Persius/hicric huggingface dataset:
POLG2
DNA polymerase subunit gamma-2, mitochondrial is a protein that in humans is encoded by the POLG2 gene.  The POLG2 gene encodes a 55 kDa accessory subunit protein that imparts high processivity and salt tolerance to the catalytic subunit of DNA polymerase gamma, encoded by the POLG gene. Mutations in this gene result in autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions.

# Structure
POLG2 is located on the q arm of chromosome 17 in position 23.3 and has 8 exons. POLG2, the protein encoded by this gene, contains a phosphoserine modified residue at p. 38 and a transit peptide. Its structure consists of 25 beta strands, 21 alpha helixes, and 8 turns.

# Function
POLG2 encodes the processivity subunit of the mitochondrial DNA polymerase gamma. The encoded protein forms a heterotrimer containing one catalytic subunit and two processivity subunits. This protein enhances DNA binding, stimulates polymerase and exonuclease activity, and promotes processive DNA synthesis.

## Catalytic activity
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)

# Clinical significance
Mutations in POLG2 have been associated with progressive external ophthalmoplegia with mitochondrial DNA deletions. This disease results in progressive weakness of ocular muscles and levator muscle of the upper eyelid and patients with it may also manifest skeletal myopathy, ragged-red fibers and atrophy shown on muscle biopsy, cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. This mutlisystemic disease has been linked to a G451E mutation that disrupts the DNA polymerase gamma subunits.
In patients with chronic hepatitis C, those carrying the DDX5 minor allele or DDX5-POLG2 haplotypes are thought to be at an increased risk of advanced fibrosis. It is important to note, however, that those carrying the CPT1A minor allele are believed to be at a decreased risk.

# Interactions
POLG2 has been shown to have 32 binary protein-protein interactions including 19 co-complex interactions. POLG2 appears to interact with POLG.
PORCN
PORCN (porcupine homolog  Drosophila) is a human gene.
The protein is homologous to other membrane-bound O-acyltransferases.

# Function
The protein encoded by this gene is an endoplasmic reticulum transmembrane protein involved in processing of wingless proteins such as WNT7A.

# Clinical significance
Mutations in this gene are associated with focal dermal hypoplasia.
Mutations in PORCN are associated to                 Goltz-Gorlin syndrome            .

# Ligands

## Inhibitors
- WNT974 (LGK-974) - 1243244-14-5, researched for anti-cancer effects in Wnt-pathway sensitive tumours. Also investigated for influencing cardiac tissue remodelling following infarction.
IWP (1-4)
RXC004
PPIL3
Peptidyl-prolyl cis-trans isomerase-like 3 is an enzyme that in humans is encoded by the PPIL3 gene.

# Function
This gene encodes a member of the cyclophilin family. Cyclophilins catalyze the cis-trans isomerization of peptidylprolyl imide bonds in oligopeptides. They have been proposed to act either as catalysts or as molecular chaperones in protein-folding events. Transcript variants derived from alternative splicing and/or alternative polyadenylation exist; some of these variants encode different isoforms.

# Model organisms
Model organisms have been used in the study of PPIL3 function. A conditional knockout mouse line called Ppil3tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed:  - In-depth immunological phenotyping
PPM1A
Protein phosphatase 1A is an enzyme that in humans is encoded by the PPM1A gene.
The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase dephosphorylates, and negatively regulates the activities of, MAP kinases and MAP kinase kinases. It has been shown to inhibit the activation of p38 and JNK kinase cascades induced by environmental stresses. This phosphatase can also dephosphorylate cyclin-dependent kinases, and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to activate the expression of the tumor suppressor gene TP53/p53, which leads to G2/M cell cycle arrest and apoptosis. Three alternatively spliced transcript variants encoding two distinct isoforms have been described.

# Interactions
PPM1A has been shown to interact with Metabotropic glutamate receptor 3.
In 2006, Dr. Feng found that PPM1A can terminate TGF-beta signaling by inactivating Smad3 via dephosphorylation. Smad3 is an essential component of the TGF-beta signalling pathway.
PPP5C
Serine/threonine-protein phosphatase 5 is an enzyme that in humans is encoded by the PPP5C gene.

