kim K.-J.;
RT "Redox-switch modulation of human SSADH by dynamic catalytic loop.";
RL EMBO J. 28:959-968(2009).
RN [13]
RP VARIANTS SSADHD GLU-268 AND ASP-409.
RX PubMed=11243727; DOI=10.1006/mgme.2000.3145;
RA Hogema B.M., Akaboshi S., Taylor M., Salomons G.S., Jakobs C.,
RA Schutgens R.B., Wilcken B., Worthington S., Maropoulos G., Grompe M.,
RA Gibson K.M.;
RT "Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency:
RT increased accuracy employing DNA, enzyme, and metabolite analyses.";
RL Mol. Genet. Metab. 72:218-222(2001).
RN [14]
RP VARIANT SSADHD GLU-487.
RX PubMed=11901270; DOI=10.1159/000048603;
RA Aoshima T., Kajita M., Sekido Y., Ishiguro Y., Tsuge I., Kimura M.,
RA Yamaguchi S., Watanabe K., Shimokata K., Niwa T.;
RT "Mutation analysis in a patient with succinic semialdehyde dehydrogenase
RT deficiency: a compound heterozygote with 103-121del and 1460T>A of the
RT ALDH5A1 gene.";
RL Hum. Hered. 53:42-44(2002).
RN [15]
RP VARIANTS SSADHD PHE-93; ARG-176; TYR-223; MET-233; SER-255; GLU-268;
RP LYS-335; GLN-382; LEU-382; ASP-409 AND ARG-533, VARIANTS ARG-36; TYR-180;
RP LEU-182; SER-237 AND ILE-406, CHARACTERIZATION OF VARIANTS ARG-36; PHE-93;
RP ARG-176; TYR-180; LEU-182; TYR-223; MET-233; SER-237; SER-255; GLU-268;
RP LYS-335; LEU-382; ASP-409 AND ARG-533, AND CATALYTIC ACTIVITY.
RX PubMed=14635103; DOI=10.1002/humu.10288;
RA Akaboshi S., Hogema B.M., Novelletto A., Malaspina P., Salomons G.S.,
RA Maropoulos G.D., Jakobs C., Grompe M., Gibson K.M.;
RT "Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1)
RT gene and functional analysis of 27 novel disease-causing mutations in
RT patients with SSADH deficiency.";
RL Hum. Mutat. 22:442-450(2003).
CC -!- FUNCTION: Catalyzes one step in the degradation of the inhibitory
CC neurotransmitter gamma-aminobutyric acid (GABA).
CC {ECO:0000269|PubMed:19300440}.
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:12208142, ECO:0000269|PubMed:14635103,
CC ECO:0000269|PubMed:19300440, ECO:0000269|PubMed:9683595};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13218;
CC Evidence={ECO:0000305|PubMed:12208142, ECO:0000305|PubMed:14635103,
CC ECO:0000305|PubMed:19300440, ECO:0000305|PubMed:9683595};
CC -!- ACTIVITY REGULATION: Redox-regulated. Inhibited under oxydizing
CC conditions. Inhibited by hydrogen peroxide H(2)O(2).
CC {ECO:0000269|PubMed:19300440}.
CC -!- PATHWAY: Amino-acid degradation; 4-aminobutanoate degradation.
CC {ECO:0000305|PubMed:12208142, ECO:0000305|PubMed:14635103,
CC ECO:0000305|PubMed:19300440, ECO:0000305|PubMed:9683595}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:19300440,
CC ECO:0000269|PubMed:9059628}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P51649-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P51649-2; Sequence=VSP_045231;
CC -!- TISSUE SPECIFICITY: Brain, pancreas, heart, liver, skeletal muscle and
CC kidney. Lower in placenta.
CC -!- DISEASE: Succinic semialdehyde dehydrogenase deficiency (SSADHD)
CC [MIM:271980]: A rare inborn error of 4-aminobutyric acid (GABA)
CC metabolism, which leads to accumulation of 4-hydroxybutyric acid in
CC physiologic fluids of patients. The disease is clinically characterized
CC by developmental delay, hypotonia, intellectual disability, ataxia,
CC seizures, hyperkinetic behavior, aggression, and sleep disturbances.
CC {ECO:0000269|PubMed:11243727, ECO:0000269|PubMed:11901270,
CC ECO:0000269|PubMed:14635103}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; Y11192; CAA72076.1; -; mRNA.
DR EMBL; AJ427354; CAD20883.2; -; mRNA.
DR EMBL; AJ427355; CAD20884.1; -; mRNA.
DR EMBL; AK315380; BAG37773.1; -; mRNA.
DR EMBL; AL031230; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471087; EAW55452.1; -; Genomic_DNA.
