Persius/hicric huggingface dataset:
XPO5
Exportin-5 (XPO5) is a protein that, in humans, is encoded by the XPO5 gene. In eukaryotic cells, the primary purpose of XPO5 is to export pre-microRNA (also known as pre-miRNA) out of the nucleus and into the cytoplasm, for further processing by the Dicer enzyme. Once in the cytoplasm, the microRNA (also known as miRNA) can act as a gene silencer by regulating translation of mRNA. Although XPO5 is primarily involved in the transport of pre-miRNA, it has also been reported to transport tRNA.
Much research on XPO5 is ongoing. miRNA is a prominent research topic due to its potential use as a therapeutic, with several miRNA-based drugs already in use.

# Mechanism

## Binding to pre-miRNA
After RanGTP binds to XPO5, the XPO5-RanGTP complex forms a U-like structure to hold the pre-miRNA. The XPO5-RanGTP complex recognizes pre-miRNA by its two-nucleotide 3 overhanga sequence consisting of two bases at the 3 end of the pre-miRNA that are not paired with other bases. This motif is unique to pre-miRNA, and by recognizing it XPO5 ensures specificity for transporting only pre-miRNA. On its own, pre-miRNA is in a closed conformation, with the 3 overhang flipped up toward the RNA minor groove. However, upon binding to XPO5, the 3 overhang is flipped downwards away from the rest of the pre-miRNA molecule into an open conformation. This helps the backbone phosphates of these two nucleotides form hydrogen bonds with many XPO5 residues, allowing XPO5 to recognize the RNA as pre-miRNA. Because these interactions involve only the RNA phosphate backbone, they are nonspecific and allow XPO5 to recognize and transport any pre-miRNA. The rest of the pre-miRNA stem binds to XPO5 via interactions between the negatively-charged phosphate backbone and several positively-charged interior XPO5 residues.

## XPO5 Ternary Complex Transport Mechanism
The combined structure of XPO5, RanGTP, and pre-miRNA is known as the ternary complex. Once the ternary complex is formed, it diffuses through a nuclear pore complex into the cytoplasm, transporting pre-miRNA into the cytoplasm in the process. Once in the cytoplasm, RanGAP hydrolyzes GTP to GDP, causing a conformational change that releases the pre-miRNA into the cytoplasm.

## Export out of the Nucleus
It has been suggested, through evidence provided by contour maps of water density, that the interior of XPO5 is hydrophilic, while the exterior of XPO5 is hydrophobic. Therefore, this enhances the binding capabilities of XPO5 to the nuclear pore complex, allowing for transport of the ternary complex out of the nucleus.

# Additional interactions
XPO5 has been shown to interact with ILF3 and Ran.

# Potential oncogenic role
Recent evidence has shown higher levels of XPO5 in prostate cancer cell lines in-vitro, suggesting that altered XPO5 expression levels may have a role in cancer development. Suppressing XPO5 has also been found to be therapeutic in-vitro.
Xist

# Overview
Xist is an RNA gene on the X chromosome of the placental mammals that acts as major effector of the X inactivation process.
The Xist RNA, a large (18 kb) transcript, is expressed on the inactive chromosome and not on the active one. It is processed similarly to mRNAs, through splicing and polyadenylation, however, it remains untranslated. It has been suggested that this RNA gene evolved at least partly from a protein coding gene that became a pseudogene.
The inactive X is coated with this transcript, which is essential for the inactivation. X lacking Xist will not be inactivated, while duplication of the Xist gene on another chromosome causes inactivation of that chromosome.
YAP1
YAP1 (yes-associated protein 1), also known as YAP or YAP65, is a protein that acts as a transcriptional regulator by activating the transcription of genes involved in cell proliferation and suppressing apoptotic genes. YAP1 is inhibited in the Hippo signaling pathway which allows the cellular control of organ size and tumor suppression. YAP1 was first identified by virtue of its ability to associate with the SH3 domain of Yes and Src protein tyrosine kinases. YAP1 is a potent oncogene, which is amplified in various human cancers.

