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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

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).By similarity

Catalytic activityi

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

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei181 – 1811Transition state stabilizerBy similarity
Active sitei280 – 2801Proton acceptorPROSITE-ProRule annotation
Active sitei314 – 3141NucleophilePROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi257 – 2626NADBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NAD

Enzyme and pathway databases

BioCyciMetaCyc:HS00013-MONOMER.
BRENDAi1.2.1.5. 2681.
ReactomeiREACT_268561. RA biosynthesis pathway.
UniPathwayiUPA00912.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:ALDH1A3
Synonyms:ALDH6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:409. ALDH1A3.

Subcellular locationi

GO - Cellular componenti

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

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti71 – 711V → M in MCOP8. 1 Publication
VAR_072332
Natural varianti89 – 891R → C in MCOP8; does not affect ALDH1A3 expression; results in strongly reduced protein levels. 1 Publication
VAR_069322
Natural varianti145 – 1451A → V in MCOP8. 1 Publication
VAR_069323
Natural varianti174 – 1741C → Y in MCOP8. 1 Publication
VAR_072333
Natural varianti355 – 3551P → R in MCOP8. 1 Publication
VAR_072334
Natural varianti369 – 3691I → F in MCOP8. 1 Publication
VAR_069324
Natural varianti382 – 3821G → R in MCOP8. 1 Publication
VAR_072335
Natural varianti411 – 4111E → K in MCOP8. 1 Publication
VAR_072336
Natural varianti466 – 4661N → K in MCOP8. 1 Publication
VAR_072337
Natural varianti493 – 4931A → P in MCOP8; does not affect ALDH1A3 expression; results in strongly reduced protein levels. 1 Publication
VAR_069325

Keywords - Diseasei

Disease mutation, Microphthalmia

Organism-specific databases

MIMi615113. phenotype.
Orphaneti2542. Isolated anophthalmia - microphthalmia.
PharmGKBiPA24694.

Chemistry

DrugBankiDB00162. Vitamin A.

Polymorphism and mutation databases

BioMutaiALDH1A3.
DMDMi52788258.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed2 Publications
Chaini2 – 512511Aldehyde dehydrogenase family 1 member A3PRO_0000056478Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine2 Publications
Modified residuei47 – 471N6-acetyllysine; alternateBy similarity
Modified residuei47 – 471N6-succinyllysine; alternateBy similarity
Modified residuei378 – 3781N6-acetyllysine; alternateBy similarity
Modified residuei378 – 3781N6-succinyllysine; alternateBy similarity
Modified residuei394 – 3941N6-acetyllysine; alternateBy similarity
Modified residuei394 – 3941N6-succinyllysine; alternateBy similarity
Modified residuei409 – 4091N6-acetyllysine; alternateBy similarity
Modified residuei409 – 4091N6-succinyllysine; alternateBy similarity
Modified residuei421 – 4211N6-acetyllysine; alternateBy similarity
Modified residuei421 – 4211N6-succinyllysine; alternateBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiP47895.
PaxDbiP47895.
PeptideAtlasiP47895.
PRIDEiP47895.

PTM databases

PhosphoSiteiP47895.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiP47895.
CleanExiHS_ALDH1A3.
ExpressionAtlasiP47895. baseline and differential.
GenevestigatoriP47895.

Organism-specific databases

HPAiHPA046271.

Interactioni

Protein-protein interaction databases

BioGridi106722. 5 interactions.
STRINGi9606.ENSP00000332256.

Structurei

3D structure databases

ProteinModelPortaliP47895.
SMRiP47895. Positions 20-511.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the aldehyde dehydrogenase family.Curated

Phylogenomic databases

eggNOGiCOG1012.
GeneTreeiENSGT00760000118999.
HOGENOMiHOG000271505.
HOVERGENiHBG000097.
InParanoidiP47895.
KOiK00129.
OMAiSLWRQMD.
PhylomeDBiP47895.
TreeFamiTF300455.

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]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti15 – 151R → G in AAA79036 (PubMed:7698756).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti71 – 711V → M in MCOP8. 1 Publication
VAR_072332
Natural varianti89 – 891R → C in MCOP8; does not affect ALDH1A3 expression; results in strongly reduced protein levels. 1 Publication
VAR_069322
Natural varianti145 – 1451A → V in MCOP8. 1 Publication
VAR_069323
Natural varianti174 – 1741C → Y in MCOP8. 1 Publication
VAR_072333
Natural varianti355 – 3551P → R in MCOP8. 1 Publication
VAR_072334
Natural varianti369 – 3691I → F in MCOP8. 1 Publication
VAR_069324
Natural varianti382 – 3821G → R in MCOP8. 1 Publication
VAR_072335
Natural varianti386 – 3861M → V.
Corresponds to variant rs3803430 [ dbSNP | Ensembl ].
VAR_019706
Natural varianti411 – 4111E → K in MCOP8. 1 Publication
VAR_072336
Natural varianti466 – 4661N → K in MCOP8. 1 Publication
VAR_072337
Natural varianti493 – 4931A → P in MCOP8; does not affect ALDH1A3 expression; results in strongly reduced protein levels. 1 Publication
VAR_069325

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.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP47895.
SMRiP47895. Positions 20-511.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106722. 5 interactions.
STRINGi9606.ENSP00000332256.

