Search results

MTHFS is a cytosolic protein which takes part in the formate metabolic process. MTHFS along with a magnesium cofactor catalyzes the ATP-dependent reaction which reduces 5-formyltetrahydrofolate (5-MTHF) to 5,10-methenyltetrahydrofolate(MTHF). MTHF is the substrate used by MTHFR (methylenetetrahydrofolate reductase) to generate 5-MTHF. In addition, MTHF is a coenzyme used in thymidine biosynthesis by thymidylate synthase (FAD).

Sulfite oxidase, also known as SUOX is a homodimeric protein localized to the intermembrane space of mitochondria. Each subunit includes a heme domain as well as a molybdopterin-binding domain. The SUOX enzyme catalyzes the oxidation of sulfite to sulfate, the last reaction in the oxidative degradation of the sulfur amino acids cysteine and methionine. In addition, the deficiency of SUOX results in neurological abnormalities which are often fatal at an early age.

UBE2D2 belongs to the E2 ubiquitin-conjugating enzyme family. UBE2D2 takes part in the ubiquitination of the tumor-suppressor protein p53, which is induced by an E3 ubiquitin-protein ligase. UBE2D2 catalyzes ubiquitination of IkB-alpha in a SCFB-TRCP and phosphorylation dependent method.

The cytokine Macrophage migration inhibitory factor (MIF) has been identified to be secreted by the pituitary gland and the monocyte/macrophage and to play an important role in endotoxic shock. MIF has the unique property of being released from macrophages and T cells in response to physiological concentrations of glucocorticoids. The secretion of MIF is tightly regulated and decreases at high, anti-inflammatory steroid concentration.

PDZK1 is a PDZ domain-containing scaffolding protein which facilitates localization of cell surface proteins and has a key part in cholesterol metabolism by regulating the HDL receptor, scavenger receptor class B type 1. Single nucleotide polymorphism in this gene is linked to metabolic syndrome, and overexpression results in drug resistance of multiple myeloma.

Retinoblastoma binding protein 4 (RBBP4) is a ubiquitously expressed nuclear protein which is a member of a highly conserved subfamily of WD-repeat proteins. RBBP4 is present in protein complexes involved in histone acetylation and chromatin assembly. In addition, RBBP4 is part of co-repressor complexes, which is a fundamental component of transcriptional silencing. RBBP4 is observed among several cellular proteins which bind directly to a retinoblastoma protein to regulate cell proliferation. RBBP4 also is a part of the Mi-2 complex which is implicated in chromatin remodeling and transcriptional repression connected with histone deacetylation.

MANF is a 20kDa protein which belongs to the ARMET family. MANF was originally known as an arginine-rich region protein which was extremely mutated in a large number of tumors. MANF Expression is induced during ER stress, signifying that MANF takes part in protein quality control during ER stress.

Cathepsin F ( CTSF) is a member of the peptidase C1 family. Cathepsins are papain familycysteine proteinases which are a main component of the lysosomal proteolytic system. The CTSF gene isubiquitously expressed, and it maps to chromosome 11q13, close to the gene encoding cathepsin W. CTSF plays a role in normal protein catabolism. CTSF involved in some degradative processes occurring in tumor progression since it is highly expressed in some cancer cell lines.

Histidine NADH Dehydrogenase Fe-S Protein 5 (NDUFS5) belongs to the NADH dehydrogenase (ubiquinone) iron-sulfur protein family. NDUFS5 is a subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), which doesn’t take part in catalysis. Complex I is transferring the electrons from NADH to the respiratory chain.

Beta-1,3-glucuronyltransferase 3 (B3GAT3) is involved in forming the linkage tetrasaccharide present in heparan sulfate and chondroitin sulfate. B3GAT3 has a part in the biosynthesis of l2/HNK-1 carbohydrate epitope on glycoproteins. B3GAT3 shows strict specificity for Gal-beta-1,3-Gal-beta-1,4-Xyl, exhibiting negligible incorporation into other galactoside substrates including Galbeta1-3Gal beta1-O-benzyl, Galbeta1-4GlcNAc and Galbeta1-4Glc.

Betaine-homocysteine methyltransferase (BHMT) is a cytosolic enzyme that catalyzes the conversion of betaine and homocysteine to dimethylglycine and methionine, respectively. BHMT displays differential expression in a model of liver cirrhosis.

