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DR1 is a phosphoprotein that inhibits both basal and activated levels of transcription. DR1 is phosphorylated in vivo which affects its interaction with TBP. DR1 has a histone fold motif at the amino terminus, a TBP-binding domain, and a glutamine- and alanine-rich region. By selectively repressing polymerases II and III, DR1 alters the physiological balance of transcriptional output in favor of polymerase I.

Growth Differentiation Factor-7 (GDF-7) belongs to the BMP family of TGF-b superfamily proteins. GDF7 elicits its bioactivity via a heterodimeric receptor complex comprised of a type 1 (BMPR-IB) and a type II (BMPR-II or Activin RII) serine/threonine kinase receptor. GDF7 signaling results in the phosphorylation and activation of Smad proteins. GDF-7 is also involved in tendon and ligament formation and repair. In addition, GDF7 regulates bone formation, mesenchymal stem cell differentiation, neuronal differentiation, and axon guidance.

VAMP8 also called endobrevin, is the main component of a SNARE complex involved in the docking and fusion of synaptic vesicles with the presynaptic membrane. VAMP8 protein is involved in the regulatation of enzyme secretion in pancreatic acinar cells and plays a part in the abscission of the midbody during cell division, which leads to completely separate daughter cells. VAMP8 is essential for dense-granule secretion in platelets. VAMP8 is related with the perinuclear vesicular structures of the early endocytic compartment. VAMP8 interacts particularly with the soluble NSF-attachment protein (alpha-SNAP), through an VAMP8-containing SNARE complex.

The heat-shock response is elicited by exposure of cells to thermal and chemical stress and through the activation of HSFs (heat shock factors) results in the elevated expression of heat-shock induced genes. Heat shock factor binding protein-1 (HSBP1), is a 76-amino-acid protein that binds to heat shock factor 1(HSF1), which is a transcription factor involved in the HS response. During HS response, HSF1 undergoes conformational transition from an inert non-DNA-binding monomer to active functional trimers. HSBP1 is nuclear-localized and interacts with the active trimeric state of HSF1 to negatively regulate HSF1 DNA-binding activity. Overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1. When overexpressed in C.elegans HSBP1 has severe effects on survival of the animals after thermal and chemical stress consistent with a role of HSBP1 as a negative regulator of heat shock response.

EDF1 controls endothelial cell differentiation. EDF1 has a role as a bridging protein that interconnects regulatory proteins and the basal transcriptional machinery, thus modulating the transcription of genes that take part in endothelial differentiation. EDF1 binds calmodulin through its IQ domain and controls nitric oxide synthase activity via calmodulin sequestration in the cytoplasm. EDF1 is localized in adult liver, heart, adipose tissues, intestine and pancreas.

Secreted frizzled-related protein 4 (SFRP4) belongs to the SFRP family which contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs serve as soluble modulators of Wnt signaling. SFRP4 may serve as a regulator of adult uterine morphology and function. SFRP4 increases apoptosis during ovulation possibly via modulation of FZ1/FZ4/WNT4 signaling. SFRP4 also has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake. SFRP4 is expressed in proliferative endometrium and several types of ovarian, endometrial and Brest tumors. SFRP4 is expressed in mesenchymal cells and in cardiomyocytes. SFRP4 expression in ventricular myocardium correlates with apoptosis related gene expression. SFRP4 is up-regulated in failing myocardium.

TSC22 domain family protein 3 (TSC22D3) protects T-cells from IL2 deprivation-induced apoptosis through the inhibition of FOXO3A transcriptional activity which initiates the down-regulation of the pro-apoptotic factor BCL2L11. In macrophages, TSC22D3 has a role in the anti-inflammatory and immunosuppressive effects of glucocorticoids and IL10. In T-cells, TSC22D3 hinders anti-CD3-induced NFKB1 nuclear translocation. In vitro, TSC22D3 curbs AP1 and NFKB1 DNA-binding activities.

E3 ubiquitin-protein ligase RNF181 (RNF181) accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the thioester form and subsequently directly transfers the ubiquitin to targeted substrates. RNF181 is widely expressed, with the highest levels in the liver and heart and the lowest levels in the brain and skeletal muscle. RNF181 is also expressed in platelets (at protein level).

Cyclophilin-D is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and speeds up the protein folding. Cyclophilin-D possess PPIase activity and binds to the immunosuppressant cyclosporin-A. Cyclophilin-D is very well known that its overexpression suppresses the apoptosis in cancer cell. Cyclophilin-D suppresses apoptotic cell death by the use of mitochondrial hexokinase-2 dependent mechanism in cancer cells.

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.

DBI, also known as Acyl-CoA-binding protein isoform 2, is a diazepam binding inhibitor, which is regulated by hormones. DBI participates in lipid metabolism and in the displacement of beta-carbolines & benzodiazepines, which modulate signal transduction at type A gamma-aminobutyric acid receptors located in brain synapses. Moreover, during adipocyte differentiation the expression of DBI is significantly induced. DBI preforms as an acyl-CoA pool former and regulates LCFA (long-chain fatty acids) metabolism in peripheral tissues.

Peroxisomal Biogenesis Factor 26 (PEX26) which is a part of the peroxin-26 gene family is probably required for protein import into peroxisomes. PEX26 attaches PEX1 and PEX6 to peroxisome membranes to form heteromeric AAA ATPase complexes needed for the import of proteins into peroxisomes. Deficiencies in this gene are the cause of peroxisome biogenesis disorder complementation group 8. PBD is a group of peroxisomal disorders evolving from a failure of protein import into the peroxisomal membrane or matrix.

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.

