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Protein

Alcohol dehydrogenase 4

Gene

ADH4

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

Functioni

Catalytic activityi

An alcohol + NAD+ = an aldehyde or ketone + NADH.

Cofactori

Zn2+Note: Binds 2 Zn2+ ions per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi47Zinc 1; catalytic1
Metal bindingi69Zinc 1; catalytic1
Metal bindingi99Zinc 21
Metal bindingi102Zinc 21
Metal bindingi105Zinc 21
Metal bindingi113Zinc 21
Metal bindingi180Zinc 1; catalytic1
Binding sitei229NAD1 Publication1
Binding sitei234NAD1 Publication1
Binding sitei375NAD1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi48 – 49NAD1 Publication2
Nucleotide bindingi205 – 210NAD1 Publication6
Nucleotide bindingi298 – 300NAD1 Publication3
Nucleotide bindingi323 – 325NAD1 Publication3

GO - Molecular functioni

  • alcohol dehydrogenase (NAD) activity Source: UniProtKB
  • alcohol dehydrogenase activity, zinc-dependent Source: UniProtKB
  • alditol:NADP+ 1-oxidoreductase activity Source: Ensembl
  • all-trans retinal binding Source: UniProtKB
  • benzaldehyde dehydrogenase activity Source: UniProtKB
  • ethanol binding Source: InterPro
  • NAD binding Source: UniProtKB
  • NADPH:quinone reductase activity Source: UniProtKB
  • oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor Source: UniProtKB
  • retinol binding Source: UniProtKB
  • retinol dehydrogenase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • alcohol catabolic process Source: UniProtKB
  • alcohol metabolic process Source: UniProtKB
  • cellular aldehyde metabolic process Source: UniProtKB
  • ethanol oxidation Source: UniProtKB
  • quinone metabolic process Source: UniProtKB
  • retinoid metabolic process Source: UniProtKB
  • retinol metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

Metal-binding, NAD, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS06569-MONOMER.
ZFISH:HS06569-MONOMER.
BRENDAi1.1.1.1. 2681.
ReactomeiR-HSA-5365859. RA biosynthesis pathway.
R-HSA-71384. Ethanol oxidation.
SABIO-RKP08319.

Chemistry databases

SwissLipidsiSLP:000000499.

Names & Taxonomyi

Protein namesi
Recommended name:
Alcohol dehydrogenase 4 (EC:1.1.1.1)
Alternative name(s):
Alcohol dehydrogenase class II pi chain
Gene namesi
Name:ADH4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:252. ADH4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi127.
OpenTargetsiENSG00000198099.
PharmGKBiPA24573.

Chemistry databases

ChEMBLiCHEMBL2990.
DrugBankiDB00898. Ethanol.

Polymorphism and mutation databases

BioMutaiADH4.
DMDMi308153684.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001606811 – 380Alcohol dehydrogenase 4Add BLAST380

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei121PhosphoserineCombined sources1
Modified residuei278PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP08319.
MaxQBiP08319.
PaxDbiP08319.
PeptideAtlasiP08319.
PRIDEiP08319.

PTM databases

iPTMnetiP08319.
PhosphoSitePlusiP08319.

Expressioni

Gene expression databases

BgeeiENSG00000198099.
CleanExiHS_ADH4.
ExpressionAtlasiP08319. baseline and differential.
GenevisibleiP08319. HS.

Organism-specific databases

HPAiHPA020525.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi106639. 3 interactors.
IntActiP08319. 1 interactor.
STRINGi9606.ENSP00000265512.

Chemistry databases

BindingDBiP08319.