# Model organisms
Model organisms have been used in the study of PPP5C function. A conditional knockout mouse line, called Ppp5ctm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program  a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and five significant abnormalities were observed. Homozygous mutant males had decreased body weight, body length and respiratory quotient. Both sexes had increased T cell numbers and a range of skeletal abnormalities identified by radiography.

# Interactions
PPP5C has been shown to interact with ASK1, CRY2 GNA12. and Rac1,
PQBP1
Polyglutamine-binding protein 1 is a protein that in humans is encoded by the PQBP1 gene.
Polyglutamine binding protein-1 is a highly conserved nuclear protein expressed in mesodermal and nuclear tissues. The molecular roles of PQBP1 in embryonic development are still being understood, but it has been found to function in mRNA splicing, and transcription regulation. Mutations in the PQBP1 gene, which encodes for this protein, have been known to cause X-linked intellectual disabilities (XLID), commonly referred to as Renpenning's syndrome. People who suffer from these disabilities share a common set of symptoms including: microcephaly, shortened stature and impaired intellectual development.   There are 11 types of mutations that have been identified, but the most common being frameshift mutations. A knockdown model of the gene in mouse embryo primary neurons revealed a decrease in splicing efficiency and resulted in abnormal gastrulation and neuralation patterning.  Attempts at creating both PQBP1 mouse knockout or over expression models have been unsuccessful, often with lethal results. Research indicates that in order to appropriately function, the protein must be expressed within a critical range.

# Function
PQBP1 is a nuclear polyglutamine-binding protein that contains a WW domain (Waragai et al., 1999).

# Interactions
PQBP1 has been shown to interact with:
- POLR2A,
- POU3F2,
- TXNL4A, and
- WBP11.
PRAME
Melanoma antigen preferentially expressed in tumors is a protein that in humans is encoded by the PRAME gene.

# Function
This gene encodes an antigen that is predominantly expressed in human melanomas and that is recognized by cytolytic T lymphocytes. It is not expressed in normal tissues, except testis. This expression pattern is similar to that of other CT antigens, such as MAGE, BAGE and GAGE. However, unlike these other CT antigens, this gene is also expressed in acute leukemias. Five alternatively spliced transcript variants encoding the same protein have been observed for this gene.
PRAME can inhibit retinoic acid signaling and retinoic acid mediated differentiation and apoptosis.

# Model organisms
Model organisms have been used in the study of PRAME function. A conditional knockout mouse line called Prametm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed:  - In-depth immunological phenotyping
PRDM1
PR domain zinc finger protein 1 also known as BLIMP-1 is a protein that in humans is encoded by the PRDM1 gene. BLIMP-1 acts as a repressor of beta-interferon (-IFN) gene expression. The protein binds specifically to the PRDI (positive regulatory domain I element) of the -IFN gene promoter. Transcription of this gene increases upon virus induction.

# Function
The increased expression of the Blimp-1 protein in B lymphocytes, T lymphocytes, NK cell and other immune system cells leads to an immune response through proliferation and differentiation of antibody secreting plasma cells.  Blimp-1 is also considered a 'master regulator' of hematopoietic stem cells.
Blimp1 (also known as Prdm1), a known transcriptional repressor, has a critical role in the foundation of the mouse germ cell lineage, as its disruption causes a block early in the process of primordial germ cell formation. Blimp1-deficient mutant embryos form a tight cluster of about 20 primordial germ cell-like cells, which fail to show the characteristic migration, proliferation and consistent repression of homeobox genes that normally accompany specification of primordial germ cells. The genetic lineage-tracing experiments indicate that the Blimp1-positive cells originating from the proximal posterior epiblast cells are indeed the lineage-restricted primordial germ cell precursors.

