Persius/hicric huggingface dataset:
ADD2
Beta-adducin is a protein that in humans is encoded by the ADD2 gene.

# Function
Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta, and gamma.  The three subunits are encoded by distinct genes and belong to a family of membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues.
While adducins alpha and gamma are ubiquitously expressed, the expression of adducin beta is restricted to brain and hematopoietic tissues.  Adducin, originally purified from human erythrocytes, was found to be a heterodimer of adducins alpha and beta.  Polymorphisms resulting in amino acid substitutions in these two subunits have been associated with the regulation of blood pressure in an animal model of hypertension.  Heterodimers consisting of alpha and gamma subunits have also been described.  Structurally, each subunit is composed of two distinct domains.
The amino-terminal region is protease resistant and globular in shape, while the carboxy-terminal region is protease sensitive.  The latter contains multiple phosphorylation sites for protein kinase C, the binding site for calmodulin, and is required for association with spectrin and actin.  Various adducin beta mRNAs, alternatively spliced at 3'end and/or internally spliced and encoding different isoforms, have been described.  The functions of all the different isoforms are not known.

# Interactions
ADD2 has been shown to interact with FYN.
ADH5
Alcohol dehydrogenase class-3 is an enzyme that in humans is encoded by the ADH5 gene.
This gene encodes glutathione-dependent formaldehyde dehydrogenase or the class III alcohol dehydrogenase chi subunit, which is a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Class III alcohol dehydrogenase is a homodimer composed of 2 chi subunits. It has virtually no activity for ethanol oxidation, but exhibits high activity for oxidation of long-chain primary alcohols and for oxidation of S-hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and glutathione.
This enzyme is an important component of cellular metabolism for the elimination of formaldehyde, a potent irritant and sensitizing agent that causes lacrymation, rhinitis, pharyngitis, and contact dermatitis.
ADME

# Overview
ADME is an acronym in pharmacokinetics and pharmacology for absorption, distribution, metabolism, and excretion, and describes the disposition of a pharmaceutical compound within an organism. The four criteria all influence the drug levels and kinetics of drug exposure to the tissues and hence influence the performance and pharmacological activity of the compound as a drug:

## Absorption

## Distribution

## Metabolism

## Excretion/Elimination
- Glomerular filtration of unbound drug.
- Active secretion of (free & protein-bound) drug by transporters e.g. anions such as urate, penicillin, glucuronide, sulphate conjugates) or cations such as choline, histamine.
- Filtrate 100-fold concentrated in tubules for a favourable concentration gradient so that it may be reabsorbed by passive diffusion and passed out through the urine.
Sometimes, the potential or real toxicity of the compound is taken into account (ADME-Tox or ADMET). When the Liberation of the substance (from protective coating, or other excipients) is considered, we speak of LADME.
Computational chemists try to predict the ADME-Tox qualities of compounds through methods like QSPR or QSAR.
The route of administration critically influences ADME.
AIM2
Interferon-inducible protein AIM2 also known as absent in melanoma 2 or simply AIM2 is a protein that in humans is encoded by the AIM2 gene. Recent research has shown that AIM2 is part of the inflammasome and contributes to the defence against bacterial and viral DNA.

# Structure
AIM2 is a 343 amino acid protein with a N-terminal DAPIN (or pyrin) domain (amino acids 1-87) and a C-terminal HIN-200 domain (amino acids 138-337), which is known to have two oligonucleotide-binding folds.

# Function
AIM2 is a member of the Ifi202/IFI16 family.  It plays a putative role in tumorigenic reversion and may control cell proliferation.  Interferon-gamma induces expression of AIM2.
Though there has been virtually no biochemistry performed, a model based on cell-based or in vivo experiments has led to the current model of how AIM2 triggers the inflammasome.  The C-terminal HIN domain binds double stranded DNA (either viral, bacterial, or even host) and acts as a cytosolic dsDNA sensor.  This leads to the oligomerization of the inflammasome complex.  The N-terminal pyrin domain of AIM2 interacts with the pyrin domain of another protein ASC (or Apoptosis-associated Speck-like protein containing a caspase activation and recruitment domain).  ASC also contains a CARD domain (caspase activation and recruitment domain), that recruits procaspase-1 to the complex.  This leads to the autoactivation of caspase-1, an enzyme that processes proinflammatory cytokines (IL-1b and IL-18).
AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity.

