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CARD18 belongs to the death-domain-fold superfamily which is induced by proinflammatory stimuli. CARD18 contains basically only a Caspase recruitment domain, inhibits generation of IL-1b by cooperating with caspase-1 and inhibiting connotation with RIP 2. The connotation of CARD18 to caspase-1 is enabled by the charge-charge interactions between the prodomain of caspase-1 and the surface charge of CARD18.

IL-21 is produced by CD4+ T cells in response to antigenic stimulation. Its action enhances antigen-specific responses of immune cells. The biological effects of IL-21 include induction of differentiation of T-cells-stimulated B-cells into plasma cells and memory B-cells, stimulation (in conjuction) with IL-4 of IgG production, and induction of apoptotic effects in na?ve B-cells and stimulated B-cells in the absence of T-cell signaling. Additionally, IL-21 promotes the anti-tumor activity of CD8+ T-cells and NK cells. IL-21 exerts its effect through binding to a specific type I cytokine receptor, IL-21R, which also contains the gamma chain (?c) found in other cytokine receptors including IL-2, IL-4, IL-7, IL-9 and IL-15. The IL-21/IL-21R interaction triggers a cascade of events which includes activation of the tyrosine kinases JAK1 and JAK3, followed by activation of the transcription factors STAT1 and STAT3.

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.

ATP synthase subunit O (ATP5O) localizes to the mitochondria and catalyzes ATP synthesis. ATP5O is a component of the F-type ATPase found in the mitochondrial matrix. F-type ATPases are composed of a catalytic core and a membrane proton channel. ATP5O seems to be part of the connector connecting these two components and may be involved in transmission of conformational changes or proton conductance.

GGPS1 is PART of the prenyltransferase family. GGPS1 is widely expressed in testis, heart and skeletal muscle, GGPS1 is localized in the cytoplasm and catalyzes the formation of geranylgeranyl pyrophosphate, a precursor of geranylgeranylated proteins and carotenoids. GGPS1 is a significant enzyme that is responsible for the C20-prenylation of proteins and for the regulation of a nuclear hormone receptor.

TSTA3 is a NADP(H)-binding protein. TSTA3 catalyzes the two-step epimerase and the reductase reactions in GDP-D-mannose metabolism, converting GDP-4-keto-6-D-deoxymannose to GDP-L-fucose. GDP-L-fucose is the substrate of numerous fucosyltransferases that take part in the expression of several glycoconjugates, including blood group ABH antigens and developmental adhesion antigens.
Mutations in TSTA3 result in leukocyte adhesion deficiency, type II.

Insulin-like growth factor-binding protein 4 (IGFBP-4) is a part of the insulin-like growth factor binding protein (IGFBP) family. IGFBP4 includes an IGFBP domain and a thyroglobulin type-I domain. IGFBP4 binds both insulin-like growth factors (IGFs) I and II. IGFBP-4 circulates in the plasma in both glycosylated and non-glycosylated forms. IGFBPs can either inhibit or enhance the biological activities of IGF, or act in an IGF independent manner. IGFBP-4 is consistently inhibits several cancer cells in vivo and in vitro, suggesting that it may function as an apoptotic factor. IGFBP4 is produced by all colon cancer cells. Binding of IGFBP-4 prolongs the half-life of the IGFs and changes their interaction with cell surface receptors.

Tissue plasminogen activator (abbreviated PLAT or tPA) is a secreted serine proteasewhich converts the proenzymeplasminogento plasmin, a fibrinolyticenzyme. Plasminogen is synthesized as a single chain which is cleaved by PLAT into the two chain disulfide linked plasmin.
This enzyme plays a role in cell migrationand tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding; decreased activity leads to hypofibrinolysiswhich can result in thrombosisor embolism.

P85a functions as the regulatory subunit of the class IA PI3-kinase isoforms a, b, and d.
It contains two SH2 domains that bind to tyrosine-phosphorylated growth factor receptors or substrate adaptor proteins.
It also contains a BH (breakpoint cluster region homology) domain that shows GAP activity towards the small GTPases Rab4, Rab5, Cdc42, Rac1 and to a lesser extend towards Rab6 and Rab11.
It was shown that PI3Ka catalytic subunit mediated phosphorylation of the p85a adapter reduces the lipid kinase activity of the heterodimer and this gives hints for PI3K-dependent signaling events not requiring production of 3’-phosphorylated phosphoinositides.
PI3Ka protein kinase activity has been implicated in IRS-1 serine phosphorylation in insulin-treated adipocytes and in STAT3 and IRS-1 phosphorylation upon activation of the type 1 IFN receptor by IFN-a.