Lymphokine-activated killer T-cell-originated protein kinase (PBK) is a serine/threonine kinase related to the dual specific mitogen-activated protein kinase (MAPKK) family. PBK is abundant in placenta (is also found in the testis’ outer cell layer of seminiferous tubules) and absent from adult brain tissue. PBK is involved in the activation of lymphoid cells and supports testicular functions, with a possible role in the process of spermatogenesis. Mitotic phosphorylation is required for PBK’s catalytic activity. Once phosphorylated,PBK forms a complex with TP53, leading to TP53 destabilization and weakening of G2/M checkpoint during some kind of DNA damage. PBK is active only during mitosis. In addition, a PDZ domain in the tumor suppressor protein Dlg can coordinate with the T/SXV motif of PBK. PBK also phosphorylates MAP kinase p38, and may have a role in the activation of lymphoid cells.

TIE-1 (tyrosine kinase with Ig and EGF homology domains 1) and TIE-2/Tek comprise a receptor tyrosine kinase (RTK) subfamily with unique structural characteristics: two immunoglobulin-like domains flanking three epidermal growth factor (EGF)-like domains and followed by three fibronectin type III-like repeats in the extracellular region and a split tyrosine kinase domain in the cytoplasmic region. These receptors are expressed primarily on endothelial and hematopoietic progenitor cells and play critical roles in angiogenesis, vasculogenesis and hematopoiesis. Human TIE-1 cDNA encodes a 1122 amino acid (aa) residue precursor protein with an 18 residue putative signal peptide, a 726 residue extracellular domain and a 353 residue cytoplasmic domain. Two ligands, angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2), which bind TIE-2 with high-affinity have been identified. Ang2 has been reported to act as an antagonist for Ang1. Mice engineered to overexpress Ang2 or to lack Ang1 or Tie-1 display similar angiogenic defects.

FKBP1A is a 12kDa protein initially discovered on an immune cells on the basis of its capability to bind as well as mediate the intracellular effect of the immunosuppressant FK506. FKBP1A is also known to mediate the action of Rapamycin-immunosuppressive agent. FKBP1A is part of the family of immunophilins, which have in common high affinity for immunosuppressant drugs and a peptidyl-prolyl cis-trans isomerase (PPIase). Activity which participates in folding of proline-containing protein. In the absence of immunosuppressive ligands, FKBP1A is involved in intracellular calcium regulation by associating with 3 types of Ca2+ release channel complexes: skeletal ryanodine receptors, cardiac ryanodine receptors and the inositol 1,4,5-triphosphate receptor. FKBP1A also interact with TGF-beta type I receptor exerting an inhibitory effect on the TGF-beta signaling pathway. FKBP12 plays a role in modulation of ryanodine receptor isoform-1 (ryr-1), a component of the calcium release channel of skeletal muscle sarcoplasmic reticulum. FKBP1A increase the folding of proteins and catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid (AA), a precursor of eicosanoids including prostaglandins and leukotrienes. The same reaction also produces lysophosholipids, which represent another class of lipid mediators.
The secretory PLA2 (sPLA2) family, in which 10 isozymes have been identified, consists of low molecular weight, Ca2+-requiring secretory enzymes that have been implicated in a number of biological processes, such as modification of eicosanoid generation, inflammation, and host defense.
This enzyme has been proposed to hydrolyze phosphatidylcholine (PC) in lipoproteins to liberate lyso- PC and free fatty acids in the arterial wall, thereby facilitating the accumulation of bioactive lipids and modified lipoproteins in atherosclerotic foci.
In mice, sPLA2 expression significantly influences HDL particle size and composition and demonstrate that an induction of sPLA2 is required for the decrease in plasma HDL cholesterol in response to inflammatory stimuli. Instillation of bacteria into the bronchi was associated with surfactant degradation and a decrease in large:small ratio of surfactant aggregates in rats.

3-ketodihydrosphingosine reductase (KDSR) is a 332 amino acid multi-pass membrane protein which localizes to the ER and is a member of the short-chain dehydrogenases/reductases (SDR) family. KDSR is a secreted protein that is weakly expressed in hematopoietic tissue. Furthermore, KDSR catalyzes the reduction of 3-ketodihydrosphingosine (KDS) to dihydrosphingosine (DHS). The putative active site residues of KDSR are found on the cytosolic side of the endoplasmic reticulum membrane. Chromosomal rearrangement in the KDSR gene is a cause of follicular lymphoma, aka type II chronic lymphatic leukemia.

