Persius/hicric huggingface dataset:
PEG10
Retrotransposon-derived protein PEG10 is a protein that in humans is encoded by the PEG10 gene.

# Function
This gene includes two overlapping reading frames of the same transcript encoding distinct isoforms. The shorter isoform has a CCHC-type zinc finger motif containing a sequence characteristic of gag proteins of most retroviruses and some retrotransposons, and it functions in part by interacting with members of the TGF-beta receptor family. The longer isoform has the active-site DSG consensus sequence of the protease domain of pol proteins. The longer isoform is the result of -1 translational frameshifting that is also seen in some retroviruses. Expression of these two isoforms only comes from the paternal allele due to imprinting. Increased gene expression (as observed by an increase in mRNA levels) is associated with hepatocellular carcinomas.
PEG10 is a paternally expressed imprinted gene that is expressed in adult and embryonic tissues. Most notable expression occurs in the placenta. This gene is highly conserved across mammalian species and retains the heptanucleotide (GGGAAAC). This gene has been reported to play a role in cell proliferation, differentiation and apoptosis. Overexpression of this gene has been associated with several malignancies, such as hepatocellular carcinoma and B-cell lymphocytic leukemia. Knockout mice lacking this gene showed early embryonic lethality with placental defects, indicating the importance of this gene in embryonic development. In preeclampsia placental tissue, PEG10 has been shown to be downregulated and upregulated implicating it as a possible causal role in the occurrence of preeclampsia.

# Interactions
PEG10 has been shown to interact with SIAH2 and SIAH1.
PEPAP
PEPAP is an opioid analgesic that is an analogue of pethidine (meperidine).
It is related to the drug MPPP, with a phenethyl group in place of the 1-methyl substitution and an acetate ester rather than propionate.
PEPAP presumably has similar effects to other opioids, producing analgesia, sedation and euphoria. Side effects can include itching, nausea and potentially serious respiratory depression which can be life-threatening.
PEPAP could be particularly dangerous as it has been found to be a potent CYP2D6 inhibitor, which makes it likely to cause adverse interactions with some other drugs.
It is however not known whether the byproducts formed during the synthesis of PEPAP are neurotoxic in the same way as the MPPP byproduct MPTP.
PEX10
Peroxisome biogenesis factor 10 is a protein that in humans is encoded by the PEX10 gene. Alternative splicing results in two transcript variants encoding different isoforms.

# Function
Peroxisome biogenesis factor 10 is involved in import of peroxisomal matrix proteins. This protein localizes to the peroxisomal membrane.

# Clinical significance
Mutations in this gene result in phenotypes within the Zellweger spectrum of peroxisomal biogenesis disorders, ranging from neonatal adrenoleukodystrophy to Zellweger syndrome.

# Interactions
PEX10 has been shown to interact with PEX12 and PEX19.
PEX12
Peroxisome assembly protein 12 is a protein that in humans is encoded by the PEX12 gene.

# Function
PEX12 is needed for protein import into peroxisomes. This gene belongs to the peroxin-12 family. Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes.

# Clinical significance
The peroxisome biogenesis disorders (PBDs; MIM 601539) are a group of genetically heterogeneous diseases that are usually lethal in early infancy. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. This cellular phenotype is shared by yeast 'pex' mutants, and human orthologs of yeast PEX genes defective in some PBD complementation groups (CGs).

# Interactions
PEX12 has been shown to interact with PEX10, PEX5 and PEX19.
PHKG2
Phosphorylase b kinase gamma catalytic chain, testis/liver isoform is an enzyme that in humans is encoded by the PHKG2 gene.
The PHKG2 gene provides instructions for making one piece, the gamma subunit, of the phosphorylase b kinase enzyme. This enzyme is made up of 16 subunits, four each of the alpha, beta, gamma, and delta subunits. (Each subunit is produced from a different gene.) The gamma subunit performs the function of phosphorylase b kinase enzyme, and the other subunits help regulate its activity. This enzyme is found in various tissues, although it is most abundant in the liver and muscles. One version of the enzyme is found in liver cells and another in muscle cells. The gamma-2 subunit produced from the PHKG2 gene is part of the enzyme found in the liver.
Phosphorylase b kinase plays an important role in providing energy for cells. The main source of cellular energy is a simple sugar called glucose. Glucose is stored in muscle and liver cells in a form called glycogen. Glycogen can be broken down rapidly when glucose is needed, for instance to maintain normal levels of glucose in the blood between meals. Phosphorylase b kinase turns on (activates) another enzyme called glycogen phosphorylase b by converting it to the more active form, glycogen phosphorylase a. When active, this enzyme breaks down glycogen.
PI4KA
Phosphatidylinositol 4-kinase alpha is an enzyme that in humans is encoded by the PI4KA gene.

