Persius/hicric huggingface dataset:
USP9Y
Ubiquitin specific peptidase 9, Y-linked (fat facets-like, Drosophila), also known as USP9Y, is an enzyme which in humans is encoded by the USP9Y gene. It is required for sperm production. This enzyme is a member of the peptidase C19 family and is similar to ubiquitin-specific proteases, which cleave the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins.

# Clinical significance
Mutations in this gene have been associated with Sertoli cell-only syndrome (SCO) and male infertility.
The USP9Y gene is found on the azoospermia factor (AZF) region on the Y chromosome. Men who have impaired or no sperm production often have a deletion in the AZF region, especially in the USP9Y gene, and it was thought that USP9Y was necessary for sperm production. However, a man and his father with a USP9Y deletion who could produce sperm were recently reported. The corresponding gene is present but inactive in chimpanzees and bonobos.
USPTO

# Overview
The United States Patent and Trademark Office (PTO or USPTO) is an agency in the United States Department of Commerce that issues patents to inventors and businesses for their inventions, and trademark registration for product and intellectual property identification.
The USPTO is currently based in Alexandria, Virginia, after a 2006 move from the Crystal City, Virginia area of Arlington County, Virginia. A few offices remain in the Potomac Gateway complex at the southern end of Crystal City; these offices will move to Randolph Square, a brand new building in Shirlington Village, in 2009. Since 1991, the office has been fully funded by fees charged for processing patents and trademarks.
The USPTO cooperates with the European Patent Office (EPO) and the Japan Patent Office (JPO) as one of the Trilateral Patent Offices. The USPTO is also a Receiving Office, an International Searching Authority and an International Preliminary Examination Authority for international patent applications filed in accordance with the Patent Cooperation Treaty.

# Mission
The mission of the PTO is to promote "industrial and technological progress in the United States and strengthen the national economy" by:
- administering the laws relating to patents and trademarks;
- advising the United States Secretary of Commerce, the President of the United States, and the administration on patent, trademark, and copyright protection; and
- providing advice on the trade-related aspects of intellectual property.
Ulcer
Synonyms and keywords: ulceration
An ulcer is a discontinuity or break in a bodily membrane that impedes the organ of which that membrane is a part from continuing its normal functions. Common forms of ulcers recognized in medicine include:
- Ulcer (dermatology), a discontinuity of the skin or a break in the skin
- Pressure ulcers, also known as bedsores
- Genital ulcer, an ulcer located on the genital area
- Ulcerative dermatitis, a skin disorder associated with bacterial growth often initiated by self-trauma
- Corneal ulcer, an inflammatory or infective condition of the cornea
- Coronary artery ulceration, defined as a cavity in the vessel wall with disruption of the intima and flow observed within the plaque cavity
- Mouth ulcer, an open sore inside the mouth
- Aphthous ulcer, a specific type of oral ulcer also known as a canker sore
- Peptic ulcer, a discontinuity of the gastrointestinal mucosa (stomach ulcer)
- Venous ulcer, a wound thought to occur due to improper functioning of valves in the veins
- Stress ulcer, located anywhere within the stomach and proximal duodenum
- Ulcerative sarcoidosis, a cutaneous condition affecting people with sarcoidosis
- Ulcerative lichen planus, a rare variant of lichen planus
- Ulcerative colitis, a form of inflammatory bowel disease (IBD)
- Ulcerative disposition, a disorder or discomfort that causes severe abdominal distress, often associated with chronic gastritis
- Medication: diclofenac (patch)
Umami
Glutamate has a long history in cooking: it appears in Asian foods such as soy sauce and fish sauce, and in Italian food in parmesan cheese and anchovies. It is the taste of Marmite in the UK, of Golden Mountain sauce in Thailand, of Maggi Sauce worldwide, of Goya Sazon on the Latin islands of the Caribbean, of Salsa Lizano in Costa Rica and of Kewpie mayonnaise in Japan. It also is directly available in monosodium glutamate.
Inasmuch as it describes the flavor common to savory products such as meat, cheese, and mushrooms, umami is similar to Brillat-Savarin's concept of osmazome (link in French), an early attempt to describe the main flavoring component of meat as extracted in the process of making stock.

# Chemical properties
Umami was first identified as a basic taste in 1908 by Kikunae Ikeda of the Tokyo Imperial University while researching the strong flavor in seaweed broth. Ikeda isolated monosodium glutamate as the chemical responsible and, with the help of the Ajinomoto company, began commercial distribution of MSG products.

