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Protein

4-trimethylaminobutyraldehyde dehydrogenase

Gene

ALDH9A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

4-trimethylammoniobutanal + NAD+ + H2O = 4-trimethylammoniobutanoate + NADH.
An aldehyde + NAD+ + H2O = a carboxylate + NADH.
4-aminobutanal + NAD+ + H2O = 4-aminobutanoate + NADH.

Kineticsi

  1. KM=11 µM for 4-aminobutyraldehyde

    pH dependencei

    Optimum pH is about 9.4 with propionaldehyde as substrate, and 7.5 with 4-aminobutyraldehyde as substrate.

    Pathwayi: carnitine biosynthesis

    This protein is involved in the pathway carnitine biosynthesis, which is part of Amine and polyamine biosynthesis.
    View all proteins of this organism that are known to be involved in the pathway carnitine biosynthesis and in Amine and polyamine biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei157Transition state stabilizerBy similarity1
    Active sitei254Proton acceptorPROSITE-ProRule annotation1
    Active sitei288NucleophilePROSITE-ProRule annotation1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi232 – 237NADBy similarity6

    GO - Molecular functioni

    GO - Biological processi

    • carnitine biosynthetic process Source: Reactome
    • cellular aldehyde metabolic process Source: UniProtKB
    • hormone metabolic process Source: UniProtKB
    • neurotransmitter biosynthetic process Source: UniProtKB
    • oxidation-reduction process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    NAD

    Enzyme and pathway databases

    BioCyciMetaCyc:HS06992-MONOMER.
    ZFISH:HS06992-MONOMER.
    BRENDAi1.2.1.47. 2681.
    ReactomeiR-HSA-71262. Carnitine synthesis.
    SABIO-RKP49189.
    UniPathwayiUPA00118.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    4-trimethylaminobutyraldehyde dehydrogenase (EC:1.2.1.47)
    Short name:
    TMABADH
    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
    Cleaved into the following chain:
    Gene namesi
    Name:ALDH9A1
    Synonyms:ALDH4, ALDH7, ALDH9
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:412. ALDH9A1.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • cytosol Source: Reactome
    • extracellular exosome Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi223.
    PharmGKBiPA24706.

    Chemistry databases

    ChEMBLiCHEMBL3542434.

    Polymorphism and mutation databases

    BioMutaiALDH9A1.
    DMDMi62511242.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00004343511 – 4944-trimethylaminobutyraldehyde dehydrogenaseAdd BLAST494
    Initiator methionineiRemoved; alternateCombined sources1 Publication
    ChainiPRO_00000564852 – 4944-trimethylaminobutyraldehyde dehydrogenase, N-terminally processedAdd BLAST493

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylserine; in 4-trimethylaminobutyraldehyde dehydrogenase, N-terminally processedCombined sources1 Publication1
    Modified residuei30N6-acetyllysine; alternateBy similarity1
    Modified residuei30N6-succinyllysine; alternateBy similarity1
    Modified residuei59N6-succinyllysineBy similarity1
    Modified residuei298N6-acetyllysineCombined sources1
    Modified residuei303N6-acetyllysine; alternateBy similarity1
    Modified residuei303N6-succinyllysine; alternateBy similarity1
    Modified residuei344N6-acetyllysineBy similarity1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiP49189.
    MaxQBiP49189.
    PaxDbiP49189.
    PeptideAtlasiP49189.
    PRIDEiP49189.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00479877.

    PTM databases

    iPTMnetiP49189.
    PhosphoSitePlusiP49189.
    SwissPalmiP49189.

    Expressioni

    Tissue specificityi

    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.1 Publication

    Developmental stagei

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

    Gene expression databases

    BgeeiENSG00000143149.
    CleanExiHS_ALDH9A1.
    ExpressionAtlasiP49189. baseline and differential.
    GenevisibleiP49189. HS.

    Organism-specific databases

    HPAiHPA006077.
    HPA010873.

    Interactioni

    Subunit structurei

    Homotetramer.

    Protein-protein interaction databases

    BioGridi106725. 16 interactors.
    IntActiP49189. 5 interactors.
    MINTiMINT-5006004.
    STRINGi9606.ENSP00000346827.

