PXDC1

The PX (Phox homology) domain-containing 1, also known as PXDC1 and C6orf145, is a protein which in humans is encoded by the protein coding gene PXDC1. Transcript variant 1 is the longest transcript at 1,878 bp and encodes the longest isoform which is 231 amino acids long.^[5] It is predicted to be involved in enabling phosphatidylinositol binding activity. The tissues with the highest expression include the liver, placenta, and gallbladder.^[6]

PXDC1 is also known as c6orf145.^[6]

Homo sapiens PXDC1 transcript variant 1 contains 8 exons, with 5 of them in the coding sequence.^[5]

Found on chromosome 6 (6p25.2) in the minus strand and spans 29,095 bp.^[6]

Transcript variants of PXDC1 gene.^[5][7][8]

PXDC1 is ubiquitously expressed in variable amounts across all tissues. The fold difference in expression ranges from 2x-11x. The tissues with the highest expression are the liver, placenta, kidney, and gallbladder.^[6]

Sources:^[5][9][10]

Transcript variants are shown in previous mRNA heading. These encode two isoforms:^[5]

• PXDC1 isoform 1: 231 amino acids
• PXDC1 isoform X1: 170 amino acids

The information below pertains to isoform 1.

The mass of the protein is about 27 kDa and has a pI of 5.^[11][12] The composition of amino acids is comparable to that of a typical human protein, however the difference between the number of lysine and arginine residues compared to that of glutamate and aspartate is negative compared to the average human protein.^[13] This is consistent with the observed pI, which indicates acidity.

Phosphorylation sites in PXDC1 protein.^[15]

Residue S147 is also predicted to be O-GalNAc (mucin type) glycosylated.^[16]

Localized to the cytosolic face of the plasma membrane, and is associated peripherally.^[19][20]

Table 4. Common interactors that were found with PXDC1.^{[21][22][23][24]}

PXDC1 orthologs are present in mammals, birds, reptiles, amphibians, bony fish, cartilaginous fish, and jawless fish, but not in any invertebrates, plants, protists, fungi, or bacteria. The protein sequence is highly conserved with over 75% similarity back to cartilaginous fish.^[25]

Table of orthologs to human PXDC1.

PXDC1 has a slow evolution rate compared to that of the fibrinogen alpha chain. It has a speed similar to that of cytochrome c.^[5][27]

There are no direct paralogs of PXDC1, however, there are 49 proteins in humans that also contain the PX domain.^[28] Within this superfamily, there is a class of proteins similar to PXDC1 in that the only domain present is PX. These are highlighted in the table below.^[29]

Various studies have been conducted in which PXDC1 expression levels have been monitored. In dioxin (TCDD) sensitive mice, PXDC1 expression in the liver significantly repressed after exposure. This suggests PXDC1 may have a role in sensitivity to this toxin.^[30] Another study showed that in the process of differentiation of dental pulp stem cells, PXDC1 was one of the genes whose expression was significantly down-regulated. This suggests it has a role in osteo/odontoblast differentiation.^[31] It has also been shown that PXDC1 has a parent-of-origin expression bias, which favored the paternal allele. It is also less that 100 kB away from a known imprinted gene FAM50B.^[32] Along with this, PXDC1 had a 2:1 paternal expression bias in lymphoblastoid cell lines and whole blood.^[33]