# Taste receptors
Acknowledged subjectively as a special taste by Eastern civilizations for generations, umami has been described in biochemical studies identifying the actual taste receptor responsible for the sense of umami, a modified form of mGluR4 named "taste-mGluR4".
Umami tastes are initiated by these specialized receptors, with subsequent steps involving secretion of neurotransmitters, including adenosine triphosphate (ATP) and serotonin. Other evidence indicates guanosine derivatives may interact with and boost the initial umami signal.
Cells responding to umami taste stimuli do not possess typical synapses but instead secrete the neurotransmitter ATP in a mechanism exciting sensory fibers that convey taste signals to the brain. These taste receptors are located everywhere on the tongue.
In monkey studies, most umami signals from taste buds excite neurons in the orbitofrontal cortex of the brain, showing spatially-specific characteristics:
- There is a cortical map representation for the taste of glutamate separate from that of other taste stimuli like sweet (glucose), salt, bitter (quinine) and sour (hydrochloric acid)
- Single neurons having vigorous responses to sodium glutamate also respond to glutamic acid
- Some neurons display a mechanism of satiety, indicating a process by which taste receptors in the mouth may interact with cortical neurons to curtail eating
- Umami flavor is strongest when combined with aromas (e.g., monosodium glutamate and garlic), a result leading to speculation that glutamate may stimulate umami effects by acting simultaneously with the aromas, texture and appearance of food.
VAC14
Protein VAC14 homolog, also known as ArPIKfyve (Associated Regulator of PIKfyve), is a protein that in humans is encoded by the VAC14 gene.

# Functions and interactions
The content of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) in endosomal membranes changes dynamically with fission and fusion events that generate or absorb intracellular transport vesicles. The ArPIKfyve protein scaffolds a trimolecular complex to tightly regulate the level of PtdIns(3,5)P2. Other components of this complex are the PtdIns(3,5)P2-synthesizing enzyme PIKFYVE  and the Sac1-domain-containing PtdIns(3,5)P2 5-phosphatase Sac3, encoded by the human gene FIG4. VAC14 functions as an activator of PIKFYVE. Studies in VAC14 knockout mice indicate that, in addition to increasing the PtdIns(3,5)P2-producing activity of PIKfyve, VAC14 also controls the steady-state levels of another rare phosphoinositide linked to PIKfyve enzyme activity  phosphatidylinositol 5-phosphate.
In addition to the formation of the ternary complex with PIKfyve and Sac3, ArPIKfyve is engaged in a number of other interactions. ArPIKfyve forms a stable complex with the PtdIns(3,5)P2-specific phosphatase Sac3, thereby protecting Sac3 from rapid degradation in the proteasome. ArPIKfyve forms a homooligomer through its carboxyl terminus. However, the number of monomers in the ArPIKfyve homooligomer, ArPIKfyve-Sac3 heterodimer or  PIKfyve-ArPIKfyve-Sac3 heterotrimer is unknown. Human Vac14/ArPIKfyve also interacts with the PDZ (post-synaptic density) domain of neuronal nitric oxide synthase  but the functional significance of this interaction is still unclear. ArPIKfyve facilitates insulin-regulated GLUT4 translocation to the cell surface.

# Lessons from VAC14 mouse models
VAC14 knock-out mice die at, or shortly after birth and exhibit massive neurodegeneration. Fibroblasts from these mice display ~50% lower levels of PtdIns(3,5)P2 and PtdIns(5)P. A spontaneous mouse VAC14-point  mutation (with arginine substitution of leucine156)  is associated with reduced life span (up to 3 weeks),  body size,   enlarged brain ventricles, 50% decrease in PtdIns(3,5)P2 levels, diluted pigmentation,  tremor and impaired motor function.

# VAC14 and human disease
The VAC14 gene is yet to be linked convincingly to human disease.
VAMP1
Vesicle-associated membrane protein 1 is a protein that in humans is encoded by the VAMP1 gene.

# Function
Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. VAMP1 is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Multiple alternative splice variants that encode proteins with alternative carboxy ends have been described, but the full-length nature of some variants has not been defined.

# Clinical significance
Homozygous mutations in VAMP1 have been identified in a series of children affected with a form of congenital myasthenic syndrome and similar presynaptic features in these patients  and the knock-out VAMP1 mouse have been demonstrated.

# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.
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VAMP2
Vesicle-associated membrane protein 2 is a protein that in humans is encoded by the VAMP2 gene.

# Function
Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. VAMP2 is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. VAMP2 is thought to participate in neurotransmitter release at a step between docking and fusion. Mice lacking functional synaptobrevin2/VAMP2 gene cannot survive after birth, and have a dramatically reduced synaptic transmission, around 10% of control. The protein forms a stable complex with syntaxin, synaptosomal-associated protein, 25 kD, and complexin. It also forms a distinct complex with synaptophysin.

