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Tumor necrosis factor receptor superfamily member 8 (TNFRSF8) is a receptor for TNFSF8/CD30L. TNFRSF8 has a role in the regulation of cellular growth and transformation of activated lymphoblasts. In addition, the TNFRSF8 protein regulates gene expression via activation of NF-kappa-B. TNFRSF8 being a regulator of apoptosis, induces cell death or proliferation, depending on the cell type.

GMCSF is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. The active form of the protein is found extracellularly as a homodimer. This gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. Other genes in the cluster include those encoding interleukins 4, 5, and 13.
GM-CSF stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.

GDF3 is a member of the TGF-beta superfamily though it does not show similarity pattern of conserved cysteine residues. GDF3 is linked to Vg-1 and human BMP-4. GDF3 transcripts are identified mainly in adult bone marrow, spleen, thymus, and adipose tissue. GDF3 expression is upregulated strongly in high-fat-fed C57Bl/6J FABP4/aP2 null mice, which develop obesity but not the related hyperglycemia or hyperinsulinemia characteristic of type II diabetes. GDF3 expression therefore bonds fatty acid metabolism in adipocytes and the expression of a differentiation regulator belonging to the bone morphogenetic proteins.

Non-homologous end-joining factor 1 (NHEJ1) is a member of the XLF family. NHEJ1 is a DNA repair factor vital for the nonhomologous end-joining pathway, which preferentially mediates repair of double-stranded breaks. NHEJ1 gene mutations cause different kinds of severe combined immunodeficiency disorders. NHEJ1 was initially detected as the protein mutated in five patients with growth retardation, microcephaly, and immunodeficiency. In addition, patients with NHEJ1 mutations have immunodeficiency caused by a defect in V(D)J recombination, which employs NHEJ to promote immune system diversity.

Human TNFRSF10A is a type 1 transmembrane protein in the TNF R superfamily. TNFRSF10A is not expressed in rodents. The trimeric ligand Trail binds TNFRSF10A and induces apoptosis, and recombinant, soluble forms of the receptor inhibit Trail-induced apoptosis. TNFRSF10A is expressed generally in damaged, infected, and malignant cells. TNFRSF10A functions in immune surveillance, inducing apoptosis in cancer cells but not normal cells.

TNFR2 belongs to the TNF-receptor superfamily. TNFR2 is receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. TNFR2 mediates the majority of the metabolic effects of TNF-alpha. In addition, knockout studies in mice propose a role for TNFR2 in protecting neurons from apoptosis by stimulating antioxidative pathways. TNFR2 expression might have a significant role in the angiogenesis, tumor cell proliferation and metastasis of Invasive micropapillary carcinoma of the breast.
There are 2 types of soluble TNF receptors: sTNFR-I and sTNFR-II, which act to neutralize the biological activities of TNF alpha and TNF beta. The levels of these soluble receptors seem to increase as a result of shedding of the extracellular domains of the membrane bound receptors. High levels of soluble TNF receptors are found in the amniotic fluid of pregnant women. TNFR2 and TNFR1 form a heterocomplex which mediates the recruitment of 2 anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. IAPs’ function in TNF-receptor signaling is unknown; nevertheless, c-IAP1 is believed to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. Oxidative stress promotes TNFR1 and TNFR2 self-interaction, ligand-independent and enhanced ligand-dependent TNF signaling. TNF-a, TNFR1 and TNFR2 have roles in cellular differentiation. TNFR1 and TNFR2 function in cell type-specific renal injury.

ASF1A is part of the H3/H4 family of histone chaperone proteins corresponding to the anti-silencing function-1 gene in yeast. ASF1A is an important element of the histone donor complex that functions in nucleosome assembly. ASF1A interacts with histones H3 and H4, and functions together with a chromatin assembly factor during DNA replication and repair. Deletion of ASF1A in yeast and Drosophila confers sensitivity to various DNA damaging agents and inhibitors of DNA replication, increases genomic instability and sister chromatid exchange, and activates the DNA damage checkpoint.

