Persius/hicric huggingface dataset:
CYFIP2
Cytoplasmic FMR1-interacting protein 2 is a protein that in humans is encoded by the CYFIP2 gene. Cytoplasmic FMR1 interacting protein is a  1253 amino acid  long protein and is highly conserved sharing 99% sequence identity to the mouse protein. It is expressed mainly in brain tissues, white blood cells and the kidney.

# Interactions
CYFIP2 has been shown to interact with FMR1. CYFIP2 is a p-53 inducible protein and also interacts with the Fragile=X mental retardation protein.

# RNA editing
The pre-mRNA of this protein is subject to RNA editing. The editing site was previously recorded as a single nucleotide polymorphism (rs3207362) in the dbSNP.

## Type
A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate  them to inosine. Inosines  are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1-3 with ADAR1  and ADAR2 being the only enzymatically active members. ADAR3 is thought to have a regulatory role in the brain.  ADAR1 and ADAR 2 are widely expressed in tissues while ADAR3 is restricted to the brain. The double stranded regions of RNA are formed  by base-pairing between residues in the close to region of the editing site with residues usually in a  neighboring intron but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS).

## Site
An editing site was found in the pre-mRNA of this protein. The substitution occurs within amino acid position 320 in humans and also in mice.A possible  double stranded RNA region has not been detected for this pre-mRNA. No double stranded region required by ADARs has predicted.Immunoprecipitation experiments and RNA interference have shown that ADAR 2 is likely to be the main editing enzyme for this site with ADAR 1 having a minor role.

## Regulation
Editing seems to be differentially regulated in different tissues. The highest level of editing occurs in the cerebellum with lower frequency of editing detected in human lung, prostrate and uterus tissues. Editing frequency varies from 30-85% depending on tissue.{ There is some evidence for a  decrease in CYFIP2 editing with increased age.

### Conservation
Editing of the pre-mRNA of this gene has been detected in mouse and chicken.

## Effects of RNA editing

### Structural
Editing results in a codon change resulting in a glutamic acid being translated instead of a lysine.

### Functional
Currently unknown but editing may have role in regulation of  apoptotic functions of this protein.It is thought that since the protein is p53 inducible that the protein may be pro-apopototic. Also ADAR1 knock out mice show increase in apoptosis which indicates editing may be involved in regulation of the cellular  process.
CYP1A1
Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein which in humans in encoded by the CYP1A1 gene. The protein a member of the cytochrome P450 superfamily of enzymes.

# Function
CYP1A1 is involved in phase I xenobiotic and drug metabolism (one substrate of it is theophylline). It is inhibited by fluoroquinolones and  macrolides and induced by aromatic hydrocarbons.
CYP1A1 is also known as AHH (aryl hydrocarbon hydroxylase). It is involved in the metabolic activation of aromatic hydrocarbons (polycyclic aromatic hydrocarbons, PAH), for example, benzopyrene (BP), by transforming it to an epoxide. In this reaction, the oxidation of benzopyrene is catalysed by CYP1A1 to form BP-7,8-epoxide, which can be further oxidized by epoxide hydrolase (EH) to form BP-7,8-dihydrodiol. Finally CYP1A1 catalyses this intermediate to form BP-7,8-dihydrodiol-9,10-epoxide, which is the ultimate carcinogen.

# Regulation
The expression of the CYP1A1 and CYP1B1 genes are regulated by the aryl hydrocarbon receptor, a ligand activated transcription factor.

# Polymorphisms
Several polymorphisms have been identified in CYP1A1, some of which lead to more highly inducible AHH activity. CYP1A1 polymorphisms include:
- M1, TC substitution at nucleotide 3801 in the 3'-non-coding region
- M2, AG substitution at nucleotide 2455 leading to an amino acid change of isoleucine to valine at codon 462
- M3, TC substitution at nucleotide 3205 in the 3'-non-coding region
- M4, CA substitution at nucleotide 2453 leading to an amino acid change of threonine to asparagine at codon 461
CYP1B1
Cytochrome P450 1B1 is an enzyme that in humans is encoded by the CYP1B1 gene.

