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Programmed cell death 1 ligand 2 (PDCD1LG2) which takes part in the costimulatory signal, is necessary for T-cell proliferation. PDCD1LG2 is also involved in IFNG production in a PDCD1-independent way. The interaction with PDCD1 inhibits T-cell proliferation by preventing cytokine production and cell cycle progression.

Inositol monophosphatase1 (IMPA1) is responsible for the provision of inositol essential for synthesis of phosphatidylinositol and polyphosphoinositides. IMPA1 has a central role in the phosphatidylinositol signaling pathway by catalyzing the hydrolysis of inositol monophosphates. IMPA1 has been recognized as the pharmacological target for lithium action in the brain. The IMPA1 enzyme has a magnesium-dependent phosphatase activity and is inhibited by therapeutic concentrations of lithium. Inhibition of inositol monophosphate hydroylosis and ensuing depletion of inositol for phosphatidylinositol synthesis may perhaps explain the anti-manic and anti-depressive effects of lithium administered to treat bipolar disorder.

FKBP3 is part of a family of immunosuppressant receptors which inhibit T-cell proliferation by arresting two distinct cytoplasmic signal transmission pathways. FKBP3 accelerates the folding of proteins. FKBP3 is part of the immunophilin protein family, which participates in immunoregulation and fundamental cellular processes concerning protein folding and trafficking. FKBP3 is a cis-trans prolyl isomerase enzyme that binds the immunosuppressants FK506 and rapamycin, as well as histone deacetylases, the transcription factor YY1, casein kinase II, and nucleolin. It has a greater affinity for rapamycin than for FK506 and therefore is a significant protein for immunosuppression by rapamycin.

GADD45G is part of the nuclear proteins to interact with various proteins whose transcript levels are raised after stressful growth arrest conditions and treatment with DNA-damaging agents. GADD45G reacts to environmental stresses by mediating activation of the p38/JNK pathway which is mediated through their protein binding and activating MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. GADD45G acts as a new-age tumor suppressor however is being frequently inactivated epigenetically in multiple tumors. GADD45G mRNA expression is down-regulated in hepatocellular carcinoma. GADD45G causes cell cycle arrest at G2/M transition when transfected into Hep-G2 cells. GADD45 Gamma induction by androgens involves new protein synthesis. Overexpression of GADD45 Gamma inhibits cell growth and causes morphological modifications in prostate cell lines thus GADD45 gamma takes part in differentiation induction by androgens.

Ubiquitin-conjugating enzyme E2 F (UBE2F) is a member of the ubiquitin-conjugating enzyme family and UBE2F subfamily. Ubiquitin-conjugating enzymes or sometimes as ubiquitin-carrier enzymes, run the second step in the ubiquitination reaction which targets a protein for degradation using the proteasome. The UBE2F receives the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins.
RBX2-UBE2F complex neddylates specific target proteins, for example CUL5 as can be seen from the specific interaction with the E3 ubiquitin ligase RBX2, but not RBX1.

Ubiquitin carboxyl-terminal hydrolase isozyme L3 belongs to a gene family whose products hydrolyze small C-terminal adducts of ubiquitin to produce the ubiquitin monomer. UCHL3 takes part in the regulation of neuronal development and spermatogenesis and is associated to neurodegenerative diseases. UCHL3 has a 54% homology to UCHL1.

PSMD9 is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. PSMD9 acts as a chaperone through the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). During the base subcomplex compilation, PSMD9 is part of an intermediate PSMD9:PSMC6:PSMC3 module, also called modulator trimer complex. PSMD9 is released during the further base assembly process.

PSMF1 is a protein which hinders the activation of the proteasome by the 11S and 19S regulators. The 26S proteasome is a multicatalytic proteinase complex with an extremely ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is comprised of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits.

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.

