P08319 (ADH4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alcohol dehydrogenase 4
EC=1.1.1.1

Alternative name(s):
Alcohol dehydrogenase class II pi chain

Gene names

Name:

ADH4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	380 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding NAD Zinc
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	alcohol catabolic process Inferred from sequence or structural similarity. 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 cofactor metabolic process Inferred from sequence or structural similarity. Source: UniProtKB retinol metabolic process Inferred from direct assay PubMed 16787387. Source: UniProtKB xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome microtubule cytoskeleton Inferred from direct assay. Source: HPA
Molecular_function	NAD binding Inferred from direct assay PubMed 10407146. Source: UniProtKB NADPH:quinone reductase activity Inferred from sequence or structural similarity. 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: Compara all-trans retinal binding Inferred from direct assay PubMed 15369820. Source: UniProtKB benzaldehyde dehydrogenase activity 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 380

379

Alcohol dehydrogenase 4

PRO_0000160681

Regions

Nucleotide binding

48 – 49

2

NAD

Nucleotide binding

205 – 210

6

NAD

Nucleotide binding

298 – 300

3

NAD

Nucleotide binding

323 – 325

3

NAD

Sites

Metal binding

47

1

Zinc 1; catalytic

Metal binding

69

1

Zinc 1; catalytic

Metal binding

99

1

Zinc 2

Metal binding

102

1

Zinc 2

Metal binding

105

1

Zinc 2

Metal binding

113

1

Zinc 2

Metal binding

180

1

Zinc 1; catalytic

Binding site

229

1

NAD

Binding site

234

1

NAD

Binding site

375

1

NAD

Natural variations

Alternative sequence

1 – 6

6

MGTKGK → MLVRGPHFELQRCKTHLFSS NYLTQ in isoform 2.

VSP_036788

Natural variant

309

1

I → V. Ref.3 Ref.6
Corresponds to variant rs1126671 [ dbSNP | Ensembl ].

VAR_023461

Natural variant

318

1

R → H. Ref.4
Corresponds to variant rs29001219 [ dbSNP | Ensembl ].

VAR_023462

Natural variant

374

1

V → I. Ref.3 Ref.6
Corresponds to variant rs1126673 [ dbSNP | Ensembl ].

VAR_023463

Experimental info

Sequence conflict

52

1

T → S in AAA51595. Ref.1

Sequence conflict

52

1

T → S in CAA39813. Ref.2

Sequence conflict

380

1

F → FGRCQEQFRILSD in AAA51595. Ref.1

Secondary structure

1

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380

Helix Strand Turn

Details...

