Succinate-semialdehyde dehydrogenase, mitochondrial

NameSuccinate-semialdehyde dehydrogenase, mitochondrial
Synonyms
  • 1.2.1.24
  • Aldehyde dehydrogenase family 5 member A1
  • NAD(+)-dependent succinic semialdehyde dehydrogenase
  • SSADH
Gene NameALDH5A1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000303|Succinate-semialdehyde dehydrogenase, mitochondrial
MATCIWLRSCGARRLGSTFPGCRLRPRAGGLVPASGPAPGPAQLRCYAGRLAGLSAALLR
TDSFVGGRWLPAAATFPVQDPASGAALGMVADCGVREARAAVRAAYEAFCRWREVSAKER
SSLLRKWYNLMIQNKDDLARIITAESGKPLKEAHGEILYSAFFLEWFSEEARRVYGDIIH
TPAKDRRALVLKQPIGVAAVITPWNFPSAMITRKVGAALAAGCTVVVKPAEDTPFSALAL
AELASQAGIPSGVYNVIPCSRKNAKEVGEAICTDPLVSKISFTGSTTTGKILLHHAANSV
KRVSMELGGLAPFIVFDSANVDQAVAGAMASKFRNTGQTCVCSNQFLVQRGIHDAFVKAF
AEAMKKNLRVGNGFEEGTTQGPLINEKAVEKVEKQVNDAVSKGATVVTGGKRHQLGKNFF
EPTLLCNVTQDMLCTHEETFGPLAPVIKFDTEEEAIAIANAADVGLAGYFYSQDPAQIWR
VAEQLEVGMVGVNEGLISSVECPFGGVKQSGLGREGSKYGIDEYLELKYVCYGGL
Number of residues535
Molecular Weight57214.23
Theoretical pI8.37
GO Classification
Functions
  • aldehyde dehydrogenase (NAD) activity
  • succinate-semialdehyde dehydrogenase (NAD+) activity
  • succinate-semialdehyde dehydrogenase [NAD(P)+] activity
  • protein homodimerization activity
Processes
  • respiratory electron transport chain
  • protein homotetramerization
  • glutamine metabolic process
  • glutathione metabolic process
  • succinate metabolic process
  • glutamate metabolic process
  • gamma-aminobutyric acid catabolic process
  • neurotransmitter catabolic process
  • central nervous system development
  • glycerophospholipid metabolic process
  • synaptic transmission
  • neurotransmitter secretion
  • acetate metabolic process
  • galactosylceramide metabolic process
  • glucose metabolic process
  • short-chain fatty acid metabolic process
Components
  • mitochondrion
  • mitochondrial matrix
General FunctionSuccinate-semialdehyde dehydrogenase [nad(p)+] activity
Specific FunctionCatalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID3766467
UniProtKB IDP51649
UniProtKB Entry NameSSDH_HUMAN
Cellular LocationMitochondrion
Gene sequence
>lcl|BSEQ0021648|Succinate-semialdehyde dehydrogenase, mitochondrial (ALDH5A1)
ATGGCGACCTGCATTTGGCTGCGGAGCTGTGGGGCCCGGCGCCTCGGGTCGACGTTTCCA
GGCTGCCGCCTCCGCCCCCGCGCCGGCGGCCTGGTCCCTGCCTCCGGGCCTGCGCCCGGC
CCGGCCCAGCTCCGCTGCTACGCTGGGCGCCTGGCGGGCCTCTCTGCGGCGCTGCTGCGC
ACCGACAGCTTCGTGGGCGGCCGCTGGCTCCCGGCCGCCGCCACCTTCCCCGTGCAAGAC
CCGGCCAGCGGCGCCGCTCTGGGCATGGTAGCCGACTGCGGGGTGCGAGAGGCCCGCGCC
GCCGTGCGCGCTGCCTACGAGGCTTTCTGCCGCTGGAGGGAGGTCTCCGCCAAGGAGAGG
AGTTCATTACTTCGGAAGTGGTACAATTTAATGATACAAAATAAGGATGACCTTGCCAGA
ATAATCACAGCTGAAAGTGGAAAGCCACTGAAGGAGGCACATGGAGAAATTCTCTATTCC
GCCTTTTTCCTAGAGTGGTTCTCTGAGGAAGCCCGCCGTGTTTACGGAGACATTATCCAC
ACCCCGGCAAAGGACAGGCGGGCCCTGGTCCTCAAGCAGCCCATAGGCGTGGCTGCAGTC
ATCACCCCGTGGAATTTCCCCAGTGCCATGATCACCCGGAAGGTGGGGGCCGCCCTGGCA
GCCGGCTGTACTGTCGTGGTGAAGCCTGCCGAAGACACGCCCTTCTCCGCCCTGGCCCTG
GCTGAGCTTGCAAGCCAGGCTGGGATTCCTTCAGGTGTATACAATGTTATTCCCTGTTCT
CGAAAGAATGCCAAGGAAGTAGGGGAGGCAATTTGTACTGATCCTCTGGTGTCCAAAATT
TCCTTTACTGGTTCAACAACTACAGGAAAGATCCTGTTGCACCACGCAGCAAACTCTGTG
AAAAGGGTCTCTATGGAGCTGGGCGGCCTTGCTCCATTTATAGTATTTGACAGTGCCAAC
GTGGACCAGGCTGTAGCAGGGGCCATGGCATCTAAATTTAGGAACACTGGACAGACTTGT
GTTTGCTCAAACCAATTCTTGGTGCAAAGGGGCATCCATGATGCCTTTGTAAAAGCATTC