Mitogen-activated protein kinase 1 (MAPK1) is also known as "extracellular signal-regulated kinase 2" (ERK2). Two similar (85% sequence identity) protein kinases were originally called ERK1 and ERK2. They were found during a search for protein kinases that are rapidly phosphorylated after activation of cell surface tyrosine kinases such as the epidermal growth factor receptor. Phosphorylation of ERKs leads to the activation of their kinase activity.The molecular events linking cell surface receptors to activation of ERKs are complex. It was found that Ras GTP-binding proteins are involved in the activation of ERKs. Another protein kinase, Raf-1, was shown to phosphorylate a "MAPK kinase", thus qualifying as a "MAPK kinase kinase". The MAPK kinase was named "MAPK/ERK kinase" (MEK). Receptor-linked tyrosine kinases, Ras, Raf, MEK and MAPK could be fitted into a signaling cascade linking an extracellular signal to MAPK activation Transgenic gene knockout mice lacking MAPK1 have major defe

MDC (CCL22) is a small cytokine that belongs to the CC chemokine family. CCL22 is one of several Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 16. MDC shows chemotactic activity for natural killer cells, chronically activated T lymphocytes, monocytes and dendritic cells. On the other hand, MDC shows a mild activity for primary activated T lymphocytes and has no chemoattractant activity for neutrophils, eosinophils and resting T lymphocytes. MDC may also have a role in the trafficking of activated T lymphocytes to inflammatory sites and other aspects of activated T lymphocyte physiology. MDC interacts with cell surface chemokine receptors CCR4.
CCL22 is vastly expressed in macrophage and in monocyte-derived dendritic cells, and thymus. CCL22 is also found in the lymph node, appendix, activated monocytes, resting and activated macrophages. Lower expression of CCL22 can be seen in the lung and the spleen and very weak expression in the small intestine. In the lymph node CCL22 is expressed in a mature subset of Langerhans' cells (CD1a+ and CD83+).
Furthermore, CCL22 is expressed in atopic dermatitis, allergic contact dermatitis skin, and psoriasis, in both the epidermis and dermis. In addition, MDC has a role in hindering progression of lung cancer. Moreover, significantly higher CCL22 expression is linked to gastric cancer.

X-Prolyl Aminopeptidase-1, also known as XPNPEP1 is a member of the peptidase M24B family. XPNPEP1 encodes the cytosolic form of a metalloaminopeptidase which catalyzes the cleavage of the N-terminal amino acid adjacent to a proline residue. Furthermore, XPNPEP1 plays a role in degradation as well as maturation of tachykinins, neuropeptides and peptide hormones.

Recoverin is a member of the recoverin family of neuronal calcium sensors. Recoverin is a heterogeneously acylated calcium-binding and intracellular signal transduction 23kDa protein in the photoreceptor cells of retina. Recoverin contains four EF-hands, of which two bind Ca. Ca-induced extrusion of the acyl group from a hydrophobic cleft in the protein drives the translocation of recoverin from solution to the disc membrane. Recoverin may prolong the termination of the phototransduction cascade in the retina by blocking the phosphorylation of photo-activated rhodopsin. Recoverin plays a key role in the inhibition of rhodopsin kinase, a molecule that regulates the phosphorylation of rhodopsin. This in due course controls the ability of the eye to adapt to, and recover from, exposure to the presence of light. Recoverin is a detectable serologic protein that is expressed in patients with cancer-associated retinopathy, a paraneoplastic syndrome.

TRAIL Receptor-3, also known as TNFRSF10C belongs to theTNF-receptor super family. TNFRSF10C contains an extracellular TRAIL-binding domain as well as a transmembranedomain, however no cytoplasmic death domain. Furthermore, TNFRSF10C is not capable of inducing apoptosis, and is considered toact as an antagonistic receptor which protects cells from TRAIL-induced apoptosis.

CFLAR contains two death effector domains (DEDs) and a caspase-like domain. CFLAR may play a critical role between cell survival and cell death pathway in mammalian cells. CFLAR also interacts with adapter protein FADD and caspase-8 and -10, and potently inhibits apoptosis induced by all known death receptors DR3 (death receptor 3), TRAIL-R (TNF-related apoptosis-inducing ligand receptor) and TNFR1 (tumor necrosis factor receptor 1).

