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Transmembrane Protein 27 (TMEM27) is a type 1 transmembrane protein which is imperative for trafficking amino acid transporters to the apical brush border of proximal tubules. TMEM27 binds to amino acid transporters and regulates their expression on the plasma membrane. The extracellular domain of TMEM27 is cleaved off the surface of beta cells.

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.

Thyroid Peroxidase (TPO) represents one of the main autoantigenic targets in autoimmune thyroid disease of humans. Its identity with the formerly so-called `microsomal antigen` has been shown several years ago. As an integral membrane glycoprotein it is restricted to the apical plasma membrane of the follicular epithelial cells and comprises two identical subunits of approx. 100 kDa molecular weight. The hemoprotein TPO plays a key role in the thyroid hormone biosynthesis by catalysing both the iodination of tyrosyl residues and the coupling of iodotyrosyl residues in thyroglobulin (TG) to form precursors of the thyroid hormones T4 and T3.

TXNL4A is a member of the Dim protein family and has a vital part in pre-mRNA splicing. As a result of a failure to express early zygotic transcripts, deletion of the gene encoding TXNL4A in Schizosaccharomyces pombe results in embryonal lethality during gastrulation. Restricted to the nucleus, TXNL4A cooperates with hnRNP F, hnRNP H2, Cas-L and PQBP-1 to influence gene expression.

PTX3 is part of the pentraxin family sharing the C-terminal domain with short pentraxins and containing a unique N-terminal domain. PTX3 is produced and released at inflammatory sites by various cell types including monocytes/macrophages, endothelial cells, vascular smooth muscle cells, fibroblasts, and adipocytes. PTX3 is involved in the regulation of innate resistance to pathogens, inflammatory reactions, possibly clearance of self-components and female fertility. PTX3 is used as a marker for disease activity of psoriasis. High serum PTX3 levels are associated with the disease severity of systemic sclerosis. Elevated serum PTX3 is associated with pulmonary fungal infections.

Tumor necrosis factor receptor superfamily member 11A or TNFRSF11A or RANK, is a protein, part of the tumor necrosis factor receptor (TNFR) group of proteins. RANK acts as the receptor of RANK-Ligand and regulates osteoclast activation & differentiation. RANK protein has been linked to activation of NF-kappa B & c-jun N-terminal kinase, enhancement of T cell growth, bone remodeling and repair, dendritic cell function, lymph node development, immune cell function, mammary gland development & thermal regulation.

The Melanoma Inhibitory protein (MIA) was identified as an inhibitor of in vitro growth of malignant melanoma cells. The protein contains a SH3 domain. MIA acts as a potent tumor cell growth inhibitor for malignant melanoma cells and some other neuroectodermal tumors, including gliomas, in an autocrine fashion. In a study of human melanoma cell lines with different metastatic capacity MIA mRNA expression appeared to be inversely correlated with pigmentation. MIA has been shown to represent a very sensitive and specific serum marker for systemic malignant melanoma that might be useful for staging of primary melanomas, detection of progression from localized to metastatic disease during follow-up, and monitoring therapy of advanced melanomas.

Beta Defensin 118 (DEFB118) which is a member of the beta subfamily of defensins, is found in a cluster with other beta-defensin genes on the long arm of chromosome 20. Beta-defensins are antimicrobial peptides which provide protection for tissues and organs from infection by a diversity of microorganisms. DEFB118 protein’s expression is regulated by androgen, and the encoded protein binds to sperm and exhibits antibacterial activity.

Myosin Light Chain 6B (MYL6B) is a heavy chain regulator located in smooth muscle and non-muscle Myosin complexes. Contractile activity in the smooth muscle is regulated by the calcium/calmodulin-dependent phosphorylation of Myosin light chain by Myosin light chain kinase. MYL6B doesn’t bind calcium during contraction. MYL6B is mostly found as a hexamer consisting of 4 light chains and 2 heavy chains. MYL6B usually interacts with Myosin Va, an Actin based motor which moves in large steps. MYL6B is expressed in the majority of tissues with neurons, while smooth muscle tissue having the highest expression.

DHH is part of the Hedgehog family which encodes signaling molecules that are involved in regulating morphogenesis. DHH protein is a precursor that is autocatalytically cleaved, the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. Additionally, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the organism. Defects in DHH protein have been associated with partial gonadal dysgenesis (PGD) accompanied by minifascicular polyneuropathy. DHH plays a role both male gonadal differentiation and perineurial development.
DHH plays a role in intercellular signaling which is essential for a variety of patterning events during development. DHH functions as a spermatocyte survival factor in the testes & is essential for testes development.

