Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P47895 (AL1A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 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:
Aldehyde dehydrogenase family 1 member A3

EC=1.2.1.5
Alternative name(s):
Aldehyde dehydrogenase 6
Retinaldehyde dehydrogenase 3
Short name=RALDH-3
Short name=RalDH3
Gene names
Name:ALDH1A3
Synonyms:ALDH6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length512 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Seems to be the key enzyme in the formation of an RA gradient along the dorso-ventral axis during the early eye development and also in the development of the olfactory system By similarity.

Catalytic activity

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

Pathway

Cofactor metabolism; retinol metabolism.

Subcellular location

Cytoplasm By similarity.

Tissue specificity

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

Involvement in disease

Microphthalmia, isolated, 8 (MCOP8) [MIM:615113]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Ref.8

Sequence similarities

Belongs to the aldehyde dehydrogenase family.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Microphthalmia
   LigandNAD
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processembryonic eye morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

face development

Inferred from electronic annotation. Source: Ensembl

inner ear morphogenesis

Inferred from electronic annotation. Source: Ensembl

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

neuromuscular process controlling balance

Inferred from electronic annotation. Source: Ensembl

nucleus accumbens development

Inferred from electronic annotation. Source: Ensembl

olfactory pit development

Inferred from electronic annotation. Source: Ensembl

optic cup morphogenesis involved in camera-type eye development

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

retinal metabolic process

Inferred from direct assay PubMed 11585737. Source: UniProtKB

retinoic acid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

retinoic acid metabolic process

Inferred from direct assay PubMed 11585737. Source: UniProtKB

retinol metabolic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

righting reflex

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 11585737. Source: UniProtKB

   Molecular_functionNAD+ binding

Inferred from electronic annotation. Source: Ensembl

aldehyde dehydrogenase (NAD) activity

Inferred from electronic annotation. Source: Ensembl

aldehyde dehydrogenase [NAD(P)+] activity

Inferred from direct assay PubMed 11585737. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 11585737. Source: UniProtKB

thyroid hormone binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.3
Chain2 – 512511Aldehyde dehydrogenase family 1 member A3
PRO_0000056478

Regions

Nucleotide binding257 – 2626NAD By similarity

Sites

Active site2801Proton acceptor By similarity
Active site3141Nucleophile By similarity
Site1811Transition state stabilizer By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.3 Ref.5

Natural variations

Natural variant891R → C in MCOP8; does not affect ALDH1A3 expression; results in strongly reduced protein levels. Ref.7
VAR_069322
Natural variant1451A → V in MCOP8. Ref.8
VAR_069323
Natural variant3691I → F in MCOP8. Ref.8
VAR_069324
Natural variant3861M → V.
Corresponds to variant rs3803430 [ dbSNP | Ensembl ].
VAR_019706
Natural variant4931A → P in MCOP8; does not affect ALDH1A3 expression; results in strongly reduced protein levels. Ref.7
VAR_069325

Experimental info

Sequence conflict151R → G in AAA79036. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P47895 [UniParc].

Last modified September 27, 2004. Version 2.
Checksum: 1BFCF4F56F0FE89A

FASTA51256,108
        10         20         30         40         50         60 
MATANGAVEN GQPDRKPPAL PRPIRNLEVK FTKIFINNEW HESKSGKKFA TCNPSTREQI 

        70         80         90        100        110        120 
CEVEEGDKPD VDKAVEAAQV AFQRGSPWRR LDALSRGRLL HQLADLVERD RATLAALETM 

       130        140        150        160        170        180 
DTGKPFLHAF FIDLEGCIRT LRYFAGWADK IQGKTIPTDD NVVCFTRHEP IGVCGAITPW 

       190        200        210        220        230        240 
NFPLLMLVWK LAPALCCGNT MVLKPAEQTP LTALYLGSLI KEAGFPPGVV NIVPGFGPTV 

       250        260        270        280        290        300 
GAAISSHPQI NKIAFTGSTE VGKLVKEAAS RSNLKRVTLE LGGKNPCIVC ADADLDLAVE 

       310        320        330        340        350        360 
CAHQGVFFNQ GQCCTAASRV FVEEQVYSEF VRRSVEYAKK RPVGDPFDVK TEQGPQIDQK 

       370        380        390        400        410        420 
QFDKILELIE SGKKEGAKLE CGGSAMEDKG LFIKPTVFSE VTDNMRIAKE EIFGPVQPIL 