# Structure
Cloning of the YAP1 gene facilitated the identification of a modular protein domain, known as the WW domain.  Two splice isoforms of the YAP1 gene product were initially identified, named YAP1-1 and YAP1-2, which differed by the presence of an extra 38 amino acids that encoded the WW domain. Apart from the WW domain, the modular structure of YAP1 contains a proline-rich region at the very amino terminus, which is followed by a TID (TEAD transcription factor interacting domain).  Next, following a single WW domain, which is present in the YAP1-1 isoform, and two WW domains, which are present in the YAP1-2 isoform, there is the SH3-BM (Src Homology 3 binding motif). Following the SH3-BM is a TAD (transcription activation domain) and a PDZ domain-binding motif (PDZ-BM) (Figure 1).

# Function
YAP1 is a transcriptional co-activator and its proliferative and oncogenic activity is driven by its association with the TEAD family of transcription factors, which up-regulate genes that promote cell growth and inhibit apoptosis. Several other functional partners of YAP1 were identified, including RUNX, SMADs, p73, ErbB4, TP53BP, LATS1/2, PTPN14, AMOTs, and ZO1/2. YAP1 and its close paralog, TAZ (WWTR1), are the main effectors of the Hippo tumor suppressor pathway. When the pathway is activated, YAP1 and TAZ are phosphorylated on a serine residue and sequestered in the cytoplasm by 14-3-3 proteins. When the Hippo pathway is not activated, YAP1/TAZ enter the nucleus and regulate gene expression.
It is reported that several genes are regulated by YAP1, including Birc2, Birc5, connective tissue growth factor (CTGF), amphiregulin (AREG), Cyr61, Hoxa1 and Hoxc13.
YAP/TAZ have also been shown to act as stiffness sensors, regulating mechanotransduction independently of the Hippo signalling cascade.

# Clinical significance
Heterozygous loss-of-function mutations in the YAP1 gene have been identified in two families with major eye malformations with or without extra-ocular features such as hearing loss, cleft lip, intellectual disability and renal disease.
The YAP1 oncogene serves as a target for the development of new cancer drugs. Small compounds have been identified that disrupt the YAP1-TEAD complex or block the binding function of WW domains. These small molecules represent lead compounds for the development of therapies for cancer patients, who harbor amplified or overexpressed YAP oncogene.
The Hippo/YAP signaling pathway may exert neuroprotective effects through mitigating blood-brain barrier disruption after cerebral ischemia/reperfusion injury.
YARS
Tyrosyl-tRNA synthetase, cytoplasmic, also known as Tyrosine-tRNA ligase, is an enzyme that in humans is encoded by the YARS gene.
Living cells translate DNA sequences into RNA sequences and then into protein sequences. Proteins are chains of amino acids, such as tyrosine. As the protein grows, each amino acid is added to the end by an enzyme called transfer RNA (tRNA). Each amino acid has its own tRNA, and tyrosyl-tRNA synthetase is the tRNA that adds tyrosine to the end of a growing protein.
Aminoacyl-tRNA synthetases catalyze the aminoacylation of transfer RNA (tRNA) by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Tyrosyl-tRNA synthetase belongs to the class I tRNA synthetase family. Cytokine activities have also been observed for the human tyrosyl-tRNA synthetase, after it is split into two parts, an N-terminal fragment that harbors the catalytic site and a C-terminal fragment found only in the mammalian enzyme. The N-terminal fragment is an interleukin-8-like cytokine, whereas the released C-terminal fragment is an EMAP II-like cytokine. Recently, tyrosyl-tRNA synthetase has been demonstrated as the biologically and functionally significant target for resveratrol.
For a comparison of cytoplasmic human tyrosyl-tRNA synthetase with its mitochondrial counterpart and with tyrosyl-tRNA synthetases of other biological kingdoms and organisms, see the Wikipedia page on Tyrosine-tRNA ligase and a general review on their structures and functions.
YES1
Proto-oncogene tyrosine-protein kinase Yes is an enzyme that in humans is encoded by the YES1 gene.
This gene is the cellular homolog of the Yamaguchi sarcoma virus oncogene. The encoded protein has tyrosine kinase activity and belongs to the src family of proteins. This gene lies in close proximity to thymidylate synthase gene on chromosome 18, and a corresponding pseudogene has been found on chromosome 22.

# Interactions
YES1 has been shown to interact with Janus kinase 2, CTNND1, RPL10 and Occludin.
ZBP1
Z-DNA-binding protein 1, also known as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1, is a protein that in humans is encoded by the ZBP1 gene.
ZBP1 is also an abbreviation for chicken or rat -actin zipcode-binding protein 1, a homolog of the human insulin-like growth factor 2 mRNA-binding protein 1 (IMP-1) and murine CRD-BP,  the proteins involved in mRNA transport (RNA-binding proteins, RBPs).

