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P49189 (AL9A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length494 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 componentCytoplasm
   Coding sequence diversityPolymorphism
   LigandNAD
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcarnitine biosynthetic process

Traceable author statement. Source: Reactome

cellular aldehyde metabolic process

Inferred from direct assay Ref.6. Source: UniProtKB

cellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

hormone metabolic process

Traceable author statement Ref.8. Source: UniProtKB

kidney development

Inferred from electronic annotation. Source: Ensembl

liver development

Inferred from electronic annotation. Source: Ensembl

neurotransmitter biosynthetic process

Inferred from direct assay Ref.8. Source: UniProtKB

oxidation-reduction process

Inferred from direct assay Ref.8. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Traceable author statement Ref.8. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

mitochondrion

Inferred from electronic annotation. Source: Ensembl

   Molecular_function1-pyrroline dehydrogenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

3-chloroallyl aldehyde dehydrogenase activity

Traceable author statement. Source: Reactome

4-trimethylammoniobutyraldehyde dehydrogenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

NAD binding

Inferred from electronic annotation. Source: Ensembl

aldehyde dehydrogenase (NAD) activity

Inferred from direct assay Ref.8. Source: UniProtKB

amine binding

Inferred from electronic annotation. Source: Ensembl

aminobutyraldehyde dehydrogenase activity

Inferred from direct assay Ref.8Ref.6. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.5
Chain2 – 4944934-trimethylaminobutyraldehyde dehydrogenase
PRO_0000056485

Regions

Nucleotide binding232 – 2376NAD By similarity

Sites

Active site2541Proton acceptor By similarity
Active site2881Nucleophile By similarity
Site1571Transition state stabilizer By similarity

Amino acid modifications

Modified residue21N-acetylserine Ref.5 Ref.9 Ref.12 Ref.13
Modified residue301N6-acetyllysine; alternate By similarity
Modified residue301N6-succinyllysine; alternate By similarity
Modified residue591N6-succinyllysine By similarity
Modified residue2981N6-acetyllysine Ref.10
Modified residue3031N6-acetyllysine; alternate By similarity
Modified residue3031N6-succinyllysine; alternate By similarity
Modified residue3441N6-acetyllysine By similarity

Natural variations

Natural variant1161C → S in allele ALDH9A1*2. Ref.1 Ref.6
VAR_011304

Experimental info

Sequence conflict19 – 257RVEPADA → AGAGGR in AAB18827. Ref.1
Sequence conflict1501C → Q AA sequence Ref.7
Sequence conflict1591P → W AA sequence Ref.7
Sequence conflict1721A → R AA sequence Ref.7

Sequences

Sequence LengthMass (Da)Tools
P49189 [UniParc].

Last modified February 1, 2005. Version 3.
Checksum: 1E1CDF910D763BA1

FASTA49453,802
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY 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]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"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].
[12]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, 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.
PIRS39532. G02054.
RefSeqNP_000687.3. NM_000696.3.
UniGeneHs.2533.

3D structure databases

ProteinModelPortalP49189.
SMRP49189. Positions 2-494.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106725. 15 interactions.
IntActP49189. 5 interactions.
MINTMINT-5006004.
STRING9606.ENSP00000346827.

Chemistry

DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP49189.

Polymorphism databases

DMDM62511242.

2D gel databases

REPRODUCTION-2DPAGEIPI00479877.

Proteomic databases

PaxDbP49189.
PRIDEP49189.

Protocols and materials databases

DNASU223.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000354775; ENSP00000346827; ENSG00000143149.
GeneID223.
KEGGhsa:223.
UCSCuc010pky.1. human.

Organism-specific databases

CTD223.
GeneCardsGC01M165632.
H-InvDBHIX0199965.
HGNCHGNC:412. ALDH9A1.
HPAHPA006077.
HPA010873.
MIM602733. gene.
neXtProtNX_P49189.
PharmGKBPA24706.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1012.
HOVERGENHBG000097.
InParanoidP49189.
KOK00149.
OrthoDBEOG7327P4.
PhylomeDBP49189.
TreeFamTF314257.

Enzyme and pathway databases

BioCycMetaCyc:HS06992-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP49189.
UniPathwayUPA00118.

Gene expression databases

ArrayExpressP49189.
BgeeP49189.
CleanExHS_ALDH9A1.
GenevestigatorP49189.

Family and domain databases

Gene3D3.40.309.10. 1 hit.
3.40.605.10. 1 hit.
InterProIPR016161. Ald_DH/histidinol_DH.
IPR016163. Ald_DH_C.
IPR016160. Ald_DH_CS.
IPR016162. Ald_DH_N.
IPR015590. Aldehyde_DH_dom.
[Graphical view]
PfamPF00171. Aldedh. 1 hit.
[Graphical view]
SUPFAMSSF53720. SSF53720. 1 hit.
PROSITEPS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSALDH9A1. human.
GeneWikiAldehyde_dehydrogenase_9_family,_member_A1.
GenomeRNAi223.
NextBio906.
PROP49189.
SOURCESearch...

Entry information

Entry nameAL9A1_HUMAN
AccessionPrimary (citable) accession number: P49189
Secondary accession number(s): B2R6X1 expand/collapse secondary AC list , Q5VV90, Q6LCL1, Q9NZT7
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 2005
Last modified: April 16, 2014
This is version 131 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM