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Protein

Aldehyde dehydrogenase family 1 member A3

Gene

ALDH1A3

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

Functioni

NAD-dependent aldehyde dehydrogenase that catalyzes the formation of retinoic acid (PubMed:27759097). Has high activity with all-trans retinal, and has much lower in vitro activity with acetaldehyde (PubMed:27759097). Required for the biosynthesis of normal levels of retinoic acid in the embryonic ocular and nasal regions; retinoic acid is required for normal embryonic development of the eye and the nasal region (By similarity).By similarity1 Publication

Catalytic activityi

An aldehyde + NAD(P)+ + H2O = a carboxylate + NAD(P)H.1 Publication

Kineticsi

  1. KM=9.3 µM for all-trans retinal1 Publication
  2. KM=4.8 µM for NAD1 Publication
  3. KM=2.4 mM for acetaldehyde1 Publication

    Pathwayi: retinol metabolism

    This protein is involved in the pathway retinol metabolism, which is part of Cofactor metabolism.1 Publication
    View all proteins of this organism that are known to be involved in the pathway retinol metabolism and in Cofactor metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei181Transition state stabilizerBy similarity1
    Binding sitei204NADCombined sources1 Publication1
    Binding sitei207NADCombined sources1 Publication1
    Active sitei280Proton acceptorPROSITE-ProRule annotation1 Publication1
    Active sitei314NucleophilePROSITE-ProRule annotation1
    Binding sitei361NADCombined sources1 Publication1
    Binding sitei411NADCombined sources1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi257 – 262NADCombined sources1 Publication6

    GO - Molecular functioni

    • aldehyde dehydrogenase (NAD) activity Source: GO_Central
    • aldehyde dehydrogenase [NAD(P)+] activity Source: UniProtKB
    • NAD+ binding Source: Ensembl
    • protein homodimerization activity Source: UniProtKB
    • retinal dehydrogenase activity Source: UniProtKB
    • thyroid hormone binding Source: Ensembl

    GO - Biological processi

    Keywordsi

    Molecular functionOxidoreductase
    LigandNAD

    Enzyme and pathway databases

    BioCyciMetaCyc:HS00013-MONOMER.
    BRENDAi1.2.1.5. 2681.
    ReactomeiR-HSA-5365859. RA biosynthesis pathway.
    UniPathwayiUPA00912.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Aldehyde dehydrogenase family 1 member A3 (EC:1.2.1.51 Publication)
    Alternative name(s):
    Aldehyde dehydrogenase 6
    Retinaldehyde dehydrogenase 3
    Short name:
    RALDH-3
    Short name:
    RalDH3
    Gene namesi
    Name:ALDH1A3
    Synonyms:ALDH61 Publication
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:409. ALDH1A3.

    Subcellular locationi

    • Cytoplasm By similarity

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • cytosol Source: HPA
    • extracellular exosome Source: UniProtKB
    • nucleus Source: HPA
    • plasma membrane Source: HPA

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Microphthalmia, isolated, 8 (MCOP8)7 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present.
    See also OMIM:615113
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07233271V → M in MCOP8. 1 PublicationCorresponds to variant dbSNP:rs386834230Ensembl.1
    Natural variantiVAR_06932289R → C in MCOP8; does not affect ALDH1A3 expression; results in strongly reduced protein levels. 1 PublicationCorresponds to variant dbSNP:rs397514652Ensembl.1
    Natural variantiVAR_069323145A → V in MCOP8. 1 PublicationCorresponds to variant dbSNP:rs754619607Ensembl.1
    Natural variantiVAR_072333174C → Y in MCOP8. 1 Publication1
    Natural variantiVAR_072334355P → R in MCOP8. 1 Publication1
    Natural variantiVAR_069324369I → F in MCOP8. 1 Publication1
    Natural variantiVAR_072335382G → R in MCOP8. 1 Publication1
    Natural variantiVAR_072336411E → K in MCOP8. 1 Publication1
    Natural variantiVAR_072337466N → K in MCOP8. 1 Publication1
    Natural variantiVAR_069325493A → P in MCOP8; does not affect ALDH1A3 expression; results in strongly reduced protein levels. 1 PublicationCorresponds to variant dbSNP:rs397514653Ensembl.1

    Keywords - Diseasei

    Disease mutation, Microphthalmia

    Organism-specific databases

    DisGeNETi220.
    MalaCardsiALDH1A3.
    MIMi615113. phenotype.
    OpenTargetsiENSG00000184254.
    Orphaneti2542. Isolated anophthalmia - microphthalmia.
    PharmGKBiPA24694.

    Chemistry databases

    ChEMBLiCHEMBL3579.
    DrugBankiDB00157. NADH.
    DB00162. Vitamin A.

    Polymorphism and mutation databases

    BioMutaiALDH1A3.
    DMDMi52788258.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedCombined sources1 Publication
    ChainiPRO_00000564782 – 512Aldehyde dehydrogenase family 1 member A3Add BLAST511

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylalanineCombined sources1 Publication1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiP47895.
    MaxQBiP47895.
    PaxDbiP47895.
    PeptideAtlasiP47895.
    PRIDEiP47895.

    PTM databases

    iPTMnetiP47895.
    PhosphoSitePlusiP47895.
    SwissPalmiP47895.

    Expressioni

    Tissue specificityi

    Expressed at low levels in many tissues and at higher levels in salivary gland, stomach, and kidney.1 Publication

    Gene expression databases

    BgeeiENSG00000184254.
    CleanExiHS_ALDH1A3.
    ExpressionAtlasiP47895. baseline and differential.
    GenevisibleiP47895. HS.

    Organism-specific databases

    HPAiHPA046271.
    HPA064749.

    Interactioni

    Subunit structurei

    Homotetramer.1 Publication

    GO - Molecular functioni

    • protein homodimerization activity Source: UniProtKB

    Protein-protein interaction databases

    BioGridi106722. 11 interactors.
    STRINGi9606.ENSP00000332256.

    Chemistry databases

    BindingDBiP47895.

    Structurei

    Secondary structure

    1512
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi33 – 36Combined sources4
    Beta strandi39 – 41Combined sources3
    Beta strandi48 – 52Combined sources5
    Turni54 – 56Combined sources3
    Beta strandi58 – 64Combined sources7
    Helixi68 – 82Combined sources15
    Helixi87 – 90Combined sources4
    Helixi93 – 109Combined sources17
    Helixi111 – 122Combined sources12
    Helixi126 – 131Combined sources6
    Helixi133 – 145Combined sources13
    Turni146 – 149Combined sources4
    Beta strandi153 – 156Combined sources4
    Beta strandi162 – 170Combined sources9
    Beta strandi172 – 177Combined sources6
    Beta strandi180 – 182Combined sources3
    Helixi185 – 196Combined sources12
    Beta strandi200 – 204Combined sources5
    Helixi211 – 222Combined sources12
    Beta strandi229 – 232Combined sources4
    Turni237 – 239Combined sources3
    Helixi240 – 245Combined sources6
    Beta strandi252 – 257Combined sources6
    Helixi259 – 272Combined sources14
    Beta strandi276 – 280Combined sources5
    Beta strandi285 – 289Combined sources5
    Helixi295 – 307Combined sources13
    Helixi308 – 311Combined sources4
    Beta strandi317 – 323Combined sources7
    Helixi324 – 340Combined sources17
    Beta strandi346 – 348Combined sources3
    Helixi359 – 374Combined sources16
    Beta strandi378 – 381Combined sources4
    Beta strandi384 – 386Combined sources3
    Beta strandi396 – 400Combined sources5
    Helixi406 – 408Combined sources3
    Beta strandi414 – 423Combined sources10
    Helixi425 – 433Combined sources9
    Beta strandi435 – 444Combined sources10
    Helixi448 – 457Combined sources10
    Beta strandi461 – 466Combined sources6
    Beta strandi484 – 486Combined sources3
    Helixi491 – 495Combined sources5
    Beta strandi498 – 506Combined sources9

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    5FHZX-ray2.90A/B/C/D/E/F/G/H1-512[»]
    ProteinModelPortaliP47895.
    SMRiP47895.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the aldehyde dehydrogenase family.Curated

    Phylogenomic databases

    eggNOGiKOG2450. Eukaryota.
    COG1012. LUCA.
    GeneTreeiENSGT00760000118999.
    HOGENOMiHOG000271505.
    HOVERGENiHBG000097.
    InParanoidiP47895.
    KOiK00129.
    OMAiNEWHESK.
    OrthoDBiEOG091G05E8.
    PhylomeDBiP47895.
    TreeFamiTF300455.

