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

P30838 (AL3A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. 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, dimeric NADP-preferring

EC=1.2.1.5
Alternative name(s):
ALDHIII
Aldehyde dehydrogenase 3
Aldehyde dehydrogenase family 3 member A1
Gene names
Name:ALDH3A1
Synonyms:ALDH3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length453 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. This protein preferentially oxidizes aromatic aldehyde substrates. It may play a role in the oxidation of toxic aldehydes.

Catalytic activity

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

Subunit structure

Homodimer.

Subcellular location

Cytoplasm.

Tissue specificity

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

Sequence similarities

Belongs to the aldehyde dehydrogenase family.

Biophysicochemical properties

Kinetic parameters:

Has a high Km for acetaldehyde.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   LigandNAD
NADP
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

cellular aldehyde metabolic process

Inferred from direct assay Ref.2. Source: UniProtKB

oxidation-reduction process

Inferred from direct assay Ref.2. Source: UniProtKB

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

response to cAMP

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum

Inferred from direct assay. Source: LIFEdb

extracellular space

Inferred from direct assay PubMed 22664934. Source: UniProt

plasma membrane

Inferred from direct assay. Source: HPA

   Molecular_function3-chloroallyl aldehyde dehydrogenase activity

Inferred from electronic annotation. Source: Ensembl

alcohol dehydrogenase (NADP+) activity

Inferred from direct assay Ref.2. Source: UniProtKB

aldehyde dehydrogenase (NAD) activity

Inferred from direct assay Ref.2. Source: UniProtKB

aldehyde dehydrogenase [NAD(P)+] activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.13
Chain2 – 453452Aldehyde dehydrogenase, dimeric NADP-preferring
PRO_0000056470

Regions

Nucleotide binding188 – 1936NAD or NADP By similarity

Sites

Active site2101 Ref.14
Active site2441 Ref.14

Amino acid modifications

Modified residue21N-acetylserine Ref.13
Modified residue1781N6-acetyllysine Ref.11
Modified residue1941N6-acetyllysine Ref.11

Natural variations

Natural variant1341S → A. Ref.1 Ref.4 Ref.5 Ref.7 Ref.8
Corresponds to variant rs887241 [ dbSNP | Ensembl ].
VAR_018981
Natural variant3091G → E.
Corresponds to variant rs3744692 [ dbSNP | Ensembl ].
VAR_018982
Natural variant3291P → A in allele ALDH3A1*2. Ref.15
Corresponds to variant rs2228100 [ dbSNP | Ensembl ].
VAR_011303

Experimental info

Mutagenesis2441C → S: Abolishes activity. Ref.14
Sequence conflict121R → P in AAB46377. Ref.2
Sequence conflict121R → P in AAB26658. Ref.3
Sequence conflict271I → F in AAA51696. Ref.1
Sequence conflict1701V → L AA sequence Ref.9
Sequence conflict4361D → E AA sequence Ref.9

Secondary structure

................................................................................. 453
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P30838 [UniParc].

Last modified November 2, 2010. Version 3.
Checksum: D35C488A022FAACA

FASTA45350,395
        10         20         30         40         50         60 
MSKISEAVKR ARAAFSSGRT RPLQFRIQQL EALQRLIQEQ EQELVGALAA DLHKNEWNAY 

        70         80         90        100        110        120 
YEEVVYVLEE IEYMIQKLPE WAADEPVEKT PQTQQDELYI HSEPLGVVLV IGTWNYPFNL 

       130        140        150        160        170        180 
TIQPMVGAIA AGNSVVLKPS ELSENMASLL ATIIPQYLDK DLYPVINGGV PETTELLKER 

       190        200        210        220        230        240 
FDHILYTGST GVGKIIMTAA AKHLTPVTLE LGGKSPCYVD KNCDLDVACR RIAWGKFMNS 

       250        260        270        280        290        300 
GQTCVAPDYI LCDPSIQNQI VEKLKKSLKE FYGEDAKKSR DYGRIISARH FQRVMGLIEG 

       310        320        330        340        350        360 
QKVAYGGTGD AATRYIAPTI LTDVDPQSPV MQEEIFGPVL PIVCVRSLEE AIQFINQREK 

       370        380        390        400        410        420 
PLALYMFSSN DKVIKKMIAE TSSGGVAAND VIVHITLHSL PFGGVGNSGM GSYHGKKSFE 