# Function
DLM1 encodes a Z-DNA binding protein. Z-DNA formation is a dynamic process, largely controlled by the amount of supercoiling. ZBP1 recognizes DNA in the cytoplasm as an antiviral mechanism. Viral life cycles often include steps where DNA is exposed in the cytoplasm. DNA is normally contained in the nucleus of a cell, and therefore cells use proteins like ZBP1 as an indicator of a viral infection. Once ZBP1 is activated, it increases the production of antiviral cytokines such as interferon beta. DLM1 then binds to cytosolic Viral DNA using two     Z-DNA-binding domains (Z and Z) at its N-terminus along with a DNA binding domain (D3).
The role of ZBP1 in DNA sensing has been questioned. It has been found to sense Influenza A Virus (IAV) infection and induce cell death. Since DNA is not synthesized in any stage of IAV life cycle, DNA sensing playing a role in this context is unlikely. A follow up study identified that ZBP1 senses the IAV ribonucleoprotein complex to induce cell death. A more recent study has identified transcription factor IRF1 as the upstream regulator of ZBP1 expression.
Zipcode binding protein 1 (ZBP1) was shown to regulate dendritogenesis (dendrite formation) in hippocampal neurons. This protein is different from the nucleic acid sensor ZBP1.
ZEB1
Zinc finger E-box-binding homeobox 1 is a protein that in humans is encoded by the ZEB1 gene.
ZEB1 (previously known as TCF8) encodes a zinc finger and homeodomain transcription factor that represses T-lymphocyte-specific IL2 gene expression by binding to a negative regulatory domain 100 nucleotides 5-prime of the IL2 transcription start site. ZEB1 and its mammalian paralog ZEB2 belongs to the Zeb family within the ZF (zinc finger) class of homeodomain transcription factors. ZEB1 protein has 7 zinc fingers and 1 homeodomain. The structure of the homeodomain shown on the right.

# Clinical significance
Mutations of the gene are linked to posterior polymorphous corneal dystrophy 3. A recent study suggested its contributing role in lung cancer invasiveness and metastasis development.
ZEB2
Zinc finger E-box-binding homeobox 2 is a protein that in humans is encoded by the ZEB2 gene. The ZEB2 protein is a transcription factor that plays a role in the transforming growth factor  (TGF) signaling pathways that are essential during early fetal development.

# Function
ZEB2 (previously also known as SMADIP1, SIP1) and its mammalian paralog ZEB1 belongs to the Zeb family within the ZF (zinc finger) class of homeodomain transcription factors. ZEB2 protein has 8 zinc fingers and 1 homeodomain.The structure of the homeodomain shown on the right.
ZEB2 interacts with receptor-mediated, activated full-length SMADs. The activation of TGF receptors brings about the phosphorylation of intracellular effector molecules, R-SMADs. ZEB2 is an R-SMAD-binding protein and acts as a transcriptional corepressor.
ZEB2 transcripts are found in tissues differentiated from the neural crest such as the cranial nerve ganglia, dorsal root ganglia, sympathetic ganglionic chains, the enteric nervous system and melanocytes. ZEB2 is also found in tissues that are not derived from the neural crest, including the wall of the digestive tract, kidneys, and skeletal muscles.

# Clinical significance
Mutations in the ZEB2 gene are associated with the MowatWilson syndrome. This disease exhibits mutations and even complete deletions of the ZEB2 gene. Mutations of the gene can cause the gene to produce nonfunctional ZEB2 proteins or inactivate the function gene as a whole. These deficits of ZEB2 protein interferes with the development of many organs. Many of the symptoms can be explained by the irregular development of the structures from the neural crest.
Hirschsprung's disease also has many symptoms that can be explained by lack of ZEB2 during development of the digestive tract nerves. This disease causes severe constipation and enlargement of the colon.
ZIC2
Zinc finger protein ZIC2 is a protein that in humans is encoded by the ZIC2 gene. ZIC2 is a member of the Zinc finger of the cerebellum (ZIC) protein family.

# Function
ZIC2 is classified as a ZIC protein due to conservation of the five C2H2 zinc fingers, which enables the protein to interact with DNA and proteins.