# Clinical relevance
Elevated levels of AIM2 expression are found in skin cells from people with psoriasis. In systemic lupus erythematosus, lysosome dysfunction allows DNA to gain access to the cytosol and activate AIM2 resulting in increased type 1 interferon production.
AKT1
RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1 gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 (Src homology 2-like) domains. It is commonly referred to as PKB, or by both names as "Akt/PKB".

# Function
The serine-threonine protein kinase AKT1 is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery.  Mice lacking Akt1 display a 25% reduction in body mass, indicating that Akt1 is critical for transmitting growth-promoting signals, most likely via the IGF1 receptor. Mice lacking Akt1 are also resistant to cancer: They experience considerable delay in tumor growth initiated by the large T antigen or the Neu oncogene. A single-nucleotide polymorphism in this gene causes Proteus syndrome.

# History
AKT (now also called AKT1) was originally identified as the oncogene in the transforming retrovirus, AKT8. AKT8 was isolated from a spontaneous thymoma cell line derived from AKR mice by cocultivation with an indicator mink cell line. The transforming cellular sequences, v-akt, were cloned from a transformed mink cell clone and these sequences were used to identify Akt1 and Akt2 in a human clone library. AKT8 was isolated by Stephen Staal in the laboratory of Wallace P. Rowe; he subsequently cloned v-akt and human AKT1 and AKT2 while on staff at the Johns Hopkins Oncology Center.
In 2011, a mutation in AKT1 was strongly associated with Proteus syndrome, the disease that probably affected the Elephant Man.
The name Akt stands for Ak strain transforming. The origins of the Akt name date back to 1928, where J. Furth performed experimental studies on mice that developed spontaneous thymic lymphomas. Mice from three different stocks were studied, and the stocks were designated A, R, and S. Stock A was noted to yield many cancers, and inbred families were subsequently designated by a second small letter (Aa, Ab, Ac, etc.), and thus came the Ak strain of mice. Further inbreeding was undertaken with Ak mice at the Rockefeller Institute in 1936, leading to the designation of the AKR mouse strain. In 1977, a transforming retrovirus was isolated from the AKR mouse. This virus was named Akt-8, the "t" representing its transforming capabilities.

# Interactions
AKT1 has been shown to interact with:
- AKTIP,
- BRAF,
- BRCA1,
- C-Raf,
- CDKN1B,
- CHUK
- GAB2,
- HSP90AA1,
- ILK,
- KRT10,
- MAP2K4,
- MAP3K11,
- MAP3K8,
- MAPK14,
- MAPKAPK2,
- MARK2,
- MTCP1,
- MTOR,
- NPM1,
- NR4A1,
- NR3C4,
- PKN2,
- PRKCQ,
- PDPK1,
- PLXNA1,
- TCL1A,
- TRIB3,
- TSC1,
- TSC2,  and
- YWHAZ.
AKT2
RAC-beta serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT2 gene.

# Function
This gene is a putative oncogene encoding a protein belonging to the AKT subfamily of serine/threonine kinases that contain SH2-like (Src homology 2-like) domains.  The encoded protein is a general protein kinase capable of phosphorylating several known proteins.

# Clinical significance
The gene was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. Overexpression contributes to the malignant phenotype of a subset of human ductal pancreatic cancers.
Mice lacking Akt2 have a normal body mass, but display a profound diabetic phenotype, indicating that Akt2 plays a key role in signal transduction downstream of the insulin receptor. Mice lacking Akt2 show worse outcome in breast cancer initiated by the large T antigen as well as the neu oncogene.

# Interactions
AKT2 has been shown to interact with:
- APPL1,
- CHUK,
- SH3RF1  and
- TCL1A.
ALG2
Alpha-1,3-mannosyltransferase ALG2 is an enzyme that is encoded by the ALG2 gene.  Mutations in the human gene are associated with congenital defects in glycosylation 

# Function
This gene encodes a member of the glycosyltransferase 1 family. The encoded protein acts as an alpha 1,3 mannosyltransferase, mannosylating Man(2)GlcNAc(2)-dolichol diphosphate and Man(1)GlcNAc(2)-dolichol diphosphate to form Man(3)GlcNAc(2)-dolichol diphosphate. Defects in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ii).

# Interactions
ALG2 has been shown to interact with  ANXA7 and ANXA11.
ALPL
Alkaline phosphatase, tissue-nonspecific isozyme is an enzyme that in humans is encoded by the ALPL gene.

