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DCTPP1, also known as dCTP pyrophosphatase 1, contains an epilepsy-associated repeat (EAR) domain that is predicted to participate in protein-protein interactions, most likely involved in ligand recognition. This protein functions to hydrolyze abnormal nucleotide triphosphates (NTPs) in cancer cells that, if unregulated, could be incorporated into nascent DNA or RNA.

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.

Pirin (PIR) which belongs to the cupin superfamily, is an Fe(II)-containing nuclear protein expressed in all tissues of the body and concentrated within dot-like subnuclear structures. Pirin may function as a transcriptional cofactor and is involved in the regulation of DNA transcription and replication, as a result of interactions with nuclear factor I/CCAAT box transcription factor as well as B cell lymphoma 3-encoded oncoprotein.

NF-kappa-B inhibitor-interacting Ras-like protein 1 (NKIRAS1) is a member of the small GTPase superfamily. NKIRAS1 is an unusual Ras-like protein which acts as a potent regulator of NF-kappa-B activity by thwarting the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, describing why NFKBIB is more resistant to degradation. NKIRAS1 functions by blocking phosphorylation of NFKBIB and mediating cytoplasmic retention of p65/RELA NF-kappa-B subunit. Both GTP- and GDP-bound forms block phosphorylation of NFKBIB.

TNNT2 is the tropomyosin-binding subunit of the troponin complex, which is situated on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration. Mutations in TNNT2 gene can lead to familial hypertrophic cardiomyopathy as well as dilated cardiomyopathy. TNNT2 mutation takes part in hypertrophic cardiomyopathy.

EFNA1 belongs to the ephrin (EPH) family. The EPH subfamily is the biggest group of receptor protein kinases and they take part in vital nervous system function and development.

Inositol monophosphatase 3 (IMPAD1) belongs to the inositol monophosphatase family. IMPAD1 is restricted to the Golgi apparatus and catalyzes the hydrolysis of phosphoadenosine phosphate (PAP) to adenosine monophosphate (AMP). IMPAD1 gene mutations cause the GRAPP type chondrodysplasia with joint dislocations, and a pseudogene of the IMPAD1 gene is located on the long arm of chromosome 1.

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.

Mesoderm development candidate 1 (MESDC1) is a member of the MESD family. MESDC1 is a 362 amino acid protein encoded by a gene which maps to human chromosome 15q25.1. MESDC1 serves as a chaperone for low-density lipoprotein receptor (LDLR) proteins in the ER, and specifically associates with Wnt signaling pathway coreceptors LRP5 and LPR6. MESDC1 is needed for proper LRP5/6 folding and maturation to the cell surface, which has a key role in Wnt signaling.

Cardiotrophin 1 (CT-1) is a 201 amino acid member of the interleukin-6 superfamily. It was identified by its ability to induce hypertrophic response in cardiac myocytes. CT-1 mRNA levels were found both in cardiac myocytes and in cardiac nonmyocytes. CT 1 was also detected in abundance in normal adult human lung and was expressed in both fetal and adult airway smooth muscle cells. CT 1 activates gp130 dependent signaling and stimulates the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway to transduce hypertrophic and cytoprotective signals in cardiac myocytes.
CT 1 has also a neurotrophic function. CTF1 deficiency causes increased motoneuron cell death in spinal cord and brainstem nuclei of mice during a period between embryonic day 14 and the first postnatal week. Moreover, CT-1 is a hepatocyte survival factor that efficiently reduces hepatocellular damage in animal models of acute liver injury. Cardiotrophin 1 expression is augmented after hypoxic stimulation and it can protect cardiac cells when added either prior to simulated ischaemia or at the time of reoxygenation following simulated ischaemia. Cardiotrophin 1 can induce expression of the protective heat shock proteins (hsps) in cardiac cells.
Cardiotrophin-1 increased ventricular expression of ANP, brain natriuretic peptide (BNP) and angiotensinogen mRNA.
Cardiophin 1 levels were significantly elevated in patients with heart failure, patients with dilatative cardiomyopathy, moderate/severe mitral regurgitation, stable and unstable angina and after acute myocardial infarction.

PDIA3 is an enzyme that belongs to the endoplasmic reticulum and interacts with lectin chaperones calreticulin and calnexin to modulate folding of newly synthesized glycoproteins. PDIA3 has protein disulfide isomerase activity. Complexes of lectins and PDIA3 mediate protein folding by promoting formation of disulfide bonds in their glycoprotein substrates. PDIA3 is expressed in the lumbar spinal cord from rats submitted to peripheral lesion during neonatal period. PDIA3 interacts with thiazide-sensitive sodium-chloride cotransporter in the kidney and is induced by glucose deprivation. PDIA3 is part of the major histocompatibility complex (MHC) class I peptide-loading complex (TAP1), which is important for formation of the final antigen conformation and export from the endoplasmic reticulum to the cell surface.

