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Protein

Aldehyde dehydrogenase, dimeric NADP-preferring

Gene

ALDH3A1

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

Functioni

ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde (Probable). They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation (Probable). Oxidizes medium and long chain aldehydes into non-toxic fatty acids (PubMed:1737758). Preferentially oxidizes aromatic aldehyde substrates (PubMed:1737758). Comprises about 50 percent of corneal epithelial soluble proteins (By similarity). May play a role in preventing corneal damage caused by ultraviolet light (By similarity).By similarityCurated1 Publication

Catalytic activityi

An aldehyde + NAD(P)+ + H2O = a carboxylate + NAD(P)H.2 Publications

Kineticsi

Has a high Km for acetaldehyde.

      Sites

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Active sitei2101 Publication1
      Active sitei2441 Publication1

      Regions

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Nucleotide bindingi188 – 193NAD or NADPBy similarity6

      GO - Molecular functioni

      • 3-chloroallyl aldehyde dehydrogenase activity Source: Ensembl
      • alcohol dehydrogenase (NADP+) activity Source: UniProtKB
      • aldehyde dehydrogenase (NAD) activity Source: UniProtKB
      • aldehyde dehydrogenase [NAD(P)+] activity Source: Reactome
      • benzaldehyde dehydrogenase (NAD+) activity Source: CACAO

      GO - Biological processi

      • cellular aldehyde metabolic process Source: UniProtKB
      • oxidation-reduction process Source: UniProtKB
      • xenobiotic metabolic process Source: Reactome

      Keywordsi

      Molecular functionOxidoreductase
      LigandNAD, NADP

      Enzyme and pathway databases

      BRENDAi1.2.1.5 2681
      ReactomeiR-HSA-211945 Phase I - Functionalization of compounds
      SABIO-RKiP30838

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Aldehyde dehydrogenase, dimeric NADP-preferring (EC:1.2.1.52 Publications)
      Alternative name(s):
      ALDHIII
      Aldehyde dehydrogenase 3
      Aldehyde dehydrogenase family 3 member A1
      Gene namesi
      Name:ALDH3A1
      Synonyms:ALDH3
      OrganismiHomo sapiens (Human)
      Taxonomic identifieri9606 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
      Proteomesi
      • UP000005640 Componenti: Chromosome 17

      Organism-specific databases

      EuPathDBiHostDB:ENSG00000108602.17
      HGNCiHGNC:405 ALDH3A1
      MIMi100660 gene
      neXtProtiNX_P30838

      Subcellular locationi

      Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

      Keywords - Cellular componenti

      Cytoplasm

      Pathology & Biotechi

      Mutagenesis

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Mutagenesisi244C → S: Abolishes activity. 1 Publication1

      Organism-specific databases

      DisGeNETi218
      OpenTargetsiENSG00000108602
      PharmGKBiPA24697

      Chemistry databases

      ChEMBLiCHEMBL3578
      DrugBankiDB00157 NADH

      Polymorphism and mutation databases

      BioMutaiALDH3A1
      DMDMi311033473

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Initiator methionineiRemovedCombined sources
      ChainiPRO_00000564702 – 453Aldehyde dehydrogenase, dimeric NADP-preferringAdd BLAST452

      Amino acid modifications

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Modified residuei2N-acetylserineCombined sources1
      Modified residuei178N6-acetyllysineCombined sources1
      Modified residuei194N6-acetyllysineCombined sources1

      Keywords - PTMi

      Acetylation

      Proteomic databases

      EPDiP30838
      MaxQBiP30838
      PaxDbiP30838
      PeptideAtlasiP30838
      PRIDEiP30838

      PTM databases

      iPTMnetiP30838
      PhosphoSitePlusiP30838

      Expressioni

      Tissue specificityi

      High levels in stomach, esophagus and lung; low level in the liver and kidney.

