PXDC1

The PX 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. It is predicted to be involved in enabling phosphatidylinositol binding activity. The tissues with the highest expression include the liver, placenta, and gallbladder.

Gene

Common Aliases

PXDC1 is also known as c6orf145.

Number of Exons

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

Span of Gene

Found on chromosome 6 in the minus strand and spans 29,095 bp.

mRNA

Transcript Variants

Transcript variants of PXDC1 gene.

Expression Pattern

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.

Conceptual Translation

Sources:

Protein

Known Isoforms

Transcript variants are shown in previous mRNA heading. These encode two isoforms:

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

The information below pertains to isoform 1.

MW, pI, Amino Acid Composition

The mass of the protein is about 27 kDa and has a pI of 5. 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. This is consistent with the observed pI, which indicates acidity.

Post-Translational Modifications

Phosphorylation sites in PXDC1 protein.
Residue S147 is also predicted to be O-GalNAc glycosylated.

Subcellular Localization

Localized to the cytosolic face of the plasma membrane, and is associated peripherally.

Protein Interactions

Table 4. Common interactors that were found with PXDC1.

Homology

Orthologs

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.

Class	Genus and Species	Common Name	Taxonomic Group	Median Date of Divergence	Accession #	Sequence Length	Identity	Similarity
Mammalia	Homo sapiens	Human	Primates	0	NP_899229.2	231	100	100
Mammalia	Mus musculus	Mouse	Rodents	87	NP_080107.3	231	92	94
Mammalia	Phascolarctos cinereus	Koala	Marsupials	160	XP_020829466.1	231	90	94
Mammalia	Notamacropus eugenii	Tammar wallaby	Marsupials	160	XP_072459796.1	231	89	94
Mammalia	Ornithorhynchus anatinus	Platypus	Monotremes	180	XP_001508393.1	231	87	92
Aves	Gallus gallus	Chicken	Fowl	319	XP_040520929.1	231	84	92
Reptilia	Pogona vitticeps	Central bearded dragon	Squamata	319	XP_020645452.1	231	86	92
Reptilia	Mauremys mutica	Yellowpond turtle	Turtles	319	XP_044863675.1	231	86	92
Amphibia	Ambystoma mexicanum	Axolotl	Salamanders	352	XP_069469606.1	231	86	92
Amphibia	Microcaecilia unicolor	Tiny cayenne caecilian	Caecilians	352	XP_030064485.1	230	85	92
Amphibia	Bufo bufo	Common toad	Anura	352	XP_040288672.1	231	81	91
Fish	Protopterus annectens	West African lungfish	Lobe-finned fish	408	XP_043937493.1	231	73	87
Fish	Latimeria chalumnae	West Indian Ocean coelacanth	Lobe-finned fish	415	XP_006007320.1	231	84	90
Fish	Seriola dumerili	Greater amberjack	Ray-finned fish	429	XP_022604539.1	233	73	86
Fish	Liparis tanakae	Tanaka's snailfish	Ray-finned fish	429	TNN44386.1	230	73	86
Fish	Carcharodon carcharias	Great white shark	Sharks	462	XP_041039133.1	228	76	89
Fish	Pristiophorus japonicus	Japanese sawshark	Sawsharks	462	XP_070735904.1	228	76	88
Fish	Callorhinchus milii	Elephant shark	Chimaeras	462	XP_007900829.1	230	74	86
Fish	Leucoraja erinaceus	Little skate	Skates	462	XP_055509634.1	227	62	76
Fish	Myxine glutinosa	Atlantic hagfish	Hagfish	563	XP_067972370.1	263	36	48

Table of orthologs to human PXDC1.

Evolution Speed

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

Paralogs

There are no direct paralogs of PXDC1, however, there are 49 proteins in humans that also contain the PX domain. 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.

Protein	Accession #	Sequence Length	Similarity	Domain Similarity
PXDC1	NP_899229.2	231	100	100
HS1BP3	NP_071905.3	392	18.4	28.6
SNX3	NP_003786.1	162	22.1	26.3
SNX11	AAD27834.1	264	24.5	21.4
SNX12	AAD48491.1	162	22.3	21.2
SNX24	NP_054754.1	169	27	20.1
SNX10	AAD27833.1	201	24.7	17.9
SNX22	NP_079074.2	193	11.2	9

Clinical Significance

Various studies have been conducted in which PXDC1 expression levels have been monitored. In dioxin sensitive mice, PXDC1 expression in the liver significantly repressed after exposure. This suggests PXDC1 may have a role in sensitivity to this toxin. 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. 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. Along with this, PXDC1 had a 2:1 paternal expression bias in lymphoblastoid cell lines and whole blood.