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. 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 (6p25.2) in the minus strand and spans 29,095 bp.
mRNA
Transcript variants Transcript variantAccession #Length (nt)ExonsProtein isoformAccession #Length (aa)Molecular Weight (kDa)Variant 1NM_183373.418781-51NP_899229.223127Variant X2XM_011514393.417182-5X1XP_011512695.117019 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.
Domains and motifs
Post-translational modifications LocationKinaseFull nameS3cdc2Cyclin-dependent kinase 1T109PKCProtein Kinase CS118unsp-S130unsp-S150cdk5Cyclin-dependent kinase 5S176unsp-S202unsp-Y213unsp-T215PKGProtein Kinase GS218DNAPKDNA-dependent protein kinaseT227CKIICasein Kinase 2 Phosphorylation sites in PXDC1 protein.Sequence- and structure-based prediction of eukaryotic protein phosphorylation sites. Blom, N., Gammeltoft, S., and Brunak, S. Journal of Molecular Biology: 294(5): 1351-1362, 1999.
Residue S147 is also predicted to be O-GalNAc (mucin type) glycosylated.Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology.
Steentoft C, Vakhrushev SY, Joshi HJ, Kong Y, Vester-Christensen MB, Schjoldager KT, Lavrsen K, Dabelsteen S, Pedersen NB, Marcos-Silva L, Gupta R, Bennett EP, Mandel U, Brunak S, Wandall HH, Levery SB, Clausen H.
EMBO J, 32(10):1478-88, May 15, 2013.
(doi: 10.1038/emboj.2013.79. Epub 2013 Apr 12)
Structure
Subcellular localization Localized to the cytosolic face of the plasma membrane, and is associated peripherally.PSORT II Server [https://psort.hgc.jp/cgi-bin/runpsort.pl].
Protein interactions InteractorFull NameDescriptionScoreLIN7CProtein lin-7 homolog CPlays a role in establishing/maintaining the asymmetric distribution of channels/receptors at the plasma membrane of polarized cells.0.731RABGAP1LRab GTPase-activating protein 1-likeGTP-hydrolysis activating protein (GAP) for small GTPase RAB22A. Plays a role in endocytosis and intracellular protein transport.0.623LIN7BProtein lin-7 homolog BPlays a role in establishing/maintaining the asymmetric distribution of channels/receptors at the plasma membrane of polarized cells.0.610 Table 4. Common interactors that were found with PXDC1.EMBL-EBI IMEx [https://www.ebi.ac.uk/intact/imex/home.xhtml].
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. ClassGenus and SpeciesCommon NameTaxonomic GroupMedian Date of Divergence (MYA)Accession #Sequence Length (aa)Identity (%)Similarity (%)MammaliaHomo sapiensHumanPrimates0NP_899229.2 231100100MammaliaMus musculusMouseRodents87NP_080107.32319294MammaliaPhascolarctos cinereusKoalaMarsupials160XP_020829466.12319094MammaliaNotamacropus eugeniiTammar wallabyMarsupials160XP_072459796.12318994MammaliaOrnithorhynchus anatinusPlatypusMonotremes180XP_001508393.12318792AvesGallus gallusChickenFowl319XP_040520929.12318492ReptiliaPogona vitticepsCentral bearded dragonSquamata319XP_020645452.12318692ReptiliaMauremys muticaYellowpond turtleTurtles319XP_044863675.12318692AmphibiaAmbystoma mexicanumAxolotlSalamanders352XP_069469606.12318692AmphibiaMicrocaecilia unicolorTiny cayenne caecilianCaecilians352XP_030064485.12308592AmphibiaBufo bufoCommon toadAnura352XP_040288672.12318191FishProtopterus annectensWest African lungfishLobe-finned fish408XP_043937493.12317387FishLatimeria chalumnaeWest Indian Ocean coelacanthLobe-finned fish415XP_006007320.12318490FishSeriola dumeriliGreater amberjackRay-finned fish429XP_022604539.12337386FishLiparis tanakaeTanaka's snailfishRay-finned fish429TNN44386.12307386FishCarcharodon carchariasGreat white sharkSharks462XP_041039133.12287689FishPristiophorus japonicusJapanese sawsharkSawsharks462XP_070735904.12287688FishCallorhinchus miliiElephant sharkChimaeras462XP_007900829.12307486FishLeucoraja erinaceusLittle skateSkates462XP_055509634.12276276FishMyxine glutinosaAtlantic hagfishHagfish563XP_067972370.12633648 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. ProteinAccession #Sequence Length (aa)Similarity (%)Domain Similarity (%)PXDC1NP_899229.2 231100100HS1BP3NP_071905.339218.428.6SNX3NP_003786.116222.126.3SNX11AAD27834.126424.521.4SNX12AAD48491.116222.321.2SNX24NP_054754.11692720.1SNX10AAD27833.120124.717.9SNX22NP_079074.219311.29
Clinical significance 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. 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 than 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.
References