DR EMBL; CH471087; EAW55453.1; -; Genomic_DNA.
DR EMBL; BC034321; AAH34321.1; -; mRNA.
DR EMBL; L34820; AAA67057.1; -; mRNA.
DR CCDS; CCDS4555.1; -. [P51649-1]
DR CCDS; CCDS4556.1; -. [P51649-2]
DR PIR; A55773; A55773.
DR RefSeq; NP_001071.1; NM_001080.3. [P51649-1]
DR RefSeq; NP_733936.1; NM_170740.1. [P51649-2]
DR PDB; 2W8N; X-ray; 2.00 A; A=49-535.
DR PDB; 2W8O; X-ray; 3.40 A; A=49-535.
DR PDB; 2W8P; X-ray; 2.30 A; A=49-535.
DR PDB; 2W8Q; X-ray; 2.40 A; A=49-535.
DR PDB; 2W8R; X-ray; 2.40 A; A=49-535.
DR PDBsum; 2W8N; -.
DR PDBsum; 2W8O; -.
DR PDBsum; 2W8P; -.
DR PDBsum; 2W8Q; -.
DR PDBsum; 2W8R; -.
DR AlphaFoldDB; P51649; -.
DR SMR; P51649; -.
DR BioGRID; 113645; 45.
DR IntAct; P51649; 18.
DR MINT; P51649; -.
DR STRING; 9606.ENSP00000314649; -.
DR BindingDB; P51649; -.
DR ChEMBL; CHEMBL1911; -.
DR DrugBank; DB00534; Chlormerodrin.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB09072; Sodium oxybate.
DR DrugBank; DB00139; Succinic acid.
DR DrugBank; DB00313; Valproic acid.
DR DrugCentral; P51649; -.
DR GuidetoPHARMACOLOGY; 2466; -.
DR GlyGen; P51649; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P51649; -.
DR PhosphoSitePlus; P51649; -.
DR SwissPalm; P51649; -.
DR BioMuta; ALDH5A1; -.
DR DMDM; 7531278; -.
DR EPD; P51649; -.
DR jPOST; P51649; -.
DR MassIVE; P51649; -.
DR PaxDb; P51649; -.
DR PeptideAtlas; P51649; -.
DR PRIDE; P51649; -.
DR ProteomicsDB; 33829; -.
DR ProteomicsDB; 56358; -. [P51649-1]
DR Antibodypedia; 25307; 453 antibodies from 34 providers.
DR DNASU; 7915; -.
DR Ensembl; ENST00000348925.2; ENSP00000314649.3; ENSG00000112294.14. [P51649-2]
DR Ensembl; ENST00000357578.8; ENSP00000350191.3; ENSG00000112294.14. [P51649-1]
DR GeneID; 7915; -.
DR KEGG; hsa:7915; -.
DR MANE-Select; ENST00000357578.8; ENSP00000350191.3; NM_001080.3; NP_001071.1.
DR CTD; 7915; -.
DR DisGeNET; 7915; -.
DR GeneCards; ALDH5A1; -.
DR GeneReviews; ALDH5A1; -.
DR HGNC; HGNC:408; ALDH5A1.
DR HPA; ENSG00000112294; Tissue enhanced (liver).
DR MalaCards; ALDH5A1; -.
DR MIM; 271980; phenotype.
DR MIM; 610045; gene.
DR neXtProt; NX_P51649; -.
DR OpenTargets; ENSG00000112294; -.
DR Orphanet; 22; Succinic semialdehyde dehydrogenase deficiency.
DR PharmGKB; PA24702; -.
DR VEuPathDB; HostDB:ENSG00000112294; -.
DR eggNOG; KOG2451; Eukaryota.
DR GeneTree; ENSGT00930000151038; -.
DR HOGENOM; CLU_005391_5_1_1; -.
DR InParanoid; P51649; -.
DR OMA; WHKLIEQ; -.
DR PhylomeDB; P51649; -.
DR TreeFam; TF352906; -.
DR BioCyc; MetaCyc:HS03550-MON; -.
DR BRENDA; 1.2.1.24; 2681.
DR PathwayCommons; P51649; -.
DR Reactome; R-HSA-916853; Degradation of GABA.
DR SABIO-RK; P51649; -.
DR SignaLink; P51649; -.
DR SIGNOR; P51649; -.
DR UniPathway; UPA00733; -.
DR BioGRID-ORCS; 7915; 7 hits in 1077 CRISPR screens.
DR ChiTaRS; ALDH5A1; human.
DR EvolutionaryTrace; P51649; -.
DR GeneWiki; Aldehyde_dehydrogenase_5_family,_member_A1; -.
DR GenomeRNAi; 7915; -.
DR Pharos; P51649; Tclin.
DR PRO; PR:P51649; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P51649; protein.