# Function
This gene encodes a 1-phosphatidylinositol 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. Two transcript variants encoding different isoforms have been described for this gene.

# Clinical significance
The alpha isoform of PI4KIII plays a role in replication of hepatitis C virus (HCV). Furthermore, the PI4KA lipid kinase affects HCV replication by altering phosphorylation of the HCV NS5A protein.
PI4KB
Phosphatidylinositol 4-kinase beta is an enzyme that in humans is encoded by the PI4KB gene.

# Classification
This gene encodes a phosphatidylinositol 4-kinase which catalyzes phosphorylation of phosphatidylinositol at the D-4 position, yielding phosphatidylinositol 4-phosphate (PI4P). Besides the fact, that PI4P serves as a precursor for other important phosphoinositides, such as phosphatidylinositol 4,5-bisphosphate, PI4P is an essential molecule in the cellular signaling and trafficking especially in the Golgi apparatus and the trans Golgi network.
Phosphatidylinositol 4-kinases are evolutionary conserved among eukaryotes and include four human isoforms
- phosphatidylinositol 4-kinase alpha (PI4KA)
- phosphatidylinositol 4-kinase beta (PI4KB)
- phosphatidylinositol 4-kinase 2-alpha (PI4K2A)
- phosphatidylinositol 4-kinase 2-beta (PI4K2B)

# Function
Phosphatidylinositol 4-kinase beta (PI4KB) is a soluble protein shuttling between the cytoplasm and the nucleus, and can be recruited to the membranes of the Golgi system via protein-protein interactions, e.g. with small GTP binding proteins Arf1 and Rab11, or a Golgi adaptor protein ACBD3. PI4KB can be phosphorylated by the protein kinase D, which promotes the interaction with 14-3-3 proteins and stabilization of the protein in its active conformation. In cytoplasm PI4KB regulates the trafficking from the Golgi system to the plasma membrane, nevertheless, its nuclear function remains to be determined.

# Clinical significance
A wide range of positive-sense single-stranded RNA viruses (e.g. picornaviruses) including many important human pathogens hijack human PI4KB kinase to generate specific PI4P-enriched organelles called membranous webs. These organelles are then used as specific platforms for the effective viral replication within the host cell.
Furthermore, PI4KB homologue from the protozoan parasite Plasmodium falciparum has been identified as a target of imidopyrazines, an antimalarial compound class.

# Structure
PI4KB is composed of a proline-rich N-terminal region, a central helical domain, and a kinase domain located C-terminally. The N-terminal region contains a physiologically important binding site for a Golgi adaptor protein ACBD3, but is likely disordered and dispensable for the kinase activity. The central helical domain is responsible for the interaction with a small guanosine triphosphatase Rab11. The kinase domain can be divided into N-terminal and C-terminal lobes with the ATP binding groove and putative phosphatidylinositol binding pocket in a cleft between the lobes. In addition, an ALPS motif has been identified in the extreme C-terminal region of PI4KB, which favors its association with unsaturated or loosely packed membranes regions.
PILRA
Paired immunoglobin like type 2 receptor alpha is a protein that in humans is encoded by the PILRA gene.

# Function
Cell signaling pathways rely on a dynamic interaction between activating and inhibiting processes. SHP-1-mediated dephosphorylation of protein tyrosine residues is central to the regulation of several cell signaling pathways. Two types of inhibitory receptor superfamily members are immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing receptors and their non-ITIM-bearing, activating counterparts.
Control of cell signaling via SHP-1 is thought to occur through a balance between PILRalpha-mediated inhibition and PILRbeta-mediated activation. These paired immunoglobulin-like receptor genes are located in a tandem head-to-tail orientation on chromosome 7. This particular gene encodes the ITIM-bearing member of the receptor pair, which functions in the inhibitory role. Alternative splicing has been observed at this locus, and three variants, each encoding a distinct isoform, are described.
PITX1
paired-like homeodomain 1 is a protein that in humans is encoded by the PITX1 gene.

# Function
This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family are involved in organ development and left-right asymmetry. This protein acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin.

# Clinical relevance
Mutations in this gene have been associated with autism, club foot and polydactyly in humans.

# Genetic Basis of Pathologies
Genomic rearrangements at the PITX1 locus are associated with Liebenberg syndrome. In PITX1 Liebenberg is associated with a translocation or deletions, which cause insert promoter groups into the PITX1 locus.  A missense mutation within the PITX1 locus is associated with the development of autosomal dominant clubfoot.

