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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.

EFNB1 is a member of the Eph family. The cell-surface proteins Ephrins split into two groups, ephrin-A and ephrin-B, based on their structure and function and perform as ligands for Eph receptors. The transmembrane EFNB1 proteins have conserved cytoplasmic tyrosine residues that are phosphorylated upon interaction with an EphB receptor. In addition, EFNB1 transduces outside-in signals by C-terminal protein interfaces which influence integrin-mediated cell attachment and migration.

Insulin-like growth factor-binding protein 4 (IGFBP-4) belongs to the insulin-like growth factor binding protein (IGFBP) family. IGFBP4 includes an IGFBP domain and a thyroglobulin type-I domain. IGFBP4 binds both insulin-like growth factors (IGFs) I and II. IGFBP-4 circulates in the plasma in both glycosylated and non-glycosylated forms. IGFBPs can either inhibit or enhance the biological activities of IGF, or act in an IGF independent manner. IGFBP-4 is exceptional since it consistently inhibits several cancer cells in vivo and in vitro, suggesting that it may function as an apoptotic factor. IGFBP4 is produced by all colon cancer cells. Binding of IGFBP-4 prolongs the half-life of the IGFs and changes their interaction with cell surface receptors.

S100A11 is a member of the S100 family of proteins which contains two EF-hand calcium-binding motifs and is thought to be involved in the regulation of a number of cellular processes including cell cycle progression and differentiation. S100A11 may function in motility, invasion and tubulin polymerisation. S100 proteins are localized either in the cytoplasm or the nucleus of a wide range of cells. There are at least 13 members in the S100 gene family, which are located as a cluster on chromosome 1q21. Chromosomal rearrangements and altered expression of S100A11 have been implicated in tumor metastasis.

Adiponectin is a recently discovered 244 amino acid protein, the product of the apM1 gene, which is physiologically active and specifically and highly expressed in adipose cells (Adipokine). The protein belongs to the soluble defense collagen super family; it has a collagen-like domain structurally homologous with collagen VIII and X and complement factor C1q-like globular domain. APM-1 forms homotrimers, which are the building blocks for higher order complexes found circulating in serum.

HEPACAM2 is necessary during prometaphase for centrosome maturation. Following poly-ADP-ribosylation (PARsylation) by TNKS, HEPACAM2 translocates from the Golgi apparatus to mitotic centrosomes and takes a significant part in the formation of robust microtubules for quick movement of chromosomes.

Akt1, also known as Akt or else protein kinase B (PKB) is an important molecule in mammaliancellular signaling. In humans, there are three genes in the "Akt family": Akt1, Akt2, and Akt3. Moreover, these enzymes are members of the serine/threonine-specific protein kinase family (EC2.7.11.1). Akt1 is involved in cellular survival pathways, by inhibiting apoptoticprocesses. Akt1 is also able to induce protein synthesis pathways, and is therefore a key signaling protein in the cellular pathways which lead to skeletal muscle hypertrophy, and general tissue growth. Since it can block apoptosis, and thereby promote cell survival, Akt1 has been implicated as a most important factor in numerous types of cancer. Akt (now also called Akt1) was at first identified as the oncogenein the transforming retrovirus, AKT8.

Kallistatin (SERPINA4) inhibits human amidolytic and kininogenase activities of tissue kallikrein. This inhibition is attained by formation of an equimolar, heat- and SDS-stable complex between the inhibitor and the enzyme, and production of a small C-terminal fragment of the inhibitor as a result of cleavage at the reactive site by tissue kallikrein.

SRGN is identified as a hematopoietic cell granule proteoglycan. Proteoglycans stored in the secretory granules of various hematopoietic cells also hold a protease-resistant peptide core, and is vital for neutralizing hydrolytic enzymes. SRGN is related to the macromolecular complex of granzymes and perforin that acts as a intermediary of granule-mediated apoptosis.