DR Bgee; ENSG00000112294; Expressed in skeletal muscle tissue of biceps brachii and 190 other tissues.
DR ExpressionAtlas; P51649; baseline and differential.
DR Genevisible; P51649; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0004777; F:succinate-semialdehyde dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IMP:UniProtKB.
DR GO; GO:0009450; P:gamma-aminobutyric acid catabolic process; IDA:UniProtKB.
DR GO; GO:0006536; P:glutamate metabolic process; ISS:UniProtKB.
DR GO; GO:0042135; P:neurotransmitter catabolic process; ISS:UniProtKB.
DR GO; GO:0006807; P:nitrogen compound metabolic process; IBA:GO_Central.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0006105; P:succinate metabolic process; ISS: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 3D-structure; Acetylation; Alternative splicing; Disease variant;
KW Disulfide bond; Mitochondrion; NAD; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..47
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 48..535
FT /note="Succinate-semialdehyde dehydrogenase, mitochondrial"
FT /id="PRO_0000007184"
FT ACT_SITE 306
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007"
FT ACT_SITE 340
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 202..204
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P20000"
FT BINDING 213
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19300440,
FT ECO:0007744|PDB:2W8Q"
FT BINDING 228..231
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:19300440,
FT ECO:0007744|PDB:2W8R"
FT BINDING 284..289
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:19300440,
FT ECO:0007744|PDB:2W8R"
FT BINDING 306
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P20000"
FT BINDING 334
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19300440,
FT ECO:0007744|PDB:2W8Q"
FT BINDING 438..440
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P20000"
FT BINDING 498
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19300440,
FT ECO:0007744|PDB:2W8Q"
FT SITE 205
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P20000"
FT MOD_RES 126
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 126
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 135
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 184
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 265
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 265
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 365
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 402
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 411
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWF0"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT DISULFID 340..342
FT /note="In inhibited form"
FT /evidence="ECO:0000269|PubMed:19300440"
FT VAR_SEQ 242
FT /note="E -> EVNQGFLLDLDPLL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12208142"
FT /id="VSP_045231"
FT VARIANT 36
FT /note="G -> R (no effect on succinate-semialdehyde
FT dehydrogenase activity; dbSNP:rs4646832)"
FT /evidence="ECO:0000269|PubMed:12208142,
FT ECO:0000269|PubMed:14635103"
FT /id="VAR_026227"
FT VARIANT 93
FT /note="C -> F (in SSADHD; 3% of activity;
FT dbSNP:rs765561257)"
FT /evidence="ECO:0000269|PubMed:14635103"
FT /id="VAR_026199"
FT VARIANT 176
FT /note="G -> R (in SSADHD; <1% of activity;
FT dbSNP:rs72552281)"
FT /evidence="ECO:0000269|PubMed:14635103"
FT /id="VAR_026200"
FT VARIANT 180
FT /note="H -> Y (83% of activity; dbSNP:rs2760118)"
FT /evidence="ECO:0000269|PubMed:12208142,
FT ECO:0000269|PubMed:14635103, ECO:0000269|PubMed:14702039"
FT /id="VAR_016758"
FT VARIANT 182
FT /note="P -> L (48% of activity; dbSNP:rs3765310)"
FT /evidence="ECO:0000269|PubMed:12208142,
FT ECO:0000269|PubMed:14635103"
FT /id="VAR_016759"
FT VARIANT 223
FT /note="C -> Y (in SSADHD; 5% of activity;
FT dbSNP:rs72552282)"
FT /evidence="ECO:0000269|PubMed:14635103"
FT /id="VAR_026201"
FT VARIANT 233
FT /note="T -> M (in SSADHD; 4% of activity;
FT dbSNP:rs1326526453)"
FT /evidence="ECO:0000269|PubMed:14635103"
FT /id="VAR_026202"
FT VARIANT 237
FT /note="A -> S (65% of activity; dbSNP:rs62621664)"
FT /evidence="ECO:0000269|PubMed:12208142,
FT ECO:0000269|PubMed:14635103"
FT /id="VAR_026228"
FT VARIANT 255
FT /note="N -> S (in SSADHD; 17% of activity;
FT dbSNP:rs145087265)"
FT /evidence="ECO:0000269|PubMed:14635103"
FT /id="VAR_026203"
FT VARIANT 268
FT /note="G -> E (in SSADHD; <1% of activity;
FT dbSNP:rs375628463)"
FT /evidence="ECO:0000269|PubMed:11243727,
FT ECO:0000269|PubMed:14635103"
FT /id="VAR_026204"
FT VARIANT 335
