Persius/hicric huggingface dataset:
ANO1
Anoctamin-1 (ANO1) also known as Transmembrane member 16A (TMEM16A) is a protein that, in humans, is encoded by the ANO1 gene. Anoctamin-1 is a voltage-sensitive calcium-activated chloride channel that is expressed in smooth muscle and epithelial cells; it is highly expressed in human interstitial cells of Cajal (ICC) throughout the gastrointestinal tract. Changes in ANO1 channel activity directly/positively correlate with ICC activity.

# Function
ANO1 is a transmembrane protein that functions as a calcium-activated chloride channel. Ca2+, Sr2+, and Ba2+ activate the channel.

# Structure
No atomic resolution structure of this channel has yet been obtained. However, biochemical evidence suggests that the channel assembles as a dimer of two ANO1 polypeptide subunits. From hydropathy plotting, each subunit is thought to encode a molecule with eight transmembrane domains, with a reentrant loop between the fifth and sixth transmembrane domains. The reentrant loop is thought to be a P loop-like structure responsible for the ion selectivity of the protein.

# Clinical significance
ANO1 is expressed in the human gastrointestinal epithelium and is highly expressed in the gastrointestinal interstitial cells of Cajal, where it plays an important role in epithelial chloride secretion mediating intestinal motility. ANO1 blockers like niflumic acid have been shown to block slow waves, which produce motility, in the human intestine.  ANO1-knockout mice fail to produce slow waves altogether. Carbachol has been shown to markedly activate the channel; in light of this, it's not surprising that secretory diarrhea is a Carbachol overdose symptom. Crofelemer, an antidiarrhoeal, inhibits this channel. Consequently, ANO1 activation is necessary for normal function of the ICC and its generated pacemaker activity in the smooth muscles of the intestine.
Its overexpression was reported in esophageal squamous cell carcinoma and breast cancer progression.
AOAH
Acyloxyacyl hydrolase, also known as AOAH, is a protein which in humans is encoded by the AOAH gene.

# Function
Acyloxyacyl hydrolase (AOAH) is a 2-subunit lipase which selectively hydrolyzes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (LPSs, also called endotoxins).  This action inactivates LPSs that are sensed by MD-2--Toll-like Receptor 4 (TLR 4) on animal cells (and probably also by the cytosolic caspase-based sensors).  The enzyme's 2 disulfide-linked subunits are encoded by a single mRNA.  The smaller subunit is a member of the saposin-like (SAPLIP) protein family and the larger subunit, which contains the active site serine,is a GDSL lipase.
AOAH is produced by neutrophils, macrophages (including Kupffer cells and microglia), dendritic cells, NK cells and renal proximal tubule cells.  Absence of the enzyme in genetically engineered mice has been associated with distinctive phenotypes.   AOAH-deficient animals are unable to inactivate even small amounts of LPS in most tissues; it remains bioactive and may pass from cell to cell in vivo for many weeks.   The LPS-exposed mice develop strikingly high titers of polyclonal antibodies, prolonged hepatomegaly, and innate immune "tolerance" that gives them slow and inadequate responses to bacterial challenge. In contrast, absence of the enzyme renders mice more likely to develop severe lung injury and die if they are challenged with intratracheal LPS or Gram-negative bacteria.
AOAH has been highly conserved through evolution; the amino acid sequence of the human enzyme is  almost 50% identical to that of the AOAH found in Dictyostelium discoideum, with 100% identity in the GDSL lipase consensus sequences.  The enzyme has been found in many invertebrates and all vertebrates studied to date except fish.  Although it seems likely that the enzyme has substrates in vivo other than LPS (it can be a phospholipase A1/B and acyl transferase in vitro), none has been identified.
A polymorphism in the gene has been associated with chronic rhinosinusitis in 2 different ethnic groups.  Other studies have found that AOAH mRNA abundance is linked to HLA-DR alleles that, in turn, have been associated strongly with colitis.
ARF1
ADP-ribosylation factor 1 is a protein that in humans is encoded by the ARF1 gene.