# Second cancers after radiation treatment
A genome-wide association study has identified two genetic variations near the PRDM1 gene that predict an increased likelihood of developing a second cancer after radiation treatment for Hodgkin lymphoma.
PRDM2
PR domain zinc finger protein 2 is a protein that in humans is encoded by the PRDM2 gene.

# Function
This tumor suppressor gene is a member of a nuclear histone/protein methyltransferase superfamily. It encodes a zinc finger protein that can bind to retinoblastoma protein, estrogen receptor, and the TPA-responsive element (MTE) of the heme-oxygenase-1 gene. Although the functions of this protein have not been fully characterized, it may (1) play a role in transcriptional regulation during neuronal differentiation and pathogenesis of retinoblastoma, (2) act as a transcriptional activator of the heme-oxygenase-1 gene, and (3) be a specific effector of estrogen action. Three transcript variants encoding different isoforms have been found for this gene.

# Interactions
PRDM2 has been shown to interact with Estrogen receptor alpha and Retinoblastoma protein.
PRDM9
PR domain zinc finger protein 9 is a protein that in humans is encoded by the Prdm9 gene. PRDM9 is responsible for positioning recombination hotspots during meiosis by binding a DNA sequence motif encoded in its zinc finger domain. PRDM9 is the only speciation gene found so far in mammals, and is one of the fastest evolving genes in the genome.

# Domain Architecture
PRDM9 has multiple domains including KRAB domain, SSXRD, PR/SET domain (H3K4 & H3K36 trimethyltransferase), and an array of C2H2 Zinc Finger domains (DNA binding).

# History
In 1974 Jiri Forejt and P. Ivanyi identified a locus which they named Hst1 which controlled hybrid sterility.
In 1982 a haplotype was identified controlling recombination rate wm7, which would later be identified as PRDM9.
In 1991 a protein binding to the minisatelite consensus sequence 5-CCACCTGCCCACCTCT-3 was detected and partially purified (named Msbp3 - minisatelite binding protein 3). This would later turn out to be the same PRDM9 protein independently identified later.
In 2005 a gene was identified (named Meisetz) that is required for progression through meiotic prophase and has H3K4 methyltransferase activity.
In 2009 Jiri Forejt and colleagues identified Hst1 as Meisetz/PRDM9 - the first and so far only speciation gene in mammals.
Later in 2009 PRDM9 was identified as one of the fastest evolving genes in the genome.
In 2010 three groups independently identified PRDM9 as controlling the positioning of recombination hotspots in humans and mice.
in 2012 it was shown that almost all hotspots are positioned by PRDM9 and that in its absence hotspots form near promoters.
In 2014 it was reported that the PRDM9 SET domain could also trimethylate H3K36 in vitro, which was confirmed in vivo in 2016.
In 2016 it was shown that the hybrid sterility caused by PRDM9 can be reversed and that the sterility is caused by asymmetric double strand breaks.

# Function in Recombination
PRDM9 mediates the process of meiosis by directing the sites of homologous recombination. In humans and mice, recombination does not occur evenly throughout the genome but at particular sites along the chromosomes called recombination hotspots.  Hotspots are regions of DNA about 1-2kb in length.  There are approximately 30,000 to 50,000 hotspots within the human genome corresponding to one for every 50-100kb DNA on average.  In humans, the average number of crossover recombination events per hotspot is one per 1,300 meioses, and the most extreme hotspot has a crossover frequency of one per 110 meioses.  These hotspots are binding sites for the PRDM9 Zinc Finger array. Upon binding to DNA, PRDM9 catalyzes trimethylation of Histone 3 at lysine 4 and Histone 4 at lysine 36.  As a result, local nucleosomes are reorganized and through an unknown mechanism the recombination machinery is recruited to form double strand breaks.

# Notes
-  positive-regulatory domain
PRDX3
Thioredoxin-dependent peroxide reductase, mitochondrial is an enzyme that in humans is encoded by the PRDX3 gene. It is a member of the peroxiredoxin family of antioxidant enzymes.

