Persius/hicric huggingface dataset:
TPH1
Tryptophan hydroxylase 1 (TPH1) is an isoenzyme of tryptophan hydroxylase which in humans is encoded by the TPH1 gene.
TPH1 was first discovered to synthesize serotonin in 1988 and was thought that there only was a single TPH gene until 2003, while a second form was found in the mouse (Tph2), rat and human brain (TPH2) and the original TPH was then renamed to TPH1.

# Function
Tryptophan hydroxylases catalyze the biopterin-dependent monooxygenation of tryptophan to 5-hydroxytryptophan (5-HTP), which is subsequently decarboxylated to form the neurotransmitter serotonin (5-hydroxytryptamine or 5-HT). It is the rate-limiting enzyme in the biosynthesis of serotonin.
TPH expression is limited to a few specialized tissues: raphe neurons, pinealocytes, mast cells, mononuclear leukocytes, beta-cells of the islets of Langerhans, and intestinal and pancreatic enterochromaffin cells.

# Clinical significance
Tryptophan hydroxylase is important for synthesizing indoleamine neurotransmitters and related compounds in the body and brain, including serotonin, melatonin, tryptamine, N-methyltryptamine, and N,N-dimethyltryptamine. TPH1 is expressed in the body, but not the brain.
Nevertheless, the effect of variations in the TPH1 gene on brain-related variables, such as personality traits and neuropsychiatric disorders, has been studied. 
For example, one study (1998) found an association between a polymorphism in the gene with impulsive-aggression measures, while a case-control study (2001) could find no association between polymorphisms and Alzheimer's Disease.
One human mutant of TPH1, A218C found in intron 7,  is highly associated with schizophrenia. Introns are regions of DNA that do not code for the amino acid sequence of a protein and were long considered to be 'junk DNA' lacking purpose. The correlation of an intron mutation with schizophrenia is significant because it suggests that introns have an important role in translation, transcription, or another, possibly unknown, aspect of the production of proteins from DNA.
TPM1
Tropomyosin alpha-1 chain is a protein that in humans is encoded by the TPM1 gene. This gene is a member of the tropomyosin (Tm) family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells.

# Structure
Tm is a 32.7 kDa protein composed of 284 amino acids. Tm is a flexible protein homodimer or heterodimer composed of two alpha-helical chains, which adopt a bent coiled coil conformation to wrap around the seven actin molecules in a functional unit of muscle. It is polymerized end to end along the two grooves of actin filaments and provides stability to the filaments.  Human striated muscles express protein from the TPM1 (-Tm), TPM2 (-Tm) and TPM3 (-Tm) genes, with -Tm being the predominant isoform in striated muscle. In human cardiac muscle the ratio of -Tm to -Tm is roughly 5:1.

# Function
Tm functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. Tm molecules are arranged head-to-tail along the actin thin filament, and are a key component in cooperative activation of muscle. A three state model has been proposed by McKillop and Geeves, which describes the positions of Tm during a cardiac cycle. The blocked (B) state occurs in diastole when intracellular calcium is low and Tm blocks the myosin binding site on actin. The closed (C) state is when Tm is positioned on the inner groove of actin; in this state myosin is in a "cocked" position where heads are weakly bound and not generating force. The myosin binding (M) state is when Tm is further displaced from actin by myosin crossbridges that are strongly-bound and actively generating force. In addition to actin, Tm binds troponin T (TnT). TnT tethers the region of head-to-tail overlap of subsequent Tm molecules to actin.

# Clinical Significance
Mutations in TPM1 have been associated with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy. HCM mutations tend to cluster around the N-terminal region and a primary actin binding region known as period 5.
TRIF
TIR-domain-containing adapter-inducing interferon- (TRIF) is an adapter in responding to activation of toll-like receptors (TLRs). It mediates the rather delayed cascade of two TLR-associated signaling cascades, where the other one is dependent upon a MyD88 adapter.
Toll-like receptors (TLRs) recognize specific components of microbial invaders and activate an immune response to these pathogens. After these receptors recognize highly conserved pathogenic patterns, a downstream signaling cascade is activated in order to stimulate the release of inflammatory cytokines and chemokines as well as to upregulate the expression of immune cells. All TLRs have a TIR domain that initiates the signaling cascade through TIR adapters. Adapters are platforms that organize downstream signaling cascades leading to a specific cellular response after exposure to a given pathogen.

