Persius/hicric huggingface dataset:
PAK3
PAK3 (p21-activated kinase 2, beta-PAK) is one of three members of Group I PAK family of evolutionary conserved serine/threonine kinases. PAK3 is preferentially expressed in neuronal cells  and involved in synapse formation and plasticity and mental retardation.

# Discovery
PAK3 was initially cloned from a murine fibroblast cDNA library and from a murine embryo cDNA library. Like other group I PAKs, PAK3 is stimulated by activated Cdc42 and Rac1.

# Gene and spliced variants
The human PAK3 gene, the longest group I family member, is 283-kb long. The PAK3 gene is composed of 22 exons of which 6 exons are for 5-UTR and generates 13 alternative spliced transcripts. Among PAK3 transcripts, 11 transcripts are for coding proteins ranging from 181- to 580-amino acids long, while remaining two transcripts are non-coding RNAs. The murine PAK3 gene contains 10 transcripts, coding six proteins from 544 amino acids and 559 amino acids long, and four smaller polypeptides from 23 to 366 amino acids.

# Protein domains
Similar to PAK1, PAK2 contains a p21-binding domain (PBD) and an auto-inhibitory domain (AID) and exists in an inactive conformation.

# Activators and inhibitors
PAK3 activity is stimulated by Dbl, Cdc42 and Cool-2, and by AP1 transcription factor. Stimulation of PAK3 activity by upstream stimulators such as Dbl or Cdc42 is inhibited by p50 (Cool-1) PAK3 activity is inhibited by FRAX597, a PAN inhibitor of PAKs.

# Functions
PAK3 is overexpressed in neuroendocrine/carcinoids tumors. PAK3 has been shown to be important for synapse formation and plasticity, and contribute to mental retardation. Further, a point mutation in PAK3 gene has been associated with nonsyndromic X-linked mental retardation.

# Notes
PAK6
Serine/threonine-protein kinase PAK 6 is an enzyme that in humans is encoded by the PAK6 gene.
PAK6 belongs to the Group II PAK family members. Like other family members, PAK6 is also evolutionary conserved across species.

# Discovery
The PAK6 was originally cloned as an androgen receptor interacting kinase which can be stimulated by androgen receptor but not Rac or Cdc42, like other family members.

# Gene and spliced variants
The human PAK6 gene consists of 16 exons of which 8 exons are used for 5-UTR splicing to generating 17 transcripts by alternative splicing, and the gene is about 38-kb long. Among PAK6 transcripts, 14 are protein coding RNAs to code four proteins of 681 and 636 amino acids while remaining PAK6 transcripts are non-coding RNAs. There are five transcripts in murine PAK6 gene, of which two transcripts are protein coding and other two non-coding RNAs(Gene from review).

# Protein domains
Following the general structural organization of the group II PAKs, PAK6 also contains a kinase, and a GTPase interacting domain.

# Function
This gene encodes a protein that shares a high degree of sequence similarity with p21-activated kinase (PAK) family members. The proteins of this family are Rac/Cdc42-associated Ste20-like Ser/Thr protein kinases, characterized by a highly conserved amino-terminal Cdc42/Rac interactive binding (CRIB) domain and a carboxyl-terminal kinase domain. PAK kinases are implicated in the regulation of a number of cellular processes, including cytoskeleton rearrangement, apoptosis and the MAP kinase signaling pathway. The protein encoded by this gene was found to interact with androgen receptor (AR), which is a steroid hormone-dependent transcription factor that is important for male sexual differentiation and development. The p21-activated protein kinase 6 gene was found to be highly expressed in testis and prostate tissues and the encoded protein was shown to cotranslocate into the nucleus with AR in response to androgen.
Genetic deletion of PAK6 alone in mice leads to increased body mass. However, PAK6 deletion along with PAK5 impairs the ability of animals to learn and move. PAK6 expression is increased in a rat model of spinal cord injury. PAK6 is also considered a candidate gene for epileptic encephalopathy, and interacts with Parkinson associated gene product leucine-rich repeat kinase 2. PAK6 expression has been found to be overexpressed in prostate cancer, hepatocellular carcinoma, and colon cancer. PAK6 levels have been correlated well with therapeutic resistance to 5-flurouracil, docetaxel, and radiation.