# Interactions
PITX1 has been shown to interact with Pituitary-specific positive transcription factor 1.
PITX3
Pituitary homeobox 3 is a protein that in humans is encoded by the PITX3 gene.

# Function
This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family act as transcription factors. This protein is involved in lens formation during eye development, and the specification and terminal differentiation of mesencephalic dopamine neurons in the substantia nigra compacta that are lost in Parkinson's disease.

# Clinical significance
Mutations of this gene have been associated with anterior segment mesenchymal dysgenesis (ASMD) and congenital cataracts.
PLCB1
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-1 is an enzyme that in humans is encoded by the PLCB1 gene.

# Function
The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene.

# Interactions
PLCB1 has been shown to interact with TRPM7.

# Pathology
Homozygous PLCB1 deletion is associated with malignant migrating partial seizures in infancy.
PLCB3
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-3 is an enzyme that in humans is encoded by the PLCB3 gene.
The gene codes for the enzyme phospholipase C 3. The enzyme catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11, as well as G-beta gamma subunits.

# Interactions
PLCB3 has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2.
PLCE1
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase epsilon-1 (PLCE1) is an enzyme that in humans is encoded by the PLCE1 gene. This gene encodes a phospholipase enzyme (PLCE1) that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate two second messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). Mutations in this gene cause early-onset nephrotic syndrome and have been associated with respiratory chain deficiency with diffuse mesangial sclerosis.

# Structure
PLCE1 is located on the q arm of chromosome 10 in position 23.33 and has 39 exons. PLCE1, the protein encoded by this gene, is located on the Golgi apparatus, the cell membrane, and in the cytosol. It contains 3 turns, 15 beta strands, and 6 alpha helixes. PLCE1 contains a 260 amino acid Ras-GEF domain at p. 531-790, a 149 amino acid PI-PLC X-box domain at p. 1392-1540, a 117 amino acid PI-PLC Y-box domain at p. 1730  1846, a 101 amino acid C2 domain at p. 1856  1956, a 103 amino acid Ras-associating 1 domain at p. 2012  2114, and a 104 amino acid Ras-associating 2 domain at p. 2135  2238. There is a region of 79 amino acids from p. 1686  1764 that is required for PLCE1 to be  activated by RHOA, RHOB, GNA12, GNA13 and G-beta gamma. PLCE1 also has a Ca2+ cofactor. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

# Function
PLCE1 belongs to the phospholipase family that catalyzes the hydrolysis of polyphosphoinositides such as phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) to generate the second messengers Ins(1,4,5)P3 and diacylglycerol. These products initiate a cascade of intracellular responses that result in cell growth and differentiation and gene expression.

## Catalytic activity
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.

# Clinical significance
Mutations in this gene cause early-onset nephrotic syndrome. This disease is characterized by proteinuria, edema, and diffuse mesangial sclerosis or focal and segmental glomerulosclerosis. Signs and symptoms include kidney biopsies demonstrating non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation as well as genetic tests revealing a pathogenic S1484L mutation. Diffuse mesangial proliferation is characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen. This disease has also been associated with mitochondrial cytopathy stemming from respiratory chain deficiency primarily affecting complex IV.
Additionally, Phospholipase C epsilon modulates beta-adrenergic receptor-dependent cardiac contraction and it has been found that this protein is over expressed during heart failure. Research has suggested that PLCE1 may thus inhibit cardiac hypertrophy.

# Interactions
PLCE1 has been shown to have 12 binary protein-protein interactions including 8 co-complex interactions. PLCE1 appears to interact with RyR2, HRAS, NRAS, and LIMS1.
PMPCA
Mitochondrial-processing peptidase subunit alpha is an enzyme that in humans is encoded by the PMPCA gene. This gene PMPCA encoded a protein that is a member of the peptidase M16 family. This protein is located in the mitochondrial matrix and catalyzes the cleavage of the leader peptides of precursor proteins newly imported into the mitochondria, though it only functions as part of a heterodimeric complex.

# Structure
The Mitochondrial-processing peptidase subunit alpha precursor protein is 58.2 KDa in size and composed of 525 amino acids. The precursor protein contains a 33 amino acid N-terminal fragment as mitochondrion targeting sequence. After cleavage, the matured PMPCA protein is 54.6 KDa in size and has a theoretical pI of 5.88.

# Function
Mitochondrial-processing peptidase (MPP) is a metalloendopeptidase, containing two structurally related subunits, Subunit alpha and mitochondrial-processing peptidase subunit beta, working in conjunction for its catalytic function. Containing the catalytic site, the beta subunit PMPCB protein cleaves presequences (transit peptides) from mitochondrial protein precursors and releases of N-terminal transit peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2.

