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Stem cell factor / KIT ligand (SCF) is a cytokine which binds CD117 (c-Kit). SCF is also known as "steel factor" or "c-kit ligand". SCF exists in two forms, cell surface bound SCF and soluble (or free) SCF. Soluble SCF is produced by the cleavage of surface bound SCF by metalloproteases.
SCF is a growth factor important for the survival, proliferation, and differentiation of hematopoietic stem cells and other hematopoietic progenitor cells. One of its roles is to change the BFU-E (burst-forming unit-erythroid) cells, which are the earliest erythrocyte precursors in the erythrocytic series, into the CFU-E (colony-forming unit-erythroid).

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.

Thymic Stromal Lymphopoietin Receptor (TSLPR) is a member of the type I cytokine receptor family. TSLPR alongside the interleukin 7 receptor (IL7R) activate STAT3, STAT5, and JAK2 pathways, which is regulated processes such as cell proliferation and development of the hematopoietic system. Two transcript variants encoding dissimilar isoforms have been found for this gene. TSLPR is expressed in heart, skeletal muscle, kidney and adult and fetal liver.

A 16-kDa peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores.

Activins are homodimers or heterodimers of the different β subunit isoforms, part of the TGFβ family. Mature Activin A has two 116 amino acids residues βA subunits (βA-βA). Activin displays an extensive variety of biological activities, including mesoderm induction, neural cell differentiation, bone remodelling, haematopoiesis, and reproductive physiology. Activins takes part in the production and regulation of hormones such as FSH, LH, GnRH and ACTH. Cells that are identified to express Activin A include fibroblasts, endothelial cells, hepatocytes, vascular smooth muscle cells, macrophages, keratinocytes, osteoclasts, bone marrow monocytes, prostatic epithelium, neurons, chondrocytes, osteoblasts, Leydig cells, Sertoli cells, and ovarian granulosa cells.

Hairy and enhancer of split 2 (HES2) belongs to the HES family and comprised of one basic helix-loop-helix (bHLH) domain and one orange domain. The HES family members form a complex with TLE, the mammalian homologue of Groucho, and this interaction is mediated by the carboxy terminal WRPW motif of the HES proteins. Activation of Notch signaling pathway initiates activation of HES family genes throughout the interaction between Notch intracellular domain and RBPSUH (CSL). HES2 is expressed in placenta, pancreatic cancer, colon cancer with RER, cervical cancer, and in head and neck tumors.

BATF is a nuclear basic leucine zipper protein which is a member of the AP-1/ATF superfamily of transcription factors. BATF is intensely expressed in mature T and B lymphocytes, and is up-regulated after transformation by human T-cell leukemia virus type I. BATF acts as a tissue-specific modulator of the AP-1 transcription complex in human cells. Furthermore, BATF connects with IFP35 which is a leucine zipper protein that translocates to the nucleus following IFN treatment.

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.

Dickkopf-related protein 3 (DKK3) belongs to the DKK protein family including Dkk-1, 2, 3 and -4. DKK3 is a 350 amino acid secreted glycoprotein which is comprised of an N-terminal signal peptide and 2 conserved cysteine-rich domains that are separated by a 12 amino acid linker region. DKK3 is involved in embryonic development through its inhibition of the WNT signaling pathway. DKK3 gene expression is decreased in a variety of cancer cell lines and it may act as a tumor suppressor gene.

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.

Though the exact role of MMACHC is unknown, its C-terminal region shows similarity to TonB, which is a bacterial protein involved in energy transduction for cobalamin (vitamin B12) uptake. Therefore, it is suggested that MMACHC may have a role in the binding and intracellular trafficking of cobalamin. MMACHC mutations are linked with methylmalonic aciduria and homocystinuria type cblC. MMACHC is widely expressed, it is expressed at higher level in the fetal liver, however it is also expressed in the spleen, lymph node, thymus and bone marrow. MMACHC is weakly or not expressed in the peripheral blood leukocytes.

Serum-and glucocorticoid-regulated kinase (SGK1) is a serine/threonine protein kinase and a member of the “AGC” subfamily, which includes protein kinases A, G, and C. The SGK1 protein has an imperative role in activating specific potassium, sodium and chloride channels, suggesting a participation in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion. SGK1 is activated in vitro by PDK-1 (3-phosphoinositide-dependent protein kinase-1) and in vivo in reaction to signals which activate phosphatidylinositol (PI) 3-kinase.