DDIT3 reduces DNA-binding activity of C/EBP and lap by forming heterodimers which don’t bind DNA. DDIT3, also known as GADD153, is a basic domain-leucine zipper(bZIP) transcription factor of C/EBP family. DDIT3 protein is up-regulated by several stresses, such as amino acid or glucose starvation, endoplasmic reticulum (ER) stress, osmotic stress and hypoxia. DDIT3 protein is invloved in ER stress-mediated apoptosis and in disease including diabetes, brain ischemia and neurodegenerative disease. DDIT3 plays a role in asoprisnil-induced apoptosis. Hypoglycaemia-induced necrotic cell death of neuroblastoma cells is an active process mediated via the induction of the transcription factor DDIT3. DDIT3 plays an important role in melanoma progression. HRG stimulation of mammary epithelial cells induces the expression of DDIT3 mRNA and protein and transcription of DDIT3 promoter.

Osteoprotegerin, which is a member of the tumor necrosis factor receptor superfamily and is involved in the regulation of bone metabolism. OPGand its ligand (OPGL) are cytokines regulating osteoclasto-genesis. OPGL binds to receptors on the surface of preosteoclasts and stimulates their differentiation into active osteoclasts. This leads to osteoresorption. OPG inhibits this osteoclasto-genesis (OPG is secreted by osteoblasts, and binds to OPGL, thus inhibiting maturation of osteoclasts and osteoresorption). The degree and activity of osteoresorption depend mainly on the balance between OPG and its ligand (OPGL); factors increasing OPGL expression mostly reduce OPG expression and vice versa.

NAP1L1 is a member of the nucleosome assembly protein (NAP) family. NAP1L1 protein plays a part in DNA replication, modulating chromatin formation and regulation of cell proliferation.

RND3 is a small GTPase which is part of the Ras superfamily that controls the association of the actin cytoskeleton in reaction to extracellular growth factors. RND3 activity causes a decrease in stress fibers and an increase in cell migration, at least in part through regulation of the Rho-dependent kinase ROCK1. RND3 inhibits DNA-damage induced apoptosis and cell cycle arrest. RND3 binds GTP and is resistant to Rho-specific GTPase-activating proteins.

sRAGE is a member of the immunoglobulin superfamily of cell surface molecules. sRAGE is a receptor for various molecules, including the amyloidogenic form of serum amyloid A, amyloid-beta protein, members of the S100/calgranulin superfamily and advanced glycation end products. sRAGE lies within the major histocompatibility complex (MHC) class III region on chromosome 6. Alternative splicing results in two transcript variants encoding different isoforms. sRAGE mediates interactions of nonenzymatic glycosylated proteins which accumulate in vascular tissue during aging & at an increasing rate in diabetes. sRAGE is a receptor for amyloid beta peptide.

PET117 is nuclear gene essential for the assembly of active cytochrome c oxidase in S. cerevisiae. Nevertheless the gene products are not subunits of the final assembled cytochrome c oxidase complex. PET117 is found in chromosome V proximate the HIS1 gene.

PKLR is a pyruvate kinase which catalyzes the transphosphorylation of phohsphoenolpyruvate into pyruvate and ATP. That is the rate-limiting step of glycolysis. PKLR gene encodes the L- and R-type isoenzymes through alternate splicing events controlled by different promoters. L-type isoform can also appear as a tetramer and is upregulated by glucose with implications in maturity-onset diabetes of the young.

Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction. TNF is mainly secreted by macrophages.
TNF causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesis and viral replication, TNF is also involved in lipid metabolism, and coagulation. TNF's primary role is in the regulation of immune cells.
Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases- autoimmune diseases, insulin resistance, and cancer.

PPM1G is part of the PP2C family of Ser/Thr protein phosphatases which are known to be negative regulators of cell stress response pathways. PPM1G is accountable for the dephosphorylation of Pre-mRNA splicing factors, an important factor for the formation of functional spliceosome. PPM1G regulates cell cycle progression.
PPM1G mediates histone dephosphorylation/exchange in response to DNA damage or checkpoint recovery in higher eukaryotes.
The degradation of p21/WAF1 induced by PPM1G is mediated in a proteasome-dependent manner.
Protein phosphatase 1G regulates assembly and function of the beta-catenin degradation complex.