    Structurei

    3D structure databases

    ProteinModelPortaliP49189.
    SMRiP49189.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the aldehyde dehydrogenase family.Curated

    Phylogenomic databases

    eggNOGiKOG2450. Eukaryota.
    COG1012. LUCA.
    HOVERGENiHBG000097.
    InParanoidiP49189.
    KOiK00149.
    OrthoDBiEOG091G05E8.
    PhylomeDBiP49189.
    TreeFamiTF314257.

    Family and domain databases

    Gene3Di3.40.309.10. 1 hit.
    3.40.605.10. 1 hit.
    InterProiIPR016161. Ald_DH/histidinol_DH.
    IPR016163. Ald_DH_C.
    IPR016160. Ald_DH_CS_CYS.
    IPR029510. Ald_DH_CS_GLU.
    IPR016162. Ald_DH_N.
    IPR015590. Aldehyde_DH_dom.
    [Graphical view]
    PfamiPF00171. Aldedh. 1 hit.
    [Graphical view]
    SUPFAMiSSF53720. SSF53720. 1 hit.
    PROSITEiPS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
    PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P49189-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MSTGTFVVSQ PLNYRGGARV EPADASGTEK AFEPATGRVI ATFTCSGEKE
    60 70 80 90 100
    VNLAVQNAKA AFKIWSQKSG MERCRILLEA ARIIREREDE IATMECINNG
    110 120 130 140 150
    KSIFEARLDI DISWQCLEYY AGLAASMAGE HIQLPGGSFG YTRREPLGVC
    160 170 180 190 200
    VGIGAWNYPF QIASWKSAPA LACGNAMVFK PSPFTPVSAL LLAEIYSEAG
    210 220 230 240 250
    VPPGLFNVVQ GGAATGQFLC QHPDVAKVSF TGSVPTGMKI MEMSAKGIKP
    260 270 280 290 300
    VTLELGGKSP LIIFSDCDMN NAVKGALMAN FLTQGQVCCN GTRVFVQKEI
    310 320 330 340 350
    LDKFTEEVVK QTQRIKIGDP LLEDTRMGPL INRPHLERVL GFVKVAKEQG
    360 370 380 390 400
    AKVLCGGDIY VPEDPKLKDG YYMRPCVLTN CRDDMTCVKE EIFGPVMSIL
    410 420 430 440 450
    SFDTEAEVLE RANDTTFGLA AGVFTRDIQR AHRVVAELQA GTCFINNYNV
    460 470 480 490
    SPVELPFGGY KKSGFGRENG RVTIEYYSQL KTVCVEMGDV ESAF
    Length:494
    Mass (Da):53,802
    Last modified:February 1, 2005 - v3
    Checksum:i1E1CDF910D763BA1
    GO
    Isoform 2 (identifier: P49189-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-70: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:424
    Mass (Da):46,455
    Checksum:i211F5F4B06E9B453
    GO

    Sequence cautioni

    The sequence CAH74061 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti19 – 25RVEPADA → AGAGGR in AAB18827 (PubMed:8786138).Curated7
    Sequence conflicti150C → Q AA sequence (PubMed:8269919).Curated1
    Sequence conflicti159P → W AA sequence (PubMed:8269919).Curated1
    Sequence conflicti172A → R AA sequence (PubMed:8269919).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_011304116C → S in allele ALDH9A1*2. 2 Publications1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0563051 – 70Missing in isoform 2. 1 PublicationAdd BLAST70

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U34252 mRNA. Translation: AAB18827.1.
    AF172093 mRNA. Translation: AAF43600.1.
    AK302183 mRNA. Translation: BAG63549.1.
    AK302191 mRNA. Translation: BAG63554.1.
    AK312751 mRNA. Translation: BAG35618.1.
    AL451074 Genomic DNA. Translation: CAH74061.1. Different initiation.
    U50203 mRNA. Translation: AAB06721.1.
    X75425 mRNA. Translation: CAA53176.1.
    PIRiG02054. S39532.
    RefSeqiNP_000687.3. NM_000696.3.
    XP_011507596.1. XM_011509294.2. [P49189-2]
    UniGeneiHs.2533.

