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P08319 (ADH4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 152. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alcohol dehydrogenase 4

EC=1.1.1.1
Alternative name(s):
Alcohol dehydrogenase class II pi chain
Gene names
Name:ADH4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length380 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

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

Cofactor

Binds 2 zinc ions per subunit.

Subunit structure

Homodimer.

Subcellular location

Cytoplasm.

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.

Sequence similarities

Belongs to the zinc-containing alcohol dehydrogenase family. Class-II subfamily.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandMetal-binding
NAD
Zinc
   Molecular functionOxidoreductase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processalcohol catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

alcohol metabolic process

Inferred from direct assay PubMed 3466164. Source: UniProtKB

cellular aldehyde metabolic process

Inferred from direct assay PubMed 3466164. Source: UniProtKB

ethanol oxidation

Inferred from direct assay PubMed 16787387. Source: UniProtKB

quinone metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

retinoid metabolic process

Inferred from direct assay PubMed 15369820. Source: UniProtKB

retinol metabolic process

Inferred from direct assay PubMed 16787387. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

   Molecular_functionNAD binding

Inferred from direct assay PubMed 10407146. Source: UniProtKB

NADPH:quinone reductase activity

Inferred from sequence or structural similarity. Source: UniProtKB

alcohol dehydrogenase (NAD) activity

Inferred from direct assay PubMed 16787387PubMed 3466164. Source: UniProtKB

alcohol dehydrogenase activity, zinc-dependent

Inferred from direct assay PubMed 10407146. Source: UniProtKB

alditol:NADP+ 1-oxidoreductase activity

Inferred from electronic annotation. Source: Ensembl

all-trans retinal binding

Inferred from direct assay PubMed 15369820. Source: UniProtKB

benzaldehyde dehydrogenase activity

Inferred from direct assay PubMed 3466164. Source: UniProtKB

ethanol binding

Inferred from electronic annotation. Source: InterPro

oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor

Inferred from direct assay PubMed 3466164. Source: UniProtKB

retinol binding

Inferred from direct assay PubMed 10407146. Source: UniProtKB

retinol dehydrogenase activity

Inferred from direct assay PubMed 15369820PubMed 16787387. Source: UniProtKB

zinc ion binding

Inferred from direct assay PubMed 10407146. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P08319-1)

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.
Isoform 2 (identifier: P08319-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 380380Alcohol dehydrogenase 4
PRO_0000160681

Regions

Nucleotide binding48 – 492NAD
Nucleotide binding205 – 2106NAD
Nucleotide binding298 – 3003NAD
Nucleotide binding323 – 3253NAD

Sites

Metal binding471Zinc 1; catalytic
Metal binding691Zinc 1; catalytic
Metal binding991Zinc 2
Metal binding1021Zinc 2
Metal binding1051Zinc 2
Metal binding1131Zinc 2
Metal binding1801Zinc 1; catalytic
Binding site2291NAD
Binding site2341NAD
Binding site3751NAD

Natural variations

Alternative sequence1 – 66MGTKGK → MLVRGPHFELQRCKTHLFSS NYLTQ in isoform 2.
VSP_036788
Natural variant3091I → V. Ref.3 Ref.6
Corresponds to variant rs1126671 [ dbSNP | Ensembl ].
VAR_023461
Natural variant3181R → H. Ref.4
Corresponds to variant rs29001219 [ dbSNP | Ensembl ].
VAR_023462
Natural variant3741V → I. Ref.3 Ref.6
Corresponds to variant rs1126673 [ dbSNP | Ensembl ].
VAR_023463

Experimental info

Sequence conflict521T → S in AAA51595. Ref.1
Sequence conflict521T → S in CAA39813. Ref.2
Sequence conflict3801F → FGRCQEQFRILSD in AAA51595. Ref.1

Secondary structure

........................................................................... 380
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 5, 2010. Version 5.
Checksum: 45721A08197629F1

FASTA38040,222
        10         20         30         40         50         60 
MGTKGKVIKC KAAIAWEAGK PLCIEEVEVA PPKAHEVRIQ IIATSLCHTD ATVIDSKFEG 

        70         80         90        100        110        120 
LAFPVIVGHE AAGIVESIGP GVTNVKPGDK VIPLYAPLCR KCKFCLSPLT NLCGKISNLK 

       130        140        150        160        170        180 
SPASDQQLME DKTSRFTCKG KPVYHFFGTS TFSQYTVVSD INLAKIDDDA NLERVCLLGC 

       190        200        210        220        230        240 
GFSTGYGAAI NNAKVTPGST CAVFGLGGVG LSAVMGCKAA GASRIIGIDI NSEKFVKAKA 

       250        260        270        280        290        300 
LGATDCLNPR DLHKPIQEVI IELTKGGVDF ALDCAGGSET MKAALDCTTA GWGSCTFIGV 

       310        320        330        340        350        360 
AAGSKGLTIF PEELIIGRTI NGTFFGGWKS VDSIPKLVTD YKNKKFNLDA LVTHTLPFDK 

       370        380 
ISEAFDLMNQ GKSVRTILIF 

« Hide

Isoform 2 [UniParc].

