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Docking Protein 4(DOK4) is a member of the DOK family. DOK proteins are enzymatically inert adaptor or scaffolding proteins. The DOK proteins present a docking platform for the compilation of multimolecular signaling complexes. DOK4 serves in RET-mediated neurite outgrowth and has a positive role in activation of the MAP kinase pathway. DOK4 is a putative link with downstream effectors of RET in neuronal differentiation. DOK4 is involved in the regulation of the immune response induced by T-cells.

A natural cytotoxicity receptor (NCR) NKp46 has been shown to represent a novel NK cell-specific molecule involved in human NK cell activation. The natural cytotoxicity receptors (NCRs) are a recently characterized family of Ig-like activation receptors that appear to be major triggering receptors in tumor cell recognition. The three known NCRs include NKp46 and NKp30, which are expressed on circulating NKcells, and NKp44, which is expressed only on activating NK cells. NKp46 has been implicated in NK cell-mediated lysis of several autologous tumor cells, pathogen-infected cell lines and mononuclear phagocytes infected with an intracellular bacterium. The Lysis of tumor cells by NK-cells involves recognition by NKp46 of heparan sulfate moieties of membrane heparan sulfate proteoglycans. Furthermore, NKp46 is a surface receptor involved in NK-cell cell death by apoptosis. NKp46 has two extracellular Ig-like domains followed by a ~40 residue stalk region, a type I transmembrane domain, and a short cytoplasmic tail. The extracellular Ig-like domain of NKp46 (22-255aa) is purified by FPLC gel-filtration chromatography, after refolding of the isolated inclusion bodies in a redox buffer. In addition, engagement of the antigen with the monoclonal antibody stimulates intracellular calcium levels and the synthesis of cytokines. CD59 is an NKp46 coreceptor (by physical association) together they activate cytotoxicity of human NK-cells, their engagement results in tyrosine phosphorylation of CD3-zeta chains associated with NKp46. Reduced cell surface expression of NKp46 and other NK-cell receptors is linked to the impaired NK-cell cytolytic function in viremic HIV-1 infection.

ATOH1 activates E box-dependent transcription in collaboration with TCF3/E47, but the activity is entirely provoked by the negative regulator of neurogenesis HES1. ATOH1 takes part in the differentiation of divisions of neural cells by activating E box-dependent transcription.

ATP synthase subunit gamma, mitochondrial isoform L (liver) (ATP5C1) is a member of the ATPase gamma chain family. ATP5C1 catalyzes ATP synthesis by using an electrochemical gradient of protons across the inner membrane throughout oxidative phosphorylation. The catalytic portion of mitochondrial ATP synthase is comprised of 5 different subunits (alpha, beta, gamma, delta, and epsilon) gathered with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3.

ETHE1 is a mitochondrial sulfur dioxygenase involved in catabolism of sulfide that accumulates to toxic levels in ethylmalonic encephalopathy. Mutations of ETHE1 were detected in all the typical ethylmalonic encephalopathy patients analysed, but no ETHE1 mutations were identified in patients presenting with early onset progressive encephalopathy with ethylmalonic aciduria.

TBCA is a tubulin-folding protein which is involved in the early step of the tubulin folding pathway. TBCA is one of four proteins (cofactors A, D, E, and C) implicated in the pathway directing to properly folded beta-tubulin from folding intermediates. Cofactors A and D are thought to be a factor in capturing and stabilizing beta-tubulin in a quasi-native confirmation. TBCA is crucial for cell viability, if reduced it causes a decrease in the amount of soluble tubulin, alterations in microtubules and G1 cell cycle arrest. Cofactor E attaches to the cofactor D-tubulin complex, afterward, interaction with cofactor C triggers the release of tubulin polypeptides that are committed to the native state.

CBX1 is an enriched heterochromatin which belongs to the heterochromatin protein family. The centromeres related CBX1 identifies and binds histone H3 tails methylated at 'Lys-9', causing epigenetic repression. Collaboration with lamin B receptor (LBR) can impact the relations between the heterochromatin and the inner nuclear membrane. CBX1 has a vital part in the epigenetic control of chromatin structure and gene expression.