# Function
This gene encodes a protein with antioxidant function and is localized in the mitochondrion. This gene shows significant nucleotide sequence similarity to the gene coding for the C22 subunit of Salmonella typhimurium alkylhydroperoxide reductase. Expression of this gene product in E. coli deficient in the C22-subunit gene rescued resistance of the bacteria to alkylhydroperoxide. The human and mouse genes are highly conserved, and they map to the regions syntenic between mouse and human chromosomes. Sequence comparisons with recently cloned mammalian homologues suggest that these genes consist of a family that is responsible for regulation of cellular proliferation, differentiation, and antioxidant functions. Two transcript variants encoding two different isoforms have been found for this gene.

# Interactions
PRDX3 has been shown to interact with MAP3K13.

# Clinical significance
It has been demonstrated that serum peroxiredoxin 3 can be a valuable biomarker for the diagnosis and assessment of hepatocellular carcinoma  It has been shown that peroxiredoxin proteins protect MCF-7 breast cancer cells against doxorubicin-mediated toxicity. Additionally, it has been shown that peroxiredoxin 3 is overexpressed in prostate cancer and promotes cancer cell survival by defending cells against the damages incurred by oxidative stress.
PRDX6
Peroxiredoxin-6 is a protein that in humans is encoded by the PRDX6 gene. It is a member of the peroxiredoxin family of antioxidant enzymes.

# Function
The protein encoded by this gene is a member of the thiol-specific antioxidant protein family. This protein is a bifunctional enzyme with two distinct active sites. It is involved in redox regulation of the cell; it can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. It may play a role in the regulation of phospholipid turnover as well as in protection against oxidative injury.

## Model organisms
Model organisms have been used in the study of PRDX6 function. A conditional knockout mouse line, called Prdx6tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program  a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists  at the Wellcome Trust Sanger Institute.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice but no significant abnormalities were observed.
PREX1
Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein is a protein that in humans is encoded by the PREX1 gene.

# Function
The protein encoded by this gene acts as a guanine nucleotide exchange factor for the RHO family of small GTP-binding proteins (RACs).  It has been shown to bind to and activate RAC1 by exchanging bound GDP for free GTP. The encoded protein, which is found mainly in the cytoplasm, is activated by phosphatidylinositol-3,4,5-trisphosphate and the beta-gamma subunits of heterotrimeric G proteins.

# Clinical significance
The protein has been implicated in the spread of melanoma skin cancer.
PRMT1
Protein arginine N-methyltransferase 1 is an enzyme that in humans is encoded by the PRMT1 gene.

# Function
The HRMT1L2 gene encodes a protein arginine methyltransferase that functions as a histone methyltransferase specific for histone H4.

# Model organisms
Model organisms have been used in the study of PRMT1 function. A conditional knockout mouse line, called Prmt1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium programa high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty three tests were carried out on mutant mice and three significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and thus none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and females displayed increased circulating creatinine levels.

# Interactions
PRMT1 has been shown to interact with:
- BTG1,
- BTG2,
- DHX9,
- FUS,
- HNRNPR,
- HNRPK,
- IFNAR1,
- ILF3,
- KHDRBS1,  and
- SUPT5H.
PRMT3
Protein arginine N-methyltransferase 3 is an enzyme that in humans is encoded by the PRMT3 gene.

# Model organisms
Model organisms have been used in the study of PRMT3 function. A conditional knockout mouse line, called Prmt3tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program  a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty seven tests were carried out on mutant mice and seven significant abnormalities were observed. Fewer than predicted homozygous mutant mice survived until weaning due to hydrocephaly. The remaining tests were carried out on both heterozygous and homozygous mutant adult mice. Male heterzygous mice had a decreased respiratory quotient. Homozygous females had decreased body weight, length and bone mineral density. Homozygous males had abnormal peripheral blood lymphocyte counts and homozygotes of both sex had eye abnormalities.

# Interactions
PRMT3 has been shown to interact with RPS2.
PROX1
Prospero homeobox protein 1 is a protein that in humans is encoded by the PROX1 gene.

