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Endothelial cells express three different vascular endothelial growth factor (VEGF) receptors, belonging to the family of receptor tyrosine kinases (RTKs). They are named VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). Their expression is almost exclusively restricted to endothelial cells, but VEGFR-1 can also be found on monocytes. All VEGF-receptors have seven immunoglobulin-like extracellular domains, a single transmembrane region and an intracellular split tyrosine kinase domain. VEGFR-2 has a lower affinity for VEGF than the Flt-1 receptor, but a higher signalling activity. Mitogenic activity in endothelial cells is mainly mediated by VEGFR-2 leading to their proliferation. Differential splicing of the flt-1 gene leads to the formation of a secreted, soluble variant of VEGFR-1 (sVEGFR-1). No naturally occurring, secreted forms of VEGFR-2 have so far been reported. The binding of VEGF165 to VEGFR-2 is dependent on heparin.

Dickkopf-related protein 2 (DKK2) is a member of the dickkopf family, which has a vital role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In adults, Dkks are involved in bone formation and bone disease, cancer and Alzheimer disease. DKK2 contains 2 cysteine rich regions and is implicated in embryonic development through its interactions with the Wnt signaling pathway. DKK2 may function as either an agonist or antagonist of Wnt/beta-catenin signaling, depending on the cellular environment and the presence of the co-factor kremen 2. DKK2 protein activity is also controlled by binding to the Wnt co-receptor LRP6 (LDL-receptor related protein 6).

Protein Phosphatase 1, Regulatory Subunit 8 (PPP1R8) is the RNA-binding subunit of a key species of protein phosphatase-1 in the nucleus. The PPP1R8 enzyme is an inhibitor subunit of the main nuclear protein phosphatase-1 (PP-1). PPP1R8 has RNA-binding activity however it doesn’t cleave RNA and may target PP-1 to RNA-associated substrates. Two isoforms of the PPP1R8 protein are specific inhibitors of type 1 serine/threonine protein phosphatases which can bind but not cleave RNA. The third isoform of the PPP1R8 protein is deficient in of the phosphatase inhibitory activity nonetheless it is a single-strand endoribonuclease comparable to RNase E of E. coli.

Alpha-parvin (PARVA) belongs to the parvin family of actin-binding proteins. PARVA has a role in the regulation of cell adhesion, cytoskeleton organization, motility and survival as well as in ciliogenesis. Parvins are related with focal contacts and contain calponin homology domains which connect to actin filaments. PARVA is extensively expressed, with the highest levels in heart, skeletal muscle, kidney and liver.

KISS1 is a metastasis suppressor protein that suppresses metastases of melanomas and breast carcinomas without affecting tumorigenicity.KISS1 functions to inhibit chemotaxis and invasion, attenuating metastasis in malignant melanomas. KISS1 is involved in the regulation of cell-matrix adhesion. KISS1 plays a role in cytoskeletal reorganization. A polymorphism in the terminal exon of KISS1 mRNA results in two protein isoforms. Expression of KiSS1 is localized to specific regions of the hypothalamus in numerous species and is regulated by gonadal steroids and across the estrous cycle..KISS1 generates a c-terminally amidated peptide, metastin which functions as the endogenous ligand of the g-protein coupled receptor gpr54. Activation of the receptor inhibits cell proliferation and cell migration, key characteristics of tumor metastasis.

NF-kappa-B inhibitor-interacting Ras-like protein 1 (NKIRAS1) is a member of the small GTPase superfamily. NKIRAS1 is an unusual Ras-like protein which acts as a potent regulator of NF-kappa-B activity by thwarting the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, describing why NFKBIB is more resistant to degradation. NKIRAS1 functions by blocking phosphorylation of NFKBIB and mediating cytoplasmic retention of p65/RELA NF-kappa-B subunit. Both GTP- and GDP-bound forms block phosphorylation of NFKBIB.

NDK (Nucleoside diphosphate kinase) exists as a hexamer composed of 'A' (encoded by NME1) and 'B' (encoded by NME2) isoforms. NME1 is involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. It also has tumor metastasis-suppressive capacity. NME1 has a key role in the synthesis of nucleoside triphosphates other than ATP. NME1 is essential for neural development including neural patterning and cell future determination.
The NME1 gene is expressed in various tumor types where its levels have been alternatively linked to reduced or increased metastatic potential.
Decrease in NME1 expression is notably connected to aggressive behavior in melanoma, breast, colon, and gastric carcinomas. In contrast, elevated levels of NME1 gene expression are noted in the advanced stage of thyroid carcinomas.
Somatic mutations of the NME1 gene are found in neuroblastoma. Increased NME1 in neuroblastoma is linked to features of the disease that are associated with aggressive tumors.

