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Reviewed, UniProtKB/Swiss-Prot P49189 (AL9A1_HUMAN)

Last modified November 25, 2008. Version 79. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    4-trimethylaminobutyraldehyde dehydrogenase
      Short name=TMABADH
    EC=1.2.1.47
Alternative name(s):
    Aldehyde dehydrogenase family 9 member A1
    EC=1.2.1.3
    Aldehyde dehydrogenase E3 isozyme
    Gamma-aminobutyraldehyde dehydrogenase
    EC=1.2.1.19
    R-aminobutyraldehyde dehydrogenase
Gene names
Name: ALDH9A1
Synonyms: ALDH4, ALDH7, ALDH9
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length494 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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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.

Catalytic activity

4-trimethylammoniobutanal + NAD(+) + H(2)O = 4-trimethylammoniobutanoate + NADH.

An aldehyde + NAD(+) + H(2)O = an acid + NADH.

4-aminobutanal + NAD(+) + H(2)O = 4-aminobutanoate + NADH.

Pathway

Amine and polyamine biosynthesis; carnitine biosynthesis.

Subunit structure

Homotetramer.

Subcellular location

CytoplasmBy 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.

Developmental stage

Strongly expressed in human embryonic brain (gestational age 12 weeks).

Post-translational modification

The N-terminus is blocked.

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.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
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

Natural variations

Natural variant1161C → S in allele ALDH9A1*2.
VAR_011304

Experimental info

Sequence conflict19 – 257RVEPADA → AGAGGR in AAB18827. Ref.1
Sequence conflict1501C → Q AA sequence Ref.6
Sequence conflict1591P → W AA sequence Ref.6
Sequence conflict1721A → R AA sequence Ref.6

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Sequences

Sequence LengthMass (Da)Tools
P49189-1 [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

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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: 8786138] [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: 10702312] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
Tissue: Liver.
[3]"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: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]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.
[5]"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: 8645224] [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.
[6]"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: 8269919] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 33-494, PARTIAL PROTEIN SEQUENCE.
[7]"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: 2925663] [Abstract]
Cited for: CHARACTERIZATION.
Tissue: Liver.
+Additional computationally mapped references.

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Cross-references

Sequence databases

U34252 mRNA. Translation: AAB18827.1.
AF172093 mRNA. Translation: AAF43600.1.
AL451074 Genomic DNA. Translation: CAH74061.1. Different initiation.
U50203 mRNA. Translation: AAB06721.1.
X75425 mRNA. Translation: CAA53176.1.
PIRS39532. G02054.
RefSeqNP_000687.3.
UniGeneHs.2533

3D structure databases

HSSPHSSP built from PDB template 1A4S based on UniProtKB P56533.
SMRP49189. Positions 2-494.
ModBaseSearch...

Protein-protein interaction databases

IntActP49189.

PTM databases

PhosphoSiteP49189.

2-D gel databases

REPRODUCTION-2DPAGEIPI00479877.

Genome annotation databases

EnsemblENSG00000143149. Homo sapiens. [Contig view]
GeneID223.
KEGGhsa:223.

Organism-specific databases

H-InvDBHIX0001281.
HGNCHGNC:412. ALDH9A1.
HPAHPA006077.
HPA010873.
MIM602733. gene.
PharmGKBPA24706.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMP49189.
HOVERGENP49189.

Gene expression databases

CleanExHS_ALDH9A1.
GermOnlineENSG00000143149. Homo sapiens.

Family and domain databases

InterProIPR016160. Ald_DHase_CS.
IPR016162. Ald_DHase_N.
IPR015590. Aldehyde_DHase.
[Graphical view]
Gene3DG3DSA:3.40.605.10. Aldehyde_dehydrogenase_N. 1 hit.
PANTHERPTHR11699. Aldehyde_dehyd. 1 hit.
PfamPF00171. Aldedh. 1 hit.
[Graphical view]
PROSITEPS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00157. NADH.
NextBio906.
SOURCESearch...

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Entry information

Entry nameAL9A1_HUMAN
AccessionPrimary (citable) accession number: P49189
Secondary accession number(s): Q5VV90, Q6LCL1, Q9NZT7
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 2005
Last modified: November 25, 2008
This is version 79 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 1

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents