P49189 (AL9A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
4-trimethylaminobutyraldehyde dehydrogenase
Short name=TMABADH
EC=1.2.1.47

Alternative name(s):
Aldehyde dehydrogenase E3 isozyme
Aldehyde dehydrogenase family 9 member A1
EC=1.2.1.3
Gamma-aminobutyraldehyde dehydrogenase
EC=1.2.1.19
R-aminobutyraldehyde dehydrogenase

Gene names

Name:	ALDH9A1
Synonyms:	ALDH4, ALDH7, ALDH9

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	494 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)

Function	Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine. Catalyzes the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction. Ref.2
Catalytic activity	4-trimethylammoniobutanal + NAD+ + H2O = 4-trimethylammoniobutanoate + NADH. An aldehyde + NAD+ + H2O = a carboxylate + NADH. 4-aminobutanal + NAD+ + H2O = 4-aminobutanoate + NADH.
Pathway	Amine and polyamine biosynthesis; carnitine biosynthesis.
Subunit structure	Homotetramer.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	High expression in adult liver, skeletal muscle, and kidney. Low levels in heart, pancreas, lung and brain. Expressed in all regions of the brain. Expression levels are variable in the different brain areas, with the highest levels in the spinal cord and the lowest in the occipital pole. Ref.6
Developmental stage	Strongly expressed in human embryonic brain (gestational age 12 weeks).
Sequence similarities	Belongs to the aldehyde dehydrogenase family.
Biophysicochemical properties	Kinetic parameters: KM=11 µM for 4-aminobutyraldehyde pH dependence: Optimum pH is about 9.4 with propionaldehyde as substrate, and 7.5 with 4-aminobutyraldehyde as substrate.
Sequence caution	The sequence CAH74061.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	carnitine biosynthetic process Traceable author statement. Source: Reactome cellular aldehyde metabolic process Inferred from direct assay Ref.6. Source: UniProtKB hormone metabolic process Traceable author statement Ref.8. Source: UniProtKB neurotransmitter biosynthetic process Inferred from direct assay Ref.8. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: Compara plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	1-pyrroline dehydrogenase activity Inferred from electronic annotation. Source: EC 3-chloroallyl aldehyde dehydrogenase activity Traceable author statement. Source: Reactome 4-trimethylammoniobutyraldehyde dehydrogenase activity Inferred from electronic annotation. Source: EC aminobutyraldehyde dehydrogenase activity Inferred from direct assay Ref.8Ref.6. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.5
	Chain	2 – 494	493	4-trimethylaminobutyraldehyde dehydrogenase		PRO_0000056485
Regions
	Nucleotide binding	232 – 237	6	NAD By similarity
Sites
	Active site	254	1	Proton acceptor By similarity
	Active site	288	1	Nucleophile By similarity
	Site	157	1	Transition state stabilizer By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylserine Ref.5
	Modified residue	298	1	N6-acetyllysine Ref.9
Natural variations
	Natural variant	116	1	C → S in allele ALDH9A1*2. Ref.1 Ref.6		VAR_011304
Experimental info
	Sequence conflict	19 – 25	7	RVEPADA → AGAGGR in AAB18827. Ref.1
	Sequence conflict	150	1	C → Q AA sequence Ref.7
	Sequence conflict	159	1	P → W AA sequence Ref.7
	Sequence conflict	172	1	A → R AA sequence Ref.7

Sequences

	Sequence		Length	Mass (Da)
	P49189 [UniParc]. Last modified February 1, 2005. Version 3. Checksum: 1E1CDF910D763BA1	FASTA	494	53,802
	10 20 30 40 50 60 MSTGTFVVSQ PLNYRGGARV EPADASGTEK AFEPATGRVI ATFTCSGEKE VNLAVQNAKA 70 80 90 100 110 120 AFKIWSQKSG MERCRILLEA ARIIREREDE IATMECINNG KSIFEARLDI DISWQCLEYY 130 140 150 160 170 180 AGLAASMAGE HIQLPGGSFG YTRREPLGVC VGIGAWNYPF QIASWKSAPA LACGNAMVFK 190 200 210 220 230 240 PSPFTPVSAL LLAEIYSEAG VPPGLFNVVQ GGAATGQFLC QHPDVAKVSF TGSVPTGMKI 250 260 270 280 290 300 MEMSAKGIKP VTLELGGKSP LIIFSDCDMN NAVKGALMAN FLTQGQVCCN GTRVFVQKEI 310 320 330 340 350 360 LDKFTEEVVK QTQRIKIGDP LLEDTRMGPL INRPHLERVL GFVKVAKEQG AKVLCGGDIY 370 380 390 400 410 420 VPEDPKLKDG YYMRPCVLTN CRDDMTCVKE EIFGPVMSIL SFDTEAEVLE RANDTTFGLA 430 440 450 460 470 480 AGVFTRDIQR AHRVVAELQA GTCFINNYNV SPVELPFGGY KKSGFGRENG RVTIEYYSQL 490 KTVCVEMGDV ESAF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human gamma-aminobutyraldehyde dehydrogenase (ALDH9): cDNA sequence, genomic organization, polymorphism, chromosomal localization, and tissue expression." Lin S.W., Chen J.C., Hsu L.C., Hsieh C.-L., Yoshida A. Genomics 34:376-380(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-116. Tissue: Liver.
[2]	"Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis." Vaz F.M., Fouchier S.W., Ofman R., Sommer M., Wanders R.J.A. J. Biol. Chem. 275:7390-7394(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Liver.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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 T.-O., 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. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Spleen.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Bienvenut W.V., Heiserich L., Gottlieb E. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-15; 247-258; 299-310; 315-326 AND 472-481, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Colon carcinoma.
[6]	"Aldehyde dehydrogenase from adult human brain that dehydrogenates gamma-aminobutyraldehyde: purification, characterization, cloning and distribution." Kikonyogo A., Pietruszko R. Biochem. J. 316:317-324(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 259-274; 353-366; 412-426 AND 434-453, NUCLEOTIDE SEQUENCE [MRNA] OF 29-494, CHARACTERIZATION, TISSUE SPECIFICITY, VARIANT SER-116. Tissue: Brain.
[7]	"Human aldehyde dehydrogenase. cDNA cloning and primary structure of the enzyme that catalyzes dehydrogenation of 4-aminobutyraldehyde." Kurys G., Shah P.C., Kikonyogo A., Reed D., Ambroziak W., Pietruszko R. Eur. J. Biochem. 218:311-320(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 33-494, PARTIAL PROTEIN SEQUENCE.
[8]	"Human aldehyde dehydrogenase. Purification and characterization of a third isozyme with low Km for gamma-aminobutyraldehyde." Kurys G., Ambroziak W., Pietruszko R. J. Biol. Chem. 264:4715-4721(1989) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION. Tissue: Liver.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-298, MASS SPECTROMETRY.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U34252 mRNA. Translation: AAB18827.1. AF172093 mRNA. Translation: AAF43600.1. AK312751 mRNA. Translation: BAG35618.1. AL451074 Genomic DNA. Translation: CAH74061.1. Different initiation. U50203 mRNA. Translation: AAB06721.1. X75425 mRNA. Translation: CAA53176.1.
IPI	IPI00479877.
PIR	S39532. G02054.
RefSeq	NP_000687.3. NM_000696.3.
UniGene	Hs.2533.
3D structure databases
ProteinModelPortal	P49189.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49189. 5 interactions.
STRING	9606.ENSP00000346827.
PTM databases
PhosphoSite	P49189.
Polymorphism databases
DMDM	62511242.
2D gel databases
REPRODUCTION-2DPAGE	IPI00479877.
Proteomic databases
PaxDb	P49189.
PRIDE	P49189.
Protocols and materials databases
DNASU	223.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000354775; ENSP00000346827; ENSG00000143149.
GeneID	223.
KEGG	hsa:223.
UCSC	uc010pky.1. human.
Organism-specific databases
CTD	223.
GeneCards	GC01M165632.
H-InvDB	HIX0199965.
HGNC	HGNC:412. ALDH9A1.
HPA	HPA010873.
MIM	602733. gene.
neXtProt	NX_P49189.
PharmGKB	PA24706.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1012.
HOVERGEN	HBG000097.
InParanoid	P49189.
KO	K00149.
OrthoDB	EOG4THVSW.
PhylomeDB	P49189.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
SABIO-RK	P49189.
UniPathway	UPA00118.
Gene expression databases
ArrayExpress	P49189.
Bgee	P49189.
CleanEx	HS_ALDH9A1.
Genevestigator	P49189.
GermOnline	ENSG00000143149. Homo sapiens.
Family and domain databases
Gene3D	3.40.309.10. 1 hit. 3.40.605.10. 1 hit.
InterPro	IPR016161. Ald_DH/histidinol_DH. IPR016163. Ald_DH_C. IPR016160. Ald_DH_CS. IPR016162. Ald_DH_N. IPR015590. Aldehyde_DH_dom. [Graphical view]
Pfam	PF00171. Aldedh. 1 hit. [Graphical view]
SUPFAM	SSF53720. Aldehyde_DH/Histidinol_DH. 1 hit.
PROSITE	PS00070. ALDEHYDE_DEHYDR_CYS. 1 hit. PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL2542.
ChiTaRS	ALDH9A1. human.
DrugBank	DB00157. NADH.
GenomeRNAi	223.
NextBio	906.
SOURCE	Search...

Entry information

Entry name

AL9A1_HUMAN

Accession

Primary (citable) accession number: P49189
Secondary accession number(s): B2R6X1 , Q5VV90, Q6LCL1, Q9NZT7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 2005
Last modified:	May 1, 2013
This is version 122 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.