Chemistry

ChEMBLiCHEMBL3579.
DrugBankiDB00162. Vitamin A.

PTM databases

PhosphoSiteiP47895.

Polymorphism and mutation databases

BioMutaiALDH1A3.
DMDMi52788258.

Proteomic databases

MaxQBiP47895.
PaxDbiP47895.
PeptideAtlasiP47895.
PRIDEiP47895.

Protocols and materials databases

DNASUi220.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000329841; ENSP00000332256; ENSG00000184254.
GeneIDi220.
KEGGihsa:220.
UCSCiuc002bwn.4. human.

Organism-specific databases

CTDi220.
GeneCardsiGC15P101419.
H-InvDBHIX0026851.
HGNCiHGNC:409. ALDH1A3.
HPAiHPA046271.
MIMi600463. gene.
615113. phenotype.
neXtProtiNX_P47895.
Orphaneti2542. Isolated anophthalmia - microphthalmia.
PharmGKBiPA24694.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1012.
GeneTreeiENSGT00760000118999.
HOGENOMiHOG000271505.
HOVERGENiHBG000097.
InParanoidiP47895.
KOiK00129.
OMAiSLWRQMD.
PhylomeDBiP47895.
TreeFamiTF300455.

Enzyme and pathway databases

UniPathwayiUPA00912.
BioCyciMetaCyc:HS00013-MONOMER.
BRENDAi1.2.1.5. 2681.
ReactomeiREACT_268561. RA biosynthesis pathway.

Miscellaneous databases

ChiTaRSiALDH1A3. human.
GeneWikiiALDH1A3.
GenomeRNAii220.
NextBioi890.
PROiP47895.
SOURCEiSearch...

Gene expression databases

BgeeiP47895.
CleanExiHS_ALDH1A3.
ExpressionAtlasiP47895. baseline and differential.
GenevestigatoriP47895.

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...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  5. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [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. Cited for: VARIANTS MCOP8 CYS-89 AND PRO-493, CHARACTERIZATION OF VARIANTS MCOP8 CYS-89 AND PRO-493.
  8. Cited for: VARIANTS MCOP8 VAL-145 AND PHE-369.
  9. "Novel splice-site and missense mutations in the ALDH1A3 gene underlying autosomal recessive anophthalmia/microphthalmia."
    Semerci C.N., Kalay E., Yildirim C., Dincer T., Olmez A., Toraman B., Kocyigit A., Bulgu Y., Okur V., Satiroglu-Tufan L., Akarsu N.A.
    Br. J. Ophthalmol. 98:832-840(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT MCOP8 LYS-466.
  10. "A homozygous mutation in a consanguineous family consolidates the role of ALDH1A3 in autosomal recessive microphthalmia."
    Roos L., Fang M., Dali C., Jensen H., Christoffersen N., Wu B., Zhang J., Xu R., Harris P., Xu X., Groenskov K., Tuemer Z.
    Clin. Genet. 86:276-281(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT MCOP8 TYR-174.
  11. "A missense mutation in ALDH1A3 causes isolated microphthalmia/anophthalmia in nine individuals from an inbred Muslim kindred."
    Mory A., Ruiz F.X., Dagan E., Yakovtseva E.A., Kurolap A., Pares X., Farres J., Gershoni-Baruch R.
    Eur. J. Hum. Genet. 22:419-422(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT MCOP8 MET-71.
  12. "Mutations in ALDH1A3 represent a frequent cause of microphthalmia/anophthalmia in consanguineous families."
    Abouzeid H., Favez T., Schmid A., Agosti C., Youssef M., Marzouk I., El Shakankiry N., Bayoumi N., Munier F.L., Schorderet D.F.
    Hum. Mutat. 35:949-953(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS MCOP8 ARG-355; ARG-382 AND LYS-411.

Entry informationi

Entry nameiAL1A3_HUMAN
AccessioniPrimary (citable) accession number: P47895
Secondary accession number(s): Q6NT64
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: September 27, 2004
Last modified: May 27, 2015
This is version 140 of the entry and version 2 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 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.