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ULBP1 together with at least ULBP2 and ULBP3, is ligand for the NKG2D receptor. ULBPs stimulate various signaling pathways in primary NK cells, which result in cytokines and chemokines production. In CMV infected cells, ULBP1 cooperates with soluble CMV glycoprotein UL16 to inhibit the interaction with the NKG2D receptor providing a mechanism by which CMV infected cells escape the immune system. Additionally, UL16 retains ULBP1 to the ER and cis-Golgi apparatus to prevent it from reaching cell surface.

MSRB2 is a member of the methionine sulfoxide reductases(MSRs) family which are antioxidant repair enzymes. MSRB2 protein catalyzes the decrease of free and protein-bound methionine sulfoxide to methionine. MSRB2 has a part in protecting against oxidative stress in numerous organs.

The IGFs comprise a family of peptides that play important roles in mammalian growth and development. IGF1 mediates many of the growth-promoting effects of growth hormone. Early studies showed that growth hormone did not directly stimulate the incorporation of sulfate into cartilage, but rather acted through a serum factor, termed 'sulfation factor,' which later became known as 'somatomedin'. Three main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A, and somatomedin B. IGF-1 is a small protein secreted mostly but not exclusively by the liver and circulating in blood mostly as a complex with several IGF binding proteins. It has growth-regulating, insulin-like, and mitogenic functions and it is secreted in response to growth hormone stimulation.

TFPI2 takes part in the regulation of plasmin-mediated matrix remodeling. Inhibits trypsin, plasmin, factor VIIa/tissue factor and weakly factor Xa. TFPI2 doesn’t have any influence on thrombin.

GDF8 is a member of the bone morphogenetic protein (BMP) family and the TGF-beta superfamily. This group of proteins is characterized by a polybasic proteolytic processing site which is cleaved to produce a mature protein containing seven conserved cysteine residues. The members of this family are regulators of cell growth and differentiation in both embryonic and adult tissues. This gene is thought to encode a secreted protein which negatively regulates skeletal muscle growth.

Osteostat is the cytokine that binds to TNFRSF18/AITR/GITR and is important for interactions between activated T-lymphocytes and endothelial cells and may modulate T-lymphocyte survival in peripheral tissues. Osteostat is expressed at high levels in the small intestine, ovary, testis, kidney and endothelial cells after stimulation by lipopolysaccharides.
Osteostat protein is detectable in human microvascular EC and is highly up-regulated by IFN-alpha and IFN-beta. Osteostat inhibit differentiation of osteoclasts from monocytic precursor cells. Osteostat suppresses the early stage of osteoclastogenesis via inhibition of macrophage colony-stimulating factorinduced receptor activator of NF-kappaB (RANK) expression in the osteoclast precursor cells. Osteostat does not inhibit lipopolysaccharide-induced RANK expression in monocytes and dendritic cells, or activation-induced RANK expression in T cells. Osteostat is a novel regulator of osteoclast generation and substantiate the major role played by the endothelium in bone physiology.

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.

TGFB1-induced anti-apoptotic factor 1 (TIAF1) hinders the cytotoxic effects of TNF-alpha and overexpressed TNF receptor adapters TRADD, FADD, and RIPK1. The TIAF1 protein is involved in TGF-beta1 inhibition of IkappaB-alpha expression and suppression of TNF-mediated IkappaB-alpha degradation. TIAF1 is not detected in normal kidney and liver. TIAF1 is up-regulated in chronic and acute allograft rejection: expressed in the inflammatory infiltrate and in tubular epithelial cells.

Cleavage And Polyadenylation Specific Factor 4 (CPSF4) is a member of the CPSF4/YTH1 family. CPSF4 complex plays a vital role in pre-mRNA 3'-end formation, distinguishing the AAUAAA signal sequence and interacting with poly(A) polymerase and further factors to bring about cleavage and poly(A) additive. CPSF4 binds RNA polymers with a preference for poly(U).

Neurotrophic Receptor Tyrosine Kinase 3 (NTRK3)belongs to the receptor tyrosine kinases family and is a high affinity catalytic receptor of neurotrophin NT-3. NTRK3 mediates multiple effects of this neurotrophic factor, which includes neuronal differentiation and survival. NTRK3 inducesvarious pleiotorpic responses in malignant cells, including enhanced tumor cell invasiveness and chemotoxis.Increased NTRK3 expression was observed in neuroblastoma, medulloblastoma, and in neuroectodermal brain tumors.

Fibroblast Growth Factors (FGFs) comprise a family of at least eighteen structurally realted proteins that are involved in a multitude of physiological and pathological cellular processes, including cell growth, differentation, angiogenesis, wound healing and tumorgenesis. The biological activities of the FGFs are mediated by a family if type I transmembrane tyrosine kinases which undergo dimerization and autophosphorylation after ligand binding. Four distinct genes encoding closely related FGF receptors, FGFR-1to -4 are known. Multiple forms of FGFR-1 to -3 are generated by alternative splicing of the mRNAs. A frequent splicing event involving FGFR-1 and -2 results in receptors containing all three Ig domains, referred to as the alpha isoform, or only IgII and IgIII, referred to as the ? isoform. Only the alpha isoform has been identified for FGFR-3 and FGFR-4. Additional splicing events for FGFR-1 to -3, involving the C-terminal half of the IgIII domain encoded by two mutually exclusive alternative exons, generate FGF receptors with alternative IgIII domains (IIIb and IIIc). A IIIa isoform which is a secreted FGF binding protein containing only the N-terminal half of the IgIII domain plus some intron sequences has also been reported for FGFR-1. Mutations in FGFR-1 to -3 have been found in patients with birth defects involving craniosynostosis.

