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Periostin is a disulfide linked 90 kDa, 811 amino acid protein originally isolated as a osteoblast-specific factor that functions as a cell adhesion molecule for preosteoblasts and is thought to be involved in osteoblast recruitment, attachment and spreading. Additionally, periostin expression has previously been shown to be significantly increased by both transforming growth factor beta-1(TGFbeta1) and bone morphogenetic protein (BMP-2). OSF-2 has a typical signal sequence, followed by a cysteine-rich domain, a fourfold repeated domain and a C-terminal domain. The fourfold repeated domain of OSF-2 shows homology with the insect protein fasciclin
Periostin mRNA is expressed in the developing mouse embryonic and fetal heart, and that it is localized to the endocardial cushions that ultimately divide the primitive heart tube into a four-chambered heart.

MCSFR which is also familiar as CSF1R, is part of the type3 subfamily of receptor tyrosine kinases. MCSFR is expressed mainly on cells of the monocyte and macrophage lineage, stem cells, and in the growing placenta. Most of the biological effects of this cytokine are mediated by MCSFR. MCSFR contains an extracellular ligand-binding domain, a single membrane-spanning segment, and an intracellular tyrosine kinase domain. Originally CSF1 and this receptor were implicated as vital for normal trophoblastic implantation as well as monocyte development. The role of CSF1/CSF1R in normal mammary gland development is actually very interesting since this connection has also been discovered in the biology of breast cancer with the results of abnormal expression of CSF1 and its receptor. Likewise, in Alzheimer's disease and after brain injuries an increased level of CSF1R was found in the microglia, which causes the microglia to become more active.

Platelet Derived Growth Factor-CC (PDGF-CC) belongs to the PGDF family of growth factors. PDGF-CC binds with high-affinity to PDGF R-a and activates PDGF R-ab heterodimers. During development, PDGF-CC is involved in ductal morphogenesis, cardiovascular smooth muscle cell proliferation; also PDGF-CC is an angiogenic factor. Furthermore, PDGF-CC is expressed in numerous tumors and tumor cell lines, and may be linked with tumorigenesis.

Epidermal growth factor receptor or EGFR or Erb-1 is a membranal protein that acts as a receptor for the extracellular EGF proteins family. This protein is a part of a family of receptors called ErbB family which are all tyrosine kinases receptors. Mutations in the gene of this receptors can cause cancer.

The Fas receptor (CD95) mediates apoptotic signaling by Fas-ligand expressed on the surface of other cells. The Fas-FasL interaction plays an important role in the immune system and lack of this system leads to autoimmunity, indicating that Fas-mediated apoptosis removes self-reactive lymphocytes. Fas signaling is also involved in immune surveillance to remove transformed cells and virus infected cells. Binding of FAS to oligimerized FasL on another cell activates apoptotic signaling through a cytoplasmic domain termed the death domain that interacts with signaling adaptors including FAF, FADD and DAX to activate the caspase proteolytic cascade. Caspase-8 and caspase-10 are first activated, to then cleave and activate downstream caspases, and a variety of cellular substrates that lead to cell death. Caspases cleave nuclear lamins, causing the nucleus to break down and lose its normal structure and another caspase substrate is DFF, inducing cleavage and degradation of the genome. Other caspase substrates are involved in cytoskeletal structure, cell cycle regulation and signaling pathways. Activation of JNK kinase, activation of Jun, and production of ceramide may also play roles in Fas-mediated apoptosis. Activation of fas-mediated apoptosis is opposed by I-FLICE and FAP. Viruses and tumors may escape immune surveillance in part through suppression of fas-mediated apoptosis using similar mechanisms.

TNFRSF13B (TACI) is a transmembrane receptor protein found predominantly on the surface of B cells (a significant part of the immune system). TACI was at first discovered owing to its ability to interact with calcium-modulator and cyclophilin ligand (CAML). Later on, it was found that TACI plays a key role in humoral immunity by interacting with two members of the TNF family. Also, TACI controls T cell-independent B cell antibody responses, isotype switching, and B cell homeostasis.

EIF4E is part of the eukaryotic initiation factor 4 families, controls translation of maternal mRNAs in early embryos before the onset of zygotic transcription. EIF4E identifies and binds to the 7 methyl GTP cap structure of eukaryotic mRNAs, thus modulates the initiation of translation. EIF4E enables ribosome binding by inducing the unwinding of the mRNAs secondary structures.

C1QTNF7 is a collagen type-IV specific for basement membranes.

Granulocyte/Macrophage Colony-Stimulating Factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. MCSF induces cells of the monocyte/macrophage lineage. MCSF plays a role in immunological defenses, bone metabolism, lipoproteins clearance, fertility and pregnancy.

Stratifin is part of the 14-3-3 family. The 14-3-3 family of proteins plays an important regulatory function in signal transduction, checkpoint control, apoptotic and nutrient-sensing pathways. 14-3-3 proteins are highly conserved and ubiquitously expressed. There are 7 isoforms, beta, gamma, epsilon, sigma, zeta, tau and eta that have been identified in mammals. Stratifin is an epithelial cell marker that functions as a tumor suppressor whose expression can be down regulated via methylation. Failure of Stratifin expression results in a defective G2/M phase checkpoint and results in epithelial and non-epithelial tumorigenesis.

Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets and binds with high affinity to heparin. Its major physiologic role appears to be neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin III activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair. Oncostatin-A is a member of the CXC chemokine family. Human PF4 is used for the proof of heparin-induced thrombocytopenia. Furthermore it is used as an inhibitor in the angiogenesis during tumor therapy.

