Search results

Uridine phosphorylase from Salmonella typhimurium (StUP) catalyzes the reversible phosphorolysis of uridine with the formation of ribose-1-phosphate and uracil.

Serine racemase (SRR) is an enzyme which generates D-serine from L-serine. D-serine functions as a neuronal signaling molecule by activating NMDA receptors in the brain. Mammalian SRR is a pyridoxal 5'-phosphate dependent enzyme which catalyzes both the racemization of L-serine to D-serine and also the elimination of water from L-serine, producing pyruvate and ammonia. The SRR enzyme is physiologically stimulated by divalent cations (e.g., magnesium) and is allosterically activated by the magnesium/ATP complex.

Chemokine (C-X-C motif) ligand 5 (CXCL5) is a small cytokine belonging to the CXC chemokine family that is also known as epithelial-derived neutrophil-activating peptide 78 (ENA-78). It is produced following stimulation of cells with the inflammatory cytokines interleukin-1 or tumor necrosis factor-alpha. Expression of CXCL5 has also been observed in eosinophils, and can be inhibited with the type II IFN. This chemokine stimulates the chemotaxis of neutrophils possesses angiogenic properties. It elicits these effects by interacting with the cell surface chemokine receptor CXCR2. The gene for CXCL5 is encoded on four exons and is located on human chromosome 4 amongst several other CXC chemokine genes. CXCL5 has been implicated in connective tissue remodelling.

CCL-20 is a chemotactic factor that draws lymphocytes & neutrophils, rathar than monocytes. MIP-3 alpha inhibits proliferation of myeloid progenitors in colony formation assays. MIP3A plays a role in the formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells. C-terminal processed forms have been shown to be equally chemotactically active for leukocytes. CCL-20 holdes antibacterial activity e.coli atcc 25922 and s.aureus atcc 29213. CCL-20 gene transcription is activated by H. pylori, which activates NF-kappaB through intracellular signal pathway which involves IkappaB kinase and NF-kappaB-inducing kinase. MIP-3 alpha is invloved in chemokine-mediated lymphocyte trafficking during gastric inflammation in Helicobacter infection. CCL-20 expression is involved in the recruitment of CD45R0-positive T cell subsets into the intestinal lamina propria.
MIP-3A is in charge of the advancement of pulpal inflammation through the recruitment of C-C motif Receptor 6-expressing lymphocytes Vaginal epithelial cells respond to factors present in semen by secreting MIP-3 alpha, which increases langerhans cells recruitment during HIV transmission.

CCL15, a new human CC chemokine, was isolated from a human fetal spleen cDNA library. CCL15 cDNA encodes a predicted 113 amino acid (aa) protein containing a putative signal peptide of 21 amino acids that is cleaved to generate a 92 aa residue mature protein. Within the CC family members, human CCL15 shares 45%, 44%, 35%, and 30% aa homology with mouse C10, human MPIF-1, human HCC-1, and mouse MIP-1?, respectively. The gene for MIP-5 is found on chromosome 17 where the genes for most of the human CC chemokines are located. Human CCL15 is expressed in T and B lymphocytes, NK cells, monocytes and monocyte-derived dendritic cells. Human MIP-5 is chemotactic for T cells and monocytes and has been shown to induce calcium flux in human CCR-1-transfected cells.

CXC chemokine ligand 16 (CXCL16) is a type I membrane protein, which contains a non-ELR motif-containing CXC chemokine domain in its extracellular region. Human and Mouse CXCL16 share a 70% a.a. sequence similarity within their chemokine domains and 49% overall a.a. sequence identity. Functional CXCL16 can be dropped from the cell surface as an approximately 35kDa soluble protein. CXCR6 is the functional receptor for CXCL16. CXCL16 functions as a scavenger receptor on macrophages, which specifically binds to OxLDL (oxidized low density lipoprotein), proposing that CXCL16 may be involved in pathophysiology such as atherogenesis. In addition, CXCL16 induces a strong chemotactic response and calcium mobilization. CXCL16 binds to CXCR6/Bonzo.

Hydroxymethylglutaryl-CoA lyase (HMGCL) is a mitochondrial matrix protein which is a member of the HMG-CoA lyase family. HMGCL is a homodimer and participates in leucine catabolism and ketogenesis, the hepatic synthesis of ketone bodies which, during fasting, provides a major source of energy for the heart, brain and kidney. More precisely, HMGCL catalyzes the final step of these processes, the cleavage of 3-hydroxy-3-methylglutaryl-CoA to acetoacetic acid and acetyl-CoA.