# Clinical significance
Correct function of these proteins is critical for early development, and as such mutations of the genes encoding these proteins is known to result in various congenital defects. For example, mutation of ZIC2 is known to result in holoprosencephaly due to defect in the function of the organizer region (node),  which leads to a defective anterior notochord (ANC). The ANC provides a maintenance signal to the Prechordal plate (PCP), thus a defective ANC results in degradation of the PCP, which is normally responsible for sending a shh signal to the developing forebrain resulting in the formation of the two hemispheres.  Holoprosencephaly is the most common structural anomaly of the human forebrain.
Recently ZIC2 has also been shown to be critical for establishment of the left-right axis, thus loss of ZIC2 function can result in defects in heart formation. Another member of the ZIC family, ZIC3, has previously been linked to establishment of the left-right axis.
A polyhistidine tract polymorphism in this gene may be associated with increased risk of neural tube defects (spina bifida). This gene is closely linked to a gene encoding ZIC5, a related family member on chromosome 13.

# Interactions
ZIC2 has recently been found to interact with TCF7L2, enabling it to act as a Wnt/-catenin  signalling inhibitor. Such a role is of critical importance, as not only is correct Wnt signalling critical for early development, Wnt signalling has also been found to be upregulated to several cancers. ZIC2 has also been shown to interact with GLI3.
ZIC3
ZIC3 is a member of the Zinc finger of the cerebellum (ZIC) protein family.
ZIC3 is classified as a ZIC protein due to conservation of the five C2H2 zinc fingers, which enables the protein to interact with DNA and proteins. Correct function of this protein family in critical for early development, and as such mutations of the genes encoding these proteins is known to result in various congenital defects. For example, mutation of ZIC3 is associated with heterotaxy, that is thought to occur due to the role of ZIC3 in initial left-right symmetry formation, which involves the maintaining redistributed Nodal after the asymmetry of the embryo is initially broken. Mutation of ZIC3 is also associated with various heart defects, such as heart looping, however these are thought to represent a mild form of heterotaxy. Mouse based studies have linked defective ZIC3 with neural tube defects (spina bifida) and skeletal defects.
ZIC3 is also of particular interest as it has been shown to be required for maintenance of embryonic stem cell pluripotency.

# Involvement in Wnt signalling
ZIC2, another member of the ZIC family, has recently been found to interact with TCF7L2, enabling it to act as a Wnt/-catenin  signalling inhibitor. Further experiments have indicated that human ZIC3 is also able to inhibit Wnt signalling and that the Zinc finger domains are absolutely critical for this role. Such a role is of critical importance, as not only is correct Wnt signalling critical for early development, Wnt signalling has also been found to be upregulated to several cancers.
ZW10
Centromere/kinetochore protein zw10 homolog is a protein that in humans is encoded by the ZW10 gene. This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. The encoded protein binds to centromeres during the prophase, metaphase, and early anaphase cell division stages and to kinetochore microtubules during metaphase.

# Function
Zeste white 10 (ZW10) was initially identified as a mitotic checkpoint protein involved in chromosome segregation, and then implicated in targeting cytoplasmic dynein and dynactin to mitotic kinetochores, but it is also important in non-dividing cells. These include cytoplasmic dynein targeting to Golgi and other membranes, and SNARE-mediated ER-Golgi trafficking. Dominant-negative ZW10, anti-ZW10 antibody, and ZW10 RNA interference (RNAi) cause Golgi dispersal. ZW10 RNAi also disperse endosomes and lysosomes.
Drosophila kinetochore components Rough deal (Rod) and Zw10 are required for the proper functioning of the metaphase checkpoint in flies. The eukaryotic spindle assembly checkpoint (SAC) monitors microtubule attachment to kinetochores and prevents anaphase onset until all kinetochores are aligned on the metaphase plate. It is an essential surveillance mechanism that ensures high fidelity chromosome segregation during mitosis. In higher eukaryotes, cytoplasmic dynein is involved in silencing the SAC by removing the checkpoint proteins Mad2 and the Rod-Zw10-Zwilch complex (RZZ) from aligned kinetochores.

# Interactions
ZW10 has been shown to interact with RINT1
ZZZ3
ZZ-type zinc finger-containing protein 3 is a protein that in humans is encoded by the ZZZ3 gene.