# Function
There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue-nonspecific). The first three are located together on chromosome 2, whereas the tissue-nonspecific form is located on chromosome 1. The product of this gene is a membrane-bound glycosylated enzyme that is not expressed in any particular tissue and is, therefore, referred to as the tissue-nonspecific form of the enzyme. The exact physiological function of the alkaline phosphatases is not known. A proposed function of this form of the enzyme is matrix mineralization.  However, mice that lack a functional form of this enzyme show normal skeletal development.

# Clinical significance
This enzyme has been linked directly to a disorder known as hypophosphatasia, a disorder that is characterized by hypercalcemia and includes skeletal defects. The character of this disorder can vary, however, depending on the specific mutation, since this determines age of onset and severity of symptoms.
The severity of symptoms ranges from premature loss of deciduous teeth with no bone abnormalities to stillbirth depending upon which amino acid
is changed in the ALPL gene. Mutations in the ALPL gene lead to varying low activity of the enzyme tissue-nonspecific alkaline phosphatase (TNSALP) resulting in hypophosphatasia (HPP). There are different clinical forms of HPP which can be inherited by an autosomal recessive trait or autosomal dominant trait, the former causing more severe forms of the disease. Alkaline phosphatase allows for mineralization of calcium and phosphorus by bones and teeth. ALPL gene mutation leads to insufficient TNSALP enzyme and allows for an accumulation of chemicals such as inorganic pyrophosphate to indirectly cause elevated calcium levels in the body and lack of bone calcification.
The mutation E174K, where a glycine is converted to an alanine amino acid at the 571st position of its respective polypeptide chain, is a result of an ancestral mutation that occurred in Caucasians and shows a mild form of HPP.
ALX1
ALX homeobox protein 1 is a protein that in humans is encoded by the ALX1 gene.

# Function
The specific function of this gene has yet to be determined in humans; however, in rodents, it is necessary for survival of the forebrain mesenchyme and may also be involved in development of the cervix. Mutations in the mouse gene lead to neural tube defects such as acrania and meroanencephaly.
In Darwin's finches, inhabiting the Galapagos islands, ALX1 has been linked to the diversity of beak shapes.

# Interactions
ALX1 has been shown to interact with IPO13.
ALX3
The ALX3 gene, also known as aristaless-like homeobox 3, is a protein coding gene that provides instructions to build a protein which is a member of the homeobox protein family. This grouping regulates patterns of anatomical development. The gene encodes a nuclear protein that functions as a transcription regulator involved in cell-type differentiation and development.
The ALX3 protein, encoded by the gene, is a transcription factor, meaning that it binds to DNA and obtains control over the action of other genes. The ALX3 protein specifically controls genes that regulate cell growth, proliferation, and migration. This protein is essential for the development of the head and face, specifically the nose. This event begins around the fourth week of development.
At least 7 mutations in the ALX3 gene are known to cause frontonasal dysplasia. The mutations eliminate the function of the ALX3 protein, resulting in decreased ability to bind to DNA. The loss of regulatory function results in uncontrolled cell proliferation and migration during fetal development. One particular form of the disorder, called frontonasal dysplasia type 1, presents with abnormal development of structures in the middle of the face. The most common malformation of this defect is a cleft in the nose, lip, and palate.
ALX3 was first discovered by a group of scientists, led by Hopi Hoekstra, a biologist from Harvard University, that investigated how stripe patterns form in animals. They investigated the Rhabdomys pumiliom, commonly known as the African striped mouse because of the alternating colored stripes observed on its back. One of the members of the team, Ricardo Mallarino, discovered that the stripes were formed during embryogenesis in the mice. Melanocytes, the specialized cells that produce the pigments in the skin, were not active in areas where the lighter stripes were observed. They then researched the genes active in those areas using RNA sequencing. They discovered that ALX3 was expressed in the light hair areas but not in the dark hair areas. They found that all mice expressed the gene on their abdomen but only the African striped mouse expressed it on its back, hence why the strips appear. Protein-DNA binding was then performed to determine where the ALX3 protein binds on the DNA. ALX3 binds to the promoter and represses MITF, which allows transcription to take place when making melanocytes. More tests were performed to confirm the function of ALX3 within the African striped mice. The gene was observed in other rodents such as the North American chipmunks and deemed responsible for the similar outcomes. The differences in evolution amongst the species did not hinder the similarities in the expression of the gene. This lead the team to believe that ALX3 may have the same effect in mammals.  However, further studies must be completed to confirm that ALX3 is responsible for the same in other mammals.
AMBN
Ameloblastin (enamel matrix protein) is a protein that in humans is encoded by the AMBN gene.