# Function
ADP-ribosylation factor 1 (ARF1) is a member of the human ARF gene family. The family members encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking as activators of phospholipase D. The gene products, including 6 ARF proteins and 11 ARF-like proteins, constitute a family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1, ARF2 and ARF3), class II (ARF4 and ARF5) and class III (ARF6), and members of each class share a common gene organization. The ARF1 protein is localized to the Golgi apparatus and has a central role in intra-Golgi transport. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene.
The major mechanism of action of Brefeldin A is through inhibition of ARF1.

# Interactions
ARF1 has been shown to interact with:
- CHRM3,
- COPB1,
- GGA3, and
- PLD2.
ARF4
ADP-ribosylation factor 4 is a protein that in humans is encoded by the ARF4 gene.

# Function
ADP-ribosylation factor 4 (ARF4) is a member of the human ARF gene family. These genes encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The gene products include 5 ARF proteins and 11 ARF-like proteins and constitute 1 family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1 and ARF3), class II (ARF4 and ARF5) and class III (ARF6). The members of each class share a common gene organization. The ARF4 gene spans approximately 12kb and contains six exons and five introns. The ARF4 is the most divergent member of the human ARFs. Conflicting Map positions at 3p14 or 3p21 have been reported for this gene.

# Interactions
ARF4 has been shown to interact with Epidermal growth factor receptor.
ARL2
ADP-ribosylation factor-like protein 2 is a protein that in humans is encoded by the ARL2 gene.

# Function
The ADP-ribosylation factor (ARF) genes are small GTP-binding proteins of the RAS superfamily.  ARL2 is a member of a functionally distinct group of ARF-like genes.

# Interactions
ARL2 has been shown to interact with Protein unc-119 homolog, TBCD and PDE6D.
ART4
Ecto-ADP-ribosyltransferase 4 is an enzyme that in humans is encoded by the ART4 gene. ART4 has also been designated as CD297 (cluster of differentiation 297).

# Function
This gene encodes a protein that contains a mono-ADP-ribosylation (ART) motif. It is a member of the ADP-ribosyltransferase gene family but enzymatic activity has not been demonstrated experimentally. Antigens of the Dombrock blood group system are located on the gene product, which is glycosylphosphatidylinositol-anchored to the erythrocyte membrane. Allelic variants, some of which lead to adverse transfusion reactions, are known.

# Blood group antigens
Several antigens have been recognised in this family. These are DO*A, DO*JO1, DO*A-WL, DO*DOYA, DO*B, DO*B-WL, DO*B-SH-Q149K, DO*B-(WL)-I175N, DO*HY1, DO*HY2 and DO*DOMR.

# Model organisms
Model organisms have been used in the study of ART4 function. A conditional knockout mouse line called Art4tm1a(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 - in-depth bone and cartilage phenotyping
ASK1
Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5) is a member of MAP kinase kinase kinase family and as such a part of mitogen-activated protein kinase pathway. It activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases in a Raf-independent fashion in response to an array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. ASK1 has been found to be involved in cancer, diabetes, cardiovascular and neurodegenerative diseases.
MAP3K5 gene coding for the protein is located on chromosome 6 at locus 6q22.33. and the transcribed protein contains 1,374 amino acids with 11 kinase subdomains. Northern blot analysis shows that MAP3K5 transcript is abundant in human heart and pancreas.

# Mechanism of activation
Under nonstress conditions ASK1 is oligomerized (a requirement for its activation) through its C-terminal coiled-coil domain (CCC), but remains in an inactive form by the suppressive effect of reduced thioredoxin (Trx) and calcium and integrin binding protein 1 (CIB1). Trx inhibits ASK1 kinase activity by direct binding to its N-terminal coiled-coil domain (NCC). Trx and CIB1 regulate ASK1 activation in a redox- or calcium- sensitive manner, respectively. Both appear to compete with TNF- receptor-associated factor 2 (TRAF2), an ASK1 activator. TRAF2 and TRAF6 are then recruited to ASK1 to form a larger molecular mass complex. Subsequently, ASK1 forms homo-oligomeric interactions not only through the CCC, but also the NCC, which leads to full activation of ASK1 through autophosphorylation at threonine 845.