# Function
CYP1B1 belongs to the cytochrome P450 superfamily of enzymes.  The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids. The enzyme encoded by this gene localizes to the endoplasmic reticulum (ER) and metabolizes procarcinogens such as polycyclic aromatic hydrocarbons and 17beta-estradiol.
Despite over 20 years of research on CYP1A1 and CYP1A2, CYP1B1 was not identified and sequenced until 1994.  Nucleic and amino acid analysis showed approximately 40% identity with CYP1A1.  Despite this similarity, these two enzymes have very different catalytic efficiencies and metabolites when incubated with common substrates, such as retinoic acid and arachidonic acid.  Recently CYP1B1 has been shown to be physiologically important in fetal development, since mutations in CYP1B1 are linked with a form of primary congenital glaucoma.
CYP1A1 and CYP1B1 are regulated by the aryl hydrocarbon receptor, a ligand activated transcription factor.  They are part of the Phase I reactions of drug metabolism.

# Clinical significance
Mutations in this gene have been associated with primary congenital glaucoma; therefore it is thought that the enzyme also metabolizes a signaling molecule involved in eye development, possibly a steroid.
CYP2A6
Cytochrome P450 2A6 (abbreviated CYP2A6) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. CYP2A6 is the primary enzyme responsible for the oxidation of nicotine and cotinine. It is also involved in the metabolism of several pharmaceuticals, carcinogens, and a number of coumarin-type alkaloids. CYP2A6 is the only enzyme in the human body that appreciably catalyzes the 7-hydroxylation of coumarin, such that the formation of the product of this reaction, 7-hydroxycoumarin, is used as a probe for CYP2A6 activity.
The CYP2A6 gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. The gene was formerly referred to as CYP2A3; however, it has been renamed CYP2A6.

# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.
-  The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601"..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}

# Distribution
CYP2A6 localizes to the endoplasmic reticulum and is found predominantly in the liver.

# Variability
Significant interindividual variability in CYP2A6 apoprotein and mRNA levels has been observed.

# Induction
CYP2A6 is known to be inducible by phenobarbital and rifampicin, and it is suspected that other antiepileptic drugs may also have this effect.

# CYP2A6 Ligands
CYP2B6
Cytochrome P450 2B6 is an enzyme that in humans is encoded by the CYP2B6 gene. CYP2B6 is a member of the Cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances.

# Function
This gene, CYP2B6, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to metabolize some xenobiotics, such as the anti-cancer drugs cyclophosphamide and ifosphamide.

# Gene
Transcript variants for this gene have been described; however, it has not been resolved whether these transcripts are in fact produced by this gene or by a closely related pseudogene, CYP2B7. Both the gene and the pseudogene are located in the middle of a CYP2A pseudogene found in a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q.

# CYP2B6 ligands
Following is a table of selected substrates, inducers and inhibitors of CYP2B6.
Inhibitors of CYP2B6 can be classified by their potency, such as:
- Strong inhibitor being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance.
- Moderate inhibitor being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.
- Weak inhibitor being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.
CYP2C8
Cytochrome P4502C8 (abbreviated CYP2C8), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body.  Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-chain polyunsaturated fatty acids, e.g. arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and Linoleic acid to their biologically active epoxides.

# CYP2C8 ligands
Following is a table of selected substrates, inducers and inhibitors of 2C8.
Inhibitors of CYP2C8 can be classified by their potency, such as:
- Strong inhibitor being one that causes at least a five-fold increase in the plasma AUC values, or more than 80% decrease in clearance.
- Moderate inhibitor being one that causes at least a two-fold increase in the plasma AUC values, or 50-80% decrease in clearance.
- Weak inhibitor being one that causes at least a 1.25-fold but less than two-fold increase in the plasma AUC values, or 20-50% decrease in clearance.
Where classes of agents are listed, there may be exceptions within the class.

# Epoxygenase activity
CYP2C8 also possesses epoxygenase activitiy: it is one of the principal enzymes responsible for attacking various long-chain polyunsaturated fatty acids at their double (i.e. alkene) bonds to form epoxide products that act as signaling agents. It metabolizes: 1) arachidonic acid to various epoxyeicosatrienoic acids (also termed EETs); 2) linoleic acid to 9,10-epoxy octadecaenoic acids (also termed vernolic acid, linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecaenoic (also termed coronaric acid, linoleic acid 12,13-oxide, or isoleukotoxin); 3) docosohexaenoic acid to various epoxydocosapentaenoic acids (also termed EDPs); and 4) eicosapentaenoic acid to various epoxyeicosatetraenoic acids (also termed EEQs).
Along with CYP2C8, CYP2C9, CYP2C19, CYP2J2, and possibly CYP2S1 are the main producers of EETs and, very likely, EEQs, EDPs, and the epoxides of linoleic acid.
CYP2R1
Vitamin D 25-hydroxylase also known as cytochrome P450 2R1 is an enzyme that in humans is encoded by the CYP2R1 gene.

