Reviewed, UniProtKB/Swiss-Prot P51649 (SSDH_HUMAN)

Names and origin

Protein names

Recommended name:
    Succinate-semialdehyde dehydrogenase, mitochondrial
    EC=1.2.1.24
Alternative name(s):
    NAD(+)-dependent succinic semialdehyde dehydrogenase
    Aldehyde dehydrogenase family 5 member A1

Gene names

Name:	ALDH5A1
Synonyms:	SSADH

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	535 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	Succinate semialdehyde + NAD(+) + H(2)O = succinate + NADH.
Pathway	Amino-acid degradation; 4-aminobutanoate degradation.
Subunit structure	Homotetramer.
Subcellular location	Mitochondrion.
Tissue specificity	Brain, pancreas, heart, liver, skeletal muscle and kidney. Lower in placenta.
Involvement in disease	Defects in ALDH5A1 are the cause of succinate semialdehyde dehydrogenase deficiency (SSADH deficiency) [MIM:271980]. SSADH deficiency is a rare inborn error in the metabolism of 4-aminobutyric acid (GABA) which leads to accumulation of 4-hydroxybutyric acid in physiologic fluids of patients. The disease is characterized by severe ataxia and by mildly retarded psychomotor development.
Sequence similarities	Belongs to the aldehyde dehydrogenase family.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	NAD
Molecular function	Oxidoreductase
Gene Ontology (GO)
Biological process	acetate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB central nervous system development Ref.1 Inferred from mutant phenotype. Source: UniProtKB galactosylceramide metabolic process Inferred from sequence or structural similarity. Source: UniProtKB gamma-aminobutyric acid catabolic process Ref.1 Inferred from direct assay. Source: UniProtKB glucose metabolic process Inferred from sequence or structural similarity. Source: UniProtKB glutamate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB glutamine metabolic process Inferred from sequence or structural similarity. Source: UniProtKB glutathione metabolic process Inferred from sequence or structural similarity. Source: UniProtKB glycerophospholipid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB neurotransmitter catabolic process Inferred from sequence or structural similarity. Source: UniProtKB protein homotetramerization Inferred from direct assay. Source: UniProtKB respiratory electron transport chain Inferred from sequence or structural similarity. Source: UniProtKB succinate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB soluble fraction Inferred from direct assay. Source: UniProtKB
Molecular function	protein homodimerization activity Inferred by curator. Source: UniProtKB succinate-semialdehyde dehydrogenase activity Ref.1 Ref.4 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 47	47	Mitochondrion Potential
	Chain	48 – 535	488	Succinate-semialdehyde dehydrogenase, mitochondrial		PRO_0000007184
Regions
	Nucleotide binding	284 – 289	6	NADP By similarity
Sites
	Active site	306	1	Proton acceptor By similarity
	Active site	340	1	Nucleophile By similarity
	Site	205	1	Transition state stabilizer By similarity
Natural variations
	Natural variant	36	1	G → R 87% of activity.		VAR_026227
	Natural variant	93	1	C → F in SSADH deficiency; 3% of activity.		VAR_026199
	Natural variant	176	1	G → R in SSADH deficiency; <1% of activity.		VAR_026200
	Natural variant	180	1	H → Y 83% of activity. dbSNP rs2760118.		VAR_016758
	Natural variant	182	1	P → L 48% of activity. dbSNP rs3765310.		VAR_016759
	Natural variant	223	1	C → Y in SSADH deficiency; 5% of activity.		VAR_026201
	Natural variant	233	1	T → M in SSADH deficiency; 4% of activity.		VAR_026202
	Natural variant	237	1	A → S 65% of activity.		VAR_026228
	Natural variant	255	1	N → S in SSADH deficiency; 17% of activity.		VAR_026203
	Natural variant	268	1	G → E in SSADH deficiency; <1% of activity.		VAR_026204
	Natural variant	335	1	N → K in SSADH deficiency; 1% of activity.		VAR_026205
	Natural variant	382	1	P → L in SSADH deficiency; 2% of activity.		VAR_026206
	Natural variant	382	1	P → Q in SSADH deficiency.		VAR_026207
	Natural variant	406	1	V → I		VAR_026229
	Natural variant	409	1	G → D in SSADH deficiency; <1% of activity.		VAR_026208
	Natural variant	487	1	V → E in SSADH deficiency.		VAR_026209
	Natural variant	533	1	G → R in SSADH deficiency; <1% of activity.		VAR_026210