# Interactions
ASK1 has been shown to interact with:
- C-Raf,
- CDC25A,
- DAXX,
- DUSP19,
- EIF2AK2,
- GADD45B,
- HSPA1A,
- MAP2K6,
- MAP3K7 and
- MAPK8IP3,
- PDCD6,
- PPP5C,
- RB1CC1,
- TRAF2,
- TRAF5,  and
- TRAF6.
ASPH
Aspartyl/asparaginyl beta-hydroxylase (HAAH) is an enzyme that in humans is encoded by the ASPH gene. ASPH is a alpha-ketoglutarate-dependent hydroxylase, a superfamily non-haem iron-containing proteins.

# Function
This gene is thought to play an important role in calcium homeostasis. Alternative splicing of this gene results in five transcript variants which vary in protein translation, the coding of catalytic domains, and tissue expression. Variation among these transcripts impacts their functions which involve roles in the calcium storage and release process in the endoplasmic and sarcoplasmic reticulum as well as hydroxylation of aspartic acid and asparagine in epidermal growth factor-like domains of various proteins.

# Clinical significance
As early as 1996, the over-expression of HAAH was recognized as an indicator of carcinoma in humans.  Further research has correlated elevated HAAH levels (variously in affected tissue or blood serum) with hepatocellular (liver) carcinoma adenocarcinoma (pancreatic cancer), colorectal cancer, prostate cancer. and lung cancer.  The pancreatic study showed elevated HAAH only in diseased tissue, but not in adjacent normal and inflamed tissue.
Mutations in ASPH cause                 Traboulsi syndrome            .Patel, N; Khan, A. O.; Mansour, A; Mohamed, J. Y.; Al-Assiri, A; Haddad, R; Jia, X; Xiong, Y; Megarbane, A; Traboulsi, E. I.; Alkuraya, F. S. (2014). "Mutations in ASPH Cause Facial Dysmorphism, Lens Dislocation, Anterior-Segment Abnormalities, and Spontaneous Filtering Blebs, or Traboulsi Syndrome". The American Journal of Human Genetics. 94 (5): 7559. doi:10.1016/j.ajhg.2014.04.002. PMID 24768550..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}
ATF1
Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.
This gene encodes an activating transcription factor, which belongs to the ATF subfamily and bZIP (basic-region leucine zipper) family. It influences cellular physiologic processes by regulating the expression of downstream target genes, which are related to growth, survival, and other cellular activities. This protein is phosphorylated at serine 63 in its kinase-inducible domain by serine/threonine kinases, cAMP-dependent protein kinase A, calmodulin-dependent protein kinase I/II, mitogen- and stress-activated protein kinase and cyclin-dependent kinase 3 (cdk-3). Its phosphorylation enhances its transactivation and transcriptional activities, and enhances cell transformation.

# Clinical significance
Fusion of this gene and FUS on chromosome 16 or EWSR1 on chromosome 22 induced by translocation generates chimeric proteins in angiomatoid fibrous histiocytoma and clear cell sarcoma. This gene has a pseudogene on chromosome 6.
ATF3
Cyclic AMP-dependent transcription factor ATF-3 is a protein that, in humans, is encoded by the ATF3 gene.

# Function
Activating transcription factor 3 is a member of the mammalian activation transcription factor/cAMP responsive element-binding (CREB) protein family of transcription factors. Multiple transcript variants encoding two different isoforms have been found for this gene. The longer isoform represses rather than activates transcription from promoters with ATF binding elements. The shorter isoform (deltaZip2) lacks the leucine zipper protein-dimerization motif and does not bind to DNA, and it stimulates transcription, it is presumed, by sequestering inhibitory co-factors away from the promoter. It is possible that alternative splicing of the ATF3 gene may be physiologically important in the regulation of target genes.

# Clinical significance
ATF-3 is induced upon physiological stress in various tissues. It is also a marker of regeneration following injury of dorsal root ganglion neurons, as injured regenerating neurons activate this transcription factor.  Functional validation studies have shown that ATF3 can promote regeneration of peripheral neurons, but is not capable of promoting regeneration of central nervous system neurons.
ATF4
Activating transcription factor 4 (tax-responsive enhancer element B67), also known as ATF4, is a protein that in humans is encoded by the ATF4  gene.

