Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Aldehyde dehydrogenase, mitochondrial

Gene

ALDH2

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

Functioni

Catalytic activityi

An aldehyde + NAD+ + H2O = a carboxylate + NADH.

Pathwayi: ethanol degradation

This protein is involved in step 2 of the subpathway that synthesizes acetate from ethanol.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. no protein annotated in this organism
  2. Aldehyde dehydrogenase, mitochondrial (ALDH2), Aldehyde dehydrogenase X, mitochondrial (ALDH1B1), Aldehyde dehydrogenase family 3 member B1 (ALDH3B1), Aldehyde dehydrogenase family 3 member B2 (ALDH3B2)
This subpathway is part of the pathway ethanol degradation, which is itself part of Alcohol metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes acetate from ethanol, the pathway ethanol degradation and in Alcohol metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei186Transition state stabilizerBy similarity1
Active sitei285Proton acceptor1
Active sitei319Nucleophile1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi262 – 267NADBy similarity6

GO - Molecular functioni

  • aldehyde dehydrogenase (NAD) activity Source: CACAO
  • aldehyde dehydrogenase [NAD(P)+] activity Source: ProtInc
  • electron transfer activity Source: UniProtKB
  • glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity Source: UniProtKB-EC
  • NAD binding Source: CAFA

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
LigandNAD

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER66-302
BRENDAi1.2.1.3 2681
ReactomeiR-HSA-380612 Metabolism of serotonin
R-HSA-71384 Ethanol oxidation
SABIO-RKiP05091
UniPathwayi
UPA00780;UER00768

Names & Taxonomyi

Protein namesi
Recommended name:
Aldehyde dehydrogenase, mitochondrial (EC:1.2.1.3)
Alternative name(s):
ALDH class 2
ALDH-E2
ALDHI
Gene namesi
Name:ALDH2
Synonyms:ALDM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000111275.12
HGNCiHGNC:404 ALDH2
MIMi100650 gene+phenotype
neXtProtiNX_P05091

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

Mitochondrion

Pathology & Biotechi

Organism-specific databases

DisGeNETi217
MalaCardsiALDH2
MIMi100650 gene+phenotype
610251 phenotype
OpenTargetsiENSG00000111275
PharmGKBiPA24696

Chemistry databases

ChEMBLiCHEMBL1935
DrugBankiDB01612 Amyl Nitrite
DB06770 Benzyl alcohol
DB04381 Crotonaldehyde
DB02115 Daidzin
DB00822 Disulfiram
DB00536 Guanidine
DB00157 NADH
DB00435 Nitric Oxide
DB00727 Nitroglycerin
GuidetoPHARMACOLOGYi2595

Polymorphism and mutation databases

BioMutaiALDH2
DMDMi118504

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 17MitochondrionAdd BLAST17
ChainiPRO_000000716818 – 517Aldehyde dehydrogenase, mitochondrialAdd BLAST500

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52N6-acetyllysineBy similarity1
Modified residuei73N6-acetyllysineBy similarity1
Modified residuei78N6-acetyllysineBy similarity1
Modified residuei159N6-acetyllysineBy similarity1
Modified residuei368N6-acetyllysineBy similarity1
Modified residuei383N6-acetyllysineBy similarity1
Modified residuei426N6-acetyllysineBy similarity1
Modified residuei428N6-acetyllysineBy similarity1
Modified residuei451N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP05091
MaxQBiP05091
PaxDbiP05091
PeptideAtlasiP05091
PRIDEiP05091
ProteomicsDBi51788

2D gel databases

REPRODUCTION-2DPAGEiIPI00006663
P05091
UCD-2DPAGEiP05091

PTM databases

iPTMnetiP05091
PhosphoSitePlusiP05091
SwissPalmiP05091

Expressioni

Gene expression databases

BgeeiENSG00000111275 Expressed in 231 organ(s), highest expression level in liver
CleanExiHS_ALDH2
ExpressionAtlasiP05091 baseline and differential
GenevisibleiP05091 HS

Organism-specific databases

HPAiHPA051065

Interactioni

Subunit structurei

Homotetramer.

Protein-protein interaction databases

BioGridi106719, 53 interactors
DIPiDIP-40262N
IntActiP05091, 23 interactors
MINTiP05091
STRINGi9606.ENSP00000261733

Chemistry databases

BindingDBiP05091

Structurei

Secondary structure

1517
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP05091
SMRiP05091
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05091

Family & Domainsi

Sequence similaritiesi

Belongs to the aldehyde dehydrogenase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2450 Eukaryota
COG1012 LUCA
GeneTreeiENSGT00760000118999
HOGENOMiHOG000271505
HOVERGENiHBG000097
InParanoidiP05091
KOiK00128
OMAiTFVQEDV
OrthoDBiEOG091G05E8
PhylomeDBiP05091
TreeFamiTF300455

Family and domain databases

Gene3Di3.40.309.10, 1 hit
3.40.605.10, 1 hit
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
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

Sequences (2+)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P05091-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MLRAAARFGP RLGRRLLSAA ATQAVPAPNQ QPEVFCNQIF INNEWHDAVS
60 70 80 90 100
RKTFPTVNPS TGEVICQVAE GDKEDVDKAV KAARAAFQLG SPWRRMDASH
110 120 130 140 150
RGRLLNRLAD LIERDRTYLA ALETLDNGKP YVISYLVDLD MVLKCLRYYA
160 170 180 190 200
GWADKYHGKT IPIDGDFFSY TRHEPVGVCG QIIPWNFPLL MQAWKLGPAL
210 220 230 240 250
ATGNVVVMKV AEQTPLTALY VANLIKEAGF PPGVVNIVPG FGPTAGAAIA
260 270 280 290 300
SHEDVDKVAF TGSTEIGRVI QVAAGSSNLK RVTLELGGKS PNIIMSDADM
310 320 330 340 350
DWAVEQAHFA LFFNQGQCCC AGSRTFVQED IYDEFVERSV ARAKSRVVGN
360 370 380 390 400
PFDSKTEQGP QVDETQFKKI LGYINTGKQE GAKLLCGGGI AADRGYFIQP
410 420 430 440 450
TVFGDVQDGM TIAKEEIFGP VMQILKFKTI EEVVGRANNS TYGLAAAVFT
460 470 480 490 500
KDLDKANYLS QALQAGTVWV NCYDVFGAQS PFGGYKMSGS GRELGEYGLQ
510
AYTEVKTVTV KVPQKNS
Length:517
Mass (Da):56,381
Last modified:January 1, 1990 - v2
Checksum:iE8F74D44D285A00E
GO
Isoform 2 (identifier: P05091-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     74-120: Missing.

Note: No experimental confirmation available.
Show »
Length:470
Mass (Da):50,989
Checksum:i5D232BE0405A5F2E
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
S4R3S4S4R3S4_HUMAN
Aldehyde dehydrogenase, mitochondri...
ALDH2
117Annotation score:
F8VSB0F8VSB0_HUMAN
Aldehyde dehydrogenase, mitochondri...
ALDH2
79Annotation score:

Sequence cautioni

The sequence AAA62825 differs from that shown. Reason: Frameshift at positions 424, 444, 448 and 461.Curated
The sequence CAA68290 differs from that shown.Curated
The sequence CAA68290 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7 – 12RFGPRL → ARAPP in CAA28990 (PubMed:3582651).Curated6
Sequence conflicti18S → A AA sequence (PubMed:4065146).Curated1
Sequence conflicti60S → F in CAG33272 (Ref. 6) Curated1
Sequence conflicti80 – 85VKAARA → REGRPG in CAA28990 (PubMed:3582651).Curated6
Sequence conflicti101R → S in CAA28990 (PubMed:3582651).Curated1
Sequence conflicti116R → Q in AAT41621 (Ref. 5) Curated1
Sequence conflicti216L → S in AAA62825 (PubMed:3610592).Curated1
Sequence conflicti218A → R in AAA62825 (PubMed:3610592).Curated1
Sequence conflicti247A → P in AAA62825 (PubMed:3610592).Curated1
Sequence conflicti332Y → C in BAG62916 (PubMed:14702039).Curated1
Sequence conflicti362V → L in CAG33272 (Ref. 6) Curated1
Sequence conflicti380E → Q in AAA51693 (PubMed:2838413).Curated1

Polymorphismi

Genetic variation in ALDH2 is responsible for individual differences in responses to drinking alcohol [MIMi:610251]. Allele ALDH2*2 is associated with a very high incidence of acute alcohol intoxication in Orientals and South American Indians, as compared to Caucasians.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011869337E → V1 PublicationCorresponds to variant dbSNP:rs1062136Ensembl.1
Natural variantiVAR_011302496E → K in allele ALDH2*3. 1 PublicationCorresponds to variant dbSNP:rs769724893Ensembl.1
Natural variantiVAR_002248504E → K in allele ALDH2*2; drastic reduction of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs671EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04671574 – 120Missing in isoform 2. 1 PublicationAdd BLAST47

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05409 mRNA Translation: CAA28990.1
Y00109 mRNA Translation: CAA68290.1 Sequence problems.
M20456
, M20444, M20445, M20446, M20447, M20448, M20449, M20450, M20451, M20452, M20453, M20454 Genomic DNA Translation: AAA51693.1
AY621070 mRNA Translation: AAT41621.1
CR456991 mRNA Translation: CAG33272.1
AK301375 mRNA Translation: BAG62916.1
AC002996 Genomic DNA No translation available.
AC003029 Genomic DNA No translation available.
BC002967 mRNA Translation: AAH02967.1
BC071839 mRNA Translation: AAH71839.1
K03001 mRNA Translation: AAB59500.1
M26760 mRNA Translation: AAA51694.1
M54931 mRNA Translation: AAA62825.1 Frameshift.
CCDSiCCDS55885.1 [P05091-2]
CCDS9155.1 [P05091-1]
PIRiA29975 DEHUE2
RefSeqiNP_000681.2, NM_000690.3 [P05091-1]
NP_001191818.1, NM_001204889.1 [P05091-2]
UniGeneiHs.604551

Genome annotation databases

EnsembliENST00000261733; ENSP00000261733; ENSG00000111275 [P05091-1]
ENST00000416293; ENSP00000403349; ENSG00000111275 [P05091-2]
GeneIDi217
KEGGihsa:217
UCSCiuc001tst.4 human [P05091-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05409 mRNA Translation: CAA28990.1
Y00109 mRNA Translation: CAA68290.1 Sequence problems.
M20456
, M20444, M20445, M20446, M20447, M20448, M20449, M20450, M20451, M20452, M20453, M20454 Genomic DNA Translation: AAA51693.1
AY621070 mRNA Translation: AAT41621.1
CR456991 mRNA Translation: CAG33272.1
AK301375 mRNA Translation: BAG62916.1
AC002996 Genomic DNA No translation available.
AC003029 Genomic DNA No translation available.
BC002967 mRNA Translation: AAH02967.1
BC071839 mRNA Translation: AAH71839.1
K03001 mRNA Translation: AAB59500.1
M26760 mRNA Translation: AAA51694.1
M54931 mRNA Translation: AAA62825.1 Frameshift.
CCDSiCCDS55885.1 [P05091-2]
CCDS9155.1 [P05091-1]
PIRiA29975 DEHUE2
RefSeqiNP_000681.2, NM_000690.3 [P05091-1]
NP_001191818.1, NM_001204889.1 [P05091-2]
UniGeneiHs.604551

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CW3X-ray2.58A/B/C/D/E/F/G/H24-517[»]
1NZWX-ray2.65A/B/C/D/E/F/G/H18-517[»]
1NZXX-ray2.45A/B/C/D/E/F/G/H18-517[»]
1NZZX-ray2.45A/B/C/D/E/F/G/H18-517[»]
1O00X-ray2.60A/B/C/D/E/F/G/H18-517[»]
1O01X-ray2.15A/B/C/D/E/F/G/H18-517[»]
1O02X-ray1.90A/B/C/D/E/F/G/H18-517[»]
1O04X-ray1.42A/B/C/D/E/F/G/H18-517[»]
1O05X-ray2.25A/B/C/D/E/F/G/H18-517[»]
1ZUMX-ray2.10A/B/C/D/E/F/G/H/I/J/K/L18-517[»]
2ONMX-ray2.50A/B/C/D/E/F/G/H/I/J/K/L18-517[»]
2ONNX-ray2.75A/B/C/D/E/F/G/H18-517[»]
2ONOX-ray2.15A/B/C/D/E/F/G/H18-517[»]
2ONPX-ray2.00A/B/C/D/E/F/G/H18-517[»]
2VLEX-ray2.40A/B/C/D/E/F/G/H24-517[»]
3INJX-ray1.69A/B/C/D/E/F/G/H18-517[»]
3INLX-ray1.86A/B/C/D/E/F/G/H18-517[»]
3N80X-ray1.50A/B/C/D/E/F/G/H18-517[»]
3N81X-ray1.70A/B/C/D/E/F/G/H18-517[»]
3N82X-ray2.25A/B/C/D/E/F/G/H18-517[»]
3N83X-ray1.90A/B/C/D/E/F/G/H18-517[»]
3SZ9X-ray2.10A/B/C/D/E/F/G/H18-517[»]
4FQFX-ray2.28A/B/C/D18-517[»]
4FR8X-ray2.20A/B/C/D/E/F/G/H18-517[»]
4KWFX-ray2.31A/B/C/D/E/F/G/H24-517[»]
4KWGX-ray2.10A/B/C/D/E/F/G/H24-517[»]
5L13X-ray2.40A/B/C/D/E/F/G/H1-517[»]
ProteinModelPortaliP05091
SMRiP05091
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106719, 53 interactors
DIPiDIP-40262N
IntActiP05091, 23 interactors
MINTiP05091
STRINGi9606.ENSP00000261733

