Online Mendelian Inheritance in Man (OMIM)

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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 and Expression

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 AF161470) with the genomic sequence (GRCh38).