ULBP2 is a member of the MHC class I family. ULBP2 is ligand for the NKG2D receptor, composed with at least ULBP1 and ULBP3. ULBPs promote multiple signaling pathways in primary NK cells, triggering the production of cytokines and chemokines. Binding of ULBPs ligands to NKG2D encourages calcium mobilization and activation of the JAK2, STAT5, ERK and PI3K kinase/Akt signal transduction pathway. In CMV infected cells, ULBP2 cooperates with soluble CMV glycoprotein UL16. This cooperation is blocked with the NKG2D receptor, providing a mechanism in which CMV infected cells can escape the immune system. Additionally, UL16 causes ULBP2 to be held in the ER and cis-Golgi apparatus so that it does not reach the cell surface.

Endothelial cells express three different vascular endothelial growth factor (VEGF) receptors, belonging to the family of receptor tyrosine kinases (RTKs). They are named VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), VEGFR-3 (Flt-4). Their expression is almost exclusively restricted to endothelial cells, but VEGFR-1 can also be found on monocytes. All VEGF-receptors have seven immunoglobulin-like extracellular domains, a single transmembrane region and an intracellular split tyrosine kinase domain. VEGFR-2 has a lower affinity for VEGF than the Flt-1 receptor, but a higher signaling activity. Mitogenic activity in endothelial cells is mainly mediated by VEGFR-2 leading to their proliferation.
Differential splicing of the flt-1 gene leads to the formation of a secreted, soluble variant of VEGFR-1 (sVEGFR-1). No naturally occuring, secreted forms of VEGFR-2 have so far been reported. The binding of VEGF165 to VEGFR-2 is dependent on heparin.

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. CSF-1 induces cells of the monocyte/macrophage lineage. It plays a role in immunological defenses, bone metabolism, lipoproteins clearance, fertility and pregnancy.

Crystallin, Mu (CRYM) is a taxon-specific crystallin protein which binds NADPH and has sequence similarity to bacterial ornithine cyclodeaminases. CRYM doesn’t perform a structural role in lens tissue; instead CRYM binds thyroid hormone for possible regulatory or developmental roles. CRYM gene mutations are linked with autosomal dominant non-syndromic deafness. CRYM specifically catalyzes the reduction of imine bonds in brain substrates which may include cystathionine ketamine and lanthionine ketamine.

Chemokine (C-X-C motif) ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as Monokine induced by MIG. CXCL9 is a T-cell chemoattractant. It is closely related to two other CXC chemokines called CXCL10 and CXCL11, whose genes are located near the gene for CXCL9 on human chromosome 4. CXCL9, CXCL10 and CXCL11 all elicit their chemotactic functions by interacting with the chemokine receptor CXCR3.

CTBP1 participates in controlling the equilibrium between tubular and stacked structures in the Golgi complex. CTBP1 functions in brown adipose tissue differentiation. CTBP1 has dehydrogenase activity. CTBP1 binds to the C-terminus of adenovirus E1A proteins. CTBP1 phosphoprotein is a transcriptional repressor and that takes part during cellular proliferation. CTBP1 & CTBP2 can dimerize and interact with a polycomb group protein complex which is involved in regulation of gene expression during development.

SAR1A is a member of the small GTPase superfamily. SAR1A is a vital component of COPII vesicle coats involved in export of cargo from the ER (Endoplasmic Reticulum). The GTPase activity of SAR1A serves as a molecular switch to control protein-protein and protein-lipid interactions which dictate vesicle budding from the ER. SAR1A, while GDP-bound interacts with the membrane-bound exchange factor Sec12 and trades its bound GDP for GTP. SAR1A is also involved in the transport from the ER to the Golgi apparatus. SAR1A is required to maintain SEC16A localization at distinct locations on the ER membrane possibly by preventing its dissociation. SAR1A-GTP-dependent compilation of SEC16A on the ER membrane creates a structured scaffold defining endoplasmic reticulum exit sites.