GCK is an enzyme that expedite the formation of glucose-6-phosphate for glucose by phosphorylation. Humans and other vertebrates have GCK in the cells of the pancreas and liver. In both organs, the enzyme has an important role in carbohydrate metabolism regulation by sensing sugar levels and acting according to the change in glucose levels, that can rise after a meal or fall during fasting. Mutations in the gene that codes for this enzyme can cause hypoglycemia or diabetes.

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Protein tyrosine phosphatase mitochondrial 1 (PTPMT1) is a broadly expressed PTP membrane protein with high expression levels in pancreatic beta cells. The PTPMT1 protein is completely restricted to the matrix face of the inner membrane of the mitochondrion. PTPMT1 is responsible for dephosphorylating mitochondrial proteins and thus has a major role in the production of ATP. PTPMT1 exhibits a specific preference for the lipid signaling molecule phosphatidylinositol 5-phosphate as substrate.

C9orf103 is a member of the gluconokinase gntK/gntV family. C9orf103 takes part in carbohydrate acid metabolism and D-gluconate degradation.

Tachykinin-3 belongs to the substance P-related tachykinin family. Tachykinins are active peptides that stimulate neurons, induce behavioral responses, are effective vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles. TAC3 and its receptor are essential switches of regulator of human puberty, regulated by the brain through the release of the GnRH which starts a chain of processes which eventually lead to the production of sex hormones.
During pregnancy, the expression of TAC3 is restricted to the outer syncytiotrophoblast of the placenta, significant concentrations of TAC3 can be identified in plasma as early as week 9, and plasma concentrations of TAC3 are grossly elevated in pregnancy-induced hypertension and pre-eclampsia. Higher Tachykinin-3 concentrations in normotensive pregnant women may be caused by the advanced gestational age and/or the result of a negative interaction of other vasoactive substances. TAC3 has a role in the continuance of high placental blood flow in normal pregnancy.

Midkine (MK) is the product of a retinoic acid responsive gene. It contains 121 amino acid residues including 10 conserved cysteine residues, all of which appear to be disulphide linked.
Midkine is expressed during embryogenesis, showing an expression pattern that suggests functions in neurogenesis, cell migration, secondary organogenetic induction, and mesoderm-epithelial interaction.
The widespread downregulation of MK in the adult human is reverted in a number of cancers, in which polypeptides are able to act as both transforming growth factors and promoters of angiogenesis.
Midkine (MK), induces chemotaxis of human neutrophils and was found to trigger mobilization of intracellular calcium of these cells.
Midkine induces histamine release from rat peritoneal mast cells with a rapid response in a dose dependent manner.
Midkine is also a potent stimulator of collagen and glycosaminoglycan synthesis.

Hexokinases phosphorylate glucose to produce glucose-6-phosphate, thus committing glucose to the glycolytic pathway. Alternative splicing of Glucokinase results in three tissue-specific forms of glucokinase, one found in pancreatic islet beta cells and two found in liver. The protein localizes to the outer membrane of mitochondria. In contrast to other forms of hexokinase, HK4 is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. Mutations in this gene have been associated with non-insulin dependent diabetes mellitus (NIDDM), maturity onset diabetes of the young, type 2 (MODY2) and persistent hyperinsulinemic hypoglycemia of infancy (PHHI).

Chitinase is a digestive enzyme which breaks down glycosidic bonds in chitin. Due to chitin being a component of the cell walls of fungi and exoskeletal elements of some animals (including worms and arthropods), chitinases are usually found in organisms that either need to remake their own chitin or to dissolve and digest the chitin of fungi or animals. Chitinivorous organisms include many bacteria genuses such as Aeromonas, Bacillus, Vibrio, among others, which may be pathogenic or detritivorous. Chitinase expression is mediated by the NPR1 gene and the salicylic acid pathway, both of which are involved in resisting fungal and insect attack. Human chitinases appear in gastric juices. They are likely to be digestive chitinases, for catabolic activity. Chitinase activity is identified systemically in humans, in the blood, and possibly cartilage. Chitinase has been related to allergies, asthma in particular has been linked to enhanced chitinase expression levels, also dust mites and mold spores which are both chitin covered.