Nucleophosmin (NPM1) is a phosphoprotein which shuffles between the nucleus and the cytoplasm. NPM1 is assumed to be involved in a number of processes including regulation of the ARF/p53 pathway. Several genes fusion partners have been described, particularly the anaplastic lymphoma kinase gene on chromosome 2. NPM1 gene mutations are linked with acute myeloid leukemia.

EMAP-II also called SCYE1 is a tumor derived cytokine that plays a role in a wide variety of activities on endothelial cells, monocytes and neutrophils. EMAP-II inhibits endothelial cell proliferation, vasculogenesis, neovessel formation, and can induce apoptosis. It is also chemotactic towards neutrophils and monocytes and induces myeloperoxidase activity from neutrophils. EMAP-II clinical value is inhibiting angiogenesis of vascular beds and suppressing the growth of primary and secondary tumors with no affect to normal tissues. SCYE1is specifically induced by apoptosis, and it is involved in the control of angiogenesis, inflammation, and wound healing. The release of this SCYE1 renders the tumor-associated vasculature sensitive to tumor necrosis factor. The precursor protein is identical to the p43 subunit, which is associated with the multi-tRNA synthetase complex, and it modulates aminoacylation activity of tRNA synthetase in normal cells. EMAP-2 plays a role in in the stimulation of inflammatory responses after proteolytic cleavage in tumor cells.

Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 103A, which has broad spectrum antimicrobial activity and may play an important role in innate epithelial defense.

TARC cDNA encodes a 94 amino acid precursor protein with a 23 amino acid residue signal peptide that is cleaved off to generate the 71 amino acid residue mature secreted protein. Along with CC chemokine family members, CCL-17 has approximately 24-29% amino acid sequence identity with RANTES, MIP-1a, MIP-1b, MCP-1, MCP-2, MCP-3 and I-309. TARC is expressed in thymus, and at a lower level in the lung, colon, and small intestine. TARC is in addition transiently expressed in stimulated peripheral blood mononuclear cells. Recombinant TARC has been shown to be chemotactic for T cell lines but not monocytes or neutrophils. CCL-17 was recently identified to be a specific functional ligand for CCR4, a receptor that is selectively expressed on T cells. CCL17 is one of quite a few Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 16. CCL17 shows chemotactic activity for T lymphocytes, but not monocytes or granulocytes. CCL17 binds to chemokine receptors CCR4 and CCR8. This chemokine plays important roles in T cell development in thymus as well as in trafficking and activation of mature T cells.

TBCB is a member of the Microtubules family. Biosynthesis of functional microtubules include the involvement of a number of chaperones, termed Tubulin folding cofactors A (TBCA), B (TBCB), C (TBCC), D (TBCD) and E (TBCE), which operate on folding intermediates downstream of the cytosolic chaperon, known as TCP. The 244 amino acid cytoplasmic protein TBCB has one CAP-Gly domain and is universally expressed. TBCB takes part in the regulation of tubulin heterodimer dissociation and operates as a negative regulator of axonal growth.

TIE-1 (tyrosine kinase with Ig and EGF homology domains 1) and TIE-2/Tek comprise a receptor tyrosine kinase (RTK) subfamily with unique structural characteristics: two immunoglobulin-like domains flanking three epidermal growth factor (EGF)-like domains and followed by three fibronectin type III-like repeats in the extracellular region and a split tyrosine kinase domain in the cytoplasmic region. These receptors are expressed primarily on endothelial and hematopoietic progenitor cells and play critical roles in angiogenesis, vasculogenesis and hematopoiesis. Human TIE-1 cDNA encodes a 1122 amino acid (aa) residue precursor protein with an 18 residue putative signal peptide, a 726 residue extracellular domain and a 353 residue cytoplasmic domain. Two ligands, angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2), which bind TIE-2 with high-affinity have been identified. Ang2 has been reported to act as an antagonist for Ang1. Mice engineered to overexpress Ang2 or to lack Ang1 or Tie-1 display similar angiogenic defects.

Transforming Growth Factor Beta Induced protein also known as TGFBI is an extracellular matrix protein induced by transforming growth factor (TGF)-beta 1. TGFBI protein is involved in cell growth, cell differentiation, wound healing and cell adhesion. In addition, some missense mutations of TGFBI were identified in families affected with human autosomal dominant corneal dystrophies. TGFBI gene encodes for a 683 amino-acid protein containing an RGD motif and four internal repeated domains which have highly conserved sequences founded in several species (Fasciclin domain).