# Regulators and interactors
PAK6 kinase activity is positively regulated by androgen receptor, p38MAPK, 5-fluorouracil and  atypical Rho family GTPase Chp/RhoV. PAK6 expression is negatively regulated by miR-328, miR-429 and miR-23a. PAK6 interacts with junctional protein IQGAP1, E3 ligase Mdm2, and leucine-rich repeat kinase 2 (LRRK2).

# Interactions
PAK6 has been shown to interact with Androgen receptor.

# Notes
PAPB
Polyaminopropyl biguanide (PAPB) is a preservative used in cleaning solutions for contact lenses.
U.S. Pat. No. 4,758,595 to Ogunbiyi et al. discloses a contact-lens solution containing a Polyaminopropyl biguanide (PAPB), also known as polyhexamethylene biguanide (PHMB) or Polyhexanide, in combination with a borate buffer. These disinfecting and preservative solutions are claimed to have a broad spectrum of bactericidal and fungicidal activity at low concentrations coupled with very low toxicity when used with soft-type contact lenses.
Some of the most popular products for disinfecting lenses are multipurpose solutions that can be used to clean, disinfect and wet contact lenses, followed by direct insertion (placement on the eye) without rinsing. Such a solution must be particularly gentle to the eye, because some of the solution will be on the lens when inserted and will come into contact with the eye.
PARL
Presenilins-associated rhomboid-like protein, mitochondrial also known as mitochondrial intramembrane cleaving protease PARL is an inner mitochondrial membrane protein that in humans is encoded by the PARL gene on chromosome 3. It is a member of the rhomboid family of intramembrane serine proteases. This protein is involved in signal transduction and apoptosis, as well as neurodegenerative diseases and type 2 diabetes.

# Structure
Rhomboid family members share a conserved core of six transmembrane helices (TMHs), with the Ser and His residues required to form the catalytic dyad embedded in TMH-4 and TMH-6, respectively. This dyad is found deep below the membrane surface, which indicates that the hydrolysis of peptide bonds occurs within the hydrophobic phospholipid bilayer membrane. As a member of the Parl subfamily, PARL has an additional N-terminal TMH which may form a loop to the catalytic core. 

# Function
This gene encodes a mitochondrial integral membrane protein. Following proteolytic processing of this protein, a small peptide (P-beta) is formed and translocated to the nucleus. This gene may be involved in signal transduction via regulated intramembrane proteolysis of membrane-tethered precursor proteins. Variation in this gene has been associated with increased risk for type 2 diabetes. Alternative splicing results in multiple transcript variants encoding different isoforms.
Additionally, PARL is involved in apoptosis through its interactions with the mitochondrial GTPase optic atrophy 1 (OPA1) and the Bcl-2 family-related protein HAX1. OPA1 mainly regulates mitochondrial fusion in the mitochondrial inner membrane, but after proteolytic cleavage by PARL, its short, soluble form contributes to inhibiting apoptosis by slowing down cytochrome c release, and thus, proapoptotic signaling. Alternatively, PARL can inhibit apoptosis by coordinating with HAX1 to activate HtrA2 protease, thus preventing the accumulation of the proapoptotic Bax.

# Clinical significance
It has been shown that the p.S77N presenilin-associated rhomboid-like protein mutation is not a frequent cause of early-onset Parkinsons disease. Variation in presenilins-associated rhomboid-like protein (PSARL) sequence and/or expression may be an important new risk factor for type 2 diabetes and other components of the metabolic syndrome. Mutations in PARL may also be involved in Leber hereditary optic neuropathy by disrupting normal function of the mitochondria, thus promoting retinal ganglion cell death and neurodegeneration.

# Interactions
PARL has been shown to interact with:
- PINK1,
- OPA1, and
- HAX1.
PAWR
PRKC, apoptosis, WT1, regulator, also known as PAWR or Prostate apoptosis response-4 (Par-4), is a human gene coding for a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal cells.

# Function
The tumor suppressor WT1 represses and activates transcription. The protein encoded by this gene is a WT1-interacting protein that itself functions as a transcriptional repressor. It contains a putative leucine zipper domain which interacts with the zinc finger DNA binding domain of WT1. This protein is specifically upregulated during apoptosis of prostate cells.
The active domain of the Par-4 protein has been found to confer cancer resistance in transgenic mice without compromising normal viability or aging, and may have therapeutic significance.