# Function
This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in proteinprotein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA-binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromosome at q28 in a region containing a large inverted duplication.
ATF4 transcription factor is also known to play role in osteoblast differentiation along with RUNX2 and osterix. Terminal osteoblast differentiation, represented by matrix mineralization, is significantly inhibited by the inactivation of JNK. JNK inactivation downregulates expression of ATF-4 and, subsequently, matrix mineralization. IMPACT protein regulates ATF4 in C. elegans to promote lifespan.

# Translation
The translation of ATF4 is dependent on upstream open reading frames located in the 5'UTR.  The location of the second uORF, aptly named uORF2, overlaps with the ATF4 open-reading frame. During normal conditions, the uORF1 is translated, and then translation of uORF2 occurs only after eIF2-TC has been reacquired. Translation of the uORF2 requires that the ribosomes pass by the ATF4 ORF, whose start codon is located within uORF2. This leads to its repression.  However, during stress conditions, the 40S ribosome will bypass uORF2 because of a decrease in concentration of eIF2-TC, which means the ribosome does not acquire one in time to translate uORF2.  Instead ATF4 is translated.
ATF5
Activating transcription factor 5, also known as ATF5, is a protein that, in humans, is encoded by the ATF5 gene.

# Function
First described by Nishizawa and Nagata, ATF5 has been classified as a member of the activating transcription factor (ATF)/cAMP response-element binding protein (CREB) family.
ATF5 transcripts and protein are expressed in a wide variety of tissues, in particular, high expression of transcripts in liver. It is also present in a variety of tumor cell types.
ATF5 expression is regulated at both the transcriptional and translational level.
ATF5 is expressed in VZ and SVZ during brain development.
The human ATF5 protein is made up of 282 amino acids.
ATF5 is a transcription factor that contains a bZip domain.
ATF7
Cyclic AMP-dependent transcription factor ATF-7 is a protein that in humans is encoded by the ATF7 gene.

# Homonym
In 2001, Peters et al. published a paper showing that ATF-7, a Novel bZIP Protein, interacts with PTP4A1.
This ATF-7 is actually ATF5 and not ATF7, as noted by the authors at the end of their paper ("Note Added in ProofWhile this manuscript was under review, sequences for mouse and human ATF-5 were deposited in GenBankTM. It appears that ATF-7 and ATF-5 are likely to be the same protein. In addition, an unrelated sequence named ATF7 has also been deposited in GenBankTM. In order to avoid confusion, future work on the protein described in this publication will likely refer to it as either ATF-5 or ATF-5/7.")
ATG7
Autophagy-related protein 7 is a protein in humans encoded by ATG7 gene. Related to GSA7; APG7L; APG7-LIKE.
ATG 7, present in both plant and animal genomes, acts as an essential protein for cell degradation and its recycling. The sequence associates with the ubiquitin- proteasome system, UPS, required for the unique development of an autophagosomal membrane and fusion within cells.
ATG7 was identified based on homology to yeast cells Pichia pastoris GSA7 and Saccharomyces cerevisiae APG7. The protein appears to be required for fusion of peroxisomal and vacuolar membranes.
Autophagy is an important cellular process that helps in maintaining homeostasis. It goes through destroying and recycling the cytoplasmic organelles and macromolecules. During the initiation of autophagy, ATG7 acts like an E-1 enzyme for ubiquitin-like proteins (UBL) such as ATG12 and ATG8. ATG7 helps these UBL proteins in targeting their molecule by binding to them and activating their transfer to an E-2 enzyme. ATG7's role in both of these autophagy-specific UBL systems makes it an essential regulator of autophagosome assembly.
Homologous to the ATP-binding and catalytic sites of E1 activator proteins, ATG7 uses its cysteine residue to create a thiol-ester bond with free Ubiquitin molecules. Through UPS, Ubiquitin will continue to bind to other autophagy-related proteins, E2 conjugation proteins and E3 protein ligases, to attach Ubiquitins to a target substrate to induce autophagy.
ATG 7 is often associated with ATG12/ ATG5 sequenced ubiquitination cascade. As well in presence of p53 cell cycle pathways during stressed and nutrient poor environments.
ATRX
Transcriptional regulator ATRX also known as  ATP-dependent helicase ATRX, X-linked helicase II, or X-linked nuclear protein (XNP) is a protein that in humans is encoded by the ATRX gene.

