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GMFG is a hematopoietic-specific protein that mediates the pluripotentiality and lineage commitment of human hematopoietic stem cells. Glia maturation factor gamma is a cytokine-responsive protein in EPO-induced and G-CSF-induced hematopoietic lineage development. Glia maturation factor also acts as a Nerve Growth Factor in nervous system development, angiogenesis and immune function. GMFG possesses hematopoietic tissue-specific gene expression, a promoter concentrated with high-score hematopoiesis-specific transcription factors, and molecular coevolution with a rudimentary blood/immune system.

RELTis expressed in hematopoietic tissues and peripheral blood leukocytesand is a part of thetumor necrosis factor receptor superfamily. RELT mediates activation of NF-kappa-B and takes part in T-cell activation.overexpression of RELT in HEK-293 cells induces p38 and JNK signalling and leads to apoptosis. it can also costimulate T-cell proliferation in the presence of CD3 signalling.

ADP-ribosylation factor 3 (ARF3) belongs to the human ARF gene family. This family encodes small guanine nucleotide-binding proteins which stimulate the ADP-ribosyltransferase activity of cholera toxin and have a role in vesicular trafficking and as activators of phospholipase D. ARF3 functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. ARF3 is involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus. The ARF3 gene is comprised of 5 exons and 4 introns.

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 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.

POU5F1 is a homeodomain transcription factor of the POU family, expressed in embryonic stem (ES) cells and embryonic carcinoma (EC) cells.POU5F1 is significantly involved in the signaling pathway for maintaining self-renewal and pluripotency of ES cells. POU5F1 has 2 distinct DNA binding domains which independently bind half-sites of the canonical octamer motif. This flexibility allows POU5F1 to bind with distinct DNA motifs by forming heterodimers with other transcription factors or by forming homodimers in several conformations. Human POU5F1 contains a 75aa POU specific (POUS) domain and a 60aa POU-Homeo-(POUH) domain connected by a linker region. The Human POU5F1 specifically interacts with Octamer motif ATGCAAAT. In addition, 2 proline-rich domains in the N-terminal and C-terminal regions are vital for POU5F1 transactivation. POU5F1 regulates a number of target genes and has been shown to work jointly with other transcription factors including Sox2 as well as Nanog to sustain stem cell potency and self-renewal.

Tripartite Motif Containing 28 (TRIM28) which is a member of the tripartite motif family includes 3 zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. TRIM28 mediates transcriptional control by interaction with the Kruppel-associated box repression domain found in many transcription factors. TRIM28 is restricted to the nucleus and connected with particular chromatin regions.

Acetyl-COA Acyltransferase 2, (ACAA2) is a member of the thiolase family. ACAA2 catalyzes the final step of the mitochondrial fatty acid beta-oxidation spiral. Not like most mitochondrial matrix proteins, ACAA2 contains a non-cleavable amino-terminal targeting signal.

Succinate Dehydrogenase Complex Assembly Factor 2 (SDHAF2) is a mitochondrial protein required for the flavination of a succinate dehydrogenase complex subunit essential for activity of the complex. DHAF2 is necessary for insertion of FAD cofactor into SDHA, the catalytic subunit of succinate dehydrogenase (SDH). SDH is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). SDHAF2 gene defects are the cause of hereditary paragangliomas type 2 (PGL2), otherwise known as familial non-chromaffin paragangliomas type 2.

Meteorin (METRN) is involved in both glial cell differentiation and axonal network formation during neurogenesis. METRN promotes astrocyte differentiation and transforms cerebellar astrocytes into radial glia. Moreover, the METRN protein stimulates axonal extension in small and intermediate neurons of sensory ganglia by activating nearby satellite glia.

Binds to tnfrsf13b/taci and tnfrsf17/bcma. tnfsf13/april binds to the same 2 receptors, together, they form a 2 ligands -2 receptors pathway involved in the stimulation of b- and t-cell function and the regulation of humoral immunity. A third b-cell specific baff-receptor (baffr/br3) promotes the survival of mature b-cells and the b-cell response. B Lymphocyte Stimulator functions as a potent B-cell growth factor in costimulation assays. Administration of BAFF Human recombinant to mice disrupts splenic B-cell and T-cell zones and results in elevated levels of serum immunoglobulin.

ARF4 belongs to the ARF gene family whose members encode small guanine nucleotide-binding proteins which stimulate the ADP-ribosyltransferase activity of cholera toxin and have a role in vesicular trafficking and as activators of phospholipase D. The ARF proteins include five ARF proteins and eleven ARF-like proteins and constitute one family of the RAS superfamily. They are classified as class I, class II and class III; the ARF4 gene is a class II member. The members of each class share a common gene organization. The ARF4 gene spans approximately 12kb and contains 6 exons and 5 introns. The ARF4 gene is the most divergent member of the human ARFs.

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.

WW Domain Containing Transcription Regulator 1 (WWTR1) is a transcriptional coactivator that plays a role as a downstream regulatory target in the Hippo signaling pathway which participates in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. WWTR1 regulates the nuclear accumulation of SMADS and has a main part in coupling them to the transcriptional machinery like the mediator complex. WWTR1 is also regulates embryonic stem-cell self-renewal.

Interleukin-1 alpha is a proinflammatory cytokine produced by a wide variety of cell types, including macrophages, osteoblasts, monocytes and hepatocytes. Circulating levels of are normally low and only rise after stimulation by agents such as those produced byinflammation, infection or microbial endotoxins. IL-1 alpha possesses a wide variety of biological activities and exerts its effects by binding to specific cell surface receptors.