# Interactions
PROX1 has been shown to interact with EP300.

# Production
PROX1 is produced primarily in the dentate gyrus in the mouse, and in the dentate gyrus and white matter in humans. Gene expression data for mouse, human and macaque from the Allen Brain Atlases can be found here.

# Clinical significance
PROX1 is used as a marker for lymphatic endothelium in biopsy samples.
PRPF6
Pre-mRNA-processing factor 6 is a protein that in humans is encoded by the PRPF6 gene.
The protein encoded by this gene appears to be involved in pre-mRNA splicing, possibly acting as a bridging factor between U5 and U4/U6 snRNPs in formation of the spliceosome. The encoded protein also can bind androgen receptor, providing a link between transcriptional activation and splicing.

# Interactions
PRPF6 has been shown to interact with TXNL4B, ARAF and Androgen receptor.
PRR29
PRR29 is a protein located on human chromosome 17 that in humans is encoded by the PRR29 gene.
It is also commonly known as C17orf72. The gene has a size of 5961 base pairs and contains five exons.

# Gene
PRR29 is located on the long arm of chromosome 17 (17q23.3), starting at 63998344 and ending at 64004305. The gene spans 5961 base pairs and is oriented on the plus strand. Genes SNHG25 and LOC105371858 neighbor PRR29 on chromosome 17.The gene ICAM2 is located on the negative strand, directly opposite of PRR29.

# mRNA
The gene has 12 common splice variants and one unspliced form. The longest transcribed mRNA is made up of 3048 base pairs and the transcribed protein sequence for this mRNA is 189 amino acids.

# Protein

## General properties
Homo sapiens PRR29 has several protein isoforms, with the longest being 236 amino acids. PRR29 has a predicted Isoelectric point of 5.23 and a predicted Molecular weight of 26.1 kilodaltons. PRR29 is characterized by a larger than average proportion of prolines (19.1%) and a smaller than average amount of asparagines (0.4%)

## Domains
PRR29 contains a proline rich region within its sequence from amino acids 73 to 166. A domain of unknown function, DUF 4587, is also present from amino acids 39 to 113. DUF 4587 is usually between 64 and 79 amino acids long and contains the two sequence motifs QNAQ and HHH. PRR29 is predicted to contain multiple alpha helix and beta-sheet forming regions. Specifically, the DUF 4587 region is predicted to form an alpha helix.

## Subcellular localization
Using PSORTII, PRR29 is predicted to localize in the nucleus of the cell. PSORTII does not predict any targeting sequences or signal peptides.

## Modification
PRR29 is predicted to undergo sumoylation, acetylation, and serine, threonine and tyrosine phosphorylation.

## Interactions
The interactome of PRR29 is not yet well characterized. One experimental study found that a Sus scrofa PRR29-like protein interacts with the N-terminal protease of classical swine fever virus (CSFV).

# Expression
PRR29 is ubiquitously expressed throughout the body. However, there is particularly high expression in the ovaries, muscle, heart, testes, and thymus. According to PaxDb, PRR29 abundance falls in the bottom 5% relative to other proteins.

# Homology
PRR29 has a single known paralog, C21orf58. PRR29 is well conserved among chordates and PRR29-like proteins containing the DUF 4587 have been predicted in protostomes, such as Mollusca and Annelida. DUF 4587 is highly conserved in all PRR29 orthologs and is also present in its paralog, C21orf58. This domain has been found in species as distantly related as Capitella teleta, which diverged from humans 847 million years ago.
PRRT2
Proline-rich transmembrane protein 2 is a protein that in humans is encoded by the PRRT2 gene.

# Structure and tissue distribution
This gene encodes a transmembrane protein containing a proline-rich domain in its N-terminal half. Studies in mice suggest that it is predominantly expressed in brain and spinal cord in embryonic and postnatal stages.

# Clinical significance
Mutations in this gene are associated with paroxysmal kinesigenic dyskinesia. Almost one third of sporadic PKC patients also carry PRRT2 mutations.