Persius/hicric huggingface dataset:
ACVRL1
Serine/threonine-protein kinase receptor R3 is an enzyme that in humans is encoded by the ACVRL1 gene.
ACVRL1 is a receptor in the TGF beta signaling pathway.  It is also known as activin receptor-like kinase 1, or ALK1.

# Function
This gene encodes a type I cell-surface receptor for the TGF-beta superfamily of ligands. It shares with other type I receptors a high degree of similarity in serine-threonine kinase subdomains, a glycine- and serine-rich region (called the GS domain) preceding the kinase domain, and a short C-terminal tail. The encoded protein, sometimes termed ALK1, shares similar domain structures with other closely related ALK or activin receptor-like kinase proteins that form a subfamily of receptor serine/threonine kinases. Mutations in this gene are associated with hemorrhagic telangiectasia type 2, also known as Rendu-Osler-Weber syndrome 2.

# Pathology
Germline mutations of ACVRL1 are associated with:
- hereditary hemorrhagic telangiectasia type 2 (Rendu-Osler-Weber syndrome 2)
- Pulmonary arteriovenous malformations
Somatic mosaicism in ACVRL1 are associated with severe pulmonary arterial hypertension.
ACVRL1 directly interacts with low-density lipoprotein (LDL), which implies that it might initiate the early phases of atherosclerosis.

# As a drug target
- Dalantercept is an experimental ALK1 inhibitor.

# Closely/family related kinases
(Not to be confused with anaplastic lymphoma kinase (ALK)  )
ALK4 is ACVR1B, ALK7 is ACVR1C, and ALK5 is  the TGF- type I receptor.
ADAM12
Disintegrin and metalloproteinase domain-containing protein 12 is an enzyme that in humans is encoded by the ADAM12 gene. ADAM12 has two splice variants: ADAM12-L, the long form, has a transmembrane region and ADAM12-S, a shorter variant, is soluble and lacks the transmembrane and cytoplasmic domains.

# Function
This gene encodes a member of the ADAM (a disintegrin and metalloprotease) protein family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This gene has two alternatively spliced transcripts: a shorter secreted form and a longer membrane-bound form. The shorter form is found to stimulate myogenesis.

# Clinical Significance
ADAM 12, a metalloprotease that binds insulin growth factor binding protein-3 (IGFBP-3), appears to be an effective early Down syndrome marker. Decreased levels of ADAM 12 may be detected in cases of trisomy 21 as early as 8 to 10 weeks gestation. Maternal serum ADAM 12 and PAPP-A levels at 8 to 9 weeks gestation in combination with maternal age yielded a 91% detection rate for Down syndrome at a 5% false-positive rate. When nuchal translucency data from approximately 12 weeks gestation was added, this increased the detection rate to 97%.
ADAM12 has also been implicated in the development of pathology in various cancers, hypertension, liver fibrogenesis, and asthma. In asthma, ADAM12 is upregulated in lung epithelium in response to TNF-alpha.

# Interactions
ADAM12 has been shown to interact with:
- ACTN2,
- IGFBP3,  and
- PIK3R1.
ADAM15
Disintegrin and metalloproteinase domain-containing protein 15 is an enzyme that in humans is encoded by the ADAM15 gene.

# Function
The protein encoded by this gene is a member of the ADAM (a disintegrin and metalloproteinase) protein family. ADAM family members are type I transmembrane glycoproteins known to be involved in cell adhesion and proteolytic ectodomain processing of cytokines and adhesion molecules. This protein contains multiple functional domains including a zinc-binding metalloprotease domain, a disintegrin-like domain, as well as an EGF-like domain. Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, beta 3. It also interacts with Src family protein-tyrosine kinases in a phosphorylation-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed.

# Clinical significance

## Arthritis
ADAM15 has been associated with a number of diseases, most recently Rheumatoid Arthritis where it is required for the activation of the FAK and Src pathways to generate apoptosis resistance in response to apoptotic signalling or cell stress. ADAM15 also has an antiapoptotic effect in osteoarthritic chondrocytes.