CUB Domain Containing Protein 1, also known as CDCP1 is a transmembrane protein which contains three extracellular CUB domains. CDCP1 is implicated in cell adhesion and cell matrix association. In addition, CDCP1 takes part in the regulation of anchorage versus migration or proliferation versus differentiation through its phosphorylation. CDCP1 is also a novel marker for leukemia diagnosis as well as for immature hematopoietic stem cell subsets. Furthermore, the extracellular region of human CDCP1 shares amino acid identity sequence with the mouse CDCP1.

EPHA2 is a member of the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors are implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into two groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. The EPHA2 gene encodes a protein that binds ephrin-A ligands. Mutations in the EPHA2 gene are the origin of certain genetically-related cataract disorders.

PPP1R14A is a phosphorylation-dependent inhibitor of smooth muscle myosin phosphatase. Inhibition of PPP1R14A results to increased myosin phosphorylation and enhances smooth muscle contraction in the absence of increased intracellular Ca(2+) concentration. Myosin phosphatase can reverse MYL (myosin light chain) phosphorylation to induce a state of relaxation. However, during agonist-induced contraction at constant Ca2+ concurrent inhibition of myosin phosphatase leads to increases in MYL phosphorylation and tension. These calcium-independent increases in myosin phosphorylation and tension are termed calcium sensitization.
Human pregnancy is characterized by the increases of PKN1 expression and CPI-17 phosphorylation in the myometrium. PPP1R14A is mapped to chromosome 19q13.13-q13.2.
PPP1R14A binds directly to protein kinase C and casein kinase I.
PPP1R14A siRNA decreased the level of merlin phosphorylation and consequently Ras and ERK activity in human tumor cell lines.
PKC/CPI-17 mediated pathway in histamine, triggeres cytoskeletal rearrangements causing lung microvascular barrier compromise.

PPP1CA is one of the 3 catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase which is involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity is detected in the end stage of heart failure. Studies in both human and mice suggest that PP1 is a significant regulator of cardiac function. Mouse studies also propose that PP1 functions as a suppressor of learning and memory.

Midkine (MK) is the product of a retinoic acid responsive gene, MK, and is a member of a family of heparin binding factors. It contains 121 amino acid residues including 10 conserved cysteine residues, all of which appear to be disulphide linked.
Midkine is expressed during embryogenesis, showing an expression pattern that suggests functions in neurogenesis, cell migration, secondary organogenetic induction, and mesoderm-epithelial interaction.
The widespread downregulation of MK in the adult human is reverted in a number of cancers, in which polypeptides are able to act as both transforming growth factors and promoters of angiogenesis.
Midkine (MK), induces chemotaxis of human neutrophils and was found to trigger mobilization of intracellular calcium of these cells.
Midkine induces histamine release from rat peritoneal mast cells with a rapid response in a dose dependent manner.
Midkine is also a potent stimulator of collagen and glycosaminoglycan synthesis.

Protein Tyrosine Phosphatase Receptor Type N (PTPRN) is a catalytically inactive protein and a major target of autoimmune response in diabetes mellitus. The long C-terminal intracellular tail covers the majority of autoantibody epitopes. PTPRN is expressed in neural, neuroendocrine and pancreatic islet cells.

Serine/Threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA) is crucial for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. The PPP1CA protein may have a significant role in dephosphorylating substrates such as the postsynaptic density-associated Ca2+/calmodulin dependent protein kinase II.

BRK1 is a member of the BRK1 family. BRK1 takes part in regulating actin and microtubule organization and is a fragment of a WAVE complex which activates the Arp2/3 complex.

NFKB inhibitor interacting Ras-like 2 (NKIRAS2) is an inhibitor of the transcription factor NF-kappaB. NKIRAS2 is similar to the Ras-like small GTPases which associate with IkappaB. The Ras-like proteins- NKIRAS1 and NKIRAS2, interact with the PEST domains of I?B? and I?B? and reduce their rate of degradation. NKIRAS2 is an atypical Ras-like protein which functions as a potent regulator of NF-kappa-B activity by preventing the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, explaining why NFKBIB is more impervious to degradation.