AnsA is a cytoplasmic asparaginase from E.coli involved in intracellular asparagine utilization. E.coli has 2 L-asparaginases: the cytoplasmic type I form (ansA) and the periplasmic type II form (ansB). AnsA (Type L asparaginase) is constitutively expressed and is obligatory for the growth of the bacteria on asparagine as the sole nitrogen source.

Src-Like-Adaptor 2, also known as SLA2, is a part of the SLAP family of adapter proteins. SLA2 acts as a significant receptor-proximal in downregulating T and B cell-mediated responses and inhibits antigen receptor-induced calcium mobilization. SLA2 interacts with Cas-Br-M (murine) ecotropic retroviral transforming sequence c.

Chemokine (C-X-C motif) ligand 11 (CXCL11) is a small cytokine belonging to the CXC chemokine family that is also called Interferon-inducible T-cell alpha chemoattractant (I-TAC) and Interferon-gamma-inducible protein 9 (IP-9). It is highly expressed in peripheral blood leukocytes, pancreas and liver, with moderate levels in thymus, spleen and lung and low expression levels were in small intestine, placenta and prostate. Gene expression of CXCL11 is strongly induced by IFN-g and IFN-b, and weakly induced by IFN-a. This chemokine elicits its effects on its target cells by interacting with the cell surface chemokine receptor CXCR3, with a higher affinity than do the other ligands for this receptor, CXCL9 and CXCL10. CXCL11 is chemotactic for activated T cells. Its gene is located on human chromosome 4 along with many other members of the CXC chemokine family.

OLR1 is a type II membrane protein which belongs to the C-type lectin family and performs as a cell-surface receptor for Ox-LDL. Ox-LDL has a part in early ather-osclerosis, which includes the transformation of monocyte-derived macro-phages to foam cells in atherosclerotic lesions. In addition, OLR1 protein triggers the activation of the NF?B signal transduction pathway.

Syntaxin is membrane integrated Q-SNARE protein participating in exocytosis. Syntaxin is composed of an N-terminal regulatory domain (Habc), a SNARE domain (known as H3), and a single C-terminal transmembrane domain. The SNARE (H3) domain binds to both synaptobrevin and SNAP-25 forming the core SNARE complex. Synaptic vesicles store neurotransmitters that are released during calcium-regulated exocytosis. The specificity of neurotransmitter release requires the localization of both synaptic vesicles and calcium channels to the presynaptic active zone. Syntaxins function in this vesicle fusion process. Syntaxins also serve as a substrate for botulinum neurotoxin type C, a metalloprotease that blocks exocytosis and has high affinity for a molecular complex that includes the alpha-latrotoxin receptor which produces exocytosis.

CCL25 (Teck) is a novel CC chemokine, which is distantly related (about 20% amino acid sequence identity) to other CC chemokines. The mouse CCL25 cDNA has also been cloned and shown to encode a 144 a.a. protein, which exhibits 49% a.a. sequence identity to the human CCL25. Human and mouse CCL25 expression was shown to be greatly restricted to the thymus and small intestine. While dendritic cells are identified as the source of CCL25 production in the thymus, dendritic cells derived from bone marrow do not express CCL25. CCL25 signals through the CCR9 receptor. Teck is possibly involved in T-cell development.
Recombinant human and mouse Teck were shown to be chemotactic for activated macrophages, dendritic cells and thymocytes. The recombinant protein demonstrates chemotactic activity on thymocytes, macrophages, THP-1 cells, and dendritic cells but is inactive on peripheral blood lymphocytes and neutrophils.

CCL3L1 is a small cytokine that belongs to the CC chemokines. The CCL3L1 gene is one of several cytokine genes clustered on the q-arm of chromosome 17. CCL3L1 is involved in immunoregulatory and inflammatory processes. CCL3L1 binds to several chemokine receptors including CCBP2 and CCR5. CCR5 is a co-receptor for HIV, and binding of the CCL3L1 protein to CCR5 inhibits HIV entry.

Immunity-related GTPase family M protein (IRGM) is essential for clearance of severe protozoan and bacterial infections. IRGM belongs to the p47 immunity-related GTPase family. IRGM serves in innate immune response possibly via regulation of autophagy. IRGM regulates proinflammatory cytokine production and inhibit endotoxemia upon infection and also has a part in macrophages adhesion and motility. Polymorphisms which modify the natural expression of the IRGM gene are associated with a susceptibility to Crohn's disease and tuberculosis.

KLRC3 belongs to the NKG2 group that can be found mostly in natural killer (NK) cells and encodes a family of transmembrane proteins known for their C-type lectin domain and their type II membrane orientation (extracellular C terminus). The NKG2 gene family is situated inside the NK complex, a region which has quite a few C-type lectin genes mostly expressed on NK cells.