       430        440        450 
TFSHRRSCLV RPLMNDEGLK VRYPPSPAKM TQH 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and complete nucleotide sequence of a cDNA encoding the full-length open reading frame of the human aldehyde dehydrogenase type III gene."
Schuuring E.M.D., Verhoeven E., Eckey R., Vos H.L., Michalides R.J.A.
Submitted (AUG-1991) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-134.
Tissue: Stomach.
[2]"Human stomach aldehyde dehydrogenase cDNA and genomic cloning, primary structure, and expression in Escherichia coli."
Hsu L.C., Chang W.-C., Shibuya A., Yoshida A.
J. Biol. Chem. 267:3030-3037(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Stomach.
[3]"Human stomach aldehyde dehydrogenase, ALDH3."
Hsu L.C., Yoshida A.
Adv. Exp. Med. Biol. 328:141-152(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Stomach.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-134.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-134.
Tissue: Cervix and Tongue.
[6]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-134.
[8]"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], VARIANT ALA-134.
Tissue: Pancreas.
[9]"Structural features of stomach aldehyde dehydrogenase distinguish dimeric aldehyde dehydrogenase as a 'variable' enzyme. 'Variable' and 'constant' enzymes within the alcohol and aldehyde dehydrogenase families."
Yin S.-J., Vagelopoulos N., Wang S.-L., Joernvall H.
FEBS Lett. 283:85-88(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 62-453.
Tissue: Stomach.
[10]"Biochemical, immunological, and molecular characterization of a 'high Km' aldehyde dehydrogenase."
Eckey R., Timmann R., Hempel J., Agarwal D.P., Goedde H.W.
Adv. Exp. Med. Biol. 284:43-52(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[11]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-178 AND LYS-194, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"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].
[13]"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 SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[14]"Discovery of a novel class of covalent inhibitor for aldehyde dehydrogenases."
Khanna M., Chen C.H., Kimble-Hill A., Parajuli B., Perez-Miller S., Baskaran S., Kim J., Dria K., Vasiliou V., Mochly-Rosen D., Hurley T.D.
J. Biol. Chem. 286:43486-43494(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) IN COMPLEX WITH INHIBITOR, MUTAGENESIS OF CYS-244, ACTIVE SITE.
[15]"Mutations associated with Sjogren-Larsson syndrome."
Tsukamoto N., Chang C., Yoshida A.
Ann. Hum. Genet. 61:235-242(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-329.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS11212.1.
PIRA42584.
RefSeqNP_000682.3. NM_000691.4.
NP_001128639.1. NM_001135167.1.
NP_001128640.1. NM_001135168.1.
UniGeneHs.531682.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP30838.
SMRP30838. Positions 2-453.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106720. 4 interactions.
IntActP30838. 2 interactions.
STRING9606.ENSP00000225740.

Chemistry

ChEMBLCHEMBL3578.
DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP30838.

Polymorphism databases

DMDM311033473.

Proteomic databases

MaxQBP30838.
PaxDbP30838.
PRIDEP30838.

Protocols and materials databases

DNASU218.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000225740; ENSP00000225740; ENSG00000108602.
ENST00000444455; ENSP00000388469; ENSG00000108602.
ENST00000457500; ENSP00000411821; ENSG00000108602.
GeneID218.
KEGGhsa:218.
UCSCuc002gwj.3. human.

Organism-specific databases

CTD218.
GeneCardsGC17M019641.
H-InvDBHIX0013622.
HGNCHGNC:405. ALDH3A1.
HPACAB045957.
HPA051150.
MIM100660. gene.
neXtProtNX_P30838.
PharmGKBPA24697.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1012.
HOGENOMHOG000271515.
HOVERGENHBG050483.
KOK00129.
OMAAWIRKEP.
PhylomeDBP30838.
TreeFamTF314264.

Enzyme and pathway databases

SABIO-RKP30838.

Gene expression databases

ArrayExpressP30838.
BgeeP30838.
CleanExHS_ALDH3A1.
GenevestigatorP30838.

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.
IPR012394. Aldehyde_DH_NAD(P).
[Graphical view]
PfamPF00171. Aldedh. 1 hit.
[Graphical view]
PIRSFPIRSF036492. ALDH. 1 hit.
SUPFAMSSF53720. SSF53720. 1 hit.
PROSITEPS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSALDH3A1. human.
EvolutionaryTraceP30838.
GeneWikiAldehyde_dehydrogenase_3_family,_member_A1.
GenomeRNAi218.
NextBio882.
PROP30838.
SOURCESearch...

Entry information

Entry nameAL3A1_HUMAN
AccessionPrimary (citable) accession number: P30838
Secondary accession number(s): A8K828, Q9BT37
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: November 2, 2010
Last modified: July 9, 2014
This is version 142 of the entry and version 3 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 17

Human chromosome 17: entries, gene names and cross-references to MIM