Cytohesin-interacting protein, also known as CYTIP contains 2 leucine zipper domains as well as a putative C-terminal nuclear targeting signal. However, CYTIP does not contain any hydrophobic regions. In addition, CYTIP is expressed weakly in resting NK and T cells. It also modulates the activation of ARF genes by CYTH1.

Amyloid beta A4 protein (APP) functions as a cell surface receptor and transmembrane precursor protein which is cleaved by secretases to form a number of peptides. A number of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to stimulate transcriptional activation, whereas others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. APP gene mutations are implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy).

DPY30 is implicated in the methylation of histone H3 at Lys-4, mainly trimethylation. Histone H3 Lys-4 methylation symbolize a specific tag for epigenetic transcriptional activation. DPY30 takes part in histone H3 acetylation. In a teratocarcinoma cell, DPY30 plays a criticalrole in retinoic acid-induced differentiation along the neural lineage, regulating gene induction and H3 Lys-4 methylation at key developmental loci. DPY30 also plays an indirect or direct part in endosomal transport.

Snail homolog 1 (SNAI1) is involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration. SNAI1 binds to 3 E-boxes of the E-cadherin gene promoter and represses its transcription. The nuclear protein encoded by SNAI1 is structurally identical to the Drosophila snail protein, and is considered as well to be vital for mesoderm formation in the developing embryo. At least two variants of a similar processed pseudogene have been found on chromosome 2. Among the diseases associated with SNAI1 are waardenburg syndrome type iid, and inappropriate adh syndrome.

ATPaseTransporting Beta 1 (ATP1B1) is a part of the family of Na+/K+ and H+/K+ ATPases beta chain proteins, and the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an essential membrane protein accountable for establishing and maintaining the electrochemical gradients of Na and K ions over the plasma membrane. These gradients are vital for osmoregulation, for sodium-coupled transport of a range of organic and inorganic molecules, and for electrical excitability of muscle and nerve. ATP1B1is combined of 2 subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The beta subunit regulates the number of sodium pumps transported to the plasma membrane through assembly of alpha/beta heterodimers. ATP1B1 is a beta 1 subunit.

EFNA3 belongs to the ephrin (EPH) family. The ephrins and EPH-related receptors include thelargest subfamily of receptor protein-tyrosine kinases which have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. Ephrins are divided into the ephrin-A (EFNA) class and the ephrin-B (EFNB) class, based on their structures and sequence relationships. The Ephrins from the EFNA class are anchored to the membrane by aglycosylphosphatidylinositol linkage, while the others from the EFNB class are transmembrane proteins.

NUDT5 is part of the nudix hydrolase family which remove toxic nucleotide derivatives from the cell. NUDT5 hydrolyzes ADP-ribose and ADP-mannose in the presence of magnesium, and in addition hydrolyzes nucleotide sugars with decreasing activity such as ADP-glucose and diadenosine diphosphate. As a nudix hydrolase, NUDT5 holds a central nudix motif and functions to eliminate toxic nucleotide metabolites from the cell while maintaining the levels of signaling nucleotides.
NUDT5 is broadly expressed but is most abundant in liver as a homodimer.

Otubain 1 (OTUB1) belongs to the ovarian tumor (OUT) superfamily of predicted cysteine proteases and inhibits cytokine gene transcription in the immune system through its interaction with a ubiquitin protease and E3 ubiquitin ligase. OTUB1 is a highly specific ubiquitin iso-peptidase, it cleaves ubiquitin from branched poly-ubiquitin chains but not from ubiquitinated substrates. OTUB1 is believed to work in specific ubiquitin-dependent pathways, possibly by providing an editing function of polyubiquitin chain growth. OTUB1 is a hydrolase that removes conjugated ubiquitin from proteins in vitro and may therefore have a significant regulatory role in the level of protein turnover by preventing degradation. Additionally, OTUB1 is a regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered impassive to antigen re-challenge and no longer respond to their cognate antigen. OTUB1 acts via its interaction with RNF128/GRAIL, which is an essential inductor of CD4 T-cell anergy.