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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.

Prothrombin produced in the liver is a vitamin K-dependent plasma protein. Before prothrombin is secreted into the plasma it goes through post translational modification by vitamin K-dependent carboxylase. The vitamin K-dependent carboxylase convertsprothrombin to 10 glutamic acid residues to gamma carboxyglutamic acid. Prothrombin comprises of 2 kringle regions which are found among residues a.a. 40 & 270 of the mature plasma protein and substitute the growth factor domains located in numerous plasma serine proteases.

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.

MMP-1 (interstitial collagenase) can break down a wide range of substrates including types I, II, III, VII, VIII, and X collagens as well as L-Selectin, pro-TNF, IL-1?, IGFBP-3, IGFBP-5, casein, gelatin, ?1 antitrypsin, myelin basic protein, pro-MMP2 and pro-MMP9. A significant function of MMP-1 is the degradation of fibrillar collagens in extracellular matrix remodeling. MMP-1 is expressed in fibroblasts, keratinocytes, endothelial cells, monocytes and macrophages. MMP1 can be divided into a number of distinct domains: a prodomain which is cleaved on activation, a catalytic domain containing the zinc binding site and a short hinge region with a carboxyl terminal domain. MMP1 is part of a cluster of MMP genes which localize to chromosome 11q22.3.

ADP-ribosylhydrolase like 2 (ADPRHL2) belongs to the ADP-ribosylglycohydrolase family. ADPRHL2 catalyzes the removal of ADP-ribose from ADP-ribosylated proteins. ADPRHL2, which is ubiquitously expressed, uses magnesium as a cofactor to catalyze the hydrolysis of poly (ADP-ribose) that is synthesized after DNA damage. Furthermore, ADPRHL2 has an essential role in the maintenance of normal neuronal cell function. The ADPRHL2 enzyme localizes to the mitochondria, in addition to the nucleus and cytoplasm.

Melanoregulin (MREG) takes part in membrane fusion and in regulating the biogenesis of disk membranes of photoreceptor rods. MREG is expressed in photoreceptor cells as two isoforms as a result of alternative splicing. MREG interacts with Peripherin-2, a photoreceptor specific tetraspanin protein which is required to preserve normal cell structure during the renewal process of membrane fusion. Moreover, MREG plays a part in the incorporation of pigments into hair.

DCUN1D1 takes part in the malignant transformation of squamous cell lineage. DCUN1D1 protein regulates Gli1, a main regulator of the hedgehog (HH) pathway which takes a vital role in development, maintenance, and regeneration of practically all adult tissues.

There are several proteolytic fragments or specific domains of proteins that act as inhibitors of angiogenesis. These include fragments of plasminogen such as Angiostatin protein kringles 1-4 and kringles 1-5, Endostatin, Restin, PEX, the N-terminal fragment of prolactin, and the Nterminally truncated platelet factor. Angiostatin is a proteolytic protein fragment of plasminogen that is comprised of the first 4 kringle regions. Angiostatin k1-4 prevents the growth of endothelial cells, and its systemic administration inhibits the growth of primary carcinomas in mice. Angiostatin Kringles 1-3 segment has a larger inhibitory activity than the Angiostatin kringles 1-4 fragment. The protease-activated angiostatin kringles 1-5 is the most potent plasminogen fragment with over 50 times larger endothelial cell specific inhibitory activity. Angiostatin kringles 1-5 systemic administration inhibits growth of fibrosarcoma and significantly reduces neovascularization.
Angiostatin is an angiogenesis inhibitor in mouse serum and urine. Angiostatin is a 38 kDa protein fragment of the plasminogen composed of the 1st 4 kringle domains of plasminogen. Angiostatin K1-4 is also named plasminogen kringles 1-4 and PK1-4.
Angiostatin protein is manufactured by the protelytic cleavage of plasminogen by a serine protease from several prostate carcinoma cell lines. The manufacturing of angiostatin by pancreatic cancer cells can be inhibited by TGF-beta 1 along with plasminogen activator inhibitor type-1 (PAI1).

Dynein Axonemal Light Intermediate Chain1 also known as DNALI1 belongs to the inner dynein arm light chain family. DNALI1 take a dynamic role in flagellar motility. DNALI1 is the human homolog of the Chlamydomonas inner dynein arm gene, p28. The exactfunction of DNALI1 is not known yet, on the other hand, it is a potential candidate for immotile cilia syndrome. In addition it has been found that the following diseases: primary ciliary dyskinesia, and huntington's disease have been associated with DNALI1. Ultrastructural defects of the inner dynein arms are seen in patients with ICS. Immotile mutant strains ofChlamydomonas, biflagellated algae, show similar defects.

Actin depolymerizing factor (Destrin/DSTN) belongs to the ADF/Cofilin/destrin superfamily which has the ability to swiftly depolymerize F-Actin in a stoichiometric mode. The ADF family of proteins is responsible for enhancing the turnover rate of actin in vivo. Destrin is a small phosphoinositide-sensitive actin-binding protein capable of depolymerizing actin-filaments in vitro. DSTN functions in a pH-independent manner. DSTN is found in a variety of epithelial and endothelial cells, however it is virtually nonexistent in adult mouse heart and skeletal muscle cells. Destrin shares a 71% sequence homology with Cofilin, however the 2 proteins vary in their interaction with Actin.