MMP-3 enzyme is also known as Stromelysin-1or as Transin-1 which hydrolyzes natural collagen at physiological pH and temperature. It dissolves the intervertebral nucleus pulposus and annulus fibrosus of Herniated Lumbar Intervertebral Disk . MMP-3 hydrolyzes components of the extracellular matrix like proteoglycan, laminin, fibronectin, gelatin and collagen types III, IV and IX. It also activates pro-MMP-9 and pro-MMP-8 and superactivates plasmin activated MMP-1. MMP-3 is secreted as a latent proenzyme and is activated by a variety of proteinases, e.g. plasmin, trypsin, chymotrypsin, cathepsin G or human neutrophil elastase. MMP-3 was found to be capable of activating the precursor of IL1-beta.

IHH belongs to the hedgehog family of secreted signaling molecules. Hedgehog proteins are vital regulators of various developmental processes including growth, patterning and morphogenesis. The vertebrate homologues of Hh comprise several proteins including sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh). IHH has a specific role in bone growth and differentiation. In addition, IHH is involved in yolk sac vasculogenesis, having a central role in differentiation of epiblast cells into endothelial and red blood cells. IHH mRNA expression is detected in fetal lung, gut, stomach, liver, kidney, pancreas and strongly in cartilage in growth regions of the developing bone. IHH gene mutations cause the brachydactyly type A1 which is characterized by shortening or malformation of the phalanges and also the acrocapitofemoral dysplasia.

TAX1BP3 holds one PDZ domain, which uses for interactions with other proteins like the interaction with the C-terminus of Rhotekin that facilitates Rho-mediated activation of the FOS serum response element. In addition, PDZ domain interacts with beta-catenin to inhibit the transcriptional activity of beta-catenin. TAX1BP3 exists in several cell lines, such as HeLa, and is expressed in small quantities in peripheral blood leukocytes.

Active IL-12 is a p70 disulphide-linked dimer composed of p35 and p40 subunits. The protein is a pleiotropic cytokine produced primarily by antigen presenting cells and has multiple effects on T lymphocytes and natural killer cells in terms of stimulating cytotoxicity, proliferation, production of other cytokines and Th1 subset differentiation.

Matrix metalloproteinase-2 (MMP-2) is involved in endometrial menstrual breakdown, regulation of vascularization and the inflammatory response. MMP-2 contains a number of distinct domains: a prodomain that is cleaved upon activation; a catalytic domain containing the zinc binding site; a fibronectin like domain believed to have a role in substrate targeting; and a carboxyl terminal (hemopexin like) domain containing 2 N-linked glycosylation. The MMP-2 can degrade an extensive array of substrates including type IV, V, VII and X collagens as well as gelatin type I. In addition, MMP-2 interacts with THBS2, TIMP2, Thrombospondin 1, CCL7 and TIMP4. MMP-2 autocatalytic cleavage in the C-terminal generates the anti-angiogenic peptide, PEX. This process seems to be made possible by binding integrinv/beta3. Defects in the MMP-2 are the cause of Torg-Winchester syndrome (TWS), aka multicentric osteolysis nodulosis and arthropathy (MONA).

GSTP1 is a polymorphic gene encoding active, functionally different GSTP1 variant proteins that are believed to function in xenobiotic metabolism and have a part in susceptibility to cancer, and other diseases. GSTP1 is a glutathione S-transferase belonging to the pi class. GST family enzymes play a significant role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Based upon the biochemical, immunologic and structural properties of the soluble GSTs they are grouped into 4 main classes: alpha, mu, pi, and theta. The GSTP1 enzyme acts by catalyzing the reaction of glutathione with an acceptor molecule to form a Sulfur-substituted glutathione. The reactions employing glutathione contribute the transformation of a broad range of electrophiles, including reactive products of lipid, protein, carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress.
The GSTP1 inactivation through CpG hypermethylation is frequent in pituitary adenomas and may be a factor in aggressive pituitary tumor behavior. GSTP1 is may be a transcriptional target of the p53 tumor suppressor gene. Single-nucleotide polymorphism in GSTP1 is linked to modified protein binding, which influence GSTP1's contribution to carcinogen and drug metabolism, and possibly disease pathogenesis and/or drug response. GST-pi might have central roles in proliferation of androgen-independent human prostate cancer cells.