# Function
Transcriptional regulator ATRX contains an ATPase / helicase domain, and thus it belongs to the SWI/SNF family of chromatin remodeling proteins. ATRX is required for deposition of the histone variant H3.3 at telomeres and other genomic repeats. These interactions are important for maintaining silencing at these sites.
In addition, ATRX undergoes cell cycle-dependent phosphorylation, which regulates its nuclear matrix and chromatin association, and suggests its involvement in the gene regulation at interphase and chromosomal segregation in mitosis.

# Clinical significance

## Inherited mutations
Inherited mutations of the ATRX  gene are associated with an X-linked mental retardation (XLMR) syndrome most often accompanied by alpha-thalassemia (ATR-X) syndrome. These mutations have been shown to cause diverse changes in the pattern of DNA methylation, which may provide a link between chromatin remodeling, DNA methylation, and gene expression in developmental processes. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported. Female carriers may demonstrate skewed X chromosome inactivation.

## Somatic mutations
Acquired mutations in ATRX have been reported in a number of human cancers including pancreatic neuroendocrine tumours, gliomas, astrocytomas, osteosarcomas, and malignant pheochromocytomas. There is a strong correlation between ATRX mutations and an Alternative Lengthening of Telomeres (ALT) phenotype in cancers.

# Interactions
ATRX forms a complex with DAXX which is an histone H3.3 chaperone.
ATRX has been also shown to interact with EZH2.
HSN2
Hereditary sensory neuropathy, type II also known as HSN2 is a protein which in humans in encoded by the HSN2. It is a single-exon ORF, and a nervous system-specific exon of the WNK1 gene.  HSN2 is as an alternatively spliced exon of WNK1 and this selectively occurs in nervous tissues, resulting in WNK1/HSN2 nervous system isoforms.

# Function
The WNK1/HSN2 isoforms are expressed in the sensory parts of the peripheral nervous system and central nervous system which are associated with the transmission of sensory and nociceptive signals. These parts include satellite cells, Schwann cells, and sensory neurons. The novel protein product of the isoform is more plentiful in sensory neurons than motor neurons. It is proposed that this gene product may play a role in the development and/or maintenance of peripheral sensory neurons or their supporting Schwann cells.

# Clinical significance
Mutations in the HSN2 gene are associated with congenital sensory neuropathy (HSAN Type II), an autosomal recessive disorder characterized by impairment of pain, temperature, and touch sensation owing to reduction or absence of peripheral sensory neurons.
Acyl

# Overview
An acyl group (IUPAC name: alkanoyl) is a functional group derived by the removal of one or more hydroxyl group from an oxoacid.. In organic chemistry, the acyl group is usually derived from a carboxylic acid of the form RC O OH. It therefore has the formula RC(=O)-, with a double bond between the carbon and oxygen atoms (i.e. a carbonyl group), and a single bond between R and the carbon. Acyl groups can also be derived from other types of acids such as sulfonic acids, phosphonic acids, and some others.
Acyl halides can be used in Friedel-Crafts acylation to introduce the acyl moiety in an aromatic compound.
In biochemistry, Acyl-CoA is a derivate of fatty acid metabolism.

# Examples
The names of acyl groups are typically derived from the corresponding acid by substituting the acid ending -ic with the ending -yl as shown in the table below. Note that methyl, ethyl, propyl, butyl etc. end in -yl are not acyl but alkyl groups, derived from alkanes.

# Acyl species
In acyloxy groups the acyl group is bonded to oxygen: R-C=O-O-R' where R-C=O is the acyl group.
Acylium ions are cations of the type R-C+=O and play an important role as intermediates in organic reactions  for example the Hayashi rearrangement.