Structurei

Secondary structure

1380
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 15Combined sources8
Beta strandi23 – 29Combined sources7
Beta strandi36 – 45Combined sources10
Helixi48 – 52Combined sources5
Beta strandi63 – 65Combined sources3
Beta strandi70 – 78Combined sources9
Beta strandi90 – 93Combined sources4
Beta strandi100 – 102Combined sources3
Turni103 – 106Combined sources4
Helixi122 – 124Combined sources3
Beta strandi135 – 138Combined sources4
Beta strandi141 – 144Combined sources4
Turni147 – 149Combined sources3
Beta strandi152 – 159Combined sources8
Beta strandi162 – 165Combined sources4
Helixi172 – 175Combined sources4
Helixi176 – 179Combined sources4
Helixi181 – 190Combined sources10
Turni191 – 193Combined sources3
Beta strandi200 – 204Combined sources5
Helixi208 – 219Combined sources12
Beta strandi223 – 228Combined sources6
Helixi232 – 234Combined sources3
Helixi235 – 240Combined sources6
Beta strandi244 – 247Combined sources4
Helixi249 – 251Combined sources3
Helixi256 – 263Combined sources8
Beta strandi268 – 273Combined sources6
Helixi278 – 286Combined sources9
Turni290 – 292Combined sources3
Beta strandi293 – 297Combined sources5
Beta strandi307 – 309Combined sources3
Helixi311 – 315Combined sources5
Beta strandi318 – 322Combined sources5
Helixi325 – 327Combined sources3
Helixi330 – 342Combined sources13
Helixi349 – 351Combined sources3
Beta strandi352 – 357Combined sources6
Helixi358 – 360Combined sources3
Helixi361 – 369Combined sources9
Beta strandi374 – 379Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3COSX-ray2.10A/B/C/D1-380[»]
ProteinModelPortaliP08319.
SMRiP08319.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08319.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0022. Eukaryota.
COG1062. LUCA.
GeneTreeiENSGT00430000030800.
HOGENOMiHOG000294674.
HOVERGENiHBG000195.
InParanoidiP08319.
KOiK13980.
OMAiDSKFEGL.
OrthoDBiEOG091G08N3.
PhylomeDBiP08319.
TreeFamiTF300429.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
3.90.180.10. 1 hit.
InterProiIPR013149. ADH_C.
IPR013154. ADH_N.
IPR002085. ADH_SF_Zn-type.
IPR002328. ADH_Zn_CS.
IPR011032. GroES-like.
IPR016040. NAD(P)-bd_dom.
IPR020843. PKS_ER.
IPR028632. Zinc_ADH_II.
[Graphical view]
PANTHERiPTHR11695. PTHR11695. 2 hits.
PTHR11695:SF308. PTHR11695:SF308. 2 hits.
PfamiPF08240. ADH_N. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
[Graphical view]
SMARTiSM00829. PKS_ER. 1 hit.
[Graphical view]
SUPFAMiSSF50129. SSF50129. 2 hits.
SSF51735. SSF51735. 1 hit.
PROSITEiPS00059. ADH_ZINC. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: P08319-1) [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
MGTKGKVIKC KAAIAWEAGK PLCIEEVEVA PPKAHEVRIQ IIATSLCHTD
60 70 80 90 100
ATVIDSKFEG LAFPVIVGHE AAGIVESIGP GVTNVKPGDK VIPLYAPLCR
110 120 130 140 150
KCKFCLSPLT NLCGKISNLK SPASDQQLME DKTSRFTCKG KPVYHFFGTS
160 170 180 190 200
TFSQYTVVSD INLAKIDDDA NLERVCLLGC GFSTGYGAAI NNAKVTPGST
210 220 230 240 250
CAVFGLGGVG LSAVMGCKAA GASRIIGIDI NSEKFVKAKA LGATDCLNPR
260 270 280 290 300
DLHKPIQEVI IELTKGGVDF ALDCAGGSET MKAALDCTTA GWGSCTFIGV
310 320 330 340 350
AAGSKGLTIF PEELIIGRTI NGTFFGGWKS VDSIPKLVTD YKNKKFNLDA
360 370 380
LVTHTLPFDK ISEAFDLMNQ GKSVRTILIF
Length:380
Mass (Da):40,222
Last modified:October 5, 2010 - v5
Checksum:i45721A08197629F1
GO
Isoform 2 (identifier: P08319-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MGTKGK → MLVRGPHFELQRCKTHLFSSNYLTQ

Show »
Length:399
Mass (Da):42,607
Checksum:iC4ABEC85C04B6C2D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti52T → S in AAA51595 (PubMed:3036213).Curated1
Sequence conflicti52T → S in CAA39813 (PubMed:1889753).Curated1
Sequence conflicti380F → FGRCQEQFRILSD in AAA51595 (PubMed:3036213).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023461309I → V.2 PublicationsCorresponds to variant rs1126671dbSNPEnsembl.1
Natural variantiVAR_023462318R → H.1 PublicationCorresponds to variant rs29001219dbSNPEnsembl.1
Natural variantiVAR_023463374V → I.2 PublicationsCorresponds to variant rs1126673dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0367881 – 6MGTKGK → MLVRGPHFELQRCKTHLFSS NYLTQ in isoform 2. 1 Publication6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M15943 mRNA. Translation: AAA51595.1.
X56411
, X56412, X56413, X56414, X56415, X56416, X56417, X56418, X56419 Genomic DNA. Translation: CAA39813.1.
AK290835 mRNA. Translation: BAF83524.1.
AK295556 mRNA. Translation: BAG58459.1.
AY974245 Genomic DNA. Translation: AAX59034.1.
AC019131 Genomic DNA. No translation available.
AP002026 Genomic DNA. No translation available.
BC022319 mRNA. Translation: AAH22319.1.
CCDSiCCDS34032.1. [P08319-1]
CCDS77942.1. [P08319-2]
PIRiA27109. DEHUAP.
RefSeqiNP_000661.2. NM_000670.4. [P08319-1]
NP_001293100.1. NM_001306171.1. [P08319-2]
NP_001293101.1. NM_001306172.1. [P08319-2]
UniGeneiHs.1219.