TIMP2 belongs to the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases that take part in degradation of the extracellular matrix. Besides having an inhibitory role against metalloproteinases, the encoded protein has a exclusive part among TIMP family members in its capability to directly suppress the proliferation of endothelial cells. Consequently, the encoded protein is crucial to the conservation of tissue homeostasis by suppressing the production of quiescent tissues as an answer to angiogenic factors, and by inhibiting protease activity in tissues undergoing renovation of the extracellular matrix.

Uromodulin (Tamm–Horsfall protein) is produced mainly by cells in the kidney’s thick ascending limb and is the most abundant protein in normal urine.
Uromodulin takes part in salt and water regulation, helps prevent urinary tract infections and kidney stones, and influences inflammation and immune activity in the kidney.
Reduced Uromodulin levels is associated with chronic kidney disease.
UMOD mutations causes unproper protein folding and thus transported incorrectly, resulting in its accumulation inside kidney tubular cells that damages the tubules and cause kidney disease (ADTKD-UMOD), associated with high uric acid, gout, and progressive kidney failure.

Immunoglobulin M (IgM) is a basic antibody produced by B cells. IgM is the first antibody to emerge in response to initial exposure to an antigen. IgM antibodies are found in the blood and lymph fluid and are the third most widespread serum Ig. Immunoglobulin M (IgM), being the 3rd most widespread serum Ig and exists in two forms- mostly as a pentamer (970kDa) but also as a hexamer. The pentameric IgM has 10 binding sites since each monomer has two antigen binding sites. Due to distance constraints in the hexameric complex, the J chain is found in pentameric IgM but not in the hexameric form. IgM antibodies, which appear early in the course of an infection, typically reappear to a smaller extent after additional exposure. IgM, as opposed to IgG antibodies, do not pass across the human placenta. These properties of IgM make it suitable for the diagnosis of infectious diseases.

DNAJC19 is part of a complex involved in the ATP-dependent transport of transit peptide-containing proteins from the inner cell membrane to the mitochondrial matrix. DNAJC19 is a single-pass membrane protein which contains a J domain and is localized to the inner membrane of the mitochondrion. Expressed ubiquitously, DNAJC19 acts as a component of the mitochondrial DNAJC19 complex that is responsible for the ATP-dependent translocation of select proteins from the inner mitochondrial membrane to the mitochondrial matrix. Defects in the DNAJC19 gene are the cause of 3-methylglutaconic aciduria type 5 (MGA5), otherwise known as dilated cardiomyopathy with ataxia (DCMA).

NT5M is a member of the 5'(3')-deoxyribonucleotidase family. NT5M localizes to the mitochondrial matrix. The NT5M enzyme dephosphorylates the 5'- and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides. The NT5M gene is located on chromosome 17 p11.2 in the critical region deleted in the Smith-Magenis syndrome (SMS), a genetic disease of unidentified etiology.

Nicotinamide riboside kinase 2 (ITGB1BP3) is a member of the uridine kinase family and NRK subfamily. ITGB1BP3 catalyzes the phosphorylation of nicotinic acid riboside and nicotinamide riboside to create nicotinic acid mononucleotide and nicotinamide mononucleotide. ITGB1BP3 reduces laminin matrix deposition and cell adhesion to laminin, but not to fibronectin. ITGB1BP3 is involved in the regulation of PXN at the protein level and of PXN tyrosine phosphorylation. ITGB1BP3 also has a role in the regulation of terminal myogenesis.

Glutamic-Pyruvate Transaminase 2 (GPT2) catalyzes the reversible transamination among alanine and 2-oxoglutarate to create pyruvate and glutamate. GPT2 expressed mainly in muscle, fat and kidney and participates in the intermediary metabolism of glucose and amino acids.

The somatomedins, or IGFs, comprise a family of peptides that play important roles in mammalian growth and development. IGF1 mediates many of the growth-promoting effects of GH. Early studies showed that GH did not directly stimulate the incorporation of sulfate into cartilage, but rather acted through a serum factor, termed 'sulfation factor,' which later became known as somatomedin. Three main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2), and somatomedin B.