Sequences

	Sequence		Length	Mass (Da)
	P51649-1 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: C63A9431D3FA16C7	FASTA	535	57,215
	10 20 30 40 50 60 MATCIWLRSC GARRLGSTFP GCRLRPRAGG LVPASGPAPG PAQLRCYAGR LAGLSAALLR 70 80 90 100 110 120 TDSFVGGRWL PAAATFPVQD PASGAALGMV ADCGVREARA AVRAAYEAFC RWREVSAKER 130 140 150 160 170 180 SSLLRKWYNL MIQNKDDLAR IITAESGKPL KEAHGEILYS AFFLEWFSEE ARRVYGDIIH 190 200 210 220 230 240 TPAKDRRALV LKQPIGVAAV ITPWNFPSAM ITRKVGAALA AGCTVVVKPA EDTPFSALAL 250 260 270 280 290 300 AELASQAGIP SGVYNVIPCS RKNAKEVGEA ICTDPLVSKI SFTGSTTTGK ILLHHAANSV 310 320 330 340 350 360 KRVSMELGGL APFIVFDSAN VDQAVAGAMA SKFRNTGQTC VCSNQFLVQR GIHDAFVKAF 370 380 390 400 410 420 AEAMKKNLRV GNGFEEGTTQ GPLINEKAVE KVEKQVNDAV SKGATVVTGG KRHQLGKNFF 430 440 450 460 470 480 EPTLLCNVTQ DMLCTHEETF GPLAPVIKFD TEEEAIAIAN AADVGLAGYF YSQDPAQIWR 490 500 510 520 530 VAEQLEVGMV GVNEGLISSV ECPFGGVKQS GLGREGSKYG IDEYLELKYV CYGGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two exon-skipping mutations as the molecular basis of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria)." Chambliss K.L., Hinson D.D., Trettel F., Malaspina P., Novelletto A., Jakobs C., Gibson K.M. Am. J. Hum. Genet. 63:399-408(1998) [PubMed: 9683595] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lymphocyte.
[2]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[4]	"Molecular cloning of the mature NAD(+)-dependent succinic semialdehyde dehydrogenase from rat and human. cDNA isolation, evolutionary homology, and tissue expression." Chambliss K.L., Caudle D.L., Hinson D.D., Moomaw C.R., Slaughter C.A., Jakobs C., Gibson K.M. J. Biol. Chem. 270:461-467(1995) [PubMed: 7814412] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 213-535. Tissue: Liver.
[5]	"Human succinic semialdehyde dehydrogenase. Molecular cloning and chromosomal localization." Trettel F., Malaspina P., Jodice C., Novelletto A., Slaughter C.A., Caudle D.L., Hinson D.D., Chambliss K.L., Gibson K.M. Adv. Exp. Med. Biol. 414:253-260(1997) [PubMed: 9059628] [Abstract] Cited for: SUBUNIT. Tissue: Brain.
[6]	"Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency: increased accuracy employing DNA, enzyme, and metabolite analyses." Hogema B.M., Akaboshi S., Taylor M., Salomons G.S., Jakobs C., Schutgens R.B., Wilcken B., Worthington S., Maropoulos G., Grompe M., Gibson K.M. Mol. Genet. Metab. 72:218-222(2001) [PubMed: 11243727] [Abstract] Cited for: VARIANTS SSADH DEFICIENCY GLU-268 AND ASP-409.
[7]	"Mutation analysis in a patient with succinic semialdehyde dehydrogenase deficiency: a compound heterozygote with 103-121del and 1460T>A of the ALDH5A1 gene." Aoshima T., Kajita M., Sekido Y., Ishiguro Y., Tsuge I., Kimura M., Yamaguchi S., Watanabe K., Shimokata K., Niwa T. Hum. Hered. 53:42-44(2002) [PubMed: 11901270] [Abstract] Cited for: VARIANT SSADH DEFICIENCY GLU-487.
[8]	"Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene and functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency." Akaboshi S., Hogema B.M., Novelletto A., Malaspina P., Salomons G.S., Maropoulos G.D., Jakobs C., Grompe M., Gibson K.M. Hum. Mutat. 22:442-450(2003) [PubMed: 14635103] [Abstract] Cited for: VARIANTS SSADH DEFICIENCY PHE-93; ARG-176; TYR-223; MET-233; SER-255; GLU-268; LYS-335; GLN-382; LEU-382; ASP-409 AND ARG-533, VARIANTS ARG-36; TYR-180; LEU-182; SER-237 AND ILE-406, CHARACTERIZATION OF VARIANTS ARG-36; PHE-93; ARG-176; TYR-180; LEU-182; TYR-223; MET-233; SER-237; SER-255; GLU-268; LYS-335; LEU-382; ASP-409 AND ARG-533.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	Y11192 mRNA. Translation: CAA72076.1. AL031230 Genomic DNA. Translation: CAA20248.1. BC034321 mRNA. Translation: AAH34321.1. L34820 mRNA. Translation: AAA67057.1.
PIR	A55773.
RefSeq	NP_001071.1.
UniGene	Hs.371723
3D structure databases
HSSP	HSSP built from PDB template 1O9J based on UniProtKB Q28399.
ModBase	Search...
PTM databases
PhosphoSite	P51649.
Genome annotation databases
Ensembl	ENSG00000112294. Homo sapiens. [Contig view]
GeneID	7915.
KEGG	hsa:7915.
Organism-specific databases
H-InvDB	HIX0005623.
HGNC	HGNC:408. ALDH5A1.
MIM	271980. phenotype. 610045. gene.
Orphanet	22. 4-hydroxybutyricaciduria.
PharmGKB	PA24702.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P51649.
Enzyme and pathway databases
BioCyc	MetaCyc:MON-11540.
Gene expression databases
ArrayExpress	P51649.
CleanEx	HS_ALDH5A1.
GermOnline	ENSG00000112294. Homo sapiens.
Family and domain databases
InterPro	IPR016160. Ald_DHase_CS. IPR016162. Ald_DHase_N. IPR015590. Aldehyde_DHase. IPR010102. Succ_semiAld_DHase. [Graphical view]
Gene3D	G3DSA:3.40.605.10. Aldehyde_dehydrogenase_N. 1 hit.
PANTHER	PTHR11699. Aldehyde_dehyd. 1 hit.
Pfam	PF00171. Aldedh. 1 hit. [Graphical view]
TIGRFAMs	TIGR01780. SSADH. 1 hit.
PROSITE	PS00070. ALDEHYDE_DEHYDR_CYS. 1 hit. PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00534. Chlormerodrin. DB00157. NADH. DB00139. Succinic acid.
NextBio	30381.
SOURCE	Search...

Entry information

Entry name

SSDH_HUMAN

Accession

Primary (citable) accession number: P51649

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	May 30, 2000
Last modified:	November 25, 2008
This is version 88 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)