FT /note="N -> K (in SSADHD; 1% of activity;
FT dbSNP:rs72552283)"
FT /evidence="ECO:0000269|PubMed:14635103"
FT /id="VAR_026205"
FT VARIANT 372
FT /note="N -> S"
FT /evidence="ECO:0000269|PubMed:12208142"
FT /id="VAR_069047"
FT VARIANT 382
FT /note="P -> L (in SSADHD; 2% of activity)"
FT /evidence="ECO:0000269|PubMed:14635103"
FT /id="VAR_026206"
FT VARIANT 382
FT /note="P -> Q (in SSADHD)"
FT /evidence="ECO:0000269|PubMed:14635103"
FT /id="VAR_026207"
FT VARIANT 406
FT /note="V -> I (in dbSNP:rs143741652)"
FT /evidence="ECO:0000269|PubMed:12208142,
FT ECO:0000269|PubMed:14635103"
FT /id="VAR_026229"
FT VARIANT 409
FT /note="G -> D (in SSADHD; <1% of activity;
FT dbSNP:rs118203984)"
FT /evidence="ECO:0000269|PubMed:11243727,
FT ECO:0000269|PubMed:14635103"
FT /id="VAR_026208"
FT VARIANT 487
FT /note="V -> E (in SSADHD)"
FT /evidence="ECO:0000269|PubMed:11901270"
FT /id="VAR_026209"
FT VARIANT 533
FT /note="G -> R (in SSADHD; <1% of activity;
FT dbSNP:rs72552284)"
FT /evidence="ECO:0000269|PubMed:14635103"
FT /id="VAR_026210"
FT MUTAGEN 213
FT /note="R->A: Reduces catalytic activity to less than 15% of
FT wild-type."
FT /evidence="ECO:0000269|PubMed:19300440"
FT MUTAGEN 334
FT /note="R->A: Reduces catalytic activity to less than 15% of
FT wild-type."
FT /evidence="ECO:0000269|PubMed:19300440"
FT MUTAGEN 342
FT /note="C->A: Loss of regulation by redox state."
FT /evidence="ECO:0000269|PubMed:19300440"
FT MUTAGEN 498
FT /note="S->A: Reduces catalytic activity to less than 15% of
FT wild-type."
FT /evidence="ECO:0000269|PubMed:19300440"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:2W8P"
FT STRAND 62..65
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:2W8N"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 86..91
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 95..112
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 117..133
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 135..146
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 150..170
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 187..194
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 209..221
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 224..228
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 235..247
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 253..256
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 261..271
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 277..284
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 286..297
FT /evidence="ECO:0007829|PDB:2W8N"
FT TURN 298..300
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 302..307
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 309..315
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:2W8O"
FT HELIX 321..332
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 334..337
FT /evidence="ECO:0007829|PDB:2W8P"
FT STRAND 341..349
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 350..367
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:2W8O"
FT HELIX 386..400
FT /evidence="ECO:0007829|PDB:2W8N"
FT TURN 401..403
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 405..408
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 423..428
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 430..433
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 441..450
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 452..459
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 466..471
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 475..484
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 487..493
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 508..510
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 511..513
FT /evidence="ECO:0007829|PDB:2W8N"
FT TURN 517..519
FT /evidence="ECO:0007829|PDB:2W8N"
FT HELIX 520..524
FT /evidence="ECO:0007829|PDB:2W8N"
FT STRAND 525..532
FT /evidence="ECO:0007829|PDB:2W8N"
SQ SEQUENCE 535 AA; 57215 MW; C63A9431D3FA16C7 CRC64;
MATCIWLRSC GARRLGSTFP GCRLRPRAGG LVPASGPAPG PAQLRCYAGR LAGLSAALLR
TDSFVGGRWL PAAATFPVQD PASGAALGMV ADCGVREARA AVRAAYEAFC RWREVSAKER
SSLLRKWYNL MIQNKDDLAR IITAESGKPL KEAHGEILYS AFFLEWFSEE ARRVYGDIIH
TPAKDRRALV LKQPIGVAAV ITPWNFPSAM ITRKVGAALA AGCTVVVKPA EDTPFSALAL
AELASQAGIP SGVYNVIPCS RKNAKEVGEA ICTDPLVSKI SFTGSTTTGK ILLHHAANSV
KRVSMELGGL APFIVFDSAN VDQAVAGAMA SKFRNTGQTC VCSNQFLVQR GIHDAFVKAF
AEAMKKNLRV GNGFEEGTTQ GPLINEKAVE KVEKQVNDAV SKGATVVTGG KRHQLGKNFF
EPTLLCNVTQ DMLCTHEETF GPLAPVIKFD TEEEAIAIAN AADVGLAGYF YSQDPAQIWR
VAEQLEVGMV GVNEGLISSV ECPFGGVKQS GLGREGSKYG IDEYLELKYV CYGGL
