P00326 (ADH1G_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alcohol dehydrogenase 1C
EC=1.1.1.1

Alternative name(s):
Alcohol dehydrogenase subunit gamma

Gene names

Name:	ADH1C
Synonyms:	ADH3

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	375 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	Dimer of identical or non-identical chains of three types; alpha, beta and gamma.
Subcellular location	Cytoplasm.
Polymorphism	Two main alleles are known, ADH3*1 or gamma-1 has Arg-272/Ile-350 while ADH3*2 or gamma-2 has Gln-272/Val-350. ADH3*1 is associated with a fast rate of ethanol oxidation and ADH3*2 with a slow rate.
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.
Caution	The reference genome assembly, GRCh37, describes a non-functional copy of that gene with a stop codon at position 78. However, this premature stop codon is not present in available mRNAs.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Metal-binding NAD Zinc
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ethanol oxidation Inferred from direct assay PubMed 6391957. Source: UniProtKB xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	alcohol dehydrogenase (NAD) activity Inferred from direct assay PubMed 6391957. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.7

Chain

2 – 375

374

Alcohol dehydrogenase 1C

PRO_0000160664

Regions

Nucleotide binding

200 – 205

6

NAD

Nucleotide binding

293 – 295

3

NAD

Sites

Metal binding

47

1

Zinc 1; catalytic

Metal binding

68

1

Zinc 1; catalytic

Metal binding

98

1

Zinc 2

Metal binding

101

1

Zinc 2

Metal binding

104

1

Zinc 2

Metal binding

112

1

Zinc 2

Metal binding

175

1

Zinc 1; catalytic

Binding site

224

1

NAD

Binding site

229

1

NAD

Binding site

370

1

NAD

Amino acid modifications

Modified residue

2

1

N-acetylserine

Natural variations

Natural variant

48

1

R → H. Ref.4
Corresponds to variant rs35385902 [ dbSNP | Ensembl ].

VAR_023992

Natural variant

166

1

P → S. Ref.4

VAR_023993

Natural variant

272

1

R → Q in allele ADH3*2/gamma-2. Ref.1 Ref.4 Ref.6
Corresponds to variant rs1693482 [ dbSNP | Ensembl ].

VAR_000428

Natural variant

350

1

I → V in allele ADH3*2/gamma-2. Ref.1 Ref.4 Ref.6
Corresponds to variant rs698 [ dbSNP | Ensembl ].

VAR_000429

Natural variant

352

1

P → T. Ref.4
Corresponds to variant rs35719513 [ dbSNP | Ensembl ].

VAR_023994

Experimental info

Sequence conflict

130

1

Missing AA sequence Ref.7

Sequence conflict

171

1

C → R in AAH67421. Ref.6

Secondary structure

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375

Helix Strand Turn

Details...