## Cancer
The precise role of ADAM15 in cancer is still unclear but the metalloprotein has been linked to a number of different cancerous diseases such as Breast cancer where the expression of the protein is increased in carcinoma in-situ, invasive carcinoma and metastatic breast cancer tissues Additionally, the alternative splice variant forms of ADAM15 have also been correlated with different prognosis in 48 breast cancer patients based upon their expression levels.   ADAM15 has also been shown to have a role in Prostate Cancer again through increased expression in neoplastic and metastatic tissues compared to normal prostate tissues and also through its modulation of epithelial cell- tumour cell interactions.

# Interactions
ADAM15 has been shown to interact with:
- Grb2,
- HCK,
- Lck and
- SH3GL2, and
- SNX9.
The alternatively spliced isoforms have also been shown to exhibit different preferential interactions with proteins containing SH3 domains.
ADARB1
Double-stranded RNA-specific editase 1 is an enzyme that in humans is encoded by the ADARB1 gene.

# Function
This gene encodes the enzyme responsible for pre-mRNA editing of the glutamate receptor subunit B by site-specific deamination of adenosines. Studies in rats found that this enzyme acted on its own pre-mRNA molecules to convert an AA dinucleotide to an AI dinucleotide which resulted in a new splice site. Alternative splicing of this gene results in several transcript variants, some of which have been characterized by the presence or absence of an ALU cassette insert and a short or long C-terminal region.
ADARB1 (ADAR2) requires the small molecule inositol hexakisphosphate (IP6) for proper function. ADAR2 is an A-to-I RNA-editing enzyme that mostly acts on protein-coding substrates.
ADARB2
Double-stranded RNA-specific editase B2 is an enzyme that in humans is encoded by the ADARB2 gene.

# Function
RNA-editing deaminase-2 (RED2, or ADARB2) is a member of the double-stranded RNA (dsRNA) adenosine deaminase family of RNA-editing enzymes. Adenosine deamination of pre-mRNA results in a change in the amino acid sequence of the gene product, which differs from that predicted by the genomic DNA sequence. Other members of this family include DRADA (ADAR) and RED1 (ADARB1).
Unlike ADAR1 and ADAR2, ADAR3 has demonstrated no editing ability in vitro. It has been shown to suppress 5-HT2C RNA editing in vitro through a yet unknown mechanism, and may thus work as a negative regulator.
ADCY10
Adenylyl cyclase 10 also known as ADCY10 is an enzyme that, in humans, is encoded by the ADCY10 gene.

# Function
The protein encoded by this gene belongs to a distinct class of mammalian adenylyl cyclase that is soluble and insensitive to G protein or forskolin regulation. It is localized in the cytoplasm and is thought to function as a general bicarbonate sensor throughout the body. It may also play an important role in the generation of cAMP in spermatozoa, implying possible roles in sperm maturation through the epididymis, capacitation, hypermotility, and/or the acrosome reaction.

# Clinical significance
Mutations in the ADCY10 gene are associated with an increased risk of adsorptive hypercalciuria.
AFP-L3

# Overview
In oncology, AFP-L3 is an isoform of Alpha-fetoprotein (AFP), a substance typically used in the triple test during pregnancy and for screening chronic liver disease patients for hepatocellular carcinoma (HCC). AFP can be fractionated by affinity electrophoresis into 3 glycoforms: L1, L2, and L3 based on the reactivity with the lectin Lens culinaris agglutinin (LCA). AFP-L3 binds strongly to LCA via an additional  1-6 fucose residue attached at the reducing terminus of N-acetylglucosamine; this is in contrast to the L1 isoform.  It is the L1 isoform which is typically associated with non-HCC inflammation of liver disease condition.  The L3 isoform is specific to malignant tumors and its detected presence can serve to identify patients whom need increased monitoring for the development of HCC in high risk populations (i.e. chronic hepatitis B & C and/or liver cirrhosis).  AFP-L3% is now being considered as a tumor marker for the North American demographic.

