Reviewed, UniProtKB/Swiss-Prot P08319 (ADH4_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 Direct protein sequencing
Gene Ontology (GO)
Biological process	alcohol catabolic process Inferred from sequence or structural similarity. Source: UniProtKB cellular aldehyde metabolic process Inferred from direct assay. Source: UniProtKB ethanol oxidation Inferred from direct assay. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW quinone cofactor metabolic process Inferred from sequence or structural similarity. Source: UniProtKB retinol metabolic process Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	NAD or NADH binding Inferred from direct assay. Source: UniProtKB NADPH:quinone reductase activity Inferred from sequence or structural similarity. Source: UniProtKB alcohol dehydrogenase activity, zinc-dependent Inferred from direct assay. Source: UniProtKB all-trans retinal binding Inferred from direct assay. Source: UniProtKB benzaldehyde dehydrogenase activity Inferred from direct assay. Source: UniProtKB retinol binding Inferred from direct assay. Source: UniProtKB retinol dehydrogenase activity Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from direct assay. 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

V → I Ref.1 Ref.2 Ref.3 Ref.4 Ref.5

VAR_023461

Natural variant

318

1

R → H Ref.4

VAR_023462

Natural variant

374

1

I → V Ref.1 Ref.2 Ref.3 Ref.4 Ref.5

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

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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 January 23, 2007. Version 4. Checksum: 9ED102B3BA763B73	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 AAGSKGLTVF PEELIIGRTI NGTFFGGWKS VDSIPKLVTD YKNKKFNLDA LVTHTLPFDK 370 380 ISEAFDLMNQ GKSIRTILIF
	Isoform 2. Checksum: 1F08F43E634B7EAF	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 AGSKGLTVFP EELIIGRTIN GTFFGGWKSV DSIPKLVTDY 370 380 390 KNKKFNLDAL VTHTLPFDKI SEAFDLMNQG KSIRTILIF

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: 3036213] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANTS ILE-309 AND VAL-374.
[2]	"Cloning and characterization of the human ADH4 gene." von Bahr-Lindstroem H., Joernvall H., Hoeoeg J.-O. Gene 103:269-274(1991) [PubMed: 1889753] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANTS ILE-309 AND VAL-374. 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS ILE-309 AND VAL-374. Tissue: Hippocampus and Liver.
[4]	NIEHS SNPs program Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-309; HIS-318 AND VAL-374.
[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: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS ILE-309 AND VAL-374.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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

EMBLGenBankDDBJ

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.
AP002026 Genomic DNA. No translation available.
BC022319 mRNA. Translation: AAH22319.1.

IPI

IPI00218899.
IPI00927949.

PIR

DEHUAP. A27109.

RefSeq

NP_000661.2.

UniGene

Hs.1219

3D structure databases

PDBPDBe

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

ModBase

Search...

Genome annotation databases

Ensembl

ENSG00000198099. Homo sapiens. [Contig view]

GeneID

127.

KEGG

hsa:127.

NMPDR

fig|9606.3.peg.24452.

Organism-specific databases

GeneCards

GC04M100290.

HGNC

HGNC:252. ADH4.

MIM

103740. gene.

PharmGKB

PA24573.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P08319.

HOVERGEN

P08319.

Enzyme and pathway databases

BRENDA

1.1.1.1. 247.

Reactome

REACT_13433. Biological oxidations.

Gene expression databases

ArrayExpress

P08319.

Bgee

A8K470.
P08319.

CleanEx

HS_ADH4.

GermOnline

ENSG00000198099. Homo sapiens.

Family and domain databases

InterPro

IPR013154. ADH_GroES-like.
IPR002085. ADH_SF_Zn.
IPR013149. ADH_Zn-bd.
IPR002328. ADH_Zn_CS.
[Graphical view]

PANTHER

PTHR11695. ADH_Sf_Zn. 1 hit.

Pfam

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

PROSITE

PS00059. ADH_ZINC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00157. NADH.

NextBio

507.

SOURCE

Search...

Entry information

Entry name

ADH4_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 103 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)