# Structure
TRIF is primarily active in the spleen and is often regulated when MyD88 is deficient in the liver, indicating organ-specific regulation of signaling pathways. Curiously, there is a lack of redundancy within the TLR4 signaling pathway that leads to microbial evasion of immune response in the host after mutations occur within intermediates of the pathway. Three TRAF-binding motifs present in the amino terminal region of TRIF are necessary for association with TRAF6.  Destruction of these motifs reduced the activation of NF-B, a transcription factor that is also activated by the carboxy-terminal domain of TRIF in the upregulation of cytokines and co-stimulatory immune molecules. This domain recruits receptor-interacting protein (RIP1) and RIP3 through the RIP homotypic interaction motif. Cells deficient for RIP1 gene display attenuated TLR3 activation of NF-B, indicating the use of the RIP1 gene in downstream TRIF activation, in contrast to other TLRs that use IRAK protein for the activation of NF-B.

# Areas of research
Investigations into the function of TRIF are of great significance to various fields of biomedical research. The pathogenesis of infectious disease, septic shock, tumor growth, and rheumatoid arthritis all have close ties with TLR signaling pathways, specifically to that of TRIF. Better understanding of the TRIF pathway will be therapeutically useful in the development of vaccines and treatments that can control associated inflammation and antiviral responses. Experiments involving wild-type and TRIF-deficient mice are critical for understanding the coordinated responses of TLR pathways. It is necessary to study the coordinated effects of these pathways in order to understand the complex responses initiated by TRIF.
TSC2
Tuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the TSC2 gene.

# Function
Mutations in this gene lead to tuberous sclerosis. Its gene product is believed to be a tumor suppressor and is able to stimulate specific GTPases. Hamartin coded by the gene TSC1 functions as a facilitator of Hsp90 in chaperoning of Tuberin, therefore preventing its ubiquitination and degradation in the proteasome. Alternative splicing results in multiple transcript variants encoding different isoforms of the protein.  Mutations in TSC2 can cause Lymphangioleiomyomatosis, a disease caused by the enlargement of tissue in the lungs, creating cysts and tumours and causing difficulty breathing.  Because Tuberin regulates cell size, along with the protein Hamartin, mutations to TSC1 and TSC2 genes may prevent the control of cell growth in the lungs of individuals.

# Signaling Pathways
Pharmacological inhibition of ERK1/2 restores GSK3 activity and protein synthesis levels in a model of tuberous sclerosis.

# Interactions
TSC2 functions within a multi-protein complex knowns as the TSC complex which consists of the core proteins TSC2, TSC1, and TBC1D7.
TSC2 has been reported to interact with several other proteins that are not a part of the TSC complex including:
- AKT1,
- AXIN1,
- FOXO1,
- GSK3B,
- Hsp70
- Hsp90
- MAPK1,
- PTK2,
- PAM,
- PRKAA1,
- RAP1A,
- RHEB,
- RPS6KA1,
- UBE3A  and
- YWHAZ.
TTC8
Tetratricopeptide repeat domain 8 (TTC8) also known as Bardet-Biedl syndrome 8 is a protein that in humans is encoded by the TTC8  gene.

# Function
TTC8 is associated with gamma-tubulin, BBS4, and PCM1 in the centrosome. PCM1 in turn is involved in centriolar replication during ciliogenesis.
TTC8 is located in the cilia of spermatids, retina, and bronchial epithelium cells.

# Clinical significance
Mutations in the TTC8 gene is one of 14 genes 
identified as causal for Bardet-Biedl syndrome.
TWF1
Twinfilin-1 is a protein that in humans is encoded by the TWF1 gene.
This gene encodes twinfilin, an actin monomer-binding protein conserved from yeast to mammals. Studies of the mouse counterpart suggest that this protein may be an actin monomer-binding protein, and its localization to cortical G-actin-rich structures may be regulated by the small GTPase RAC1.

# Model organisms
Model organisms have been used in the study of TWF1 function. A conditional knockout mouse line, called Twf1tm1a(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  at the Wellcome Trust Sanger Institute.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty three tests were carried out on mutant mice, but no significant abnormalities were observed.
TXN2
Thioredoxin, mitochondrial also known as thioredoxin-2 is a protein that in humans is encoded by the TXN2 gene on chromosome 22. This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis.

# Structure
As a thioredoxin, TXN2 is a 12-kDa protein characterized by the redox active site Trp-Cys-Gly-Pro-Cys. In its oxidized (inactive) form, the two cysteines form a disulfide bond. This bond is then reduced by thioredoxin reductase and NADPH to a dithiol, which serves as a disulfide reductase. In contrast to TXN1, TXN2 contains a putative N-terminal mitochondrial targeting sequence, responsible for its mitochondria localization, and lacks structural cysteines. Two mRNA transcripts of the TXN2 gene differ by ~330 bp in the length of the 3-untranslated region, and both are believed to exist in vivo.