    Family and domain databases

    Gene3Di3.40.605.10. 1 hit.
    InterProiView protein in InterPro
    IPR016161. Ald_DH/histidinol_DH.
    IPR016160. Ald_DH_CS_CYS.
    IPR029510. Ald_DH_CS_GLU.
    IPR016162. Ald_DH_N.
    IPR015590. Aldehyde_DH_dom.
    PfamiView protein in Pfam
    PF00171. Aldedh. 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.

    P47895-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MATANGAVEN GQPDRKPPAL PRPIRNLEVK FTKIFINNEW HESKSGKKFA
    60 70 80 90 100
    TCNPSTREQI CEVEEGDKPD VDKAVEAAQV AFQRGSPWRR LDALSRGRLL
    110 120 130 140 150
    HQLADLVERD RATLAALETM DTGKPFLHAF FIDLEGCIRT LRYFAGWADK
    160 170 180 190 200
    IQGKTIPTDD NVVCFTRHEP IGVCGAITPW NFPLLMLVWK LAPALCCGNT
    210 220 230 240 250
    MVLKPAEQTP LTALYLGSLI KEAGFPPGVV NIVPGFGPTV GAAISSHPQI
    260 270 280 290 300
    NKIAFTGSTE VGKLVKEAAS RSNLKRVTLE LGGKNPCIVC ADADLDLAVE
    310 320 330 340 350
    CAHQGVFFNQ GQCCTAASRV FVEEQVYSEF VRRSVEYAKK RPVGDPFDVK
    360 370 380 390 400
    TEQGPQIDQK QFDKILELIE SGKKEGAKLE CGGSAMEDKG LFIKPTVFSE
    410 420 430 440 450
    VTDNMRIAKE EIFGPVQPIL KFKSIEEVIK RANSTDYGLT AAVFTKNLDK
    460 470 480 490 500
    ALKLASALES GTVWINCYNA LYAQAPFGGF KMSGNGRELG EYALAEYTEV
    510
    KTVTIKLGDK NP
    Length:512
    Mass (Da):56,108
    Last modified:September 27, 2004 - v2
    Checksum:i1BFCF4F56F0FE89A
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti15R → G in AAA79036 (PubMed:7698756).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07233271V → M in MCOP8. 1 PublicationCorresponds to variant dbSNP:rs386834230Ensembl.1
    Natural variantiVAR_06932289R → C in MCOP8; does not affect ALDH1A3 expression; results in strongly reduced protein levels. 1 PublicationCorresponds to variant dbSNP:rs397514652Ensembl.1
    Natural variantiVAR_069323145A → V in MCOP8. 1 PublicationCorresponds to variant dbSNP:rs754619607Ensembl.1
    Natural variantiVAR_072333174C → Y in MCOP8. 1 Publication1
    Natural variantiVAR_072334355P → R in MCOP8. 1 Publication1
    Natural variantiVAR_069324369I → F in MCOP8. 1 Publication1
    Natural variantiVAR_072335382G → R in MCOP8. 1 Publication1
    Natural variantiVAR_019706386M → V. Corresponds to variant dbSNP:rs3803430Ensembl.1
    Natural variantiVAR_072336411E → K in MCOP8. 1 Publication1
    Natural variantiVAR_072337466N → K in MCOP8. 1 Publication1
    Natural variantiVAR_069325493A → P in MCOP8; does not affect ALDH1A3 expression; results in strongly reduced protein levels. 1 PublicationCorresponds to variant dbSNP:rs397514653Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U07919 mRNA. Translation: AAA79036.1.
    BC069274 mRNA. Translation: AAH69274.1.
    CCDSiCCDS10389.1.
    PIRiA55684.
    RefSeqiNP_000684.2. NM_000693.3.
    NP_001280744.1. NM_001293815.1.
    UniGeneiHs.459538.
    Hs.612155.

    Genome annotation databases

    EnsembliENST00000329841; ENSP00000332256; ENSG00000184254.
    GeneIDi220.
    KEGGihsa:220.
    UCSCiuc002bwn.5. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiAL1A3_HUMAN
    AccessioniPrimary (citable) accession number: P47895
    Secondary accession number(s): Q6NT64
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: September 27, 2004
    Last modified: August 30, 2017
    This is version 161 of the entry and version 2 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

    Documents

    1. Human chromosome 15
      Human chromosome 15: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families