    Genome annotation databases

    EnsembliENST00000354775; ENSP00000346827; ENSG00000143149.
    ENST00000538148; ENSP00000440026; ENSG00000143149.
    GeneIDi223.
    KEGGihsa:223.
    UCSCiuc001gdh.2. human. [P49189-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U34252 mRNA. Translation: AAB18827.1.
    AF172093 mRNA. Translation: AAF43600.1.
    AK302183 mRNA. Translation: BAG63549.1.
    AK302191 mRNA. Translation: BAG63554.1.
    AK312751 mRNA. Translation: BAG35618.1.
    AL451074 Genomic DNA. Translation: CAH74061.1. Different initiation.
    U50203 mRNA. Translation: AAB06721.1.
    X75425 mRNA. Translation: CAA53176.1.
    PIRiG02054. S39532.
    RefSeqiNP_000687.3. NM_000696.3.
    XP_011507596.1. XM_011509294.2. [P49189-2]
    UniGeneiHs.2533.

    3D structure databases

    ProteinModelPortaliP49189.
    SMRiP49189.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi106725. 16 interactors.
    IntActiP49189. 5 interactors.
    MINTiMINT-5006004.
    STRINGi9606.ENSP00000346827.

    Chemistry databases

    ChEMBLiCHEMBL3542434.

    PTM databases

    iPTMnetiP49189.
    PhosphoSitePlusiP49189.
    SwissPalmiP49189.

    Polymorphism and mutation databases

    BioMutaiALDH9A1.
    DMDMi62511242.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00479877.

    Proteomic databases

    EPDiP49189.
    MaxQBiP49189.
    PaxDbiP49189.
    PeptideAtlasiP49189.
    PRIDEiP49189.

    Protocols and materials databases

    DNASUi223.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000354775; ENSP00000346827; ENSG00000143149.
    ENST00000538148; ENSP00000440026; ENSG00000143149.
    GeneIDi223.
    KEGGihsa:223.
    UCSCiuc001gdh.2. human. [P49189-1]

    Organism-specific databases

    CTDi223.
    DisGeNETi223.
    GeneCardsiALDH9A1.
    H-InvDBHIX0199965.
    HGNCiHGNC:412. ALDH9A1.
    HPAiHPA006077.
    HPA010873.
    MIMi602733. gene.
    neXtProtiNX_P49189.
    PharmGKBiPA24706.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2450. Eukaryota.
    COG1012. LUCA.
    HOVERGENiHBG000097.
    InParanoidiP49189.
    KOiK00149.
    OrthoDBiEOG091G05E8.
    PhylomeDBiP49189.
    TreeFamiTF314257.

    Enzyme and pathway databases

    UniPathwayiUPA00118.
    BioCyciMetaCyc:HS06992-MONOMER.
    ZFISH:HS06992-MONOMER.
    BRENDAi1.2.1.47. 2681.
    ReactomeiR-HSA-71262. Carnitine synthesis.
    SABIO-RKP49189.

    Miscellaneous databases

    ChiTaRSiALDH9A1. human.
    GeneWikiiAldehyde_dehydrogenase_9_family,_member_A1.
    GenomeRNAii223.
    PROiP49189.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000143149.
    CleanExiHS_ALDH9A1.
    ExpressionAtlasiP49189. baseline and differential.
    GenevisibleiP49189. HS.

    Family and domain databases

    Gene3Di3.40.309.10. 1 hit.
    3.40.605.10. 1 hit.
    InterProiIPR016161. Ald_DH/histidinol_DH.
    IPR016163. Ald_DH_C.
    IPR016160. Ald_DH_CS_CYS.
    IPR029510. Ald_DH_CS_GLU.
    IPR016162. Ald_DH_N.
    IPR015590. Aldehyde_DH_dom.
    [Graphical view]
    PfamiPF00171. Aldedh. 1 hit.
    [Graphical view]
    SUPFAMiSSF53720. SSF53720. 1 hit.
    PROSITEiPS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
    PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiAL9A1_HUMAN
    AccessioniPrimary (citable) accession number: P49189
    Secondary accession number(s): B2R6X1
    , B4DXY7, Q5VV90, Q6LCL1, Q9NZT7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: February 1, 2005
    Last modified: November 2, 2016
    This is version 158 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.