# Function
This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein is ubiquitously expressed in all prokaryotic and eukaryotic organisms, but demonstrates especially high expression in tissues with heavy metabolic activity, including the stomach, testis, ovary, liver, heart, neurons, and adrenal gland. It may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis. Specifically, the ability of TXN2 to reduce disulfide bonds enables the protein to regulate mitochondrial redox and, thus, the production of reactive oxygen species (ROS). By extension, downregulation of TXN2 can lead to increased ROS generation and cell death. The antiapoptotic function of TXN2 is attributed to its involvement in GSH-dependent mechanisms to scavenge ROS, or its interaction with, and thus regulation of, thiols in the mitochondrial permeability transition pore component adenine nucleotide translocator (ANT).
Overexpression of TXN2 was shown to have attenuated hypoxia-induced HIF-1alpha accumulation, which is in direct opposition of the cytosolic TXN1, which enhanced HIF-1alpha levels. Moreover, although both TXN2 and TXN1 are able to reduce insulin, TXN2 does not depend on the oxidative status of the protein for this activity, a quality which may contribute to their difference in function.

# Clinical Significance
It has been demonstrated that genetic polymorphisms in the TXN2 gene may be associated with the risk of spina bifida.
TXN2 is known to inhibit transforming growth factor (TGF)--stimulated ROS generation independent of Smad signaling. TGF- is a pro-oncogenic cytokine that induces epithelialmesenchymal transition (EMT), which is a crucial event in metastatic progression. In particular, TXN2 inhibits TGF--mediated induction of HMGA2, a central EMT mediator, and fibronectin, an EMT marker.

# Interactions
TXN2 is shown to interact with ANT.
UBL5
Ubiquitin-like protein 5 is a protein that in humans is encoded by the UBL5 gene.
It has been shown that in C. elegans mitochondria treated to lower expression of certain electron transport chain proteins during the L3/L4 stage, its expression levels is higher leading to increased lifespans.
Ubiquitin-like proteins (UBLs) are thought to be reversible modulators of protein function rather than protein degraders like ubiquitin (MIM 191339).
UFM1
Ubiquitin-fold modifier 1, also known as UFM1, is a protein which in humans is encoded by the UFM1 gene.
UFM1 is a ubiquitin-like protein that is conjugated to target proteins by E1-like activating enzyme UBA5 (UBE1DC1) and E2-like conjugating enzyme UFC1 (see UBE2M).

# Function
UFM1 shares several common properties with ubiquitin (Ub) and the other ubiquitin-like proteins (UBLs). Ufm1 has similar tertiary structure to Ub but lacks any obvious sequence similarity. It is synthesized as an inactive precursor form (pro-Ufm1) which has 2 additional amino acids beyond the conserved glycine. The mechanism of Ufm1 conjugation is similar to that of ubiquitin. Mature Ufm1 has an exposed C-terminal glycine which is essential for subsequent activation by its cognate E1 protein (Uba5). This activation step results in the formation of a high-energy thiolester bond in the presence of ATP. The Ufm1 is subsequently transferred to its cognate E2-like enzyme (Ufc1) via a similar thioester linkage with a cysteine at the E2 active site. Ufm1 is conjugated to a variety of target proteins and forms complexes with as yet unidentified proteins. Thus, presumably there exist E3 ligases (none have been identified to date) to perform the final step in Ufm1 conjugation to relevant targets. The modification of proteins with Ufm1 is also reversible. Two novel cysteine proteases have been identified to date (UFSP1 and UFSP2) which cleave Ufm1-peptide C-terminal fusions and also removes Ufm1 from native intracellular conjugates. These proteases have no obvious homology to ubiquitin deconjugating enzymes. The proteins for Ufm1 conjugation (Uba5, Ufc1 and Ufm1) are all conserved in animals and plants (but not yeast) suggesting important roles in multicellular organisms. The exact role of Ufm1 modification in vivo is not yet known.
UGCG
Ceramide glucosyltransferase is an enzyme that in humans is encoded by the UGCG gene.
Glycosphingolipids             (GSLs) are a group of membrane components that contain lipid and sugar moieties. They are present in essentially all animal cells and are believed to have important roles in various cellular processes.  UDP-glucose ceramide glucosyltransferase catalyzes the first glycosylation step in glycosphingolipid biosynthesis.  The product, glucosylceramide, is the core structure of more than 300 GSLs. UGCG is widely expressed and transcription is upregulated during keratinocyte differentiation.