L-threonine to glycine degradation consists of a two-step biochemical pathway which involvs the enzymes L-threonine dehydrogenase and 2-amino-3-ketobutyrate coenzyme A ligase. L-Threonine is initially converted into 2-amino-3-ketobutyrate by L-threonine dehydrogenase. Glycine C-Acetyltransferase (GCAT) is the 2nd enzyme in this pathway, which subsequently catalyzes the reaction between 2-amino-3-ketobutyrate and coenzyme A to form glycine and acetyl-CoA. The GCAT enzyme is regard as a class II pyridoxal-phosphate-dependent aminotransferase. GCAT is strongly expressed in the heart, brain, liver and pancreas. GCAT is also found in lung.

CDC123 is a member of the CDC123 family. CDC123is required for S phase entry of the cell cycle. It is also broadly expressed in spleen,thymus, prostate, testis, ovary, small intestine, colon and leukocytes with the uppermost expression in testis.

PSMG4 is a chaperone protein that enhances assembly of the 20S proteasome. PSMG4 cooperates with alpha and beta subunits of the 20S proteasome and with PSMG3 but disconnects when the POMP is recruited before the formation of half-proteasomes.

UROD is the fifth enzyme in the human heme biosynthetic pathway and is in charge for the transfer of uroporphyrinogen to coproporphyrinogen through the deletion of four carboxymethyl side chains. UROD Mutations and deficiency result in 3 autosomal disorders in humans: familial porphyria cutanea tarda (f-PCT), sporadic porphyria cutanea tarda (s-PCT) and hepatoerythropoietic porphyria (HEP).

P85a functions as the regulatory subunit of the class IA PI3-kinase isoforms a, b, and d.
It contains two SH2 domains that bind to tyrosine-phosphorylated growth factor receptors or substrate adaptor proteins.
It also contains a BH (breakpoint cluster region homology) domain that shows GAP activity towards the small GTPases Rab4, Rab5, Cdc42, Rac1 and to a lesser extend towards Rab6 and Rab11.
It was shown that PI3Ka catalytic subunit mediated phosphorylation of the p85a adapter reduces the lipid kinase activity of the heterodimer and this gives hints for PI3K-dependent signaling events not requiring production of 3’-phosphorylated phosphoinositides.
PI3Ka protein kinase activity has been implicated in IRS-1 serine phosphorylation in insulin-treated adipocytes and in STAT3 and IRS-1 phosphorylation upon activation of the type 1 IFN receptor by IFN-a.

Complement Factor B, also known as CFB, encodes complement factor B which is a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single chain polypeptide. Once the alternative pathway is activated it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. The active subunit Bb is a serine protease which connects with C3b to form the alternative pathway C3 convertase. Also, Bb is involved in the proliferation of preactivated B lymphocytes, while Ba inhibits their proliferation.

PC4 and SFRS1 Interacting Protein 1 (PSIP1) is a transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. PSIP1 is also involved particularly in lens epithelial cell gene regulation and stress responses. PSIP1 has a significant role in lens epithelial to fiber cell terminal differentiation. In addition, PSIP1 plays a protective role during stress-induced apoptosis. Furthermore, PSIP1 is a cellular cofactor for lentiviral integration.

The secreted polypeptide noggin, encoded by the NOG gene, binds and inactivates members of the transforming growth factor-beta (TGF-beta) superfamily signaling proteins, such as bone morphogenetic protein-4 (BMP4). By diffusing through extracellular matrices more efficiently than members of the TGF-beta superfamily, noggin may have a principal role in creating morphogenic gradients. Noggin appears to have pleiotropic effect, both early in development as well as in later stages. It was originally isolated from Xenopus based on its ability to restore normal dorsal-ventral body axis in embryos that had been artificially ventralized by UV treatment. The results of the mouse knockout of noggin suggest that it is involved in numerous developmental processes, such as neural tube fusion and joint formation. Recently, several dominant human NOG mutations in unrelated families with proximal symphalangism (SYM1) and multiple synostoses syndrome (SYNS1) were identified; both SYM1 and SYNS1 have multiple joint fusion as their principal feature, and map to the same region (17q22) as NOG. All NOG mutations altered evolutionarily conserved amino acid residues. The amino acid sequence of human noggin is highly homologous to that of Xenopus, rat and mouse.