Beta strand

8 – 15

8

Beta strand

23 – 29

7

Beta strand

36 – 45

10

Helix

48 – 52

5

Beta strand

63 – 65

3

Beta strand

70 – 78

9

Beta strand

90 – 93

4

Beta strand

100 – 102

3

Turn

103 – 106

4

Helix

122 – 124

3

Beta strand

135 – 138

4

Beta strand

141 – 144

4

Turn

147 – 149

3

Beta strand

152 – 159

8

Beta strand

162 – 165

4

Helix

172 – 175

4

Helix

176 – 179

4

Helix

181 – 190

10

Turn

191 – 193

3

Beta strand

200 – 204

5

Helix

208 – 219

12

Beta strand

223 – 228

6

Helix

232 – 234

3

Helix

235 – 240

6

Beta strand

244 – 247

4

Helix

249 – 251

3

Helix

256 – 263

8

Beta strand

268 – 273

6

Helix

278 – 286

9

Turn

290 – 292

3

Beta strand

293 – 297

5

Beta strand

307 – 309

3

Helix

311 – 315

5

Beta strand

318 – 322

5

Helix

325 – 327

3

Helix

330 – 342

13

Helix

349 – 351

3

Beta strand

352 – 357

6

Helix

358 – 360

3

Helix

361 – 369

9

Beta strand

374 – 379

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 5, 2010. Version 5. Checksum: 45721A08197629F1	FASTA	380	40,222
	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
	Isoform 2 [UniParc]. Checksum: C4ABEC85C04B6C2D	FASTA	399	42,607
	10 20 30 40 50 60 MLVRGPHFEL QRCKTHLFSS NYLTQVIKCK AAIAWEAGKP LCIEEVEVAP PKAHEVRIQI 70 80 90 100 110 120 IATSLCHTDA TVIDSKFEGL AFPVIVGHEA AGIVESIGPG VTNVKPGDKV IPLYAPLCRK 130 140 150 160 170 180 CKFCLSPLTN LCGKISNLKS PASDQQLMED KTSRFTCKGK PVYHFFGTST FSQYTVVSDI 190 200 210 220 230 240 NLAKIDDDAN LERVCLLGCG FSTGYGAAIN NAKVTPGSTC AVFGLGGVGL SAVMGCKAAG 250 260 270 280 290 300 ASRIIGIDIN SEKFVKAKAL GATDCLNPRD LHKPIQEVII ELTKGGVDFA LDCAGGSETM 310 320 330 340 350 360 KAALDCTTAG WGSCTFIGVA AGSKGLTIFP EELIIGRTIN GTFFGGWKSV DSIPKLVTDY 370 380 390 KNKKFNLDAL VTHTLPFDKI SEAFDLMNQG KSVRTILIF

References

	« Hide 'large scale' referencesShow '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. , 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. , 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

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00218899.
IPI00927949.

PIR

DEHUAP. A27109.

RefSeq

NP_000661.2. NM_000670.3.

UniGene

Hs.1219.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3COS	X-ray	2.10	A/B/C/D	1-380	[»]

ProteinModelPortal

P08319.

SMR

P08319. Positions 1-380.

ModBase

Search...

Protein-protein interaction databases

IntAct

P08319. 1 interaction.

STRING

9606.ENSP00000265512.

PTM databases

PhosphoSite

P08319.

Polymorphism databases

DMDM

308153684.

Proteomic databases

PaxDb

P08319.

PRIDE

P08319.

Protocols and materials databases

DNASU

127.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265512; ENSP00000265512; ENSG00000198099.
ENST00000423445; ENSP00000397939; ENSG00000198099.
ENST00000505590; ENSP00000425416; ENSG00000198099.
ENST00000508393; ENSP00000424630; ENSG00000198099.

GeneID

127.

KEGG

hsa:127.

UCSC

uc003hun.3. human.
uc011ced.2. human.

Organism-specific databases

CTD

127.

GeneCards

GC04M100044.

H-InvDB

HIX0200651.

HGNC

HGNC:252. ADH4.

HPA

HPA020525.

MIM

103740. gene.

neXtProt

NX_P08319.

PharmGKB

PA24573.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1062.

HOGENOM

HOG000294674.

HOVERGEN

HBG000195.

InParanoid

P08319.

KO

K13980.

OMA

MNQGKSI.

OrthoDB

EOG4VHK6N.

PhylomeDB

P08319.

Enzyme and pathway databases

BioCyc

MetaCyc:HS06569-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P08319.

Gene expression databases

ArrayExpress

P08319.

Bgee

P08319.

CleanEx

HS_ADH4.

Genevestigator

P08319.

GermOnline

ENSG00000198099. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

IPR013149. ADH_C.
IPR013154. ADH_GroES-like.
IPR002085. ADH_SF_Zn-type.
IPR002328. ADH_Zn_CS.
IPR011032. GroES-like.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

PANTHER

PTHR11695. PTHR11695. 1 hit.

Pfam

PF08240. ADH_N. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
[Graphical view]

SUPFAM

SSF50129. GroES_like. 2 hits.

PROSITE

PS00059. ADH_ZINC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P08319.

ChEMBL

CHEMBL2990.

DrugBank

DB00157. NADH.

EvolutionaryTrace

P08319.

GenomeRNAi

127.

NextBio

507.

SOURCE

Search...

Entry information

Entry name

ADH4_HUMAN

Accession

Primary (citable) accession number: P08319
Secondary accession number(s): A8K470 , B4DIE7, C9J4A9, Q8TCD7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	October 5, 2010
Last modified:	April 3, 2013
This is version 143 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.