Genome annotation databases

EnsembliENST00000265512; ENSP00000265512; ENSG00000198099. [P08319-1]
ENST00000505590; ENSP00000425416; ENSG00000198099. [P08319-2]
ENST00000508393; ENSP00000424630; ENSG00000198099. [P08319-2]
GeneIDi127.
KEGGihsa:127.
UCSCiuc003hun.4. human. [P08319-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M15943 mRNA. Translation: AAA51595.1.
X56411
, X56412, X56413, X56414, X56415, X56416, X56417, X56418, X56419 Genomic DNA. Translation: CAA39813.1.
AK290835 mRNA. Translation: BAF83524.1.
AK295556 mRNA. Translation: BAG58459.1.
AY974245 Genomic DNA. Translation: AAX59034.1.
AC019131 Genomic DNA. No translation available.
AP002026 Genomic DNA. No translation available.
BC022319 mRNA. Translation: AAH22319.1.
CCDSiCCDS34032.1. [P08319-1]
CCDS77942.1. [P08319-2]
PIRiA27109. DEHUAP.
RefSeqiNP_000661.2. NM_000670.4. [P08319-1]
NP_001293100.1. NM_001306171.1. [P08319-2]
NP_001293101.1. NM_001306172.1. [P08319-2]
UniGeneiHs.1219.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3COSX-ray2.10A/B/C/D1-380[»]
ProteinModelPortaliP08319.
SMRiP08319.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106639. 3 interactors.
IntActiP08319. 1 interactor.
STRINGi9606.ENSP00000265512.

Chemistry databases

BindingDBiP08319.
ChEMBLiCHEMBL2990.
DrugBankiDB00898. Ethanol.
SwissLipidsiSLP:000000499.

PTM databases

iPTMnetiP08319.
PhosphoSitePlusiP08319.

Polymorphism and mutation databases

BioMutaiADH4.
DMDMi308153684.

Proteomic databases

EPDiP08319.
MaxQBiP08319.
PaxDbiP08319.
PeptideAtlasiP08319.
PRIDEiP08319.

Protocols and materials databases

DNASUi127.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265512; ENSP00000265512; ENSG00000198099. [P08319-1]
ENST00000505590; ENSP00000425416; ENSG00000198099. [P08319-2]
ENST00000508393; ENSP00000424630; ENSG00000198099. [P08319-2]
GeneIDi127.
KEGGihsa:127.
UCSCiuc003hun.4. human. [P08319-1]

Organism-specific databases

CTDi127.
DisGeNETi127.
GeneCardsiADH4.
H-InvDBHIX0200651.
HGNCiHGNC:252. ADH4.
HPAiHPA020525.
MIMi103740. gene.
neXtProtiNX_P08319.
OpenTargetsiENSG00000198099.
PharmGKBiPA24573.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0022. Eukaryota.
COG1062. LUCA.
GeneTreeiENSGT00430000030800.
HOGENOMiHOG000294674.
HOVERGENiHBG000195.
InParanoidiP08319.
KOiK13980.
OMAiDSKFEGL.
OrthoDBiEOG091G08N3.
PhylomeDBiP08319.
TreeFamiTF300429.

Enzyme and pathway databases

BioCyciMetaCyc:HS06569-MONOMER.
ZFISH:HS06569-MONOMER.
BRENDAi1.1.1.1. 2681.
ReactomeiR-HSA-5365859. RA biosynthesis pathway.
R-HSA-71384. Ethanol oxidation.
SABIO-RKP08319.

Miscellaneous databases

EvolutionaryTraceiP08319.
GeneWikiiADH4.
GenomeRNAii127.
PROiP08319.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198099.
CleanExiHS_ADH4.
ExpressionAtlasiP08319. baseline and differential.
GenevisibleiP08319. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
3.90.180.10. 1 hit.
InterProiIPR013149. ADH_C.
IPR013154. ADH_N.
IPR002085. ADH_SF_Zn-type.
IPR002328. ADH_Zn_CS.
IPR011032. GroES-like.
IPR016040. NAD(P)-bd_dom.
IPR020843. PKS_ER.
IPR028632. Zinc_ADH_II.
[Graphical view]
PANTHERiPTHR11695. PTHR11695. 2 hits.
PTHR11695:SF308. PTHR11695:SF308. 2 hits.
PfamiPF08240. ADH_N. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
[Graphical view]
SMARTiSM00829. PKS_ER. 1 hit.
[Graphical view]
SUPFAMiSSF50129. SSF50129. 2 hits.
SSF51735. SSF51735. 1 hit.
PROSITEiPS00059. ADH_ZINC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiADH4_HUMAN
AccessioniPrimary (citable) accession number: P08319
Secondary accession number(s): A8K470
, B4DIE7, C9J4A9, Q8TCD7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: October 5, 2010
Last modified: November 2, 2016
This is version 177 of the entry and version 5 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

Miscellaneous

There are 7 different ADH's isozymes in human: three belongs to class-I: alpha, beta, and gamma, one to class-II: pi, one to class-III: chi, one to class-IV: ADH7 and one to class-V: ADH6.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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 one 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.