      Gene expression databases

      BgeeiENSG00000108602
      CleanExiHS_ALDH3A1
      ExpressionAtlasiP30838 baseline and differential
      GenevisibleiP30838 HS

      Organism-specific databases

      HPAiCAB045957
      HPA051150
      HPA063783

      Interactioni

      Subunit structurei

      Homodimer.1 Publication

      Binary interactionsi

      WithEntry#Exp.IntActNotes
      POT1Q9NUX52EBI-3905126,EBI-752420

      Protein-protein interaction databases

      BioGridi106720, 20 interactors
      IntActiP30838, 5 interactors
      STRINGi9606.ENSP00000225740

      Chemistry databases

      BindingDBiP30838

      Structurei

      Secondary structure

      1453
      Legend: HelixTurnBeta strandPDB Structure known for this area
      Show more details
      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Helixi3 – 16Combined sources14
      Turni17 – 20Combined sources4
      Helixi23 – 39Combined sources17
      Helixi41 – 52Combined sources12
      Helixi56 – 61Combined sources6
      Helixi64 – 82Combined sources19
      Helixi91 – 93Combined sources3
      Beta strandi96 – 104Combined sources9
      Beta strandi106 – 111Combined sources6
      Beta strandi114 – 116Combined sources3
      Helixi119 – 130Combined sources12
      Beta strandi134 – 138Combined sources5
      Beta strandi141 – 143Combined sources3
      Helixi144 – 157Combined sources14
      Turni160 – 162Combined sources3
      Helixi170 – 176Combined sources7
      Beta strandi182 – 188Combined sources7
      Helixi190 – 201Combined sources12
      Turni202 – 204Combined sources3
      Beta strandi207 – 210Combined sources4
      Beta strandi216 – 219Combined sources4
      Helixi225 – 237Combined sources13
      Helixi238 – 241Combined sources4
      Beta strandi249 – 252Combined sources4
      Helixi254 – 256Combined sources3
      Helixi257 – 272Combined sources16
      Helixi276 – 278Combined sources3
      Helixi288 – 298Combined sources11
      Beta strandi301 – 305Combined sources5
      Turni311 – 314Combined sources4
      Beta strandi319 – 323Combined sources5
      Helixi329 – 331Combined sources3
      Beta strandi337 – 344Combined sources8
      Helixi348 – 357Combined sources10
      Beta strandi362 – 367Combined sources6
      Helixi371 – 380Combined sources10
      Beta strandi384 – 389Combined sources6
      Helixi393 – 395Combined sources3
      Helixi406 – 408Combined sources3
      Helixi416 – 421Combined sources6
      Beta strandi423 – 430Combined sources8
      Helixi437 – 442Combined sources6
      Beta strandi443 – 445Combined sources3

      3D structure databases

      Select the link destinations:
      PDBei
      RCSB PDBi
      PDBji
      Links Updated
      PDB entryMethodResolution (Å)ChainPositionsPDBsum
      3SZAX-ray1.48A/B1-453[»]
      3SZBX-ray1.51A/B1-453[»]
      4H80X-ray2.50A/B/C/D/E/F/G/H1-453[»]
      4L1OX-ray2.30A/B1-453[»]
      4L2OX-ray1.94A/B/E/G1-453[»]
      ProteinModelPortaliP30838
      SMRiP30838
      ModBaseiSearch...
      MobiDBiSearch...

      Miscellaneous databases

      EvolutionaryTraceiP30838

      Family & Domainsi

      Sequence similaritiesi

      Belongs to the aldehyde dehydrogenase family.Curated

      Phylogenomic databases

      eggNOGiKOG2456 Eukaryota
      COG1012 LUCA
      GeneTreeiENSGT00390000002825
      HOGENOMiHOG000271515
      HOVERGENiHBG050483
      InParanoidiP30838
      KOiK00129
      OMAiQKLPEWA
      OrthoDBiEOG091G05HC
      PhylomeDBiP30838
      TreeFamiTF314264

      Family and domain databases

      Gene3Di3.40.309.10, 1 hit
      3.40.605.10, 2 hits
      InterProiView protein in InterPro
      IPR016161 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
      IPR012394 Aldehyde_DH_NAD(P)
      PfamiView protein in Pfam
      PF00171 Aldedh, 1 hit
      PIRSFiPIRSF036492 ALDH, 1 hit
      SUPFAMiSSF53720 SSF53720, 1 hit
      PROSITEiView protein in PROSITE
      PS00070 ALDEHYDE_DEHYDR_CYS, 1 hit
      PS00687 ALDEHYDE_DEHYDR_GLU, 1 hit

      Sequencei

      Sequence statusi: Complete.