# Clinical significance
VAMP2 is a likely candidate gene for familial infantile myasthenia (FIMG) because of its map location and because it encodes a synaptic vesicle protein of the type that has been implicated in the pathogenesis of FIMG.

# Interactions
VAMP2 has been shown to interact with:
- RABAC1,
- SNAP-25,
- SNAP23,
- STX1A,  and
- STX4.
VAMP4
Vesicle-associated membrane protein 4 is a protein that in humans is encoded by the VAMP4 gene.

# Function
Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. This protein may play a role in trans-Golgi network-to-endosome transport.

# Interactions
VAMP4 has been shown to interact with AP1M1, STX6 and STX16.
VIPR1
Vasoactive intestinal polypeptide receptor 1 also known as VPAC1, is a protein, that in humans is encoded by the VIPR1 gene. VPAC1 is expressed in the brain (cerebral cortex, hippocampus, amygdala), lung, prostate, peripheral blood leukocytes, liver, small intestine, heart, spleen, placenta, kidney, thymus and testis.

# Function
VPAC1 is a receptor for vasoactive intestinal peptide (VIP), a small neuropeptide. Vasoactive intestinal peptide is involved in smooth muscle relaxation, exocrine and endocrine secretion, and water and ion flux in lung and intestinal epithelia. Its actions are effected through integral membrane receptors associated with a guanine nucleotide binding protein which activates adenylate cyclase.
VIP acts in an autocrine fashion via VPAC11 to inhibit megakaryocyte proliferation and induce proplatelet formation.

# Clinical significance
Patients with idiopathic achalasia show a significant difference in the distribution of SNPs affecting VIPR1.
VIP and PACAP levels were decreased in anterior vaginal wall of stress urinary incontinence and pelvic organ prolapse patients, they may participate in the pathophysiology of these diseases.
VIPR2
Vasoactive intestinal peptide receptor 2 also known as VPAC2, is a G-protein coupled receptor that in humans is encoded by the VIPR2 gene.

# Tissue distribution
VIPR2 is expressed in the uterus, prostate, smooth muscle of the gastrointestinal tract, seminal vesicles and skin, blood vessels and thymus. VIPR2 is also expressed in the cerebellum.

# Function
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are homologous peptides that function as neurotransmitters and neuroendocrine hormones. While the receptors for VIP (VIRP 1 and 2) and PACAP (ADCYAP1R1) share homology, they differ in their substrate specificities and expression patterns. VIPR2 transduction results in upregulation of adenylate cyclase activity. Furthermore, VIPR2 mediates the anti-inflammatory effects of VIP.
Research using VPAC2 knockout mice implicate it in the function of the circadian clock, growth, basal energy expenditure and male reproduction.
VIPR2 and/or PAC1 receptor activation is involved in cutaneous active vasodilation in humans.
Splice variants may modify the immunoregulatory contributions of the VIP-VIPR2 axis.
VIPR2 may contribute to autoregulation and/or coupling within the suprachiasmatic nucleus (SCN) core and to control of the SCN shell.

# Clinical significance
VIPR2 may play a role in schizophrenia.
The abnormal expression of VIPR2 messenger RNA in gallbladder tissue may play a role in the formation of gall stones and polyps.
VPS11
Vacuolar protein sorting-associated protein 11 homolog is a protein that in humans is encoded by the VPS11 gene.

# Function
Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps11 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway.

# Interactions
VPS11 has been shown to interact with VPS18, VPS33A and STX7.
VPS25
Vacuolar protein-sorting-associated protein 25 is a protein that in humans is encoded by the VPS25 gene.
It is a component of the endosome-associated complex ESCRT-II (Endosomal Sorting Complexes Required for Transport protein II). ESCRT (ESCRT-I, -II, -III) complexes orchestrate efficient sorting of ubiquitinated transmembrane receptors to lysosomes via multivesicular bodies (MVBs). ESCRT-II recruits the transport machinery for protein sorting at MVB. In addition, the human ESCRT-II has been shown to form a complex with RNA polymerase II elongation factor ELL in order to exert transcriptional control activity. ESCRT-II transiently associates with the endosomal membrane and thereby initiates the formation of ESCRT-III, a membrane-associated protein complex that functions immediately downstream of ESCRT-II during sorting of MVB cargo. ESCRT-II in turn functions downstream of ESCRT-I, a protein complex that binds to ubiquitinated endosomal cargo.
ESCRT-II is a trilobal complex composed of two copies of vps25, one copy of vps22 and the C-terminal region of vps36. The crystal structure of vps25 revealed two winged-helix domains, the N-terminal domain of vps25 interacting with vps22 and vps36.
VPS29
VPS29 is a human gene coding for the vacuolar protein sorting protein Vps29, a component of the retromer complex.

