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Extracellular signal-regulated kinases (ERKs) or classical MAP kinases are widely expressed protein kinaseintracellular signalingmolecules which are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells. Many different stimuli, including growth factors, cytokines, virusinfection, ligands for heterotrimeric G protein-coupled receptors, transforming agents, and carcinogens, activate the ERK pathway.
The term, "extracellular signal-regulated kinases", is sometimes used as a synonym for mitogen-activated protein kinase(MAPK), but has more recently been adopted for a specific subset of the mammalianMAPK family. In the MAPK/ERK pathway, Rasactivates c-Raf, followed by MEKand then MAPK1/2 (below). Ras is typically activated by growth hormones through receptor tyrosine kinasesand GRB2/SOS, but may also receive other signals. ERKs are known to activate many transcription factors and some downstream protein kinases. Disruption of the ERK pathway is common in cancers, especially Ras, c-Raf and receptors such as HER2.
Mitogen-activated protein kinase 3 (MAPK3) is also known as "extracellular signal-regulated kinase 1" (ERK1). Transgenic gene knockoutmice lacking MAPK3 are viable and it is thought that MAPK1 can fulfill most MAPK3 functions in most cells. The main exception is in T cells. Mice lacking MAPK3 have reduced T cell development past the CD4+CD8+ stage.

TIE1 is an angiopoitein receptor which takes part in hematopoiesis,angiogenesis and vasculogenesis.TIE1 is expressed primarily on endothelial and hematopoietic progenitor cells. TIE1 is expressed in immature hematopoietic Recombinant Human TIE1 protein cells and platelets. TIE1 upregulates the cell adhesion molecules(CAMs) VCAM-1,ICAM-1 and E-selectinthrough a p38-dependent mechanism. TIE1 has a proinflammatory effect and takes part in the endothelial inflammatory diseases such as atherosclerosis.

Akt1, also known as Akt or else protein kinase B (PKB) is an important molecule in mammaliancellular signaling. In humans, there are three genes in the "Akt family": Akt1, Akt2, and Akt3. Moreover, these enzymes are members of the serine/threonine-specific protein kinase family (EC2.7.11.1). Akt1 is involved in cellular survival pathways, by inhibiting apoptoticprocesses. Akt1 is also able to induce protein synthesis pathways, and is therefore a key signaling protein in the cellular pathways which lead to skeletal muscle hypertrophy, and general tissue growth. Since it can block apoptosis, and thereby promote cell survival, Akt1 has been implicated as a most important factor in numerous types of cancer. Akt (now also called Akt1) was at first identified as the oncogenein the transforming retrovirus, AKT8.

Gankyrin (proteasome 26S subunit) is a multicatalytic proteinase oncoprotein commonly overexpressed in most hepatocellular carcinomas. Proteasomes are found throughout eukaryotic cells at a high concentrations and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. Gankyrin interacts with S6 ATPase of the 19S regulatory particle of the 26S proteasome. Gankyrin is involved in theregulation of the phosphorylation of the retinoblastoma protein by CDK4, and to enhance the ubiquitinylation of p53 by MDM2. Gankyrin consists of 7 ankyrin repeats and is structurally similar to I kappa Bs. Gankyrin acts as a regulatory subunit of the 26s proteasome which is involved in the atp-dependent degradation of ubiquitinated proteins. Gankyrin is involved in progression of esophageal squamous cell carcinoma. gankyrin plays an oncogenic role especially in early stages of human epatocarcinogenesis. Gankyrin binds to NF-kappaB and suppresses its activity at the transcription level by modulating acetylation through SIRT1. Structural comparison between Gankyrin & p16(INK4A) identified numerous residues of gankyrin that are potentially important for CDK4 binding.

AKR1C4 is a member of the aldo/keto reductase superfamily that has over 40 known enzymes and proteins. AKR1C4 enables the conversion of aldehydes and ketones to their corresponding alcohols by using NADH and/or NADPH as cofactors. AKR1C4 takes part in the bioreduction of chlordecone, a toxic organochlorine pesticide, to chlordecone alcohol in liver.

