UPB1 Protein

Research Background :
β-Ureidopropionase is a cytoplasmic protein which belongs to the CN hydrolase family of BUP subfamily. β-Ureidopropionase binds one zinc ion per subunit, catalyzes the last step in the pyrimidine degradation pathway. β-Ureidopropionase can convert N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine to beta-aminoisobutyric acid and beta-alanine, ammonia and carbon dioxide, respectively. 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. Defects in β-Ureidopropionase are the cause of β-Ureidopropionase deficiency that is characterized by muscular hypotonia, dystonic movements, scoliosis, microcephaly and severe developmental delay.

Research Background :
Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF) and VEGF-A, is a potent mediator of both angiogenesis and vasculogenesis in the fetus and adult. It is a member of the platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF) family and often exists as a disulfide-linked homodimer. VEGF-A protein is a glycosylated mitogen that specifically acts on endothelial cells and has various effects, including mediating increased vascular permeability, inducing angiogenesis, vasculogenesis and endothelial cell growth, promoting cell migration, inhibiting apoptosis and tumor growth. VEGF-A protein is also a vasodilator that increases microvascular permeability, thus it was originally referred to as vascular permeability factor.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy

Research Background :
The TAM receptors (TYRO3, Axl and MerTK) are promising therapeutic targets on tumor-associated macrophages. The TAM receptors are a family of receptor tyrosine kinases with shared ligands Gas6 and Protein S that skew macrophage polarization towards a pro-tumor M2-like phenotype.In macrophages, the TAM receptors also promote apoptotic cell clearance, a tumor-promoting process called efferocytosis. The TAM receptors bind the “eat-me” signal phosphatidylserine on apoptotic cell membranes using Gas6 and Protein S as bridging ligands.

Research Background :
Protein-tyrosine sulfotransferase 1, also known as Tyrosylprotein sulfotransferase 1 and TPST1, is a single-pass type II membrane protein that belongs to the protein sulfotransferase family. Tyrosine O-sulfation is a common posttranslational modification of proteins in all multicellular organisms. This reaction is mediated by a Golgi enzyme activity called tyrosylprotein sulfotransferase (TPST) that catalyzes the transfer of sulfate from 3′-phosphoadenosine 5′-phosphosulfate to tyrosine residues within acidic motifs of polypeptides. Tyrosine O-sulfation has been shown to be important in protein-protein interactions in several systems. Tyrosine sulfation is mediated by one of two Golgi isoenzymes, called tyrosylprotein sulfotransferases (TPST-1 and TPST-2). A relatively small number of proteins are known to undergo tyrosine sulfation, including certain adhesion molecules, G-protein-coupled receptors, coagulation factors, serpins, extracellular matrix proteins, and hormones. TPST1 is a human tyrosylprotein sulfotransferase that uses 3’phosphoadenosine-5’phosphosulfate (PAPS) to transfer the sulfate moiety to proteins predominantly designated for secretion. TPST1 bears N-linked glycosyl residues exclusively at position Asn6 and Asn262. TPST1 and TPST2 have distinct biological roles that may reflect differences in their macromolecular substrate specificity.

Research Background :
Chemokines are a family of small chemotactic cytokines, or proteins secreted by cells. Chemokines share the same structure similarities such as small size, and the presence of four cysteine residues in conserved locations in order to form their 3-dimensional shape. Some of the chemokines are considered pro-inflammatory which can be induced to recruit cells of the immune system to a site of infection during an immune response, while others are considered homeostatic and are implied in controlling the migration of cells during normal processes of tissue maintenance and development. There are four members of the chemokine family: C-C kemokines, C kemokines, CXC kemokines and CX3C kemokines. The C-C kemokines have two cysteines nearby the amino terminus. There have been at least 27 distinct members of this subgroup reported for mammals, called C-C chemokine ligands-1 to 28. Chemokin ligand 17 (CCL17), also known as thymus and activation regulated chemokine(TARC), is a small cytokine belonging to the C-C chemokine family. CCL17 is expressed maily in thymus and transiently in phytohemagglutinin-stimulated peripheral blood mononuclear cells. CCL17 can induce chemotaxis in T cells by binding with the chemokine receptor CCR4.

Research Background :
Tyrosine-protein phosphatase non-receptor type 2, also known as T-cell protein-tyrosine phosphatase, PTPN2 and PTPT, is a cytoplasm protein that belongs to the protein-tyrosine phosphatase family and Non-receptor class 1 subfamily. Members of the protein tyrosine phosphatase ( PTP ) family share a highly conserved catalytic motif, which is essential for the catalytic activity. TC-PTP / PTPN2 is a cytosolic tyrosine phosphatase that functions as a negative regulator of a variety of tyrosine kinases and other signaling proteins. The expression of TC-PTP / PTPN2 plays a role of tumor suppressor and may modulate response to treatment. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. TC-PTP / PTPN2 is an enzyme that is essential for the proper functioning of the immune system and that participates in the control of cell proliferation, and inflammation. TC-PTP / PTPN2 was identified as a negative regulator of NUP214-ABL1 kinase activity.

Research Background :
SIRT1 belongs to the sirtuin family. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. SIRT1 is included in class I of the sirtuin family. It is a NAD-dependent protein deacetylase, which regulates processes such as apoptosis and muscle differentiation by deacetylating key proteins. It deacetylates ‘Lys-382’ of p53/TP53 and impairs its ability to induce proapoptotic program and modulate cell senescence. SIRT1 also deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I. It is involved in HES1- and HEY2-mediated transcriptional repression. SIRT1 inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1. It may serve as a sensor of the cytosolic ratio of NAD(+)/NADH, which is essential in skeletal muscle cell differentiation. It also deacetylates ‘Lys-16’ of histone H4 (in vitro). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at ‘Lys-9’ (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus.

Research Background :
SLAM family member 6, also known as Activating NK receptor, NK-T-B-antigen, NTB-A, SLAMF6, KALI and Ly18, is a single-pass type I membrane protein that belongs to the CD2 subfamily of the immunoglobulin superfamily. SLAMF6 / Ly18 contains one Ig-like (immunoglobulin-like) domain. It is expressed by all (resting and activated) natural killer cells (NK), T- and B-lymphocytes. SLAMF6 / Ly18 triggers cytolytic activity only in natural killer cells (NK) expressing high surface densities of natural cytotoxicity receptors. SLAMF6 / Ly18 is a homodimer. It interacts with PTN6 and, upon phosphorylation, with PTN11 and SH2D1A/SAP. SLAMF6 / Ly18 undergoes tyrosine phosphorylation and associates with the Src homology 2 domain-containing protein (SH2D1A) as well as with SH2 domain-containing phosphatases (SHPs). It may function as a coreceptor in the process of NK cell activation. SLAMF6 / Ly18 can also mediate inhibitory signals in NK cells from X-linked lymphoproliferative patients.

Research Background :
Stromal derived factors (SDFs) are a loosely defined group of molecules that are generated by stromal cells. Two of the stromal derived factors, SDF-1 and SDF-4 belong to the chemokine family. Other SDFs, such as SDF-2 and SDF-5 are not well defined and their biological functions are less known. SDF-2 is first isolated from the mouse stromal cell line ST2 as a secretory protein. The amino acid sequence deduced from the murine clone and the human homolog are conserved more than 92 %, and the aa sequence of SDF-2 shows similarity to those of yeast dolichyl phosphate-D-mannose, protein mannosyltransferases. SDF-1 and its receptor are strongly indicated in the progression of various cancers including breast cancer. SDF-2, SDF2-L1, SDF-4, and SDF-5 are ubiquitously expressed in various cancer cell lines and SDF-2, SDF-4 and SDF-5 are expressed in mammary tissues. These SDFs have prognostic value and warrant further investigation in their biological functions and clinical value.