PMP2 is a small protein found in peripheral nerve myelin and spinal cord myelin, belongs to a family of fatty acid binding proteins. PMP2 partly decreases the inhibitory effect of T suppressors in the culture of immune lymph node cells. PMP2 protein is a lipid transport protein in schwann cells.

MANF is a 20kDa protein which belongs to the ARMET family. MANF was originally known as an arginine-rich region protein which was extremely mutated in a large number of tumors. MANF Expression is induced during ER stress, signifying that MANF takes part in protein quality control during ER stress.

Prefoldin subunit 3 (VBP1) is a member of the prefoldin subunit alpha family. VBP1 interacts with the Von Hippel-Lindau protein in order to create an intracellular complex. Since VBP1 serves as a chaperone protein, it is assumed to have a role in the transport of the Von Hippel-Lindau protein from the perinuclear granules to the nucleus or cytoplasm. VBP1 binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. VBP1 also binds to nascent polypeptide chain and stimulates folding in an environment in which there are numerous competing pathways for nonnative proteins.

MAP kinase-activated protein kinase 3 (MAPKAPK3) is involved in inflammatory Reaction by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally. MAPKAPK3 phosphorylates AU-rich elements (AREs)-binding proteins, like TTP/ZFP36, leading to control of stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36 (a major post-transcriptional regulator of TNF), promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity resulting in inhibition of dependent degradation of ARE-containing transcript. MAPKAPK3 is activated by growth inducers and stress stimulation of cells.

MAPRE1 (EB1) is a member of the intermediate/early gene family. MAPRE1 was first identified by its binding to the APC protein, which is often mutated in familial and sporadic, forms of colorectal cancer. MAPRE1 localizes to microtubules, especially the growing ends, in interphase cells. During mitosis, MAPRE1 is associated with the centrosomes and spindle microtubules. MAPRE1 is involved in microtubule polymerization, and spindle function by stabilizing microtubules and anchoring them at centrosomes.

Von Hippel-Lindau disease is a dominant inherited syndrome characterized by the predisposition to develop various kinds of benign and malignant tumors, including clear cell renal carcinomas, pheochromocytomas and hemangioblastomas of the central nervous system and retina. VHL syndrome is caused by germline mutation in the VHL tumor suppressor, and VHL tumors are associated with loss or mutation of the remaining wild-type allele. VHL has two domains: a roughly 100-residue NH2-terminal domain rich in b sheet (b-domain) and a smaller a-helical domain (a-domain), held together by two linkers and a polar interface. VHL protein is also involved in the degradation of hypoxia-inducible factor (HIF).

Ring Finger Protein 34 (RNF34) has E3 ubiquitin-protein ligase activity. RNF34 has a RINF finger, a motif recognized to be involved in protein-protein and protein-DNA interactions. RNF34 regulates the levels of CASP8 and CASP10 by targeting them for proteasomal degradation. In addition, RNF34 protects cells against apoptosis induced by TNF. RNF34 also binds phosphatidylinositol 5-phosphateand phosphatidylinositol 3-phosphate. Alternatively splicing results in multiple transcript variants encoding distinct isoforms.

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.

Activins are homodimers or heterodimers of the different β subunit isoforms, part of the TGFβ family. Mature Activin A has two 116 amino acids residues βA subunits (βA-βA). Activin displays an extensive variety of biological activities, including mesoderm induction, neural cell differentiation, bone remodelling, haematopoiesis, and reproductive physiology. Activins takes part in the production and regulation of hormones such as FSH, LH, GnRH and ACTH. Cells that are identified to express Activin A include fibroblasts, endothelial cells, hepatocytes, vascular smooth muscle cells, macrophages, keratinocytes, osteoclasts, bone marrow monocytes, prostatic epithelium, neurons, chondrocytes, osteoblasts, Leydig cells, Sertoli cells, and ovarian granulosa cells.

HERPUD1 is a multi-pass membrane protein which is a part of the endoplasmic reticulum quality control system. HERPUD1 owns 1 N-terminal ubiquitin-like domain and is expressed highly in the brain. HERPUD1 is also known as ER-associated degradation (ERAD) which takes part in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins.