# Function
Ameloblastin, also known as amelin, is a gene-specific protein found in tooth enamel. Although less than 5% of enamel consists of protein, ameloblastins comprise 510% of all enamel protein. This protein is formed by ameloblasts during the early secretory to late maturation stages of amelogenesis. Although not completely understood, the function of ameloblastins is believed to be in controlling the elongation of enamel crystals and generally directing enamel mineralization during tooth development.
Other significant proteins in enamel are amelogenins, enamelins, and tuftelins.
This gene encodes the nonamelogenin enamel matrix protein ameloblastin. The encoded protein may be important in enamel matrix formation and mineralization. This gene is located in the calcium-binding phosphoprotein gene cluster on chromosome 4. Mutations in this gene may be associated with dentinogenesis imperfecta and autosomal dominant amelogenesis imperfecta. .

# Clinical significance
Mutations in AMBN cause amelogenesis imperfecta.
AMFR
Autocrine motility factor receptor, isoform 2 is a protein that in humans is encoded by the AMFR gene.
Autocrine motility factor is a tumor motility-stimulating protein secreted by tumor cells. The protein encoded by this gene is a glycosylated transmembrane protein and a receptor for autocrine motility factor. The receptor, which shows some sequence similarity to tumor protein p53, is localized to the leading and trailing edges of carcinoma cells.

# Model organisms
Model organisms have been used in the study of AMFR function. A conditional knockout mouse line, called Amfrtm1a(KOMP)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 six tests were carried out on mutant mice and one significant abnormality was observed: Fewer than expected homozygous mutant mice survived until weaning.

# Interactions
AMFR has been shown to interact with Valosin-containing protein.
ANK1
Ankyrin 1, erythrocytic, also known as ANK1, is a protein that in humans is encoded by the ANK1 gene.

# Tissue distribution
The protein encoded by this gene, Ankyrin 1, is the prototype of the ankyrin family, was first discovered in erythrocytes, but since has also been found in brain and muscles.

# Genetics
Complex patterns of alternative splicing in the regulatory domain, giving rise to different isoforms of ankyrin 1 have been described, however, the precise functions of the various isoforms are not known.  Alternative polyadenylation accounting for the different sized erythrocytic ankyrin 1 mRNAs, has also been reported.  Truncated muscle-specific isoforms of ankyrin 1 resulting from usage of an alternate promoter have also been identified.

# Disease linkage
Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary spherocytosis.
ANK1 shows altered methylation and expression in Alzheimer's disease. A gene expression study of postmortem brains has suggested ANK1 interacts with interferon- signalling.

# Function
The ANK1 protein belongs to the ankyrin family that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and maintenance of specialized membrane domains.  Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner.  Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin-binding domain; and a carboxy-terminal regulatory domain, which is the least conserved and subject to variation.
The small ANK1 (sAnk1) protein splice variants makes contacts with obscurin, a giant protein surrounding the contractile apparatus in striated muscle.

# Interactions
ANK1 has been shown to interact with T-cell lymphoma invasion and metastasis-inducing protein 1, Titin, RHAG and OBSCN.
ANK3
Ankyrin-3 (ANK-3), also known as  ankyrin-G, is a protein from ankyrin family that in humans is encoded by the ANK3 gene.

# Function
The protein encoded by this gene, ankyrin-3 is an immunologically distinct gene product from ankyrins ANK1 and ANK2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Alternatively spliced variants may be expressed in other tissues. Although multiple transcript variants encoding several different isoforms have been found for this gene, the full-length nature of only two have been characterized.
Within the nervous system, ankyrin-G is specifically localized to the neuromuscular junction, the axon initial segment and the Nodes of Ranvier. Within the nodes of Ranvier where action potentials are actively propagated, ankyrin-G has long been thought to be the intermediate binding partner to neurofascin and voltage-gated sodium channels. The genetic deletion of ankyrin-G from multiple neuron types has shown that ankyrin-G is required for the normal clustering of voltage-gated sodium channels at the axon hillock and for action potential firing.

# Disease linkage
The  ANK3 protein associates with the cardiac sodium channel Nav1.5 (SCN5A). Both proteins are highly expressed at ventricular intercalated disc and T-tubule membranes in cardiomyocytes. A mutation in the Nav1.5 protein blocks interaction with ANK3 binding and therefore disrupts surface expression of Nav1.5 in cardiomyocytes resulting in Brugada syndrome, a type of cardiac arrhythmia.
Other mutations in the ANK3 gene may be involved in the bipolar disorder and intellectual disability.

# Ankyrin family
The protein encoded by the ANK3 gene is a member of the ankyrin  family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation.