Draft:PCNX4

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Pecanex-like protein 4 (PCNX4) is a protein which in humans is encoded by the PCNX4 gene[1]. PCNX4 is a gene expressed moderately in 27 different tissue types in humans, but most abundantly in brain, endometrium, prostate, and adrenal tissue[1]. Its likely function is a transmembrane protein in the endoplasmic reticulum[2].

Gene

Figure 2. Chromosome 14 gene locations; PCNX4 and surrounding neighbors.

PCNX4 is a protein encoding gene located on chromosome 14 in Homo sapiens at location q23.1 (see Figure 1)[3].Neighboring genes to PCNX4 are LRRC9 on the positive strand and DHRS7 on the bottom strand[1]. LRRC9 is expressed most in the testis—a leucine rich repeat; while DHRS7 a dehydrogenase/reductase is expressed most in the prostate, similar to PCNX4 [4][5].

Figure 1. Annotated Homo sapiens chromosome 14. Shaded areas demonstrate gene locations on the chromosome. PCNX4 is indicated by the red line at shaded region q23.1. The gene is also located on the plus-strand.

Other names for this gene are: PCNXL4, C14orf135, Chromosome 14 open reading frame 135, Hepatitis C Virus F Protein-Binding Protein 2, and HCV F Protein-Binding Protein 2[3].

Expression

Expression of this gene can be predominately seen in the endometrium, prostate, and adrenal, but is known to be expressed in 27 total tissue types[1]. Overall, there are some clear levels of expression in reproductive tissues, brain, and GI organs seen in multiple different tissue analysis[1].

Throughout early development, the expression of PCNX4 is variable to an adult and can be as high as two-fold to normal adult expression patterns[1].

mRNA

The protein sequence of PCNX4, isoform 1, includes 15 transmembrane regions, 2 glycosylation sites, and 12 exons[6]. PCNX4 has two isoforms with isoform-1 being the longest while isoform-2 has missing exons or shorter N-terminus'[3].

Protein

The PCNX4 protein molecular weight is approximately 133 kDa with an amino acid makeup of 1,172[3][6]. The isoelectric point is 5.9[7]. The classification type is a transmembrane protein[2].

Structure

The structure of PCNX4 can be seen in figures 3 & 4. Figure 3 contains 13 beta strands and 16 alpha helices. Figure 4 contain 5 beta strands and 24 alpha helices. Both figures make up the entire human PXNC4 protein together.

Figure 3. PCNX4 I-TASSER predicted transmembrane structure[8].
Figure 4. PCNX4 I-TASSER predicted structure of non-transmembrane region and Pecanx-4 domain[8].

Background

Graph 1. Evolutionary history of human PCNX4 orthologs in relation to the evolution in cytochrome c and fibrinogen alpha.

The evolution of the PCNX4 protein can be visualized along with cytochrome c and fibrinogen alpha as references of known evolution rates in graph 1. Cytochrome c has a small and conserved sequence compared to fibrinogen alpha which has a larger and more malleable sequence. Based on the trends provided by multiple ortholog sequences, PCNX4 illustrates a moderately evolved protein. Its sequence is fairly large, but is not as changed in terms of fibrinogen alpha.

Orthology

PCNX4 is found to have around 600 vertebrate orthologs[9]. Some additional orthologs include invertebrates such as Arachnida, Bivalvia, and Echinoidea. Orthologs are not present in land plants and bacteria.

Paralogs

Figure 5. Sequence alignment of all 4 known PCNX proteins[10].

An important paralog to PCNX4 is PCNX3[3]. PCNX1 and PCNX2 exists, but they are not as closely related to PCNX4. When comparing protein sequences, the four different PCNX do not align as closely as even close orthologs do, see Figure 5.

Table 1. Twenty-four PCNX4 orthologs including additional information relating to sequence relatedness and history. Colors added to highlight similarities within taxonomic groups.

Protein sub-cellular localization

Mostly, PCNX4 is found to be in the ER, cytosol, and plasma membrane[2][11]. With no signifiant signal peptides identified, it is also congruent with being local and not traveling to areas such as the nucleus in the cell[12].

Protein analysis

PCNX4 is rich in hydrophobic amino acids, somewhat more rich than the average human protein. This is likely due to its high count of transmembrane domains[13].

Clinical significance

Current literature contains some information of PCNX4 in relation to the study of mental illness in women, such as major depressive disorder[14]. Torii et al. found that in women, for early onset major depressive disorder, expression of PCNX4 was higher due to the expression of the gene in the brain and in the reproductive tissue. The expression of PCNX4 in the tissues leads to a possible additive effect for women’s susceptibility to mental health ailments.

Conceptual translation

Figure 6. Conceptual translation of human PCNX4 protein. Important features are marked such as exon boundaries, transmembrane domains, protein domain, conserved amino acids, and glycosylation sites.

Conserved amino acids were determined by preservation throughout orthologs when aligned with Clustal Omega[10]. From there, 20% of the amino acids were bolded on the conceptual translation (figure 6).


References

  1. ^ a b c d e f "Pecanx-4 [Homo sapiens (Human)] -Gene-NCBI". National Center for Biotechnology Information, U.S. National Library of Medicine.
  2. ^ a b c "PCNX4 -DeepLoc". DTU Health Tec- DeepLoc.
  3. ^ a b c d e "PCNX4 Gene". GeneCards.
  4. ^ "LRRC9 leucine rich repeat containing 9 [Homo sapiens (human)]-Gene-NCBI". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "DHRS7B dehydrogenase/reductase 7B [Homo sapiens (human)]-Gene-NCBI". National Center for Biotechnology Information, U.S. National Library of Medicine.
  6. ^ a b "Pecanx-4 [Homo sapiens (Human)] -Protein NCBI". National Center for Biotechnology Information, U.S. National Library of Medicine.
  7. ^ "PCNX4". Expasy.
  8. ^ a b "I-TASSER". Protein Structure and Function Predictions.
  9. ^ "PCNX4 [Homo sapiens (Human)] -Orthologs -NCBI". National Center for Biotechnology Information, U.S. National Library of Medicine.
  10. ^ a b "Clustal Omega; Multiple Sequence Alignment". EMBL's European Bioinformatics Institute.
  11. ^ "PCNX4". Human Protein Atlas.
  12. ^ "PCNX4 -SignalP". DTU Health Tech -SignalP.
  13. ^ "PCNX4 SAPS". SAPS Sequence Statistics.
  14. ^ Torii; Ohi; Fujikane; Takai; Kuramitsu; Muto; Sugiyama; Shioiri (2024-06-7). "Tissue-specific gene expression of genome-wide significant loci associated with major depressive disorder subtypes". Progress in Neuropsychopharmacology & Biological Psychiatry. 133: 7. doi:10.1016/j.pnpbp.2024.111019. PMID 38663672 – via ELSEVIER. {{cite journal}}: Check date values in: |date= (help)
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