Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 3 (HACD3)
The protein contains 362 amino acids for an estimated molecular weight of 43160 Da.
Catalyzes the third 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 catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation. Thereby, it participates 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 be involved in Rac1-signaling pathways leading to the modulation of gene expression. Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571). (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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:rs11632737 | |
| dbSNP:rs2279854 |
Biological Process
Activation of JUN kinase activity
Fatty acid elongation
I-kappaB kinase/NF-kappaB signaling
Positive regulation by virus of viral protein levels in host cell
Positive regulation of viral genome replication
Rac protein signal transduction
Rho protein signal transduction
Small GTPase mediated signal transduction
Sphingolipid biosynthetic process
Very long-chain fatty acid biosynthetic process
The reference OMIM entry for this protein is 615940
Protein tyrosine phosphatase-like a domain-containing protein 1; ptplad1
Butyrate-induced protein 1; bind1
3-@hydroxyacyl-coa dehydratase 3; hacd3
Very long chain-3-hydroxyacyl-coa dehydratase 3
DESCRIPTION
Long chain fatty acids (LCFAs) can be converted to very long chain fatty acids (VLCFAs) by endoplasmic reticulum (ER) membrane-bound enzymes in a 4-step cycle of condensation, reduction, dehydration, and further reduction, with 2 carbons added per cycle. PTPLAD1 belongs to a family of enzymes that catalyze the dehydration step of VLCFA synthesis (summary by Ikeda et al., 2008).CLONING
Using mouse Bind1 to probe a human brain cDNA library, Courilleau et al. (2000) cloned PTPLAD1, which they designated BIND1. The deduced 370-amino acid protein shares significant similarity with PTPLA (610467) and p23 (PTGES3; 607061). Northern blot analysis detected variable Bind1 expression in all mouse tissues examined, with highest expression in testis, kidney, brain, and liver, and much lower expression in skeletal muscle, spleen, and heart. Orthologs of PTPLAD1 were detected in C. elegans and yeast. By PCR of a HEK293 cell cDNA library, Ikeda et al. (2008) cloned PTPLAD1, which they designated HACD3. The deduced 362-amino acid protein has 6 transmembrane domains and a PTP-like motif between transmembrane domains 2 and 3. Northern blot analysis detected variable expression of a predominant 3.2-kb HACD3 transcript in all human tissues examined except leukocytes. Highest expression occurred in brain, kidney, liver, and placenta. Epitope-tagged HACD3 was expressed in the ER of transfected HeLa cells.GENE FUNCTION
Sodium butyrate is a reversible inhibitor of histone deacetylase (see 601241), resulting in histone hyperacetylation and changes in gene expression to induce differentiation and inhibit cell proliferation. Using differential display PCR analysis, Courilleau et al. (2000) found that sodium butyrate induced expression of mouse Bind1. Human BIND1 interacted directly with RAC1 (602048) in transfected cells and potentiated RAC1-induced activation of NFKB (see 164011) and JNK (see 601158). Using deletion analysis, Sabbah et al. (2006) identified elements in the human BIND1 promoter that mediated its activation by HDAC inhibitors. Ikeda et al. (2008) found that HACD3 affinity purified from transfected HeLa cells converted 3-hydroxypalmitoyl-CoA to 2,3-trans hexadecenoyl-CoA. Other members of the HACD enzyme family, including HACD1 (PTPLA), HACD2 (PTPLB; 615939), and HACD4 (PTPLAD2; 615941), showed the same activity, but each had distinct affinity and rate of reaction. Coimmunoprecipitation analysis of transfected HEK293T cells revealed that HACD3 preferentially interacted with several FA condensation enzymes (see 611813), likely in an FA elongase complex.GENE STRUCTURE
Sabbah et al. (2006) determined that the promoter region of PTPLAD1 contains proximal CG boxes and several binding sites for transcription factors.MAPPING
Hartz (2014) mapped the PTPLAD1 gene to chromosome 15q22.31 based on an alignment of the PTPLAD1 sequence (GenBank GENBANK AF161470) with the genomic sequence (GRCh38). ... More on the omim web site
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 615940 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).