AK3L1 is an affiliate of the adenylate kinase family of enzymes. AK3L1 enzyme is restricted to the mitochondrial matrix. Adenylate kinases-3 regulates the adenine and guanine nucleotide compositions within a cell by means of catalyzing the reversible transfer of phosphate group among these nucleotides. 5 different isozymes of adenylate kinase have been identified in vertebrates. The enzyme expression of various adenylate kinase isozymes is growth regulated and tissue-specific.

Phosphoglycerate mutase 2 (PGAM2) is a member of the phosphoglycerate mutase family. PGAM is a dimeric enzyme which contains in separate tissues, different proportions of a slow-migrating muscle (MM) isozyme, a fast-migrating brain (BB) isozyme, and a hybrid form (MB). PGAM (Phosphoglycerate mutase) catalyzes the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. PGAM2 gene mutations cause muscle phosphoglycerate mutase efficiency, otherwise known as glycogen storage disease X.

Aldo-Keto Reductase Family 7 Member A3 or AKR7A3, is an enzyme, it is part of the detoxification of aldehydes and ketones process. AKR7A3 diminishes the dialdehyde protein-binding form of aflatoxin B1 to the non-binding AFB1 dialcohol. The enzyme takes partin protection of liver from toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen.

Calcium/Calmodulin Dependent Protein Kinase II Inhibitor 1 (CAMK2N1), which interacts with CAMK2B, is a part of the CAMK2N family. CAMK2N1 is also interacts with CAMK2A in a way which requires CAMK2A activation by Ca2+. CAMK2N1 is potent and specific inhibitor of CaM-kinase II (CAMK2).

Glutathione synthetase (GSS) is the second enzyme in the glutathione biosynthesis pathway. GSS catalyses the condensation of gamma-glutamylcysteine and glycine to form glutathione. Defects in the GSS are the cause of glutathione synthetase deficiency aka GSS deficiency or 5-oxoprolinuria or pyroglutamic aciduria, which is a severe form characterized by an increased rate of hemolysis and defective function of the central nervous system.

CDKN1A holds a key part in the cellular response to DNA mutation. CDKN1A overexpression causes cell cycle to stop. When collaborating with CDK2 complexes, CDKN1A aids to prevent kinase activity and inhibits progression through G1/S. Nevertheless, CDKN1A can additionally increase assembly and activity in complexes of CDK4 or CDK6 and cyclin D. CDKN1A is a vital intermediary by which p53/TP53 facilitates its part as an inhibitor of cellular proliferation as a reaction to DNA impairment.

GARS is an (alpha)2 dimer which is a member of the class II family of tRNA synthetases. GARS is a glycyl-tRNA synthetase, one of the aminoacyl-tRNA synthetases which charge tRNAs with their cognate amino acids. GARS catalyzes the attachment of glycine to tRNA(Gly). In addition, GARS is able to produce diadenosine tetraphosphate (Ap4A), which is a universal pleiotropic signaling molecule required for cell regulation pathways, by direct condensation of two ATPs. GARS has been demonstrated to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis.

VRK3 is a member of the protein kinase superfamily. The VRK3 gene has replacements at a number of residues within the ATP binding motifs which in other kinases were proved to be required for catalysis in both human and mouse. In vitro assays show that VRK3 has no phosphorylation activity but probably holds its substrate binding capability. VRK3 is universally expressed in human tissues and its protein is restricts to the nucleus.

CDKN2C is a member of the CDKN2 cyclin-dependent kinase inhibitor family. CDKN2C cooperates with CDK4 or CDK6, and inhibits the activation of the CDK kinases, therefore acts as a cell growth regulator which regulates cell cycle G1 progression. CDKN2C suppresses the cell growth and proliferation with a correlated dependency on endogenous retinoblastoma protein RB. Studies in the knockout mice show CDKN2C takes part in regulating spermatogenesis, in addition to suppressing tumorigenesis.