# AFP-L3% assay
AFP-L3 is isolated via an immunoassay and quantified using chemiluminesence on an automated platform.  Results for AFP-L3 are represented as a ratio of LCA-reactive AFP to total AFP (AFP-L3%).  The AFP-L3% assay, a liquid-phase binding assay, will help to identify at-risk subjects earlier, allowing for more intense evaluation for evidence of HCC according to existing practice guidelines in oncology.  AFP-L3% is the standard for quantifying the L3 isoform of AFP in serum of high risk chronic liver disease (CLD) patients.  Studies have shown that AFP-L3% test results of more than 10% can be indicative of early HCC or early nonseminomatous germ cell tumor.
Early testimonials from hepatologists indicate that there is a target patient population for the AFP-L3% assay.  This target population are those CLD patients who have AFP concentrations in the indeterminate range of 20-200+ ng/mL and a small or indeterminate mass on imaging.  It is in this range that doctors experience trouble differentiating non-HCC fluctuations in AFP vs indication of HCC.  In such patients these hepatologists recommend utilizing AFP-L3% to clarify the disease state.  Some hepatologists also use a positive result to urge insurance companies to pay for more frequent and intensive imaging.
Ultimately AFP-L3% may be used as a rule-in or rule-out assay for transplantation consideration and/or an intermediate step in surveillance precluding costly imaging on patients with fluctuating AFP results but negative for HCC.
AGPAT3
1-acyl-sn-glycerol-3-phosphate acyltransferase gamma is an enzyme that in humans is encoded by the AGPAT3 gene.
The protein encoded by this gene is an acyltransferase that converts lysophosphatidic acid into phosphatidic acid, which is the second step in the de novo phospholipid biosynthetic pathway. The encoded protein may be an integral membrane protein. Two transcript variants encoding the same protein have been found for this gene.

# Model organisms
Model organisms have been used in the study of AGPAT3 function. A conditional knockout mouse line, called Agpat3tm1a(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 one significant abnormality was observed. Few homozygous mutant animals survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these.
AKAP11
A-kinase anchor protein 11 is an enzyme that in humans is encoded by the AKAP11 gene.

# Function
The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is expressed at high levels throughout spermatogenesis and in mature sperm. It binds the RI and RII subunits of PKA in testis. It may serve a function in cell cycle control of both somatic cells and germ cells in addition to its putative role in spermatogenesis and sperm function.

# Interactions
AKAP11 has been shown to interact with:
- GSK3B,
- PPP1CA,
- PRKAR2A,
- PRKAR2B.
- VAPB. Binding is via a FFAT motif in the N-terminal portion of AKAP11, similar to that found in AKAP3.
AKAP13
A-kinase anchor protein 13 is an enzyme that in humans is encoded by the AKAP13 gene.

# Function
The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins that have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. Alternative splicing of this gene results in at least 3 transcript variants encoding different isoforms containing a dbl oncogene homology (DH) domain and a pleckstrin homology (PH) domain. The DH domain is associated with guanine nucleotide exchange activation for the Rho/Rac family of small GTP-binding proteins, resulting in the conversion of the inactive GTPase to the active form capable of transducing signals. The PH domain has multiple functions. Therefore, these isoforms function as scaffolding proteins to coordinate a Rho signaling pathway and, in addition, function as protein kinase A-anchoring proteins.

# Interactions
AKAP13 has been shown to interact with Estrogen receptor alpha, CTNNAL1 and PRKAR2A.
AKR1B1
Aldo-keto reductase family 1, member B1 (AKR1B1), also known as aldose reductase, is an enzyme that in humans is encoded by the AKR1B1 gene. It is a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent enzyme catalyzing the reduction of various aldehydes and ketones to the corresponding alcohol. The involvement in oxidative stress diseases, cell signal transduction and cell proliferation process endows AKR1B1 the potential as a therapeutic target.

