Alcohol dehydrogenase class-3 (ADH5)
The protein contains 374 amino acids for an estimated molecular weight of 39724 Da.
Catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione (PubMed:8460164). Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate (PubMed:16081420). Class-III ADH is remarkably ineffective in oxidizing ethanol (PubMed:8460164). (updated: July 31, 2019)
Protein identification was indicated in the following studies:
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs28730623 | |
| dbSNP:rs28730628 | |
| dbSNP:rs16996593 |
No binding partner found
Biological Process
Ethanol oxidation
Fatty acid omega-oxidation
Formaldehyde catabolic process
Peptidyl-cysteine S-nitrosylation
Positive regulation of blood pressure
Respiratory system process
Response to lipopolysaccharide
Response to nitrosative stress
Response to redox state
Retinoid metabolic process
Molecular Function
Alcohol dehydrogenase activity, zinc-dependent
Electron transfer activity
Fatty acid binding
Formaldehyde dehydrogenase activity
Identical protein binding
S-(hydroxymethyl)glutathione dehydrogenase activity
S-(hydroxymethyl)glutathione dehydrogenase NAD activity
S-(hydroxymethyl)glutathione dehydrogenase NADP activity
Zinc ion binding
The reference OMIM entry for this protein is 103710
Alcohol dehydrogenase 5, chi polypeptide; adh5
Alcohol dehydrogenase, chi isozyme
Adh, class iii; adhx
Formaldehyde dehydrogenase; fdh
Formaldehyde dehydrogenase, glutathione-dependent
S-nitrosoglutathione reductase; gsnor
DESCRIPTION
There are at least 7 alcohol dehydrogenase (ADH) genes that catalyze the conversion of alcohols to aldehydes. Seven genes exist in a cluster on chromosome 4q (see ADH1A, 103700). ADH class III (ADH5; EC 1.1.1.1) is a zinc-containing dimeric enzyme responsible for the oxidation of long-chain alcohols and omega-hydroxy fatty acids. Unlike ADH classes I and II, ADH class III does not metabolize ethanol (Goldman et al., 1989). ADH5 is the same as formaldehyde dehydrogenase (FDH; EC 1.2.1.1), a widely occurring enzyme that catalyzes the oxidation of S-hydroxymethylglutathione, formed from formaldehyde and glutathione, into S-formylglutathione in the presence of NAD (Koivusalo et al., 1989).CLONING
Adinolfi et al. (1984) purified the chi isozyme of ADH (ADH5) from human liver and used it to raise immune sera. Its immunologic properties suggested that it has no structural similarity to either class I (see ADH1A, 103700) or class II (ADH4; 103740) isozymes. The chi isozyme was found in most human tissues, including fetal specimens of 16 weeks gestational age, and showed a preference for long chain primary alcohols with a double bond in the beta position and complex alcohols of high molecular weight, such as cinnamyl alcohol. Adinolfi et al. (1984) concluded that the locus, designated ADH5, has a separate evolutionary origin from class I and II ADH genes. Using oligonucleotide probes based on the peptide sequence of human class III ADH, Sharma et al. (1989) screened a human placenta cDNA library and isolated an incomplete cDNA clone, which they used to obtain a full-length clone from a human testicular library. The encoded protein was identical to the enzyme purified from human liver by Adinolfi et al. (1984). Goldman et al. (1989) isolated and sequenced a full-length cDNA for ADH5, the class III alcohol dehydrogenase. In contrast to other ADHs whose expression is more restricted, ADH5 was found to be expressed ubiquitously in human and rodent tissues. Giri et al. (1989) reported 2 possible translation initiation sites that would produce proteins of 374 and 392 amino acid residues. Class III ADH shared highest sequence identity with class II ADH. Beisswenger et al. (1985) showed that ADH-chi is the only ADH isozyme in brain. By examining amino acid sequences and structural and kinetic properties, Koivusalo et al. (1989) determined that ADH class III and glutathione-dependent formaldehyde dehydrogenase are identical enzymes. - Pseudogenes Matsuo and Yokoyama (1990) demonstrated a processed pseudogene most likely derived from the ADH5 gene. Hur and Edenberg (1992) isolated several ADH5 processed pseudogenes.GENE STRUCTURE
Hur and Edenberg (1992) determined that the ADH5 gene contains 9 exons. Its 5-prime region contains consensus binding sites for several transcriptional regulatory proteins.MAPPING
By analysis of gene products in starch gel electrophoresis, Carlock et al. (1985) assigned the class III ADH locus to chromosome 4q21-q25. Smith (1986) gave the regional assignment as 4q21-q24. By analysis of human/hamster hybrid cell lines, Goldman et al. (1989) mapped ADH5 to chromosome 4 where other ADH genes had been located. Analysis of mouse/hamster hybrid cell lines showed that the corresponding gene maps to mouse chromosome 3, which carries the other murine ADH genes. Meera Khan et al. (1984), Van Cong et al. (1985), Hiroshige et al. (1985), and van der Goes et al. (1985) mapped the FDH ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: OMIM entry 103710 was added.
Aug. 19, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).