Very-long-chain 3-oxoacyl-CoA reductase (HSD17B12)
The protein contains 312 amino acids for an estimated molecular weight of 34324 Da.
Catalyzes the second of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme has a 3-ketoacyl-CoA reductase activity, reducing 3-ketoacyl-CoA to 3-hydroxyacyl-CoA, within each cycle of fatty acid elongation. Thereby, it may participate in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May also catalyze the transformation of estrone (E1) into estradiol (E2) and play a role in estrogen formation. (updated: Oct. 25, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
This protein is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs11555762 |
Biological Process
Cellular lipid metabolic process
Estrogen biosynthetic process
Extracellular matrix organization
Fatty acid biosynthetic process
Long-chain fatty-acyl-CoA biosynthetic process
Positive regulation of cell-substrate adhesion
Small molecule metabolic process
Triglyceride biosynthetic process
Cellular Component
Endoplasmic reticulum membrane
Extracellular matrix
Fatty acid elongase complex
Integral component of membrane
Proteinaceous extracellular matrix
Molecular Function
17-beta-hydroxysteroid dehydrogenase (NAD+) activity
17-beta-hydroxysteroid dehydrogenase (NADP+) activity
3-oxo-arachidoyl-CoA reductase activity
3-oxo-behenoyl-CoA reductase activity
3-oxo-cerotoyl-CoA reductase activity
3-oxo-lignoceroyl-CoA reductase activity
Collagen binding
Estradiol 17-beta-dehydrogenase activity
Fibronectin binding
Heparin binding
Long-chain-3-hydroxyacyl-CoA dehydrogenase activity
Long-chain-fatty-acyl-CoA reductase activity
The reference OMIM entry for this protein is 609574
17-@beta-hydroxysteroid dehydrogenase xii; hsd17b12
17-@beta-hsd xii
3-@ketoacyl-coa reductase; kar
DESCRIPTION
The enzyme 17-beta hydroxysteroid dehydrogenase-12 (HSD17B12) uses NADPH to reduce 3-ketoacyl-CoA to 3-hydroxyacyl-CoA during the second step of fatty acid elongation.CLONING
Using BLAST analysis with the sequence of yeast genes encoding a 3-ketoacyl-CoA reductase as query, Moon and Horton (2003) identified human and mouse cDNAs corresponding to HSD17B12. The human HSD17B12 gene encodes a protein of 312 amino acids containing a dilysine endoplasmic reticulum (ER)-retention motif at the C terminus and 4 predicted transmembrane domains. Mouse and human HSD17B12 share 82% amino acid identity. Northern blot analysis showed expression of a 2.9-kb HSD17B12 transcript in all human tissues tested, with highest levels seen in liver, muscle, and kidney. Using immunofluorescence, Moon and Horton (2003) showed that HSD17B12 localizes to the ER.GENE FUNCTION
Moon and Horton (2003) showed that KAR functions as a 3-ketoacyl-CoA reductase, reducing both long chain 3-ketoacyl-CoAs and long chain fatty acyl-CoAs. Analysis of liver HSD17B12 mRNA in transgenic mice with altered levels of sterol regulatory element-binding proteins (SREBPs; see 184756) showed no change in HSD17B12 expression compared to wildtype mice, suggesting that HSD17B12 is not regulated by SREBPs. ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 609574 was added.