Immunoglobulin J chain (IGJ) helps to link 2 monomer units of either IgM or IgA and also also helps to bind these immunoglobulins to secretory component. When it comes to IgM, the J chain-joined dimer is a nucleating unit for the IgM pentamer and in the case of IgA it induces larger polymers.

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

Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets.PF4’s major physiologic role appears to be neutralization of 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. Furthermore, it is used as an inhibitor in the angiogenesis during tumor therapy.

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

Ubiquitin-like-conjugating enzyme ATG10 (ATG10) is a 220 amino acid protein which localizes to the cytoplasm and has a role in autophagy, specifically acting as an E2-like enzyme providing Atg recognition sites during autophagosome synthesis. ATG10 functions as an E2-like enzyme which catalyzes the conjugation of ATG12 to ATG5, which is required for autophagy. In addition, ATG10 interacts with ATG12 in human embryonic kidney cells in the presence of ATG7. ATG10 probably serves as an ATG5-recognition molecule. Furthermore, ATG10 has a role in adenovirus-mediated cell lysis.

Nephroblastoma Overexpressed (NOV) is a member of the CCN family of secreted cysteine rich regulatory proteins. The full length NOV protein is comprised of 4 structural domains, which present distinct, and sometimes opposing, biological activities. An elevated expression of NOV is linked with certain tumors, including Wilm’s tumor and most nephroblastomas. On the other hand, in other tumor types and certain cancer cell lines, increased tumorgenicity and proliferation is associated with decreased NOV expression.

Fibroblast growth factors (FGFs) comprise a family of at least eighteen structurally related proteins that are involved in a multitude of physiological and pathological cellular processes, including cell growth, differentiation, angiogenesis, wound healing and tumorgenesis. The biological activities of the FGFs are mediated by a family of type I transmembrane tyrosine kinases which undergo dimerization and autophosphorylation after ligand binding. Four distinct genes encoding closely related FGF receptors, FGF R1 - 4, are known. All four genes for FGF Rs encode proteins with an N-terminal signal peptide, three immunoglobulin (Ig)-like domains, an acid-box region containing a run of acidic residues between the IgI and IgII domains, a transmembrane domain and the split tyrosine-kinase domain. Multiple forms of FGF R1 - 3 are generated by alternative splicing of the mRNAs. A frequent splicing event involving FGF R1 and 2 results in receptors containing all three Ig domains, referred to as the a isoform, or only IgII and IgIII, referred to as the b isoform. Only the a isoform has been identified for FGF R3 and FGF R4. Additional splicing events for FGF R1 - 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 FGF R1. Mutations in FGF R1 - 3 have been found in patients with birth defects involving craniosynostosis. The complex patterns of expression of these receptors as well as the specificity of their interactions with the various FGF ligand family members are under investigation.

Complement Factor D (Adipsin), which belongs to the trypsin family of peptidases, is involved in the alternative complement pathway of the complement system where it cleaves factor B. In the alternative complement pathway, Adipsin is best known for its role in humoral suppression of infectious agents. In addition, Adipsin is a serine protease which is secreted by adipocytes into the bloodstream. Ultimately, Adipsin has a high level of expression in fat, proposing a role for adipose tissue in immune system biology.

GRAP2 belongs to the GRB2/Sem5/Drk family. GRAP2 is an adaptor-like protein has a part in leukocyte-specific protein-tyrosine kinase signaling. Similar to related family member, GRB2-related adaptor protein contains an SH2 domain flanked by two SH3 domains and it interacts with other proteins, for example GRB2-associated binding protein 1 (GAB1) and the SLP-76 leukocyte protein (LCP2), through its SH3 domains.

S100A8 is a part of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a broad range of cells, and participate in the regulation of cellular processes such as cell cycle progression and differentiation. S100A8 plays a role in the inhibition of casein kinase and as a cytokine. S100A8 altered expression is related with cystic fibrosis disease. S100A8 is a calcium-binding protein that has antimicrobial activity against bacteria and fungi.S100A8 is crucial for resistance towards invasion by pathogenic bacteria. S100A8 up-regulates transcription of genes that are under the control of NF-kappa-B. S100A8 plays a role in the development of endotoxic shock in response to bacterial lipopolysaccharide. S100A8 endorses tubulin polymerization and promotes phagocyte migration and infiltration of granulocytes at sites of wounding. S100A8 takes part as a pro-inflammatory mediator in acute and chronic inflammation and up-regulates the release of IL8 and cell-surface expression of ICAM1.

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.