Furin is a member of the peptidase S8 family. Furin signifies the ubiquitous endoprotease activity within constitutive secretory pathwaysas well as capable of cleavage at the RX (K/R) R consensus motif.Furin is considered to be one of the proteases responsible for the activation of HIV envelope glycoproteins gp160 as well as gp140 and might take part in tumor progression. Among the diseases associated with FURIN are dementia, familial british and plague.

Tumor Suppressor Candidate 2, also known as TUSC2, is a part of the TUSC2 family. TUSC2 protein functions as a tumor suppressor, inhibiting colony formation, causing G1 arrest and eventually inducing apoptosis in homozygous 3p21.3 120-kb region-deficient cells.

GREM1 belongs to the BMP (bone morphogenic protein) antagonist family. Like BMPs, BMP antagonists comprise cystine knots and usually form homo- and heterodimers. The CAN (cerberus and dan) subfamily of BMP antagonists, to which GREM1 belongs, is characterized by a C-terminal cystine knot with an eight-membered ring. The antagonistic effect of the secreted glycosylated protein is because of its direct binding to BMP proteins. As an antagonist of BMP, GREM1 takes a place in regulating organogenesis, body patterning, and tissue differentiation. In mouse, GREM1 has been shown to convey the sonic hedgehog (SHH) signal from the polarizing region to the apical ectodermal ridge during limb bud outgrowth. Alternatively merged transcript variants encoding different isoforms have been found for this gene.

PTX3 is part of the pentraxin family sharing the C-terminal domain with short pentraxins and containing a unique N-terminal domain. PTX3 is produced and released at inflammatory sites by various cell types including monocytes/macrophages, endothelial cells, vascular smooth muscle cells, fibroblasts, and adipocytes. PTX3 is involved in the regulation of innate resistance to pathogens, inflammatory reactions, possibly clearance of self-components and female fertility. PTX3 is used as a marker for disease activity of psoriasis. High serum PTX3 levels are associated with the disease severity of systemic sclerosis. Elevated serum PTX3 is associated with pulmonary fungal infections.

Excess adiposity is the most important risk in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Adipose tissue produces several proteins (adipocytokines) such as leptin, adiponectin, resistin, tumor necrosis factor-?, and IL-6, that modulate insulin sensitivity and appear to play an important role in the pathogenesis of insulin resistance, diabetes, dyslipidemia, inflammation, and atherosclerosis. However, the mechanisms by which fat tissue induces insulin resistance and the role of adipocytokines in the pathogenesis of T2DM have not been well established. Visfatin, also known as pre-B cell colony-enhancing factor (PBEF), is a cytokine that is highly expressed in visceral fat and was originally isolated as a secreted factor that synergizes with IL-7 and stem cell factors to promote the growth of B cell precursors. Visfatin homologs have been identified in carp, invertebrate mollusks, and bacteria, as well as in vertebrates, including humans and the mouse. It has been postulated to play a role in innate immunity.
Visfatin exerts insulin-mimetic effects that are dose-dependent and quantitatively similar to those of insulin in stimulating muscle and adipocyte glucose transport, and in inhibiting hepatocyte glucose production. Intravenous injection of recombinant visfatin in mice decreased plasma glucose in a dose-dependent fashion. In keeping with its insulin-mimetic effects, visfatin was as effective as insulin in reducing hyperglycemia in insulin-deficient diabetic mice. Visfatin was also found to be bound to and activate insulin receptor, causing receptor phosphorylation and the activation of downstream signaling molecules. However, visfatin and insulin did not compete for binding to the insulin receptor, indicating that the two proteins were recognized by different regions of the receptor. Thus, visfatin might play a role in glucose homeostasis and dysregulation in biosynthesis or signal transduction, and might contribute to the pathogenesis of diabetes.

The 14-3-3 family of proteins plays a key regulatory role in signal transduction, checkpoint control, apoptotic and nutrient-sensing pathways. 14-3-3 proteins are highly conserved and ubiquitously expressed. There are at least seven isoforms, ?, ?, ?, ?, ?, ? and ? that have been identified in mammals. The 14-3-3 tau, a subtype of the 14-3-3 family of proteins, was found in T Cells, brain and testes. This 14-3-3 tau is upregulated in patients with amyotrophic lateral sclerosis.

The acute phase plasma protein ORM1 synthesized by the liver mediates the interaction between blood cells and endothelial cells. In addition, together with haptoglobin and C reactive protein, ORM1 regulates the extravasation of the cells through infection and inflammation. Expression of ORM1 is induced by acute-phase stimulatory mediators such as bacterial lipopolysaccharides.