# Yeast homolog
The homologous protein (one that performs the same function) in yeast is Vacuolar protein sorting 29 homolog (S. cerevisiae).

# Function
VPS29 belongs to a group of genes coding for vacuolar protein sorting (VPS) proteins that, when functionally impaired, disrupt the efficient delivery of vacuolar hydrolases. The protein encoded by this gene, Vps29, is a component of a large multimeric complex, termed the retromer complex, which is involved in retrograde transport of proteins from endosomes to the trans-Golgi network. Vps29 may be involved in the formation of the inner shell of the retromer coat for retrograde vesicles leaving the prevacuolar compartment. Alternative splice variants encoding different isoforms, and usage of multiple polyadenylation sites have been found for this gene.
VPS35
Vacuolar protein sorting-associated protein 35 is a protein that in humans is encoded by the VPS35 gene.
This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex.

# Structure
Vps35 is the largest subunit of retromer with the molecular weight of 92-kDa and functions as the central platform for the assembly of Vps26 and Vps29. Vps35 resembles many other helical solenoid proteins including AP adaptor protein complexes that are characterized with repeated structural units in a continuous superhelix arrangement involved in coated vesicle trafficking. The curved surface of the 6 even-numbered helices within solenoid structure with series of ridges separating hydrophobic grooves function as potential cargo binding sites. The C-terminal of Vps35 contains an -solenoid fold that fits into the metal binding pocket of Vps29.
A conserved PRLYL motif at the N-terminus of Vps35 is involved in the binding of Vps26. The structural binding motifs enable this subunit to act as a linker between the SNX dimers and Vps trimer complex, and the binding sites targeting to the N-terminal region of SNX subunits are located at the both ends of the trimer. A study has shown that the knockdown of Vps35 in human HEp-2 epithelial cells had defect on the endosomal recycling of transferrin by DMT1 due to the mis-sorting of DMT1-II to the lysosomal membrane associated protein (LAMP2) structures.
VPS53
Vacuolar protein sorting 53 homolog (S. cerevisiae) is a protein that in humans is encoded by the VPS53 gene.

# Function
This gene encodes a protein with sequence similarity to the yeast Vps53p protein. Vps53p is involved in retrograde vesicle trafficking in late Golgi. .
Mutations in VPS53 cause                 cerebello-cerebral atrophy type 2            .
Vinca
Vinca (from Latin  vincire "to bind, fetter") is a genus of five species in the family Apocynaceae, native to Europe, northwest Africa and southwest Asia. The common name, shared with the related genus Catharanthus, is Periwinkle.
They are subshrubs or herbaceous, and have slender trailing stems 1-2 m (3-6 feet) long but not growing more than 20-70 cm (8-30 inches) above ground; the stems frequently take root where they touch the ground, enabling the plant to spread widely. The leaves are opposite, simple broad lanceolate to ovate, 1-9 cm (0.25-3.5 inches) long and 0.5-6 cm (0.25-2.25 inches) broad; they are evergreen in four species, but deciduous in the herbaceous V. herbacea, which dies back to the root system in winter.
The flowers, produced through most of the year, are salverform (like those of Phlox), simple, 2.5-7 cm (1-3 inches) broad, with five usually violet (occasionally white) petals joined together at the base to form a tube. The fruit consists of a group of divergent follicles; a dry fruit which is dehiscent along one rupture site in order to release seeds.

# Cultivation and uses
Two species, the Small Periwinkle V. minor and the Large Periwinkle V. major, are very popular ornamental plants in gardens, grown for dense evergreen ground cover and their delicate violet flowers. V. major has broader leaves with a hairy margin and larger flowers, is less cold hardy, and has twice as many chromosomes as V. minor. A variegated selection of V. major is commonly cultivated. Both species are considered invasive weeds in parts of the United States and Australia. They do not respond to common herbicides and require hormone based sprays to control.

## Medical uses
This plant was formerly used in homeopathy for catarrh, dyspepsia but due to the nature and effects of the alkaloids vincamine, isovincamine and vincamidine, it is rarely used. This plant also contains tannin. All parts of the periwinkles may cause stomach distress if ingested.
The chemotherapy drugs vincristine and vinblastine are derived from this plant.