# Interactions
PAWR has been shown to interact with:
- Apoptosis antagonizing transcription factor,
- DAPK3,
- Protein kinase M,
- SLC5A1,
- THAP1,  and
- WT1.
PAX5
Paired box protein Pax-5 is a protein that in humans is encoded by the PAX5 gene.

# Function
The PAX5 gene is a member of the paired box (PAX) family of transcription factors.  The central feature of this gene family is a novel, highly conserved DNA-binding domain, known as the paired box.  The PAX proteins are important regulators in early development, and alterations in the expression of their genes are thought to contribute to neoplastic transformation.  The PAX5 gene encodes the B-cell lineage specific activator protein (BSAP) that is expressed at early, but not late stages of B-cell differentiation.  Its expression has also been detected in developing CNS and testis, therefore, PAX5 gene product may not only play an important role in B-cell differentiation, but also in neural development and spermatogenesis.

# Clinical significance
The PAX5 gene is located in chromosome 9p13 region, which is involved in t(9;14)(p13;q32) translocations recurring in small lymphocytic lymphomas of the plasmacytoid subtype, and in derived large-cell lymphomas.  This translocation brings the potent E-mu enhancer of the IgH gene locus into close proximity of the PAX5 promoters, suggesting that the deregulation of PAX5 gene transcription contributes to the pathogenesis of these lymphomas.
Up to 97% of the ReedSternberg cells of Hodgkin's lymphoma express Pax-5.

# Interactions
PAX5 has been shown to interact with TLE4 and Death associated protein 6.
PAX7
Paired box protein Pax-7 is a protein that in humans is encoded by the PAX7 gene.

# Function
Pax-7 plays a role in neural crest development and gastrulation, and it is an important factor in the expression of neural crest markers such as Slug, Sox9, Sox10 and HNK-1. PAX7 is expressed in the palatal shelf of the maxilla, Meckel's cartilage, mesencephalon, nasal cavity, nasal epithelium, nasal capsule and pons.
Pax7 is a transcription factor that plays a role in myogenesis through regulation of muscle precursor cells proliferation. It can bind to DNA as an heterodimer with PAX3. Also interacts with PAXBP1; the interaction links PAX7 to a WDR5-containing histone methyltransferase complex By similarity. Interacts with DAXX too.
PAX7 functions as a marker for a rare subset of spermatogonial stem cells, specifically a sub set of Asingle spermatogonia. These PAX7+ spermatogonia are rare in adult testis but are much more prevalent in newborns, making up 28% of germ cells in neonate testis. Unlike PAX7+ muscle satellite cells, PAX7+ spermatogonia rapidly proliferate and are not quiescent. PAX7+ spermatogonia are able to give rise to all stages of spermatogenesis and produce motile sperm. However, PAX7 is not required for spermatogenesis, as mice without PAX7+ spermatogonia show no deficits in fertility.
PAX7 may also function in the recovery in spermatogenesis. Unlike other spermatogonia, PAX7+ spermatogonia are resistant to radiation and chemotherapy. The surviving PAX7+ spermatogonia are able to increase in number following these therapies and differentiate into the other forms of spermatogonia that did not survive. Additionally, mice lacking PAX7 had delayed recovery of spermatogenesis following exposure to busulfan when compared to control mice.

# Clinical significance
Pax proteins play critical roles during fetal development and cancer growth. The specific function of the paired box gene 7 is unknown but speculated to involve tumor suppression since fusion of this gene with a forkhead domain family member has been associated with alveolar rhabdomyosarcoma.  Alternative splicing in this gene has produced two known products but the biological significance of the variants is unknown. Animal studies show that mutant mice have malformation of maxilla and the nose.
PAX9
Paired box gene 9, also known as PAX9, is a protein which in humans is encoded by the PAX9  gene. It is also found in other mammals.