TNFRSF4, also known as TNF Receptor Superfamily Member 4, is a T cell co-stimulatory molecule which belongs to the TNF receptor superfamily. TNFRSF4 coordinates with other co-stimulatory substances such as CD28, CD40, CD30, CD27 and 4-1BB to control the activation of the immune response. TNFRSF4 takes a vital part in antigen-specific T cell expansion as well as survival. TNFRSF4 is up-regulated on CD4+ and CD8+ T cells upon engagement of the TCR by antigen presenting cells along with co-stimulation by CD40-CD40 Ligand and CD28-B7. In addition, TNFRSF4 regulates cytokine production from T cells, antigen presenting cells, natural killer cells and natural killer cells. TNFRSF4 regulates cytokine receptor signaling.

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.

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.

Thrombopoietin is a glycoprotein hormone produced mainly by the liver and the kidney that regulates the production of platelets by the bone marrow. It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that fragment into large numbers of platelets.

Glial cell-derived neurotrophic factor or GDNF is part of the GDNF group of ligands proteins. GDNF has a crucial part in numerous cell mechanisms such as neurite outgrowth, cell differentiation, cell survival and migration of cells. GDNF enhances neurons survival via GFRa receptors (mainly GFRa1). The mentioned neurons can die as a result from Parkinson's disease or ALS (amyotrophic lateral sclerosis). This protein takes part in the development of the spermatogenesis & kidney, also, it has a role in alcohol metabolism as ameliorating.

TNFR1 belongs to the TNF-receptor superfamily. TNFR1 is a receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha.
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. TNF-a, TNFR1 and TNFR2 have roles in cellular differentiation. TNFR1 and TNFR2 function in cell type-specific renal injury.
TNFR1 is capable of signaling both cell survival and apoptosis. TNFR1-induced apoptosis requires 2 sequential signaling complexes. TNFR1 is capable of activating NF-kappaB, mediate apoptosis, and function as a regulator of inflammation. Oxidative stress promotes TNFR1 and TNFR2 self-interaction, ligand-independent and enhanced ligand-dependent TNF signaling. TNFR1 contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase. Human TNFR1 has a major region which controls cell surface expression. High levels of soluble TNF receptors are found in the amniotic fluid of pregnant women.
Germline mutations of the extracellular domains of TNFR1 are linked to the autosomal dominant periodic fever syndrome. The impaired receptor clearance is believed to be a mechanism of the disease. Familial hibernian fever (FHF) is caused by defects in TNFRSF1A gene.

POU2AF1 is a lymphocyte specific transcription coactivator protein. POU2AF1 cooperates only with the Oct1/2 proteins using sub domains in the POU domain of the Oct1/2 proteins, increasing their transcriptional efficiency. Even though POU2AF1 have no basic ability to bind DNA, it links firmly with the octomer motif in the presence of Oct1 and Oct2. POU2AF1 is expressed at maximum levels in spleen and peripheral blood leukocytes.

Growth/differentiation factors (GDF1-GDF15) belong to the BMP family of TGF-beta superfamily proteins. These factors are produced as inactive preproproteins which are subsequently cleaved and assembled into active secreted homodimers. BMP13 is a growth factor which controls proliferation and cellular differentiation in the retina and bone formation. BMP13 has a central role in regulating apoptosis during retinal development. GDF proteins are vital during embryonic development, particularly in the skeletal, nervous, and muscular systems. BMP13 gene mutations result in colobomata, which are congenital abnormalities in ocular development, and in Klippel-Feil syndrome (KFS), which is a congenital disorder of spinal segmentation.

Leptin is a protein hormone. It is mainly produced in adipose cells that regulate energy homeostasis by restraining hunger. Leptin ties to nuclear receptors in the hypothalamus (arcuate nucleus). Similar to insulin resistance in type II diabetes, in obesity there is a decrease in the sensitivity towards leptin, ending in a failure to identify satiety, even in high levels of energy stores or leptin itself. Full-length cDNA encoding 2 leptin sequences (tLepA and tLepB) and 1 leptin receptor sequence (tLepR) exists in tilapia (Oreochromis niloticus). The full-length cDNA of tLepR is 3423 bp, encoding a protein of 1140 amino acid which contained all functionally important domains conserved among vertebrate leptin receptors. The cDNAs of tLepA and tLepB are 486 bp and 459 bp in length, encoding proteins of 161 aa and 152 aa, respectively. The three-dimensional structures of tLepA and tLepB demonstrates strong conservation of tertiary structure with that of human leptin comprised of 4 helixes.

PEX19 is vital for peroxisome biogenesis in Saccharomyces cerevisiae. PEX19 is limited to the outer surface of peroxisomes in liver cells and is has a part in the early stage of peroxisome membrane assembly, prior to the import of matrix protein.

Leukemia Inhibitory Factor also called LIF is a lymphoid factor that promotes long-term maintenance of embryonic stem cells by suppressing spontaneous differentiation. Leukemia Inhibitory Factor has several functions such as cholinergic neuron differentiation, control of stem cell pluripotency, bone & fat metabolism, mitogenesis of factor dependent cell lines & promotion of megakaryocyte production in vivo. Human and mouse LIF exhibit a 78% identity in its amino acid sequence.

The somatomedins, or insulin-like growth factors (IGFs), comprise a family of peptides that takes part in mammalian growth and development. IGF1 mediates various growth-promoting effects of growth hormone (GH; MIM 139250). 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' (Daughaday et al., 1972). 3 main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2; MIM 147470), and somatomedin B (MIM 193190) (Rotwein, 1986; Rosenfeld, 2003).