Lipopolysaccharide-induced TNF-alpha factor (LITAF) is a small integral membrane protein of lysosome/late endosome. The expression of inflammatory cytokines such as TNF-alpha in Lipopolysaccharide-induced processes is mediated by LITAF. LITAF connects to STAT6B, which belongs to the STAT6 family forming a complex on the TNF-alpha promoter that modifies TNF activity. High levels of expression of LITAF mRNA are observed mostly in the placenta, peripheral blood leukocytes, lymph nodes and spleen.

AMRC10 is a protein which contains an armadillo repeat and transmembrane domain. Upregulation of the AMRC10 gene has a role in hepatocellular carcinoma. AMRC10 decreases the transcriptional activity of the tumor suppressor protein p53 through direct interaction with the DNA-binding domain of p53, moreover it might play a role in cell growth and survival.

SAP18 is a component of the histone deacetylase complex which has a significant role in the regulation of eukaryotic gene expression. SAP18 directly interacts with SIN3 and enhances SIN3-mediated transcriptional repression once bound to the promoter. SAP18 plays an important part in gene-specific recruitment of the HDAC complex by a number of transcription factors including Gli, GAGA, and Bicoid. Histone acetylation is significant in the regulation of eukaryotic gene expression. Histone acetylation and deacetylation is catalyzed by multisubunit complexes. SAP18 is a component of the histone deacetylase complex, which includes SIN3, SAP30, HDAC1, HDAC2, RbAp46, RbAp48, and other polypeptides. SAP18 is a component of a splicing-dependent multiprotein EJC (exon junction complex) placed at splice junction on mRNAs.

PDRG1 is a 133 amino acid protein that localizes to the cytoplasm and belongs to the prefoldin subunit beta family. PDRG1 is expressed primarily in normal testicular tissue, it is functionally induced by ultraviolet light and is thought to have a role in chaperone-mediated protein folding, possibly having a role in cellular degradation. PDRG1 is linked to Creutzfeldt-Jakob disease, amyotrophic lateral sclerosis, spinal muscular atrophy, ring chromosome 20 epilepsy syndrome and Alagille syndrome.

Growth Differentiation Factor-7 (GDF-7) belongs to the BMP family of TGF-b superfamily proteins. GDF7 elicits its bioactivity via a heterodimeric receptor complex comprised of a type 1 (BMPR-IB) and a type II (BMPR-II or Activin RII) serine/threonine kinase receptor. GDF7 signaling results in the phosphorylation and activation of Smad proteins. GDF-7 is also involved in tendon and ligament formation and repair. In addition, GDF7 regulates bone formation, mesenchymal stem cell differentiation, neuronal differentiation, and axon guidance.

PDAP1, increases PDGFA-stimulated cell growth in fibroblasts, however inhibits the mitogenic effect of PDGFB. PDAP1 expression is induced by TNF-alpha, and cells overexpressing PDAP1 show significantly less apoptosis on exposure to TNF-alpha.

VEGF-C, also known as Vascular Endothelial Growth Factor Related Protein (VRP), is a recently discovered VEGF growth factor family member that is most closely related to VEGF-D. Human VEGF-C cDNA encodes a pre-pro-protein of 416 amino acids residues. It is almost identical to the mouse VEGF-C protein. Similar to VEGF-D, VEGF-C has a VEGF homology domain spanning the middle third of the precursor molecule and long N- and C-terminal extensions. In adults, VEGF-C is highly expressed in heart, placenta, ovary and small intestine. Recombinant human VEGF-C, lacking the N- and C-terminal extensions and containing only the middle VEGF homology domain, forms primarily non-covalently linked dimers. This protein is a ligand for both VEGFR-2/KDR and VEGFR-3/FLT-4. Since VEGFR-3 is strongly expressed in lymphatic endothelial cells, it has been postulated that VEGF-C is involved in the regulation of the growth and/or differentiation of lymphatic endothelium. Although recombinant human VEGF-C is also a mitogen for vascular endothelial cells, it is much less potent than VEGF-A.

TNFAIP8 which is a part of the TNFAIP8 family acts as a negative mediator of apoptosis and takes part in tumor progression. TNFAIP8 suppresses the TNF-mediated apoptosis by inhibiting caspase-8 activity but not the processing of procaspase-8, resulting in inhibition of BID cleavage and activation of caspase-3.

PRDX3 is part of the peroxiredoxin family of antioxidant enzymes, that reduces hydrogen peroxide and alkyl hydroperoxides. PRDX3 is particularly located in the mitochondria and involved in the regulation of cellular redox status by serving as a primary line of defense against H2O2 produced during respiration. PRDX3 is a significant regulator of the abundance of mitochondrial H(2)O(2), which itself promotes apoptosis in cooperation with other mediators of apoptotic signaling. PRDX3 mitochondrial protein is significantly decreased in Alzheimer Disease and Down Syndrome.

PEDF is a noninhibitory serpin with neurotrophic, anti-angiogenic, and anti-tumorigenic properties. PEDF is a 50,000 dalton glycoprotein created and secreted in many tissues all the way through the body. A key component of the anti-angiogenic action of PEDF is the induction of apoptosis in proliferating endothelial cells. Additionally, PEDF is capable to inhibit the activity of angiogenic factors such as VEGF and FGF-2. The neuro-protective effects of PEDF are achieved through suppression of neuronal apoptosis induced by peroxide, glutamate, or other neurotoxins. The recognition of a lipase-linked cell membrane receptor for PEDF (PEDF-R) that binds to PEDF with high affinity should facilitate further elucidation of the underlying mechanisms of this pluripotent serpin. To date, PEDF-R is the only signaling receptor known to be used by a serpin family member. The unique range of PEDF activities associate it as a potential therapeutic agent for the treatment of vasculature related neurodegenerative diseases such as age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR). PEDF in addition has the potential to be functional in the treatment of various angiogenesis-related diseases including a number of cancers.