# Expression and function
This gene is a member of the paired box (PAX) family of transcription factors.  During mouse embryogenesis Pax9 expression starts from embryonic day 8.5 and becomes more evident by E9.5; at this stage its expression is restricted to the pharyngeal endoderm. Later on, Pax9 is also expressed in the axial skeleton. Pax9 is required for craniofacial, tooth and limb development, and may more generally involve development of stratified squamous epithelia as well as various organs and skeletal elements.  PAX9 plays a role in the absence of wisdom teeth in some human populations (possibly along with the less well studied AXIN2 and MSX1).

# Clinical significance
This gene was found amplified in lung cancer.  The amplification covers three tissue developmental genes - TTF1, NKX2-8, and PAX9. It appears that certain lung cancer cells select for DNA copy number amplification and increased RNA/protein expression of these three coamplified genes for functional advantages.

## Oligodontia
Oligodontia is a genetic disorder caused by the mutation of the PAX 9 gene. This disorder results in the congenital absence of 6 or more permanent teeth, with the exception of the third molar. Also known as selective tooth agenesis (STHAG), it is the most common disorder in regard to human dentition, affecting a little less than one fourth of the population. The gene PAX 9 which can be found on chromosome 14 encodes a group of transcription factors that play an important role in early tooth development. In humans, a frameshift mutation in the paired domain of PAX 9 was discovered in those affected with oligodontia. Multiple mechanisms are possible by which the mutation may arise. Recently, a study involving the missense mutation of a PAX 9 gene suggests that the loss of function due to the absence DNA binding domain is a mechanism that causes oligodontia. Those who express the PAX 9 mutation and develop the disorder continue to have a normal life expectancy. Along with the mutation of the PAX 9 gene, MSX1 gene mutations have also shown to affect dental development in fetuses.

# Interactions
PAX9 has been shown to interact with JARID1B.
PCA3
Prostate cancer antigen 3 (PCA3, also referred to as DD3) is a gene that expresses a non-coding RNA. PCA3 is only expressed in human prostate tissue, and the gene is highly overexpressed in prostate cancer. Because of its restricted expression profile, the PCA3 RNA is useful as a tumor marker.

# Use as biomarker
The most frequently used biomarker for prostate cancer today is the serum level of prostate-specific antigen (PSA), or derived measurements. However, since PSA is prostate-specific but not cancer-specific, it is an imperfect biomarker. For example, PSA can increase in older men with benign prostatic hyperplasia. Several new biomarkers are being investigated to improve the diagnosis of prostate cancer. Some of these can be measured in urine samples, and it is possible that a combination of several urinary biomarkers will replace PSA in the future.
Compared to serum PSA, PCA3 has a lower sensitivity but a higher specificity and a better positive and negative predictive value. It is independent of prostate volume, whereas PSA is not. It should be measured in the first portion of urine after prostate massage with digital rectal examination.
PCA3 has been shown to be useful to predict the presence of malignancy in men undergoing repeat prostate biopsy. This means that it could be useful clinically for a patient for whom digital rectal examination and PSA suggest possible prostate cancer, but the first prostate biopsy returns a normal result. This occurs in approximately 60% of cases, and on repeat testing, 20-40% have an abnormal biopsy result.
Other uses that are being studied for PCA3 include its correlation with adverse tumor features such as tumor volume, grading (Gleason score) or extracapsular extension. These studies have so far produced conflicting results.

# Society and culture
A commercial kit called the Progensa PCA3 test is marketed by the Californian company Gen-Probe.  Gen-Probe acquired rights to the PCA3 test from Diagnocure in 2003.  In April 2012, Hologic bought Gen-Probe for $3.75 billion by cash.

# Discovery
PCA3 was discovered to be highly expressed by prostate cancer cells in 1999.
PCAF
P300/CBP-associated factor (PCAF), also known as K(lysine) acetyltransferase 2B (KAT2B), is a human gene and transcriptional coactivator associated with p53.

# Structure
Several domains of PCAF can act independently or in unison to enable its functions. PCAF has separate acetyltransferase and E3 ubiquitin ligase domains as well as a bromodomain for interaction with other proteins. PCAF also possesses sites for its own acetylation and ubiquitination.

# Function
CBP and p300 are large nuclear proteins that bind to many sequence-specific factors involved in cell growth and/or differentiation, including c-jun and the adenoviral oncoprotein E1A. The protein encoded by the PCAF gene associates with p300/CBP. It has in vitro and in vivo binding activity with CBP and p300, and competes with E1A for binding sites in p300/CBP. It has histone acetyl transferase activity with core histones and nucleosome core particles, indicating that this protein plays a direct role in transcriptional regulation.