TOR1A which is a member of the AAA family of adenosine triphosphatases (ATPases) is associated to the Clp protease/heat shock family and is expressed highly in the substantia nigra pars compacta.TOR1A functions as a molecular chaperone assisting in the suitable folding of secreted and/or membrane proteins. Mutations in TOR1A result in the autosomal dominant disorder, torsion dystonia one.

CD74 (HLA class II histocompatibility antigen gamma chain isoform b), is a transmembrane protein (on antigen presenting cells) which is the invariant chain that chaperones MHC class IIdimers from the endoplasmic reticulum to the cell surface. CD74 is expressed by cells of both T lymphocyte and Blymphocyte lineages. CD74 upregulated in several cancers and is also expressed by non immune cells during inflammation. Diseases related with CD74 include thymic epithelial neoplasm and gastroduodenitis. Among its related super-pathways are Immune System and Immune response Antigen presentation by MHC class II. In addition CD74 functions as cell surface receptor for the cytokine MIF.

Leucine zipper down-regulated in cancer 1-like (LDOC1L) is a member of the LDOC1 family. LDOC1L is a nuclear protein containing a leucine zipper-like motif and a proline-rich region that shares noticeable similarity with an SH3-binding domain. LDOC1L localizes to the nucleus and is downregulated in certain cancer cell lines. LDOC1L is believed to regulate the transcriptional response mediated by the nuclear factor kB (NFkB).

LRPAP1 is a member of the alpha-2-MRAP family. LRPAP1 cooperates with LRP1/alpha-2-macroglobulin receptor and glycoprotein 330. LRPAP1, located on the cell surface, creates a complex with the alpha 2 macroglobulin receptor light and heavy chains and has part in the pathogenesis of membrane glomerular nephritis.

Chloride channels are various group of proteins that control fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, regulation of intracellular pH, and maintenance of cell volume. CLIC1 is part of the p64 family and is localized to the cell nucleus. CLIC1 displays both nuclear and plasma membrane chloride ion channel activity. CLIC1 inserts into membranes and forms chloride ion channels. CLIC1 channel activity depends on the pH. CLIC1 membrane insertion is redox-regulated and happens under oxydizing conditions.

Excess adiposity is the most important risk in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Adipose tissue produces several proteins (adipocytokines) such as leptin, adiponectin, resistin, tumor necrosis factor-?, and IL-6, that modulate insulin sensitivity and appear to play an important role in the pathogenesis of insulin resistance, diabetes, dyslipidemia, inflammation, and atherosclerosis. However, the mechanisms by which fat tissue induces insulin resistance and the role of adipocytokines in the pathogenesis of T2DM have not been well established. Visfatin, also known as pre-B cell colony-enhancing factor (PBEF), is a cytokine that is highly expressed in visceral fat and was originally isolated as a secreted factor that synergizes with IL-7 and stem cell factors to promote the growth of B cell precursors. Visfatin homologs have been identified in carp, invertebrate mollusks, and bacteria, as well as in vertebrates, including humans and the mouse. It has been postulated to play a role in innate immunity.
Visfatin exerts insulin-mimetic effects that are dose-dependent and quantitatively similar to those of insulin in stimulating muscle and adipocyte glucose transport, and in inhibiting hepatocyte glucose production. Intravenous injection of recombinant visfatin in mice decreased plasma glucose in a dose-dependent fashion. In keeping with its insulin-mimetic effects, visfatin was as effective as insulin in reducing hyperglycemia in insulin-deficient diabetic mice. Visfatin was also found to be bound to and activate insulin receptor, causing receptor phosphorylation and the activation of downstream signaling molecules. However, visfatin and insulin did not compete for binding to the insulin receptor, indicating that the two proteins were recognized by different regions of the receptor. Thus, visfatin might play a role in glucose homeostasis and dysregulation in biosynthesis or signal transduction, and might contribute to the pathogenesis of diabetes.

RELM-gamma is a novel member of the resistin-like molecule/found in inflammatory zone (RELM/FIZZ) family in mice and rats. Microarray and real-time RT-PCR experiments revealed a repression of RELMgamma mRNA in nasal respiratory epithelium of cigarette smoke-exposed versus untreated rats. The analysis of the physiological tissue-specific expression revealed highest expression in hematopoietic tissues, suggesting a cytokine-like role for RELM-gamma. RELM-gamma-mRNA is detectable in bone marrow, spleen, and lung as well as in peripheral blood granulocytes. Promyelocytic HL60 cells transfected with a RELM-gamma expression plasmid have an increased proliferation rate compared to mock-transfected cells and display an altered response to retinoic acid-induced granulocytic differentiation. Taken together, these data provide the first experimental evidence that RELM-gamma is a secreted molecule with a restricted expression pattern that may play a role in promyelocytic differentiation.