Checksum: C4ABEC85C04B6C2D
Show »

FASTA39942,607

References

« Hide 'large scale' references
[1]"Structure of the class II enzyme of human liver alcohol dehydrogenase: combined cDNA and protein sequence determination of the pi subunit."
Hoeoeg J.-O., von Bahr-Lindstroem H., Heden L.-O., Holmquist B., Larsson K., Hempel J., Vallee B.L., Joernvall H.
Biochemistry 26:1926-1932(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
[2]"Cloning and characterization of the human ADH4 gene."
von Bahr-Lindstroem H., Joernvall H., Hoeoeg J.-O.
Gene 103:269-274(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
Tissue: Fetal liver.
[3]"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] (ISOFORMS 1 AND 2), VARIANTS VAL-309 AND ILE-374.
Tissue: Hippocampus and Liver.
[4]NIEHS SNPs program
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-318.
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORM 1), VARIANTS VAL-309 AND ILE-374.
Tissue: Liver.
[7]"Crystal structure of human class II alcohol dehydrogenase (ADH4) in complex with NAD and Zn."
Structural genomics consortium (SGC)
Submitted (APR-2008) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH NAD AND ZINC IONS.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M15943 mRNA. Translation: AAA51595.1.
X56411 expand/collapse EMBL AC list , 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.
PIRDEHUAP. A27109.
RefSeqNP_000661.2. NM_000670.3.
UniGeneHs.1219.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3COSX-ray2.10A/B/C/D1-380[»]
ProteinModelPortalP08319.
SMRP08319. Positions 1-380.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106639. 3 interactions.
IntActP08319. 1 interaction.
STRING9606.ENSP00000265512.

Chemistry

BindingDBP08319.
ChEMBLCHEMBL2990.
DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP08319.

Polymorphism databases

DMDM308153684.

Proteomic databases

PaxDbP08319.
PRIDEP08319.

Protocols and materials databases

DNASU127.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265512; ENSP00000265512; ENSG00000198099. [P08319-1]
ENST00000423445; ENSP00000397939; ENSG00000198099. [P08319-2]
ENST00000505590; ENSP00000425416; ENSG00000198099. [P08319-2]
ENST00000508393; ENSP00000424630; ENSG00000198099. [P08319-2]
GeneID127.
KEGGhsa:127.
UCSCuc003hun.3. human. [P08319-1]
uc011ced.2. human. [P08319-2]

Organism-specific databases

CTD127.
GeneCardsGC04M100044.
H-InvDBHIX0200651.
HGNCHGNC:252. ADH4.
HPAHPA020525.
MIM103740. gene.
neXtProtNX_P08319.
PharmGKBPA24573.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1062.
HOGENOMHOG000294674.
HOVERGENHBG000195.
InParanoidP08319.
KOK13980.
OMAHKPIQEV.
OrthoDBEOG72NRQ6.
PhylomeDBP08319.
TreeFamTF300429.

Enzyme and pathway databases

BioCycMetaCyc:HS06569-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP08319.

Gene expression databases

ArrayExpressP08319.
BgeeP08319.
CleanExHS_ADH4.
GenevestigatorP08319.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
3.90.180.10. 1 hit.
InterProIPR013149. ADH_C.
IPR013154. ADH_GroES-like.
IPR002085. ADH_SF_Zn-type.
IPR002328. ADH_Zn_CS.
IPR011032. GroES-like.
IPR016040. NAD(P)-bd_dom.
IPR028632. Zinc_ADH_II.
[Graphical view]
PANTHERPTHR11695. PTHR11695. 1 hit.
PTHR11695:SF308. PTHR11695:SF308. 1 hit.
PfamPF08240. ADH_N. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
[Graphical view]
SUPFAMSSF50129. SSF50129. 2 hits.
PROSITEPS00059. ADH_ZINC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP08319.
GeneWikiADH4.
GenomeRNAi127.
NextBio507.
PROP08319.
SOURCESearch...

Entry information

Entry nameADH4_HUMAN
AccessionPrimary (citable) accession number: P08319
Secondary accession number(s): A8K470 expand/collapse secondary AC list , B4DIE7, C9J4A9, Q8TCD7
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: October 5, 2010
Last modified: April 16, 2014
This is version 152 of the entry and version 5 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 4

Human chromosome 4: entries, gene names and cross-references to MIM