ATPase inhibitory factor 1 (ATPIF1) attaches to the C-terminal region of a beta subunit of the F1-ATPase at low pH values and, through interference of the beta and gamma subunit interaction, ATPIF1 controls the activity of the F1 (the hydrophilic catalytic core), F0 (the membrane embedded protein channel) ATPase. ATPIF1 overexpression in a number of human carcinomas additionally reinforces its participation in oncogenesis and offers insight into the transformed metabolism of cancer cells, including the reprogramming of energy metabolism in relation to glycolysis. Endogenous F1F(o)-ATPase inhibitor curbing ATP depletion when the mitochondrial membrane potential drops below a threshold and the F1F(o)-ATP synthase begins hydrolyzing ATP to pump protons out of the mitochondrial matrix.

Transcription Factor 4 (TCF4) acts as a transcription factor and takes part in the initiation of neuronal differentiation. TCF4 recognizes an Ephrussi-box ('E-box') binding site ('CANNTG') - a motif primary identified in immunoglobulin enhancers. TCF4 is mainly expressed in pre-B-cells, even though it is present in other tissues as well.

PFDN4 belongs to the prefoldin beta subunit family. PFDN4 is a heterohexameric chaperone protein that can capture unfolded actin and is a possible transcription factor. Six prefoldin polypeptides, prefoldin 1-6, are known.

Peptidase Inhibitor 16 (PI16) which a member of the CRISP family, is a putative serine protease inhibitor. PI16 interacts with PSP94/MSMB. PI16 is expressed in the prostate, testis, ovary and intestine. It also concentrates in prostate cancer patient's sera. PI16 may serve as a marker following prostatectomy for prostate cancer.

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, dendritic cells and on trophoblast cells. The flt-1 gene was first described in 1990. The receptor contains seven immunoglobulin-like extracellular domains, a single transmembrane region and an intracellular splited tyrosine kinase domain. Compared to VEGFR-2 the Flt-1 receptor has a higher affinity for VEGF but a weaker signaling activity. VEGFR-1 thus leads not to proliferation of endothelial cells, but mediates signals for differentiation. Interestingly a naturally occuring soluble variant of VEGFR-1 (sVEGFR-1) was found in HUVE supernatants in 1996, which is generated by alternative splicing of the flt-1 mRNA. The biological functions of sVEGFR-1 still are not clear, but it seems to be an endogenous regulator of angiogenesis, binding VEGF with the same affinity as the full-length receptor.

JAZF zinc finger 1 (JAZF1) is a nuclear protein with 3 C2H2-type zinc fingers, which functions as a transcriptional repressor. Chromosomal anomalies involving the JAZF1 are linked with endometrial stromal tumors. Alternatively spliced variants which encode different protein isoforms have been described; though, not all variants have been fully characterized.

TPPP3 is a member of the TPPP family and is found in the cytoplasm. TPPP3 binds tubulin, has microtubule bundling activity takes part in mitosis and cell proliferation.

PPP3R1 is a Ser/Thr-specific calcium and calmodulin-dependent protein phosphatase which takes a vital part in the T cell activation pathway. Calcineurin is composed of two subunits; calcineurin A (CnA) and calcineurin B (CnB). Dephosphorylation of the nuclear factor of activated T-cells (NF-AT) by Calcineurin is essential for NF-AT activation, nuclear translocation, and early gene expression in T-cells.

PPP3R2 is a calcium-dependent, calmodulin stimulated serine/threonine protein phosphatase. In eukaryotes, the phosphorylation and dephosphorylation of proteins on serine and threonine residues is a crucial means of regulating a wide range of cellular functions including division, homeostasis and apoptosis. Ordinarily the protein phosphatase (PP) holoenzyme is a trimeric complex composed of a regulatory subunit, a variable subunit and a catalytic subunit.

Phosphoserine aminotransferase (PSAT1) catalyzes the conversion of 3-phosphohydroxypyruvate into 3-phosphoserine which is dephosphorylated consequently by phosphoserine phosphatase to form L-serine. PSAT1 is probably a phosphoserine aminotransferase, based on similarity to proteins in mouse, rabbit, and Drosophila. PSAT1 is expressed at high levels in the brain, liver, kidney and pancreas, and very weakly expressed in the thymus, prostate, testis and colon. Defects in the PSAT1 gene are the cause of phosphoserine aminotransferase deficiency (PSATD). PSATD is distinguished biochemically by low plasma and cerebrospinal fluid concentrations of serine and glycine and clinically by intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation.

Chemokine (C-X-C motif) ligand 2 (CXCL2) is a small cytokine belonging to the CXC chemokine family that is also called macrophage inflammatory protein 2-alpha (MIP2-alpha), Growth-regulated protein beta (Gro-beta) and Gro oncogene-2 (Gro-2). CXCL2 is 90% identical in amino acid sequence as a related chemokine, CXCL1. This chemokine is secreted by monocytes and macrophages and is chemotactic for polymorphonuclear leukocytes and hematopoietic stem cells. The gene for CXCL2 is located on human chromosome 4 in a cluster of other CXC chemokines. CXCL2 mobilizes cells by interacting with a cell surface chemokine receptor called CXCR2.

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.

General Transcription Factor IIF Polypeptide 2 (GTF2F2) is a general transcription initiation factor which binds to RNA polymerase II and helps engage it in the initiation complex in collaboration with TFIIB. GTF2F2 promotes transcription elongation. GTF2F2 shows ATP-dependent DNA-helicase activity.