Beta strand

8 – 15

8

Beta strand

23 – 29

7

Beta strand

36 – 45

10

Helix

48 – 54

7

Beta strand

62 – 65

4

Beta strand

69 – 77

9

Beta strand

89 – 92

4

Beta strand

99 – 101

3

Helix

102 – 105

4

Beta strand

117 – 119

3

Beta strand

131 – 133

3

Beta strand

136 – 139

4

Turn

142 – 144

3

Beta strand

147 – 154

8

Helix

155 – 157

3

Beta strand

158 – 160

3

Helix

167 – 170

4

Helix

171 – 174

4

Helix

176 – 185

10

Turn

186 – 188

3

Beta strand

195 – 199

5

Helix

203 – 214

12

Beta strand

218 – 223

6

Helix

227 – 229

3

Helix

230 – 235

6

Beta strand

239 – 242

4

Helix

244 – 246

3

Helix

251 – 258

8

Turn

259 – 261

3

Beta strand

262 – 268

7

Helix

273 – 282

10

Turn

285 – 287

3

Beta strand

289 – 292

4

Beta strand

302 – 304

3

Helix

307 – 310

4

Beta strand

314 – 317

4

Helix

320 – 322

3

Helix

325 – 337

13

Helix

344 – 346

3

Beta strand

347 – 352

6

Helix

353 – 355

3

Helix

356 – 364

9

Beta strand

369 – 374

6

Sequences

	Sequence		Length	Mass (Da)
	P00326 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 414D73CC4C104C84	FASTA	375	39,868
	10 20 30 40 50 60 MSTAGKVIKC KAAVLWELKK PFSIEEVEVA PPKAHEVRIK MVAAGICRSD EHVVSGNLVT 70 80 90 100 110 120 PLPVILGHEA AGIVESVGEG VTTVKPGDKV IPLFTPQCGK CRICKNPESN YCLKNDLGNP 130 140 150 160 170 180 RGTLQDGTRR FTCSGKPIHH FVGVSTFSQY TVVDENAVAK IDAASPLEKV CLIGCGFSTG 190 200 210 220 230 240 YGSAVKVAKV TPGSTCAVFG LGGVGLSVVM GCKAAGAARI IAVDINKDKF AKAKELGATE 250 260 270 280 290 300 CINPQDYKKP IQEVLKEMTD GGVDFSFEVI GRLDTMMASL LCCHEACGTS VIVGVPPDSQ 310 320 330 340 350 360 NLSINPMLLL TGRTWKGAIF GGFKSKESVP KLVADFMAKK FSLDALITNI LPFEKINEGF 370 DLLRSGKSIR TVLTF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The gamma 1 and gamma 2 subunits of human liver alcohol dehydrogenase. cDNA structures, two amino acid replacements, and compatibility with changes in the enzymatic properties." Hoeoeg J.-O., Heden L.-O., Larsson K., Joernvall H. Eur. J. Biochem. 159:215-218(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GAMMA-2 GLN-272 AND VAL-350. Tissue: Liver.
[2]	"Three human alcohol dehydrogenase subunits: cDNA structure and molecular and evolutionary divergence." Ikuta T., Szeto S., Yoshida A. Proc. Natl. Acad. Sci. U.S.A. 83:634-638(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Molecular structure of the human alcohol dehydrogenase 3 gene." Yokoyama S., Matsuo Y., Rajasekharan S., Yokoyama R. Jpn. J. Genet. 67:167-171(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	NIEHS SNPs program Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-48; SER-166; GLN-272; VAL-350 AND THR-352.
[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], VARIANTS GAMMA-2 GLN-272 AND VAL-350. Tissue: Brain and Femoral artery.
[7]	"Human liver alcohol dehydrogenase. 2. The primary structure of the gamma 1 protein chain." Buhler R., Hempel J., Kaiser R., de Zalenski C., von Wartburg J.-P., Joernvall H. Eur. J. Biochem. 145:447-453(1984) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-375. Tissue: Liver.
[8]	"Three-dimensional structures of the three human class I alcohol dehydrogenases." Niederhut M.S., Gibbons B.J., Perez-Miller S., Hurley T.D. Protein Sci. 10:697-706(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NAD AND ZINC IONS.
[9]	"Structure of three class I human alcohol dehydrogenases complexed with isoenzyme specific formamide inhibitors." Gibbons B.J., Hurley T.D. Biochemistry 43:12555-12562(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) IN COMPLEX WITH NAD AND ZINC IONS.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X04299 mRNA. Translation: CAA27842.1.
X04350 mRNA. Translation: CAA27876.1.
M12272 mRNA. Translation: AAC41757.1.
D11067 Genomic DNA. Translation: BAC06856.1.
DQ088981 Genomic DNA. Translation: AAY68222.1.
AC097530 Genomic DNA. No translation available.
BC062476 mRNA. Translation: AAH62476.1.
BC066227 mRNA. Translation: AAH66227.1.
BC066228 mRNA. Translation: AAH66228.1.
BC067419 mRNA. Translation: AAH67419.1.
BC067420 mRNA. Translation: AAH67420.1.
BC067421 mRNA. Translation: AAH67421.1.
BC067422 mRNA. Translation: AAH67422.1.
BC074771 mRNA. Translation: AAH74771.1.
BC074786 mRNA. Translation: AAH74786.1.

IPI

IPI00465343.

PIR

DEHUAG. C25428.

RefSeq

NP_000660.1. NM_000669.3.

UniGene

Hs.654537.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DDA	model	-	A/B	1-375	[»]
1HT0	X-ray	2.00	A/B	2-375	[»]
1U3W	X-ray	1.45	A/B	2-375	[»]

ProteinModelPortal

P00326.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000209668.

PTM databases

PhosphoSite

P00326.

Polymorphism databases

DMDM

113398.

Proteomic databases

PRIDE

P00326.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

126.

KEGG

hsa:126.

Organism-specific databases

CTD

126.

GeneCards

GC04M100257.

HGNC

HGNC:251. ADH1C.

MIM

103730. gene.

neXtProt

NX_P00326.

PharmGKB

PA24572.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG000195.

InParanoid

P00326.

KO

K13951.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

SABIO-RK

P00326.

Gene expression databases

CleanEx

HS_ADH1C.

Genevestigator

P00326.

GermOnline

ENSG00000196616. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.
3.90.180.10. 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

P00326.

ChEMBL

CHEMBL3285.

DrugBank

DB01213. Fomepizole.
DB00157. NADH.

EvolutionaryTrace

P00326.

GenomeRNAi

126.

NextBio

503.

SOURCE

Search...

Entry information

Entry name

ADH1G_HUMAN

Accession

Primary (citable) accession number: P00326
Secondary accession number(s): Q4PJ18 , Q5WRV0, Q6LBW4, Q6NWV0, Q6NZA7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 141 of the entry and version 2 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.