GDF-11 belongs to the bone morphogenetic protein (BMP) family and the TGF-beta superfamily. GDF-11 is a central developmental factor which controls muscular and neural development. In adults, GDF-11 encourages cardiac hypertrophy reverse by the revival of cardiomyocytes.

CNTF is a polypeptide hormone whose actions appear to be restricted to the nervous system where it promotes neurotransmitter synthesis and neurite outgrowth in certain neuronal populations. The protein is a potent survival factor for neurons and oligodendrocytes and may be relevant in reducing tissue destruction during inflammatory attacks. A mutation in this gene, which results in aberrant splicing, leads to ciliary neurotrophic factor deficiency, but this phenotype is not causally related to neurologic disease. In addition to the predominant monocistronic transcript originating from this locus, the gene is also co-transcribed with the upstream ZFP91 gene. Co-transcription from the two loci results in a transcript that contains a complete coding region for the zinc finger protein but lacks a complete coding region for ciliary neurotrophic factor.
CNTF is a survival factor for various neuronal cell types. Seems to prevent the degeneration of motor axons after axotomy.

TNFRSF14, a member of the TNF receptor superfamily, is a type I transmembrane protein. TNFRSF14 is expressed in peripheral blood T cells, B cells, monocytes and in various tissues enriched in lymphoid cells. TNFRSF14 operates as a co-stimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. Additionally, TNFRSF14 encourages the proliferation of T cells, and triggers apoptosis of various tumor cells.

Vascular endothelial growth factor is an important signaling protein involved in both vasculogenesis and angiogenesis. As its name implies, VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/ macrophagemigration, neurons, cancer cells, kidney epithelial cells ).VEGF mediates increased vascular permeability, induces angiogenesis, vasculogenesis and endothelial cell growth, promotes cell migration, and inhibits apoptosis. In vitro, VEGF has been shown to stimulate endothelial cell mitogenesisand cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor.
Elevated levels of this protein are linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

TNFR binds specifically to tumor necrosis factor (TNF) and blocks its interaction with cell surface TNF receptors. TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. It plays an important role in the inflammatory processes of rheumatoid arthritis (RA), polyarticular-course juvenile rheumatoid arthritis (JRA), and ankylosing spondylitis and the resulting joint pathology. In addition, TNF plays a role in the inflammatory process of plaque psoriasis. Elevated levels of TNF are found in involved tissues and fluids of patients with RA, psoriatic arthritis, ankylosing spondylitis (AS), and plaque psoriasis. Two distinct receptors for TNF (TNFRs), a 55 kilodalton protein (p55) and a 75 kilodalton protein (p75), exist naturally as monomeric molecules on cell surfaces and in soluble forms. Biological activity of TNF is dependent upon binding to either cell surface TNFR. Recombinant Human TNFR is a dimeric soluble form of the p75 TNF receptor that can bind to two TNF molecules.
It inhibits the activity of TNF in vitro and has been shown to affect several animal models of inflammation, including murine collagen-induced arthritis. TNFR inhibits binding of both TNF? and TNF? (lymphotoxin alpha [LT?]) to cell surface TNFRs, rendering TNF biologically inactive. Cells expressing transmembrane TNF that bind to TNFR are not lysed in vitro in the presence or absence of complement.
TNFR can also modulate biological responses that are induced or regulated by TNF, including expression of adhesion molecules responsible for leukocyte migration (i.e., E-selectin and to a lesser extent intercellular adhesion molecule-1 [ICAM-1]), serum levels of cytokines (e.g., IL-6), and serum levels of matrix metalloproteinase-3 (MMP-3 or stromelysin).

Myeloid-derived growth factor (Mydgf) is a paracrine-acting protein and a bone marrow-derived monocyte which stimulates cardiac myocyte survival and adaptive angiogenesis for cardiac protection and repair after myocardial infarction. Mydgf induces endothelial cell proliferation through a MAPK1/3-, STAT3- and CCND1-mediated signaling lane. When comparing wild-type mice to mice with a Mydgf-deficiency, the later develop larger infarct scars and more acute contractile dysfunction.