NudE Neurodevelopment Protein 1-Like 1 also known as NDEL1 is a coiled-coil protein which participates in multiple processes as well as cytoskeletalorganization, cell signaling and neuron migration, outgrowth and maintenance. Alternatively spliced transcriptvariants encoding multiple isoforms have been observed for NDEL1, and a pseudogene of this gene is placed onthe long arm of chromosome X. One of the diseases associated with NDEL1 is iridocyclitis.

BCDIN3D is a member of the methyltransferase superfamily and contains 1 Bin3-type SAM domain. BCDIN3D acts in the catalysis of the transfer of a methyl group to an acceptor molecule. BCDIN3D is an O-methyltransferase which specifically dimethylates the 5' monophosphate of pre-miRNAs, serving as a negative regulator of miRNA processing. BCDIN3D mediates the methylation of pre-miR-145, as well as other pre-miRNAs.

Celiac disease is an enteropathy that is characterized by intestinal lesions of variable severity. Tissue-type transglutaminase (tTG) is believed to be the predominant autoantigen for celiac disease and the corresponding autoantibodies show higher sensitivity and specificity than anti-gliadin antibodies. Highly pure recombinant human tTG is now available to replace the traditionally used tTG fraction from guinea pig.
Tissue-type transglutaminase antigens have been specifically modified for improved handling: exchange of an active site amino acid eliminates the protein cross-linking activity of the enzyme, while maintaining the native three-dimensional structure and the enzyme's secondary GTPase activity. This engineering assures reproducible properties of the antigen preparations through the absence of variable and ill-defined covalent aggregates of tTG antigen and host cell proteins.

Polymeric immunoglobulin receptor (PIGR) is responsible for transcytosis of soluble dimeric IgAs and immune. PIGR binds polymeric IgA and IgM at the basolateral surface of epithelial cells, then the complex is transported across the cell to be secreted at the apical surface.cytokines, hormones, and pathogenic stimuliregulate PIGR expression. The expression of PIGR is critically regulated by the pro-inflammatory cytokines, such as IL-1, IL-4, TNF-α, and IFN-γ.

GMCSF is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. The active form of the protein is found extracellularly as a homodimer. This gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. Other genes in the cluster include those encoding interleukins 4, 5, and 13.
GM-CSF stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes. Granulocyte Macrophage Colony Stimulating Factor is a potent species-specific growth factor produced by a variety of cell types including T cells, B cells, macrophages, mast cells and endothelial cells. GM-CSF is produced in response to cytokine or immune stimulation and has been shown to stimulate the proliferation, maturation and function of hematopoietic cells.

VCAM1 is a member of the Ig superfamily. It is a cell surface sialoglycoprotein expressed by cytokine activated endothelium. VCAM-1 contains 6 or 7 immunoglobulin domains, and is expressed on both large and small vessels only after the endothelial cells are stimulated by cytokines. The protein has a number of functions including the regulation of leukocyte migration, leukocyte endothelial cell adhesion and signal transduction and may play a role in a number of inflammatory diseases (artherosclerosis and rheumatoid arthritis).

Native human C8 is a glycosylated protein consist of 3 polypeptide chains: The alpha chain and the gamma chain are disulfide linkedwhereas, The beta chain is non-covalently bound to the a-g complex. C8 is necessary for formation of the membrane attack complex and is activated by binding on the cell membrane newly-formed C5b,C6,C7 complexes. Each pathway of complement activation generates proteolytic enzyme complexes which bind the target surface. These enzymes cleave a peptide bond in the larger alpha chain of C5 releasing C5a and activating C5b. Although C5b is unstable it remains bound to the activating complex for a few minutes during which it binds a single C6 from the surrounding fluid or it decays and is no longer capable of forming MAC.The C5b,6 complex may also remain connected to the C3/C5 convertase where the binding of a single C7 exposes a membrane-binding region and C5b,6,7 can enter into the bilipid layer of the target cell. Each C5b-7 complex can bind 1 molecule of C8 causing the complex to enter more firmly into the membrane.