# Regulation
The acetyltransferase activity and cellular location of PCAF are regulated through acetylation of PCAF itself. PCAF may be autoacetylated (acetylated by itself) or by p300. Acetylation leads to migration to the nucleus and enhances its acetyltransferase activity. PCAF interacts with and is deacetylated by HDAC3, leading to a reduction in PCAF acetyltransferase activity and cytoplasmic localisation.

# Protein interactions
PCAF forms complexes with numerous proteins that guide its activity. For example PCAF is recruited by ATF to acetylate histones and promote transcription of ATF4 target genes.

# Targets
There are various protein targets of PCAF's acetyltransferase activity including transcription factors such as Fli1, p53 and numerous histone residues.
Hdm2, itself a ubiquitin ligase that targets p53, has also been demonstrated to be a target of the ubiquitin-ligase activity of PCAF.

# Interactions
PCAF has been shown to interact with:
- BRCA2,
- CTNNB1,
- CREBBP,
- EVI1,
- HNF1A,
- IRF1,
- IRF2,
- KLF13,
- Mdm2
- Myc,
- NCOA1,
- POLR2A,
- RBPJ,
- TCF3,
- TRRAP,  and
- TWIST1.
PCK1
Phosphoenolpyruvate carboxykinase 1 (soluble), also known as PCK1, is an enzyme which in humans is encoded by the PCK1 gene.

# Function
This enzyme is a main control point for the regulation of gluconeogenesis. The cytosolic enzyme encoded by this gene, along with GTP, catalyzes the formation of phosphoenolpyruvate from oxaloacetate, with the release of carbon dioxide and GDP. The expression of this gene can be regulated by insulin, glucocorticoids, glucagon, cAMP, and diet. A mitochondrial isozyme of the encoded protein also has been characterized.

# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. 
-  The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
PCLO
Protein piccolo is a protein that in humans is encoded by the PCLO gene.

# Function
Synaptic vesicles dock and fuse in the active zone of the plasma membrane at chemical synapses. The presynaptic cytoskeletal matrix (PCM), which is associated with the active zone and is situated between synaptic vesicles, is thought to be involved in maintaining the neurotransmitter release site in register with the postsynaptic reception apparatus. The cycling of synaptic vesicles is a multistep process involving a number of proteins (see MIM 603215). Among the components of the PCM that orchestrate these events are Bassoon (BSN; MIM 604020), RIM (RIMS1; MIM 606629), Oboe (RIMS2; MIM 606630), and Piccolo (PCLO).

# Interactions
The protein product of PCLO called Piccolo has been shown to interact with number of proteins including GIT1,  the F-actin-binding protein Abp1, PRA1, TRIO, DAAM1, and Profilin.

# Clinical relevance
Recurrent mutations in this gene have been associated to cases of diffuse large B-cell lymphoma. Recent evidence has shown that a homozygous, nonsense PCLO mutation is the genetic cause of the autosomal recessive neurodegenerative disorder, pontocerebellar hypoplasia type III (PCH3).
PCNA

# Overview
Proliferating Cell Nuclear Antigen, commonly known as PCNA, is a protein that acts as a processivity factor for DNA polymerase delta in eukaryotic cells.  It achieves this processivity by encircling the DNA, thus creating a topological link to the genome.  It is an example of a DNA clamp.
The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome.

# Expression in the nucleus during DNA synthesis
PCNA was originally identified as an antigen that is expressed in the nuclei of cells during the DNA synthesis phase of the cell cycle
. Part of the protein was sequenced and that sequence was used to allow isolation of a cDNA clone . PCNA helps hold DNA polymerase delta (Pol ) to DNA. PCNA is clamped  to DNA through the action of replication factor C (RFC) , which is a heteropentameric member of the AAA+ class of ATPases. Expression of PCNA is under the control of E2F transcription factor-containing complexes .

# Role in DNA repair
Since DNA polymerase delta is involved in resynthesis of excised damaged DNA strands during DNA repair, PCNA is important for both DNA synthesis and DNA repair . PCNA is also involved in the switch to DNA  damage bypass translation synthesis.