# Function
Vitamin D 25-hydroxylase is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. Found in the liver, this enzyme is a microsomal vitamin D hydroxylase that converts vitamin D into 25-hydroxyvitamin D (calcidiol), which is the major circulatory form of the vitamin.

# Clinical significance
An inherited mutation in the CYP2R1 gene which results in the substitution of a proline for a leucine residue at codon 99 eliminates the enzyme activity and is associated with low circulating levels of 25-hydroxyvitamin D and classic symptoms of vitamin D deficiency. The gene product which it encodes, vitamin D 25-hydroxylase, has therefore been proposed as the key enzyme in the conversion of cholecalciferol (vitamin D3) to calcidiol. Calcidiol is subsequently converted by the action of 25-hydroxyvitamin D3 1-alpha-hydroxylase to calcitriol, the active form of vitamin D3 that binds to the vitamin D receptor (VDR) which mediates most of the physiological actions of the vitamin.

## Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. 
-  The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531"..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}

# Model organisms
Model organisms have been used in the study of CYP2R1 function. A conditional knockout mouse line called Cyp2r1tm1b(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
CYP2U1
CYP2U1 (cytochrome P450, family 2, subfamily U, polypeptide 1) is a protein that in humans is encoded by the CYP2U1 gene

# Function
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and the hydroxylation of fatty acids and fatty acid metabolites. CYP2U1 metabolized arachidonic acid, docosahexaenoic acid (DHA), and other long chain fatty acids which suggests that CYP2U1 may play a role in brain and immune functions. CYP2U1 also metabolizes propanone, acetone, and 2-oxypropane.

# Tissue distribution
The CYP2U1 gene is a highly conserved gene that is mainly expressed in brain and thymus, but also at lower levels in kidney, lung, and heart.

# Reactions
CYP2U1 hydroxylates arachidonic acid, docosahexaenoic acid (DHA), and other long chain fatty acids at their terminal (i.e., ) carbon to form 20-hydroxy-arachidonic acid (i.e. 20-Hydroxyeicosatetraenoic acid or 20-HETE), 22-hydroxy-docosahexaneoic acid, and other -hydroxy long chain fatty acids, respectively, plus lesser amounts of these fatty acids -1 hydroxy metabolites, i.e. 19-HETE, 21-hydroxy-docosahexaenoic acid, and other -1 hydroxy long chain fatty acids, respectively.  One of these metabolites, 20-HETE, is a regulator of blood pressure and blood flow to organs in animal models and, based on genetic studies, possibly in humans (see20-Hydroxyeicosatetraenoic acid).

# Clinical significance
A mutation (c.947A>T) in CYP2U1 has been associated in a very small number of patients with Hereditary spastic paraplegia in that it segregates with the disease at the homozygous state in two afflicted families.  This mutation affects an amino acid (p.Asp316Val) that is highly conserved among CYP2U1 orthologs as well as other cytochrome P450 proteins; this p.Asp314Val mutation is located in the enzyme's functional domain, is predicted to be damaging to the enzyme's activity, and is associated with mitochondria dysfunction.  A second homozygous enzyme-disabling mutation has been identified in CYP2U1, c.1A>C/p.Met1?, that is associated with <1% of hereditary spastic paraplegia sufferers.  The reduction in 20-HETE production by these mutations, and thereby in 20-HETE's activation of the TRPV1 neural receptor, it is hypothesized, may contribute to the development of this disease (see 20-Hydroxyeicosatetraenoic acid for details).
CYPU21 along with members of the CYP4A and CYP4F sub-families also -hydroxylate and thereby reduce the activity of various fatty acid metabolites of arachidonic acid including LTB4, 5-HETE, 5-oxo-eicosatetraenoic acid, 12-HETE, and several prostaglandins that are involved in regulating various inflammatory, vascular, and other responses in animals and humans. This hydroxylation-induced inactivation may underlie the proposed roles of the cytochromes in dampening inflammatory responses and the reported associations of certain CYP4F2 and CYP4F3 single nucleotide variants with human Krohn's disease and Coeliac disease, respectively.
CYP3A7
CYP3A7 is an enzyme belonging to the cytochrome P450 family. It is 503 amino acids in size and shares 87% of its sequence with CYP3A4. It carries out a similar role in fetuses that CYP3A4 serves in adults. The gene location is 7q22.1.
The CYP3A group of enzymes are the most abundantly expressed members of the cytochrome P450 family in liver. They are responsible for the metabolism of more than 50% of all clinical pharmaceuticals.