# Structure

## Gene
The AKR1B1 gene lies on the chromosome location of 7q33 and consists of 10 exons. There are a few putative pseudogenes for this gene, and one of them has been confirmed and mapped to chromosome 3.

## Protein
AKR1B1 consists of 316 amino acid residues and weighs 35853Da. It does not possess the traditional dinucleotide binding fold. The way it binds NADPH differs from other nucleotide adenine dinucleotide-dependent enzymes. The active site pocket of human aldose reductase is relatively hydrophobic, lined by seven aromatic and four other non-polar residues.

# Function
AR belongs to the aldehyde-keto reductase superfamily, with a widely expression in human organs including the kidney, lens, retina, nerve, heart, placenta, brain, skeletal muscle, testis, blood vessels, lung, and liver.  It is a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent enzyme catalyzing the reduction of various aldehydes and ketones to the corresponding alcohol. It also participates in glucose metabolism and osmoregulation and plays a protective role against toxic aldehydes derived from lipid peroxidation and steroidogenesis.

# Clinical significance
Under diabetic conditions AR converts glucose into sorbitol, which is then converted to fructose. 20466987 It has been found to play an important role in many diabetes complications such as diabetes retinopathy and renopathy. It is also involved in many oxidative stress diseases, cell signal transduction and cell proliferation process including cardiovascular disorders, sepsis, and cancer.
It has been reported that he action of AR contributes to the activation of retinal microglia, suggesting that inhibition of AR may be of a therapeutic importance to reduce inflammation associated with activation of RMG. Adapting AR inhibitors could as well prevent sepsis complications, prevent angiogenesis, ameliorate mild or asymptomatic diabetic cardiovascular autonomic neuropathy and may be a promising strategy for the treatment of endotoxemia and other ROS-induced inflammatory diseases.

# Interactions
AKR1B1 has been found to interact with:
- ginsenoside 20(S)-Rh2 
- alkaloid 
- carboxylic acid derivatives
- spirohydantoins
- cyclic amides
AKR1C3
Aldo-keto reductase family 1 member C3 (AKR1C3), also known as 17-hydroxysteroid dehydrogenase type 5 (17-HSD5, HSD17B5) is a key steroidogenic enzyme that in humans is encoded by the AKR1C3 gene.

# Function
This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14.

# Pathology
AKR1C3 is overexpressed in prostate cancer (PCa) and is associated with the development of castration-resistant prostate cancer (CRPC). In addition, AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression.
ALD-52
ALD-52 or N-acetyl-LSD, is a chemical analogue of LSD (Lysergic Acid Diethylamide). It was originally discovered by Albert Hofmann but was not widely studied until the rise in popularity of psychedelics in the 1960s.

# Effects
In TiHKAL, Shulgin touches briefly on ALD-52 in entry 26, LSD. His writings are vague, second hand accounts, saying doses in the 50-175g range have resulted in various conclusions. One found that there was less visual distortion than with LSD and it seems to produce less anxiety and was somewhat less potent than LSD. Another report claimed it was more effective in increasing blood pressure. Yet another could not tell them apart.
It has the same characteristics as LSD, but supposedly "without the anxiety, tenseness, and other problems inherent to it".

# Dangers
In The Hallucinogens by Hoffer and Osmond (1967), ALD-52 (D,L-Acetyllysergic acid diethylamide) is listed as having a lower (approximately 1/5) intravenous toxicity (in rabbits), a lower (approximately 1/8) pyretogenic effect, an equal psychological effect in man, and double the antiserotonin effect as compared with LSD.