KIT, also known as KIT Proto-Oncogene Receptor Tyrosine, is a cytokine receptor which is expressed not only in hematopoietic stem cells but likewise in other cell types. KIT binds to receptor tyrosine kinase type III, which is a stem cell factor, also named a "rigid factor" or "c-kit ligand". Once this receptor binds to stem cell factor (SCF), it forms a dimer which activates intrinsic tyrosine kinase activity, which sequentially phosphorylates & activates signaling molecules which breed signals in cells. This receptor protects vascular smooth muscle cells from apoptosis in addition to restoring cardiac function after myocardial infarction.

The 14-3-3 family of proteins plays a key regulatory role in signal transduction, checkpoint control, apoptotic and nutrient-sensing pathways. 14-3-3 proteins are highly conserved and ubiquitously expressed. There are at least seven isoforms that have been identified in mammals. The 14-3-3gamma, a subtype of the 14-3-3 family of proteins, was thought to be brain and neuron-specific. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways.

AKR1C1 transfers progesterone to its inactive state or in other words catalyzes the reaction of 20-alpha-hydroxy progesterone (20-alpha-OHP). In the liver and intestine. AKR1C1 transfers bile and monitors the intrahepatic bile acid concentration though it has a low bile-binding ability. AKR1C1 participates in myelin formation. AKR1C1 is part of the aldo/keto reductase superfamily, which has over 40 known enzymes which catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors thus display overlapping but distinct substrate specificity.

MOB3B is similar to yeast Mob1 protein which binds Mps1p, a protein kinase vital for spindle pole body duplication and mitotic checkpoint regulation. MOB3B is situated on the opposite strand as the INF kappa precursor (IFNK) gene.

Kallikreins are a subgroup of serine proteases having various physiological functions. Numerous kallikreins are involved in carcinogenesis. Kallikrein-11 (KLK11) which is a multifunctional protease is 1 of the 15 kallikrein subfamily members found in a cluster on chromosome 19. KLK11 cleaves synthetic peptides after arginine but not lysine residues.

Fucosyltransferase 7 (FUT7) is a golgi stack membrane protein which is involved in the creation of sialyl-Lewis X antigens. The FUT7 protein leads the synthesis of the E-selectin-binding sialyl-Lewis X moiety. FUT7 catalyzes alpha-1,3 glycosidic linkages involved in the expression of sialyl Lewis X antigens.

Kallikrein-3 (KLK3) is a part of the kallikrein-related peptidase family. Kallikreins are a subgroup of serine proteases having various physiological functions. Numerous kallikreins take part in carcinogenesis and some may be prospective cancer and other disease biomarkers. Kallikrein-3 is 1 of the 15 kallikrein subfamily members located in a cluster on chromosome 19 and is a protease present in seminal plasma. KLK3 hydrolyzes semenogelin-1 consequently leading to the liquefaction of the seminal coagulum. KLK3 acts normally in the liquefaction of seminal coagulum, probably by hydrolysis of the high molecular mass seminal vesicle protein. Serum level of the KLK3 protein, called PSA in the clinical setting, is beneficial in the diagnosis and monitoring of prostatic carcinoma.

GPI or Glucose-6-phosphate isomerase, is a protein, part of the multifunctional phosphoglucose isomerase family, which its members take part in energy pathways. GPI is a dimeric enzyme that enhances the isomerization of glucose-6-phosphate and fructose-6- phosphate (both reversible). In mammals, GPI acts as an angiogenic factor & tumor-secreted cytokine. The enzyme also acts as a neurotrophic factor for spinal & sensory neurons.

Proto-oncogene tyrosine-protein kinase MER is a protein, this enzyme is coded from the MERTK gene. This gene is a part of the TYRO3/AXL/MER receptor kinase group and encodes a transmembrane protein with two fibronectin type-III domains, two Ig-like C2-type (immunoglobulin-like) sites, and one tyrosine kinase site. Mutations in this gene have been correlated with interruption of the retinal pigment epithelium phagocytosis process and commencement of autosomal recessive retinitis pigmentosa.

Uroporphyrinogen III synthase (UROS) is an enzyme involved in the 4th step of porphyrin metabolism and in the conversion of hydroxymethyl bilane into uroporphyrinogen III. Defects in the UROS protein can cause molecular lesions which lead to the autosomal recessive Gunther disease, otherwise known as congenital erythropoietic porphyria (CEP).