       430        440        450        460        470        480 
KFKSIEEVIK RANSTDYGLT AAVFTKNLDK ALKLASALES GTVWINCYNA LYAQAPFGGF 

       490        500        510 
KMSGNGRELG EYALAEYTEV KTVTIKLGDK NP 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning, genomic organization, and chromosomal localization of an additional human aldehyde dehydrogenase gene, ALDH6."
Hsu L.C., Chang W.-C., Hiraoka L., Hsieh C.-L.
Genomics 24:333-341(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Salivary gland.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas.
[3]Bienvenut W.V., Dozynkiewicz M., Norman J.C.
Submitted (MAR-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-15; 253-263; 407-421; 432-446 AND 488-501, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Ovarian carcinoma.
[4]"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].
[5]"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 ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"ALDH1A3 loss of function causes bilateral anophthalmia/microphthalmia and hypoplasia of the optic nerve and optic chiasm."
Yahyavi M., Abouzeid H., Gawdat G., de Preux A.S., Xiao T., Bardakjian T., Schneider A., Choi A., Jorgenson E., Baier H., El Sada M., Schorderet D.F., Slavotinek A.M.
Hum. Mol. Genet. 22:3250-3258(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MCOP8.
[7]"ALDH1A3 mutations cause recessive anophthalmia and microphthalmia."
Fares-Taie L., Gerber S., Chassaing N., Clayton-Smith J., Hanein S., Silva E., Serey M., Serre V., Gerard X., Baumann C., Plessis G., Demeer B., Bretillon L., Bole C., Nitschke P., Munnich A., Lyonnet S., Calvas P. expand/collapse author list , Kaplan J., Ragge N., Rozet J.M.
Am. J. Hum. Genet. 92:265-270(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MCOP8 CYS-89 AND PRO-493, CHARACTERIZATION OF VARIANTS MCOP8 CYS-89 AND PRO-493.
[8]"Mutations in ALDH1A3 cause Microphthalmia."
Aldahmesh M.A., Khan A.O., Hijazi H., Alkuraya F.S.
Clin. Genet. 84:128-131(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MCOP8 VAL-145 AND PHE-369.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U07919 mRNA. Translation: AAA79036.1.
BC069274 mRNA. Translation: AAH69274.1.
CCDSCCDS10389.1.
PIRA55684.
RefSeqNP_000684.2. NM_000693.2.
UniGeneHs.459538.

3D structure databases

ProteinModelPortalP47895.
SMRP47895. Positions 20-511.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106722. 2 interactions.
STRING9606.ENSP00000332256.

Chemistry

DrugBankDB00157. NADH.
DB00162. Vitamin A.

PTM databases

PhosphoSiteP47895.

Polymorphism databases

DMDM52788258.

Proteomic databases

MaxQBP47895.
PaxDbP47895.
PeptideAtlasP47895.
PRIDEP47895.

Protocols and materials databases

DNASU220.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000329841; ENSP00000332256; ENSG00000184254.
GeneID220.
KEGGhsa:220.
UCSCuc002bwn.4. human.

Organism-specific databases

CTD220.
GeneCardsGC15P101419.
H-InvDBHIX0026851.
HGNCHGNC:409. ALDH1A3.
HPAHPA046271.
MIM600463. gene.
615113. phenotype.
neXtProtNX_P47895.
Orphanet2542. Isolated anophthalmia - microphthalmia.
PharmGKBPA24694.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1012.
HOGENOMHOG000271505.
HOVERGENHBG000097.
InParanoidP47895.
KOK00129.
OMAHAQTPFG.
PhylomeDBP47895.
TreeFamTF300455.

Enzyme and pathway databases

BioCycMetaCyc:HS00013-MONOMER.
UniPathwayUPA00912.

Gene expression databases

ArrayExpressP47895.
BgeeP47895.
CleanExHS_ALDH1A3.
GenevestigatorP47895.

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_CYS.
IPR029510. Ald_DH_CS_GLU.
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

GeneWikiALDH1A3.
GenomeRNAi220.
NextBio890.
PROP47895.
SOURCESearch...

Entry information

Entry nameAL1A3_HUMAN
AccessionPrimary (citable) accession number: P47895
Secondary accession number(s): Q6NT64
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: September 27, 2004
Last modified: July 9, 2014
This is version 131 of the entry and version 2 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 15

Human chromosome 15: entries, gene names and cross-references to MIM