# Interactions
UGCG has been shown to interact with                 RTN1            .
UGGT
UGGT, or UDP-glucose:glycoprotein glucosyltransferase, is a soluble enzyme resident in the lumen of the endoplasmic reticulum (ER).
The main function of UGGT is to recognize misfolded glycoproteins and transfer a glucose (Glc) monomer (monoglucosylate) to the terminal mannose of the A-branch of the glycan on the glycoprotein. It uses UDP-glucose (UDP-Glc) as the glucosyl donor and requires calcium ions for its activity:
misfolded-glycoprotein-Asn-GlcNAc2Man9 + UDP-Glc => misfolded-glycoprotein-Asn-GlcNAc2Man9Glc1 + UDP
UGGT is about 170 kDa and it consists of two structurally independent portions: a variable N-terminal portion of ~1200 amino acids, which in turn comprises 4 thioredoxin-like domains and two beta-sandwich domains, and senses glycoprotein misfolding; and a highly conserved C-terminal catalytic portion of ~300 amino acids, folding as a glucosyltransferase domain belonging to fold family GT24. Higher eukaryotes possess two isoforms, UGGT1 and UGGT2, but only the former has been conclusively shown to be active in misfolded glycoprotein recognition.
UGGT is part of the ER quality control system of glycoprotein folding and its activity increases the potential for correctly folded glycoproteins. The main proteins involved in the ER quality control system are UGGT, the ER lectin chaperones (calnexin and calreticulin), and glucosidase II. UGGT first recognizes the incompletely folded glycoprotein and monoglucosylates it. The lectins, calnexin and calreticulin, have high affinities for monoglucosylated proteins and the ER chaperones that associate with these lectins assist the folding of the misfolded glycoprotein. Subsequently, glucosidase II will deglucosylate the glycoprotein. If the glycoprotein is still misfolded, UGGT will re-glucosylate it and allow it to go through the cycle again.
Currently, it is unclear how UGGT recognizes misfolded glycoprotein. It has been proposed that UGGT may bind to exposed hydrophobic stretches, a characteristic feature of misfolded proteins. UGGT crystal structures suggest marked conformational mobility, which could explain the ability of the protein to recognise a wide variety of client glycoproteins of different shapes and forms. The same conformational mobility could account for the ability of the protein to re-glucosylate N-linked glycans at different distances from the misfold site. See for example the picture in which glycoproteins are symbolized by nuts and UGGT by an adjustable wrench.
UPB1
Beta-ureidopropionase is an enzyme that in humans is encoded by the UPB1 gene.
This gene encodes a protein that belongs to the CN hydrolase family. Beta-ureidopropionase catalyzes the last step in the pyrimidine degradation pathway. The pyrimidine bases uracil and thymine are degraded via the consecutive action of dihydropyrimidine dehydrogenase (DHPDH), dihydropyrimidinase (DHP) and beta-ureidopropionase (UP) to beta-alanine and beta-aminoisobutyric acid, respectively. UP deficiencies are associated with N-carbamyl-beta-amino aciduria and may lead to abnormalities in neurological activity.

# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.
-  The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601"..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}
UPF2
Regulator of nonsense transcripts 2 is a protein that in humans is encoded by the UPF2 gene.

# Function
This gene encodes a protein that is part of a post-splicing multiprotein complex, the exon junction complex, involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein is located in the perinuclear area. It interacts with translation release factors and the proteins that are functional homologs of yeast Upf1p and Upf3p. Two splice variants have been found for this gene; both variants encode the same protein.

# Interactions
UPF2 has been shown to interact with UPF1, UPF3A and UPF3B.
UPP1
Uridine phosphorylase 1 is an enzyme that in humans is encoded by the UPP1 gene.

# Interactions
UPP1 has been shown to interact with Vimentin.

# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.
-  The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601"..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}
URI1
Unconventional prefoldin RPB5 interactor, also called URI1, is a protein that in humans is encoded by the URI1 gene.

# Function
The protein encoded by this gene binds to RNA polymerase II subunit 5 (RPB5) and negatively modulates transcription through its binding to RPB5. The encoded protein seems to have inhibitory effects on various types of activated transcription, but it requires the RPB5-binding region. This protein acts as a corepressor. It is suggested that it may require signaling processes for its function or that it negatively modulates genes in the chromatin structure. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.

# Interactions
URI1 has been shown to interact with DMAP1 and STAP1.

# Model organisms
Model organisms have been used in the study of URI1 function. A conditional knockout mouse line called Uri1tm1a(EUCOMM)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
USF1
Upstream stimulatory factor 1 is a protein that in humans is encoded by the USF1 gene.

# Function
This gene encodes a member of the basic helix-loop-helix leucine zipper family and can function as a cellular transcription factor. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs. This gene has been linked to familial combined hyperlipidemia (FCHL). Two transcript variants encoding distinct isoforms have been identified for this gene.
A study of mice suggested reduced USF1 levels increases metabolism in brown fat.

# Interactions
USF1 (human gene) has been shown to interact with USF2, FOSL1 and GTF2I.