# History
It is possible ALD-52 was the active chemical in the "Orange Sunshine" LSD that was widely available in California through 1968 and 1969. The Sonoma County underground chemistry lab of Tim Scully and Nicholas Sand was the source for "Orange Sunshine." It was shut down by the police, and Scully was arrested and prosecuted. This resulted in the first drug analogue trial, where Scully claimed that he and his partners did nothing wrong, because they were producing ALD-52 which was not an illicit drug. However, as the prosecution claimed, there were problems with such a rationale: first, ALD-52 readily undergoes hydrolysis  to LSD, and second, the synthesis of ALD-52 required LSD (this was based on the methods available in the scientific literature at the time). Scully was convicted and served time in prison.

# Sources
- Entry #26 from TiHKAL
- everything2
- Totse
- Lycaeum
- White Light
ANAPC1
Anaphase-promoting complex subunit 1 is an enzyme that in humans is encoded by the ANAPC1 gene.
ANAPC1 is one of at least ten subunits of the anaphase-promoting complex (APC), which functions at the metaphase-to-anaphase transition of the cell cycle and is regulated by spindle checkpoint proteins. The APC is an E3 ubiquitin ligase that targets cell cycle regulatory proteins for degradation by the proteasome, thereby allowing progression through the cell cycle (supplied by OMIM).

# Interactions
ANAPC1 has been shown to interact with ANAPC5, ANAPC4, ANAPC2, CDC27 and ANAPC7.
ANAPC4
Anaphase-promoting complex subunit 4 is an enzyme that in humans is encoded by the ANAPC4 gene.
A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor, which are subsequently degraded by the 26S proteasome. Biochemical studies have shown that the vertebrate APC contains eight subunits. The composition of the APC is highly conserved in organisms from yeast to humans. The exact function of this gene product is not known.

# Interactions
ANAPC4 has been shown to interact with ANAPC1, ANAPC5, CDC27 and ANAPC7.
ANAPC5
Anaphase-promoting complex subunit 5 is an enzyme that in humans is encoded by the ANAPC5 gene.
The anaphase-promoting complex (APC) consists of at least 8 protein subunits, including APC5, CDC27 (APC3; MIM 116946), CDC16 (APC6; MIM 603461), and CDC23 (APC8; MIM 603462).

# Interactions
ANAPC5 has been shown to interact with ANAPC1, ANAPC4, CDC27 and PABPC1.
ANAPC7
Anaphase-promoting complex subunit 7 is an enzyme that in humans is encoded by the ANAPC7 gene. Multiple transcript variants encoding different isoforms have been found for this gene.

# Function
This gene encodes a tetratricopeptide repeat containing component of the anaphase-promoting complex/cyclosome (APC/C), a large E3 ubiquitin ligase that controls cell cycle progression by targeting a number of cell cycle regulators such as B-type cyclins for 26S proteasome-mediated degradation through ubiquitination. The encoded protein is required for proper protein ubiquitination function of APC/C and for the interaction of APC/C with certain transcription coactivators.

# Interactions
ANAPC7 has been shown to interact with ANAPC1, ANAPC4,  CDC27 and CDC20.
ANGPT4
Angiopoietin-4 is a protein that in humans is encoded by the ANGPT4 gene.
Angiopoietins are proteins with important roles in vascular development and angiogenesis. 
All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. 
The mechanism by which they contribute to angiogenesis is thought to involve regulation of endothelial cell interactions with supporting perivascular cells.
The protein encoded by this gene functions as an agonist and is an angiopoietin.
ARGLU1
Arginine and glutamate-rich protein 1 is a protein that in humans is encoded by the ARGLU1 gene located at 13q33.3.
The protein product of this gene has been proposed as a MED1-interacting protein required for estrogen-dependent gene transcription and breast cancer cell growth.
The ARGLU1 gene expresses at least three distinct RNA splice isoforms - a fully spliced isoform coding for the protein, an isoform containing a retained intron that is detained in the nucleus, and an isoform containing an alternative exon that targets the transcript for nonsense mediated decay. Furthermore, ARGLU1 contains a long, highly evolutionarily conserved sequence known as an Ultraconserved Element (UCE) that is within the retained intron and overlaps the alternative exon.