NFATC2, also known as nuclear factor of activated T-cells 2, belongs to the nuclear factor of activated T cells family. NFATC2 takes a significant part in the course of T helper cell differentiation, activation, and effector function. Even though KO of an individual NFAT isoform in T cells directs to rather minor effects, T cells lacking for NFATC1 and 2 totally fail to produce T helper cell effector cytokines, for instance the interleukins IL-4 and IL-2. Moreover, NFATC2 is highly phosphorylated and kept in the cytoplasm. Next T cell receptor stimulation, dephosphorylation via calcium-activated calcineurin induces a conformational modification of NFATC2 which reveals a few nuclear localization sequences.

Acidic fibroblast growth factor is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Three alternatively spliced variants encoding different isoforms have been described. The heparin-binding growth factors are angiogenic agents in vivo and are potent mitogens for a variety of cell types in vitro. There are differences in the tissue distribution and concentration of these 2 growth factors.

Epidermal growth factor has a profound effect on the differentiation of specific cells in vivo and is a potent mitogenic factor for a variety of cultured cells of both ectodermal and mesodermal origin. The EGF precursor is believed to exist as a membrane-bound molecule which is proteolytically cleaved to generate the 53-amino acid peptide hormone that stimulates cells to divide.
EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture.

The hematopoietic growth factor GM-CSF or granulocyte macrophage colony-stimulating factor, stimulates the development of neutrophils & macrophages, enhance proliferation and development of early erythroid megakaryocytic & eosinophilic progenitor cells. GM-CSF is secreted from the fibroblasts, monocytes, T-lymphocytes & endothelial cells. This protein blocks the migration of neutrophils & induces the biological activity of mature end-cells.

Fibroblast growth factor 18 (FGF18) is a member of the large FGF family which has at least 23 members. FGF18 is a heparin binding growth factor with a core 120 amino acid FGF domain which allows for a common tertiary structure. FGFs are expressed in the course of the embryonic development and in restricted adult tissues. FGF-18 is an indispensable regulator of long bone and calvarial development. FGF-18 signals via FGFR 1c, 2c, 3c, and 4.

CEBPB is an intronless gene and its protein is a bZIP transcription factor which can bind as a homodimer to certain DNA regulatory regions. CEBPB can also form heterodimers with the related proteins CEBP-alpha, CEBP-delta, and CEBP-gamma. CEBPB is important in the regulation of genes involved in immune and inflammatory responses and has been shown to bind to the IL-1 response element in the IL-6 gene, as well as to regulatory regions of several acute-phase and cytokine genes. In addition, CEBPB can bind the promoter and upstream element and stimulate the expression of the collagen type I gene.

Alpha-2-antiplasmin (SERPINF2) is a serine protease inhibitor. The main targets of SERPINF2 are plasmin and trypsin; however SERPINF2 also inactivates matriptase-3/TMPRSS7 and chymotrypsin.

Neuromedin B (NMB) which is a part of the bombesin/neuromedin-B/ranatensin family and stimulates smooth muscle contraction in a way similar to that of bombesin.

Nogginwhich is 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 play and important role in creating morphogenic gradients. Noggin appears to have pleiotropic effect, both early in development as well as in later stages. Noggin 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. There are several dominant human NOG mutations in unrelated families with proximal symphalangism (SYM1) and multiple synostoses syndrome (SYNS1). 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.

RANKL binds to tnfrsf11b/opg and to tnfrsf11a/rank. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive t-cell proliferation. May be an important regulator of interactions between t-cells and dendritic cells and may play a role in the regulation of the t-cell-dependent immune response. sRANKL may also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.

Developmentally-regulated GTP-binding protein 1 (DRG1) is a member of the GTP1/OBG family. DRG1 has a role in cell proliferation and differentiation, as well as in apoptosis, proposing a role in tumor formation and metastasis. Expression of the DRG1 was considerably reduced in breast tumor cells, particularly in patients with lymph node or bone metastasis as compared to those with localized breast cancer. The DRG1 protein is expressed at high levels in the heart, kidney and skeletal muscle and at lower levels in the brain, liver, placenta, lung, colon and spleen.