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

      P30838-1 [UniParc]FASTAAdd to basket

      « Hide

              10         20         30         40         50
      MSKISEAVKR ARAAFSSGRT RPLQFRIQQL EALQRLIQEQ EQELVGALAA
      60 70 80 90 100
      DLHKNEWNAY YEEVVYVLEE IEYMIQKLPE WAADEPVEKT PQTQQDELYI
      110 120 130 140 150
      HSEPLGVVLV IGTWNYPFNL TIQPMVGAIA AGNSVVLKPS ELSENMASLL
      160 170 180 190 200
      ATIIPQYLDK DLYPVINGGV PETTELLKER FDHILYTGST GVGKIIMTAA
      210 220 230 240 250
      AKHLTPVTLE LGGKSPCYVD KNCDLDVACR RIAWGKFMNS GQTCVAPDYI
      260 270 280 290 300
      LCDPSIQNQI VEKLKKSLKE FYGEDAKKSR DYGRIISARH FQRVMGLIEG
      310 320 330 340 350
      QKVAYGGTGD AATRYIAPTI LTDVDPQSPV MQEEIFGPVL PIVCVRSLEE
      360 370 380 390 400
      AIQFINQREK PLALYMFSSN DKVIKKMIAE TSSGGVAAND VIVHITLHSL
      410 420 430 440 450
      PFGGVGNSGM GSYHGKKSFE TFSHRRSCLV RPLMNDEGLK VRYPPSPAKM

      TQH
      Length:453
      Mass (Da):50,395
      Last modified:November 2, 2010 - v3
      Checksum:iD35C488A022FAACA
      GO

      Experimental Info

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Sequence conflicti12R → P in AAB46377 (PubMed:1737758).Curated1
      Sequence conflicti12R → P in AAB26658 (PubMed:8493892).Curated1
      Sequence conflicti27I → F in AAA51696 (Ref. 1) Curated1
      Sequence conflicti170V → L AA sequence (PubMed:2037078).Curated1
      Sequence conflicti436D → E AA sequence (PubMed:2037078).Curated1

      Natural variant

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Natural variantiVAR_018981134S → A5 PublicationsCorresponds to variant dbSNP:rs887241Ensembl.1
      Natural variantiVAR_018982309G → E. Corresponds to variant dbSNP:rs3744692Ensembl.1
      Natural variantiVAR_011303329P → A in allele ALDH3A1*2. 1 PublicationCorresponds to variant dbSNP:rs2228100Ensembl.1

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      M74542 mRNA Translation: AAA51696.1
      M77477 mRNA Translation: AAB46377.1
      S61044 mRNA Translation: AAB26658.1
      BT007102 mRNA Translation: AAP35766.1
      AK292193 mRNA Translation: BAF84882.1
      AK314584 mRNA Translation: BAG37160.1
      AC005722 Genomic DNA No translation available.
      CH471212 Genomic DNA Translation: EAW50909.1
      BC004370 mRNA Translation: AAH04370.1
      BC008892 mRNA Translation: AAH08892.1
      BC021194 mRNA Translation: AAH21194.1
      CCDSiCCDS11212.1
      PIRiA42584
      RefSeqiNP_000682.3, NM_000691.4
      NP_001128639.1, NM_001135167.1
      NP_001128640.1, NM_001135168.1
      UniGeneiHs.531682

      Genome annotation databases

      EnsembliENST00000225740; ENSP00000225740; ENSG00000108602
      ENST00000444455; ENSP00000388469; ENSG00000108602
      ENST00000457500; ENSP00000411821; ENSG00000108602
      GeneIDi218
      KEGGihsa:218
      UCSCiuc002gwj.4 human

      Keywords - Coding sequence diversityi

      Polymorphism

      Similar proteinsi

      Entry informationi

      Entry nameiAL3A1_HUMAN
      AccessioniPrimary (citable) accession number: P30838
      Secondary accession number(s): A8K828, Q9BT37
      Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
      Last sequence update: November 2, 2010
      Last modified: March 28, 2018
      This is version 173 of the entry and version 3 of the sequence. See 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

      3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
      UniProt is an ELIXIR core data resource
      Main funding by: National Institutes of Health