# Notable alleles
The CYP3A7*1C allele is associated with poor outcomes in some cancer patients, possibly because of the effect of the enzyme on some chemotherapy agents.
CYP4F2
Leukotriene-B(4) omega-hydroxylase 1 is an enzyme that in humans is encoded by the CYP4F2 gene.

# Function
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, fatty acids, and other lipids. This protein localizes to the endoplasmic reticulum. The enzyme starts the process of inactivating and degrading leukotriene B4, a potent mediator of inflammation. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F11, is approximately 16 kb away.
CYP4F2 along with CYP4A22, CYP4A11, and CYP4F3 and CYP2U1 also metabolize arachidonic acid to 20-Hydroxyeicosatetraenoic acid (20-HETE) by an Omega oxidation reaction with the predominant 20-HETE-synthesizing enzymes in humans being CYP4F2 followed by CYP4A11; 20-HETE regulates blood flow, vascularization, blood pressure, and kidney tubule absorption of ions in rodents and possibly humans.  Gene polymorphism variants of CYP4F2 are associated with the development of hypertension, cerebral infarction (i.e. ischemic stroke), and myocardial infarction in humans (see 20-Hydroxyeicosatetraenoic acid for details).,
Members of the CYP4A and CYP4F sub-families may also -hydroxylate and thereby reduce the activity of various fatty acid metabolites of arachidonic acid including LTB4, 5-HETE, 5-oxo-eicosatetraenoic acid, 12-HETE, and several prostaglandins that are involved in regulating various inflammatory, vascular, and other responses in animals and humans. This hydroxylation-induced inactivation may underlie the proposed roles of the cytochromes in dampening inflammatory responses and the reported associations of certain CYP4F2 single nucleotide variants (SNPs) with human Crohn's disease (rs2108622) and Coeliac disease (rs3093156 and  rs3093156).
CYP4F3
Leukotriene-B(4) omega-hydroxylase 2 is an enzyme that in humans is encoded by the CYP4F3 gene.  CYP4F3 encodes two distinct enzymes, CYP4F3A and CYP4F3B, which originate from the alternative splicing of a single pre-mRNA precursor molecule; selection of either isoform is tissue-specific with CYP3F3A being expressed mostly in leukocytes and CYP4F3B mostly in the liver.

# Function
The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, fatty acids and other lipids. CYP4F3 actually encodes two splice-variants, CYP4F3A and CYP4F3B, of the cytochrome P450 superfamily of enzymes. The gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F8, is approximately 18 kb away. Both variants localize on the endoplasmic reticulum and metabolize leukotriene B4 and very likely 5-hydroxyeicosatetraenoic acid, 5-oxo-eicosatetraenoic acid, and 12-hydroxyeicosatetraenoic acid by an omega oxidation reaction, i.e. by adding a hydroxyl residue to their terminal (i.e. C-20) carbon. This addition starts the process of inactivating and degrading all of these well-known mediators of inflammation and/or allery. CYP3FA is the major enzyme accomplishing these omega oxidations in leukocytes. The hydroxylation-induced inactivation of these mediators, perhaps particularly of leukotriene B4, may underlie the proposed roles of these cytochromes in dampening inflammatory responses as well as the reported associations of certain CYP4F3 single nucleotide variants (SNPs) with human Krohn's disease (SNPs are designated Rs1290617 and  rs1290620 and Celiac disease (rs1290622 and rs1290625).
CYP4F3A and/or CYP43B also omega oxidize arachidonic acid to 20-Hydroxyeicosatetraenoic acid (20-HETE) as well as epoxyeicosatrienoic acids (EETs) to 20-hydroxy-EETs. 20-HETE regulates blood flow, vascularization, blood pressure, and kidney tubule absorption of ions in rodents and possibly humans; it has also been proposed to be involved in regulating the growth of various types of human cancers (see 20-Hydroxyeicosatetraenoic acid#cancer). EETS have a similar set of regulatory functions but often act in a manner opposite to 20-HETE (see epoxyeicosatrienoic acid#cancer); since, however, the activities of the 20-HEETs have not been well-defined, the function of EET omega oxidation is unclear.