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.

Y Box Binding Protein 1 (YBX1) is a part of the CRD-mediated complex which promotes MYC mRNA stability. YBX1 takes part in mammalian selenoprotein translation and mediates pre-mRNA alternative splicing regulation. YBX1 uses as a drug target in cancer therapy due to its ability to replicate adenovirus type 5, a commonly used vector in gene therapy.

HDAC2 is a member of the histone deacetylase family that performs through the construction of large multiprotein complexes and are in charge of the deacetylation of lysine residues on the N-terminal region of the core histones. HDAC2 forms transcriptional repressor complexes by relating to a diversity of proteins, like YY1- a mammalian zinc-finger transcription factor.
In addition, HDAC2 has a vital part in transcriptional regulation, cell cycle progression and developmental procedures.

Connective Tissue Growth Factor belongs to the CCN family of proteins. The CCN family presently consists of six members in human also known as: Cyr61 (Cystein rich 61), CTGF (Connective Tissue Growth Factor), Nov (Nephroblastoma Overexpressed gene), WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins). The CCN genes encode secreted proteins associated with the Extracellular Matrix (ECM) and cell membrane.
CCN proteins are matricellular proteins which are involved in the regulation of various cellular functions including: proliferation, differentiation, survival, adhesion and migration. They are expressed in derivatives of the three embryonic sheets and are implicated in the development of kidney, nervous system, muscle, bone marrow, cartilage and bone. During adulthood, they are implicated in wound healing, bone fracture repair, and pathologies such as: fibrosis, vascular ailments and tumorigenesis.
Full length secreted CCN proteins can show an antiproliferative activity, whereas truncated isoforms are likely to stimulate proliferation and behave as oncogenes.
The full length protein consists of four modulesModule I shares partial identity with the N-terminal part of the Insulin-like Growth Factor Binding Proteins (IGFBPs).
Module II includes a stretch of 70amino acid residues – which shares sequence identity with the Von Willebrand Factor Type C repeat (VWC).
Module III contains sequences sharing identity with the Thrombospondin type 1 repeat (TSP1) (WSXCSXXCG), which is thought to be implicated in the binding of sulfated glycoconjugates and to be important for cell adhesion.
Module IV, also designated CT, is encoded by exon5. It is the leasts conserved one of the four domains at the level of nucleotide sequence, but it appears to be critical for several of the biological functions attributed to the CCN proteins. Module IV resembles the CT domain of several extracellular protein including, Von Willebrand's factor and mucins. Sequence similarities to heparin-binding motifs are also found within this domain.
Proteolysis of the secreted full-length CCN proteins that has been reported in the case of CCN2 and CCN3 might result in the production of CCN-derived peptides with high affinity for ligands that full-length CNN proteins bind only poorly. Amino-truncated CCN2 isoforms were biologically active whereas no specific biological activity has been attributed to the truncated CCN3. Although the molecular processes underlying the production of these secreted isoforms is presently unknown, it is important to note that proteolysis occur at the same amino acid residues in both CCN2 and CCN3. An elevated expression of CCN2 has also been detected by Northern blotting in human invasive mammary ductal carcinomas, dermatofibromas, pyogenic granuloma, endothelial cells of angiolipomas and angioleiomyomas, and in pancreatic tumors. A study performed with chondrosarcomas representative of various histological grades established that CCN2 expression was closely correlated with increasing levels of malignancy.
In agreement with CCN2 playing a role in brain tumor angiogenesis, immunocytochemistry studies indicated that both glioblastoma tumor cells and proliferating endothelial cells stained positive for CCN2. In astrocytomas, CCN2 expression was particularly elevated in high grade tumors, with a marked effect of CCN2 on cell proliferation. Downregulation of CCN2 expression in these cells was associated with a growth arrest at the G1/S transition while over-expression of CCN2 induced a two-fold increase of the number of cells in the G1 phase. Gene profiling analysis allowed to identify a set of about 50 genes whose expression might account for the proliferative activity of CCN2 in these cells.
CCN2 was seen in a higher proportion of mononuclear cells of patients with acute lymphoblastic leukemia.

ACADS is a tetrameric mitochondrial flavoprotein, which is part of the acyl-CoA dehydrogenase family. ACADS catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. Mutations in ACADS have been associated with Short Chain Acyl-CoA Dehydrogenase Deficiency.

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.

RAET1E is a member of the MHC class I family. MHC class I family contains main histocompatibility complex (MHC) class I-related genes positioned in a cluster on chromosome 6q24.2-q25.3. RAET1E and RAET1G protein are different from other RAET1 proteins since they have type I membrane-spanning sequences at their C termini instead glycosylphosphatidylinositol anchor sequences.RAET1E acts as a ligand for NKG2D receptor, expressed on the surface of numerous types of immune cells, involves in innate adaptive immune reactions.RAET1E delivers signals to NK cells and advances tumor immune surveillance by inducing the growth of anti-tumor cytotoxic lymphocyte.

Ornithine Aminotransferase is a mitochondrial enzyme which is an important factor that converts arginine and ornithine into the major excitatory and inhibitory neurotransmitters glutamate and GABA. Ornithine Aminotransferase mutations result in a deficiency that cause the autosomal recessive eye disease Gyrate Atrophy.