Cardiotrophin-like cytokine factor 1 (CLCF1) is a member of the interleukin 6 family of cytokines, which are involved in cell signaling via phosphorylation of gp130. CLCF1 has a sequence of 225 amino acids with a 27 aa signal peptide, having a molecular mass of 22kDa in the mature form, and the maximum homology to cardiotrophin-1 and ciliary neurotrophic factor. CLCF1 is actively secreted from cells by forming a complex with soluble type I CRLF1 or soluble CNTFR. Defects in the CLCF1 gene cause cold-induced sweating syndrome 2 (CISS2). The CISS2 syndrome is typified by profuse sweating after exposure to cold as well as congenital physical abnormalities of the head and spine.

Small Nuclear RNA Activating Complex, Polypeptide 1 (SNAPC1) is a part of the SNAPc complex necessary for the transcription of both RNA polymerase II and III small-nuclear RNA genes. SNAPC1 binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Moreover, SNAPC1 recruits TBP and BRF2 to the U6 snRNA TATA box.

Transforming growth factor betas (TGFBetas) mediate many cell-cell interactions that occur during embryonic development. Three TGFBetas have been identified in mammals. TGFBeta1, TGFBeta2 and TGFBeta3 are each synthesized as precursor proteins that are very similar in that each is cleaved to yield a 112 amino acid polypeptide that remains associated with the latent portion of the molecule. This antibody reacts with the precursor and mature form of TGFBeta2 and to a lesser extent TGFBeta3, but does not cross react with TGFBeta1.

FARSB, also known as Phenylalanyl-TRNA Synthetase Beta is a member of the phenylalanyl-tRNA synthetase beta subunit family. FARSB is composed tetramer of two alpha and two beta subunits. In the presence of ATP, this tetramer is accountable for attaching L-phenylalanine to the terminal adenosine of the appropriate tRNA.

GDF10 is a member of the BMP family and the TGF-beta superfamily. GDF10 is expressed in femur, brain, lung, skeletal, muscle, pancreas and testis, and has a role in head formation and possibly multiple roles in skeletal morphogenesis. In humans, GDF10 mRNA is found in the cochlea and lung of fetuses, and in testis, retina, pineal gland, and other neural tissues of adults. The BMP family members are regulators of cell growth and differentiation in both embryonic and adult tissues. These proteins are characterized by a polybasic proteolytic processing site which is cleaved to produce a mature protein containing 7 conserved cysteine residues.

SDF-1 (stromal cell-derived factor-1) is small cytokine belonging to the chemokine family that is officially designated Chemokine (C-X-C motif) ligand 12 (CXCL12). It is produced in two forms, SDF-1?/CXCL12a and SDF-1?/CXCL12b, by alternate splicing of the same gene. Chemokines are characterized by the presence of four conserved cysteines, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening amino acid. CXCL12 is strongly chemotactic for lymphocytes and has been implicated as an important cell co-ordinator during development. During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow. Mice which were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life. As another role, CXCL12a alters also the electrophysiology of neurons. CXCL12 was shown to be expressend in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).
The receptor for this chemokine is CXCR4, which was previously called fusin. This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 is also bound by CXCR7 receptor.
The gene for CXCL12 is located on human chromosome 10. In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.

Leukemia Inhibitory Factor Receptor Alpha or LIFR is a protein, part of the Interleukin-6 receptor group of proteins. As such, LIFR acts as a mediator for various proteins (IL-6, IL-11, IL-27, Oncostatin M etc). LIFR has many functions as a cytokine, he has an affect on the cell proliferation, differentiation and survival in the different stages of life. In different types of breast cancer LIFR is down regulated, and as such, can be used as a prognostic tool.

GDNF promotes the survival and differentiation of neurons in culture, and is able to prevent apoptosis of motor neurons induced by axotomy. The encoded protein is processed to a mature secreted form that exists as a homodimer. The mature form of the protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. In addition to the transcript encoding GDNF, two additional alternative transcripts encoding distinct proteins, referred to as astrocyte-derived trophic factors, have also been described. Mutations in this gene may be associated with Hirschsprung disease.
GDNF enhances survival and morphological differentiation of neurons and increases their high-affinity uptake.

FGF12 is part of the Fibroblast Growth Factor (FGF) family which has a vast mitogenic and cell survival functions, and play a role in a range of biological activities, among them are embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. FGF-12 doesn’t obtain the N-terminal signal sequence present in the majority of the FGF family members, but it contains clusters of basic residues that act as a nuclear localization signal. When transfected into mammalian cells, FGF12 accumulated in the nucleus, but was not secreted. FGF12 is involved in nervous system development and function. FGF12 binds to IB2 (islet brain-2), a cellular kinase scaffold, and voltage gated sodium channels and is also involved in intracellular signalling and ion exchange.

The cytokine Macrophage migration inhibitory factor (MIF) has been identified to be secreted by the pituitary gland and the monocyte/macrophage and to play an important role in endotoxic shock. MIF has the unique property of being released from macrophages and T cells in response to physiological concentrations of glucocorticoids. The secretion of MIF is tightly regulated and decreases at high, anti-inflammatory steroid concentration.

FGF8 is part of the fibroblast growth factor family. FGF family members have wide mitogenic and cell survival activities, and participate in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF8 supports androgen and anchorage independent growth of mammary tumor cells. FGF8 over expression increases tumor growth and angiogensis. The adult expression of FGF-8 gene is restricted to testes and ovaries. FGF8 functions as an embryonic epithelial factor. FGF8 takes part in midbrain and limb development, organogenesis, embryo gastrulation and left-right axis determination.

IGFBP6 plays a role in lipoprotein assembly and dietary cholesterol absorption. in addition to its acyltransferase activity, it may act as a ligase. may provide cholesteryl esters for lipoprotein secretion from hepatocytes and intestinal mucosa.