DR1 is a phosphoprotein that inhibits both basal and activated levels of transcription. DR1 is phosphorylated in vivo which affects its interaction with TBP. DR1 has a histone fold motif at the amino terminus, a TBP-binding domain, and a glutamine- and alanine-rich region. By selectively repressing polymerases II and III, DR1 alters the physiological balance of transcriptional output in favor of polymerase I.

OTOR proteins is also known as fibrocyte-derived protein (Fdp) and Melanoma inhibitory activity-like (MIAL). Otoraplin is a member of the melanoma-inhibiting activity gene family. Otoraplin is a secreted 16 kDa globular protein that is expressed in the inner ear by periotic mesenchyme and developing and mature fibrocytes. OTOR is highly homologous to MIA/cartilage-derived retinoic acid-sensitive protein (CD-RAP), which is a cartilage-specific protein that is also expressed in malignant melanoma cells. The 111 amino acid mature human otoraplin contains 1 SH3 domain (46 – 107 amino acids) and a Tyr at position 50 that is reportedly sulfated. Otoraplin takes pasrt in the initiation of periotic mesenchyme chondrogenesis.
Otoraplin is secreted through the Golgi apparatus and plays a role in cartilage development and maintenance. A frequent polymorphism in the translation start codon of OTOR can abolish translation and may be associated with forms of deafness.

SUMO1 is a protein that belongs to the SUMO (small ubiquitin-like modifier) protein family. SUMO1 functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. Still, unlike ubiquitin which targets proteins for degradation, SUMO1 is involved in a variety of cellular processes, for example nuclear transport, transcriptional regulation, apoptosis, and protein stability. SUMO1 is not active until the last four amino acids of the carboxy-terminus are cleaved off.

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.

Vascular endothelial growth factoris an important signaling proteininvolved in both vasculogenesisand 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 is linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

Transforming growth factor betas (TGFBetas) mediate many cell-cell interactions which occur during embryonic development. Three TGFBetas have been identified in mammals. TGFBeta1, TGFBeta2 and TGFBeta3 are each synthesized as precursor proteins which are very similar in that each is cleaved to yield a 112 amino acid polypeptide which remains associated with the latent portion of the molecule.

GRHPR located in the cytosol, belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family of proteins. GRHPR is widely expressed in liver. GRHPR has widespread tissue expression and is involved in metabolism. GRHPR is an enzyme with hydroxypyruvate reductase, glyoxylate reductase, and D-glycerate dehydrogenase enzymatic activities.

FSTL1 protein resembles follistatin, an activin-binding protein. FSTL1 is an autoantigen associated with rheumatoid arthritis and it holds an FS section, a follistatin-like sequence having 10 conserved cysteine residues.

Epiregulin is part of the EGF family. Epiregulin functions as a ligand of EGFR, as well as a ligand of most members of the ERBB (v-erb-b2 oncogene homolog) family of tyrosine-kinase receptors.Epiregulin is expressed mostly in the placenta and peripheral blood leukocytes and in specific carcinomas of the bladder, lung, kidney and colon. Epiregulin stimulates the proliferation of keratinocytes, hepatocytes, fibroblasts and vascular smooth muscle cells. Epiregulin inhibits the growth of several tumor-derived epithelial cell lines. Human Epiregulin is initially synthesized as a glycosylated 19.0 kDa transmembrane precursor protein, which is processed by proteolytic cleavage to produce a 6.0 kDa mature secreted sequence.

Inducible T-Cell Costimulator Ligand also known as ICOSLG, is part of the B7 family of co-stimulatory molecules related to B7-1 and B7-2. ICOSLG is a transmembrane glycoprotein with extracellular IgV and IgC domains, in addition it binds to ICOS on activated T cells. The dependent signaling of ICOSLG takes part in a proliferative response.

Chemokine (C-X-C motif) ligand 1 (CXCL1) is a small cytokine belonging to the CXC chemokine family that was previously called GRO1 oncogene, Neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MSGA-α). It is secreted by human melanoma cells, has mitogenic properties and is implicated in melanoma pathogenesis. CXCL1 is expressed by macrophages, neutrophils and epithelial cells, and has neutrophil chemoattractant activity. CXCL1 plays a role in spinal cord development by inhibiting the migration of oligodendrocyte precursors and is involved in the processes of angiogenesis, inflammation, wound healing, and tumorigenesis. This chemokine elicits its effects by signaling through the chemokine receptor CXCR2. The gene for CXCL1 is located on human chromosome 4 amongst genes for other CXC chemokines.