Chemistry databases

BindingDBiP05091
ChEMBLiCHEMBL1935
DrugBankiDB01612 Amyl Nitrite
DB06770 Benzyl alcohol
DB04381 Crotonaldehyde
DB02115 Daidzin
DB00822 Disulfiram
DB00536 Guanidine
DB00157 NADH
DB00435 Nitric Oxide
DB00727 Nitroglycerin
GuidetoPHARMACOLOGYi2595

PTM databases

iPTMnetiP05091
PhosphoSitePlusiP05091
SwissPalmiP05091

Polymorphism and mutation databases

BioMutaiALDH2
DMDMi118504

2D gel databases

REPRODUCTION-2DPAGEiIPI00006663
P05091
UCD-2DPAGEiP05091

Proteomic databases

EPDiP05091
MaxQBiP05091
PaxDbiP05091
PeptideAtlasiP05091
PRIDEiP05091
ProteomicsDBi51788

Protocols and materials databases

DNASUi217
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261733; ENSP00000261733; ENSG00000111275 [P05091-1]
ENST00000416293; ENSP00000403349; ENSG00000111275 [P05091-2]
GeneIDi217
KEGGihsa:217
UCSCiuc001tst.4 human [P05091-1]

Organism-specific databases

CTDi217
DisGeNETi217
EuPathDBiHostDB:ENSG00000111275.12
GeneCardsiALDH2
HGNCiHGNC:404 ALDH2
HPAiHPA051065
MalaCardsiALDH2
MIMi100650 gene+phenotype
610251 phenotype
neXtProtiNX_P05091
OpenTargetsiENSG00000111275
PharmGKBiPA24696
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2450 Eukaryota
COG1012 LUCA
GeneTreeiENSGT00760000118999
HOGENOMiHOG000271505
HOVERGENiHBG000097
InParanoidiP05091
KOiK00128
OMAiTFVQEDV
OrthoDBiEOG091G05E8
PhylomeDBiP05091
TreeFamiTF300455

Enzyme and pathway databases

UniPathwayi
UPA00780;UER00768

BioCyciMetaCyc:MONOMER66-302
BRENDAi1.2.1.3 2681
ReactomeiR-HSA-380612 Metabolism of serotonin
R-HSA-71384 Ethanol oxidation
SABIO-RKiP05091

Miscellaneous databases

ChiTaRSiALDH2 human
EvolutionaryTraceiP05091
GeneWikiiALDH2
GenomeRNAii217
PROiPR:P05091
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111275 Expressed in 231 organ(s), highest expression level in liver
CleanExiHS_ALDH2
ExpressionAtlasiP05091 baseline and differential
GenevisibleiP05091 HS

Family and domain databases

Gene3Di3.40.309.10, 1 hit
3.40.605.10, 1 hit
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
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
ProtoNetiSearch...

Entry informationi

Entry nameiALDH2_HUMAN
AccessioniPrimary (citable) accession number: P05091
Secondary accession number(s): B4DW54
, E7EUE5, Q03639, Q6IB13, Q6IV71
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 1, 1990
Last modified: November 7, 2018
This is version 225 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again