# Interactions
As the alpha subunit of Mitochondrial-processing peptidase, PMPCA forms a heterodimer with the subunit PMPCB.

# Clinical significance
The majority of mitochondrial proteins is nuclear-coded, which necessitates proper translocations of mitochondrial targeting proteins. Many mitochondrial proteins are synthesized in a precursor form that contains mitochondria targeting sequence. These precursors are usually cleaved by peptidases and proteases before they arrive their sub-organellar locations. It is likely that altered activity of the mitochondrial processing peptidases is essential to ensure the correct maturation of mitochondrial proteins and that altered activity of these proteases will have dramatic effects in the activity, stability and assembly of mitochondrial proteins. Evidences showed that MPP was involved in the proteolytic maturation of Frataxin, a protein responsible for iron homeostasis. Accordingly, MPP deficiency was shown to be involved in Friedreich ataxia, an autossomic recessive neurodegenerative disorder
PMPCB
Mitochondrial-processing peptidase subunit beta is an enzyme that in humans is encoded by the PMPCB gene. This gene is a member of the peptidase M16 family and encodes a protein with a zinc-binding motif. This protein is located in the mitochondrial matrix and catalyzes the cleavage of the leader peptides of precursor proteins newly imported into the mitochondria, though it only functions as part of a heterodimeric complex.

# Structure
The Mitochondrial-processing peptidase subunit beta precursor protein is 54.4 KDa in size and composed of 489 amino acids. The precursor protein contains a 45 amino acid N-terminal fragment as mitochondrion targeting sequence. After cleavage, the matured PMPCB protein is 49.5 KDa in size and has a theoretical pI of 5.76.

# Function
Mitochondrial-processing peptidase (MPP) is a metalloendopeptidase, containing two structurally related subunits, mitochondrial-processing peptidase subunit alpha and subunit beta, working in conjunction for its catalytic function. Containing the catalytic site, the beta subunit PMPCB protein cleaves presequences (transit peptides) from mitochondrial protein precursors and releases of N-terminal transit peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2.

# Interactions
As the beta subunit of Mitochondrial-processing peptidase, PMPCB forms a heterodimer with the subunit Mitochondrial-processing peptidase subunit alpha. In addition, PMPCB has been shown to interact with PMPCA and Frataxin.

# Clinical significance
The majority of mitochondrial proteins is nuclear-coded, which necessitates proper translocations of mitochondrial targeting proteins. Many mitochondrial proteins are synthesized in a precursor form that contains mitochondria targeting sequence. These precursors are usually cleaved by peptidases and proteases before they arrive their sub-organellar locations. It is likely that altered activity of the mitochondrial processing peptidases is essential to ensure the correct maturation of mitochondrial proteins and that altered activity of these proteases will have dramatic effects in the activity, stability and assembly of mitochondrial proteins. Evidences showed that MPP was involved in the proteolytic maturation of Frataxin, a protein responsible for iron homeostasis. Accordingly, MPP deficiency was shown to be involved in Friedreich ataxia, an autossomic recessive neurodegenerative disorder
PODXL
Podocalyxin-like protein 1 is a protein that in humans is encoded by the PODXL gene.

# Function
This gene encodes a member of the CD34 sialomucin protein family. The encoded protein was originally identified as an important component of glomerular podocytes. Inactivation of the encoding gene in mice leads to anuria, omphalocele and perinatal death. Podocytes are highly differentiated epithelial cells with interdigitating foot processes covering the outer aspect of the glomerular basement membrane. Other biological activities of the encoded protein include: binding in a membrane protein complex with Na+/H+ exchanger regulatory factor to intracellular cytoskeletal elements, playing a role in hematopoetic cell differentiation, and being expressed in vascular endothelium cells and binding to L-selectin.

# Expression
The expression and localisation of PODXL in human cells, tissues and organs have been investigated by the Human Protein Atlas consortium. According to antibody-based profiling, the protein is present in glomerular podocytes, endothelial cells, glandular cells in fallopian tube, uterus and seminal vesicle and according to RNA expression analysis, the PODXL transcripts are present in all analysed human tissues. Based on confocal microscopy, the protein is mainly localised to the plasma membrane and microtubule organizing center and in addition localized to vesicles.

# Interactions
PODXL has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2.

# Clinical significance
Podocalyxin is upregulated in a number of cancers and is frequently associated with poor prognosis. Based on patient survival data, high level of PODXL transcripts in tumor cells is associated with poor prognosis in renal cancer.