# Model organisms
Model organisms have been used in the study of ZZZ3 function. A conditional knockout mouse line, called Zzz3tm1a(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 four tests were carried out on mutant mice and two significant abnormalities were observed.  No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and no further abnormal phenotypes were identified.
Ziac
Synonyms / Brand Names: Bisoprolol Fumarate, Bisoprolol fumerate, Bisoprolol Hemifumarate, Cardicor, Concor, Condyline, Detensiel, Emconcor, Emcor, Euradal, Isoten, Monocor, Soloc, Soprol, Zebeta

# Dosing and Administration
Bisoprolol is an effective treatment of hypertension in once-daily doses of 2.5 to 40 mg,
while hydrochlorothiazide is effective in doses of 12.5 to 50 mg. In clinical trials of
bisoprolol/hydrochlorothiazide combination therapy using bisoprolol doses of
2.5 to 20 mg and hydrochlorothiazide doses of 6.25 to 25 mg, the antihypertensive effects
increased with increasing doses of either component.
FDA Package Insert Resources
Indications, Contraindications, Side Effects, Drug Interactions, etc.
Calculate Creatine Clearance
On line calculator of your patients Cr Cl by a variety of formulas.
Convert pounds to Kilograms
On line calculator of your patients weight in pounds to Kg for dosing estimates.
 Publication Resources
Recent articles, WikiDoc State of the Art Review, Textbook Information
Trial Resources
Ongoing Trials, Trial Results
Guidelines & Evidence Based Medicine Resources
US National Guidelines, Cochrane Collaboration, etc.
Media Resources
Slides, Video, Images, MP3, Podcasts, etc.
Patient Resources
Discussion Groups, Handouts, Blogs, News, etc.
International Resources
en Espanol

# FDA Package Insert Resources
Indications
Contraindications
Side Effects
Drug Interactions
Precautions
Overdose
Instructions for Administration
How Supplied
Pharmacokinetics and Molecular Data
FDA label
FDA on Ziac
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# Publication Resources
Most Recent Articles on Ziac
Review Articles on Ziac
Articles on Ziac in N Eng J Med, Lancet, BMJ
WikiDoc State of the Art Review
Textbook Information on Ziac
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# Trial Resources
Ongoing Trials with Ziac at Clinical Trials.gov
Trial Results with Ziac
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# Guidelines & Evidence Based Medicine Resources
US National Guidelines Clearinghouse on Ziac
Cochrane Collaboration on Ziac
Cost Effectiveness of Ziac
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# Media Resources
Powerpoint Slides on Ziac
Images of Ziac
Podcasts & MP3s on Ziac
Videos on Ziac
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# Patient Resources
Patient Information from National Library of Medicine
Patient Resources on Ziac
Discussion Groups on Ziac
Patient Handouts on Ziac
Blogs on Ziac
Ziac in the News
Ziac in the Marketplace
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# International Resources
Ziac en Espanol
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Adapted from the FDA Package Insert.
AK2
Adenylate kinase 2 is an enzyme that is encoded in humans by the AK2 gene. The AK2 protein is found in the intermembrane space of the mitochondrion.

# Function
Adenylate kinases are involved in regulating the adenine nucleotide composition within a cell by catalyzing the reversible transfer of phosphate groups among adenine nucleotides. Three isozymes of adenylate kinase, namely 1, 2, and 3, have been identified in vertebrates; this gene encodes isozyme 2. Expression of these isozymes is tissue-specific and developmentally regulated. Isozyme 2 is localized in the mitochondrial intermembrane space and may play a role in apoptosis. Two transcript variants encoding distinct isoforms have been identified for this gene.

## AK2 deficiency
Adenylate Kinase 2 (AK2) deficiency in humans causes hematopoietic defects associated with sensorineural deafness.  Recticular dysgenesis is an autosomal recessive form of human combined immunodeficiency.  It is also characterized by an impaired lymphoid maturation and early differentiation arrest in the myeloid lineage.  AK2 deficiency results in absent or a large decrease in the expression of proteins.  AK2 is specifically expressed in the stria vascularis of the inner ear which indicates why individuals with an AK2 deficiency will have sensorineural deafness.
C3b
C3b is a one of the elements formed by the cleavage of complement component 3.
C3b may bind to microbial cell surfaces within an organism's body. This can lead to the production of surface-bound C3 convertase and thus more C3b components. Also known as C3bBb, this convertase is similar to soluble C3-convertase except that it is membrane bound.
Alternatively, bound C3b may aid in opsonization of the microbe by macrophages. Complement receptor 1 or CR1 on macrophages allows the engaging of C3b covered microbes.
C3b is cleaved into C3c and C3d.