GCCGAGGCCATGAAGAAGAACCTGCGCGTAGGTAATGGATTTGAGGAAGGAACTACTCAG
GGCCCATTAATTAATGAAAAAGCGGTAGAAAAGGTGGAGAAACAGGTGAATGATGCCGTT
TCTAAAGGTGCCACCGTTGTGACAGGTGGAAAACGACACCAACTTGGAAAAAATTTCTTT
GAGCCTACCCTGCTGTGCAATGTCACCCAGGACATGCTGTGCACTCATGAAGAGACTTTC
GGGCCTCTGGCACCAGTTATCAAGTTCGATACAGAGGAGGAGGCTATAGCAATCGCTAAC
GCAGCTGATGTTGGGTTAGCAGGTTATTTTTACTCTCAAGACCCAGCCCAGATCTGGAGA
GTGGCAGAGCAGCTGGAAGTGGGCATGGTTGGCGTCAACGAAGGATTAATTTCCTCTGTG
GAGTGCCCTTTTGGTGGAGTGAAGCAGTCCGGCCTTGGGCGAGAGGGGTCCAAGTATGGC
ATTGATGAGTATCTGGAACTCAAGTATGTGTGTTACGGGGGCTTGTAG
GenBank Gene IDY11192
GeneCard IDNot Available
GenAtlas IDALDH5A1
HGNC IDHGNC:408
Chromosome Location6
Locus6p22.2-p22.3
References
  1. Chambliss KL, Hinson DD, Trettel F, Malaspina P, Novelletto A, Jakobs C, Gibson KM: Two exon-skipping mutations as the molecular basis of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria). Am J Hum Genet. 1998 Aug;63(2):399-408. 9683595
  2. Blasi P, Boyl PP, Ledda M, Novelletto A, Gibson KM, Jakobs C, Hogema B, Akaboshi S, Loreni F, Malaspina P: Structure of human succinic semialdehyde dehydrogenase gene: identification of promoter region and alternatively processed isoforms. Mol Genet Metab. 2002 Aug;76(4):348-62. 12208142
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  4. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. 14574404
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  6. Chambliss KL, Caudle DL, Hinson DD, Moomaw CR, Slaughter CA, Jakobs C, Gibson KM: Molecular cloning of the mature NAD(+)-dependent succinic semialdehyde dehydrogenase from rat and human. cDNA isolation, evolutionary homology, and tissue expression. J Biol Chem. 1995 Jan 6;270(1):461-7. 7814412
  7. Trettel F, Malaspina P, Jodice C, Novelletto A, Slaughter CA, Caudle DL, Hinson DD, Chambliss KL, Gibson KM: Human succinic semialdehyde dehydrogenase. Molecular cloning and chromosomal localization. Adv Exp Med Biol. 1997;414:253-60. 9059628
  8. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. 19608861
  9. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  10. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  11. Kim YG, Lee S, Kwon OS, Park SY, Lee SJ, Park BJ, Kim KJ: Redox-switch modulation of human SSADH by dynamic catalytic loop. EMBO J. 2009 Apr 8;28(7):959-68. doi: 10.1038/emboj.2009.40. Epub 2009 Mar 19. 19300440
  12. Hogema BM, Akaboshi S, Taylor M, Salomons GS, Jakobs C, Schutgens RB, Wilcken B, Worthington S, Maropoulos G, Grompe M, Gibson KM: Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency: increased accuracy employing DNA, enzyme, and metabolite analyses. Mol Genet Metab. 2001 Mar;72(3):218-22. 11243727
  13. Aoshima T, Kajita M, Sekido Y, Ishiguro Y, Tsuge I, Kimura M, Yamaguchi S, Watanabe K, Shimokata K, Niwa T: Mutation analysis in a patient with succinic semialdehyde dehydrogenase deficiency: a compound heterozygote with 103-121del and 1460T > A of the ALDH5A1 gene. Hum Hered. 2002;53(1):42-4. 11901270
  14. Akaboshi S, Hogema BM, Novelletto A, Malaspina P, Salomons GS, Maropoulos GD, Jakobs C, Grompe M, Gibson KM: Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene and functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency. Hum Mutat. 2003 Dec;22(6):442-50. 14635103