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IL-1Ra is the natural antagonist of the pro-inflammatory cytokines Interleukin-1? and Interleukin-1?. IL-1Ra is produced by a variety of cells including monocytes, macrophages, neutrophils and fibroblasts in response to the binding of various pro-inflammatory cytokines.

TGFB2 is a 27.08 kDa protein having two identical 118 amino acid peptide chains linked by a single disulfide bond. TGFB2 is part of a family of five related cytokines that have an extensive variation of normal and neoplastic cells, indicating the importance of these homo-dimmer proteins as multi-functional regulators of cellular activity. The three mammalian isoforms of TGF-beta (TGFb1, TGFb2 and TGFb3) signal through the same receptor and stimulate similar biological responses. They are involved in physiological processes as embryogenesis, tissue remodelling and wound healing.

The fasting-induced adipose factor (FIAF, ANGPTL4, PGAR, HFARP) was identified as an adipocytokine up-regulated by fasting, by peroxisome proliferator-activated receptor agonists, and by hypoxia. At the protein level, in human and mouse blood plasma, FIAF was found to be present both as a native protein and in a truncated form. Differentiation of mouse 3T3-L1 adipocytes was associated with the production of truncated FIAF, whereas in human white adipose tissue and SGBS adipocytes, only the native FIAF could be detected. Interestingly, the truncated FIAF was produced by human liver.
Experimental data suggest that FIAF is mainly presented in human blood plasma in a truncated form (FIAF-S2), whose level is increased by fenofibrate treatment. Levels of both truncated and native FIAF showed marked inter individual variation but were not associated with body mass index and were not influenced by prolonged semistarvation.

Human thyrostimulin ranks among the glycoprotein hormone family. These hormones consist of two subunits, the common alpha- and specific beta-subunits, which associate noncovalently to form a heterodimer. The alpha-subunit combines with four distinct beta-subunits giving rise to four biologically active hormones in human: FSH, LH, TSH, and CG. FSH, LH, and TSH, mainly expressed in the anterior pituitary, are essential for coordinated endocrine regulation in the hypothalamus- pituitary axis and show to activate specific G protein–coupled receptors in the thyroid (TSH receptor) and gonads (LH and FSH receptors), respectively.
The heterodimeric glycoprotein hormones have only been identified in vertebrates and are highly conserved in organisms from primitive rayfin fish (Chondrostei) to human in both primary sequences and functional characteristics.
Corticotroph-derived glycoprotein hormone (CGH), also referred to as thyrostimulin, is a noncovalent heterodimer of glycoprotein hormone alpha 2 (GPHA2) and glycoprotein hormone beta 5 (GPHB5).
Recombinant A2/B5 heterodimeric glycoproteins activates human TSH receptors, but not LH and FSH receptors, and shows high affinity to TSH receptors in a radioligand receptor assay. The heterodimer also stimulates cAMP production and thymidine incorporation by cultured thyroid cells and increases serum thyroxine levels in TSH-suppressed rats in vivo. This new heterodimeric glycoprotein hormone was named as thyrostimulin based on its thyroid-stimulating activity. The expression of thyrostimulin in the anterior pituitary known to express TSH receptors suggested a paracrine mechanism.

Heparanase is an endo β-D-glucuronidase, which degrades heparan sulfate side chains of heparan sulfate proteoglycans (HSPGs) in the extracellular matrix. Heparanase plays an important role in ECM degradation, facilitating the migration and extravasation of tumor cells and inflammatory leukocytes (1,2,3). Upon degradation, heparanase releases growth factors and cytokines that stimulate cell proliferation and chemotaxis (4,5). Heparanase is a heterodimer comprised of a 50 kDa subunit harboring the active site and a 8 kDa subunit. It is produced as a latent 65 kDa precursor and proteolytically processed to its active form (1,6). Heparanase is highly expressed in myeloid leukocytes (i.e. neutrophils) in platelets and in human placenta. Human heparanase was found to be upregulated in various types of primary tumors, correlating in some cases with increased tumor invasiveness and vascularity and with poor prospective survival (7,8).

Cytokeratin 8 (KRT8) belongs to the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. KRT8 typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. KRT8 has a role in retaining cellular structural integrity and also functions in signal transduction and cellular differentiation. KRT8 gene mutations cause cryptogenic cirrhosis.

a-Synuclein (amino acids 1-140), an acidic neuronal protein of 140 amino acids, is extremely heat-resistant and is natively unfolded with an extended structure primarily composed of random coils. a-synuclein has been suggested to be implicated in the pathogenesis of Parkinson’s disease and related neurodegenerative disorders, and more recently, to be an important regulatory component of vesicular transport in neuronal cells. Moreover, recent studies have shown that a-synuclein has chaperone activity and that this activity is lost upon removing its C-terminal acidic tail (amino acids 96-140).

A human infecting coronavirus (viral pneumonia) called 2019 novel coronavirus, 2019-nCoV was found in the fish market at the city of Wuhan, Hubei province of China on December 2019.The 2019-nCoV shares an 87% identity to the 2 bat-derived severe acute respiratory syndrome 2018 SARS-CoV-2 located in Zhoushan of eastern China. 2019-nCoV has an analogous receptor-BD-structure to that of 2018 SARS-CoV, even though there is a.a. diversity so thus the 2019-nCoV might bind to ACE2 receptor protein (angiotensin-converting enzyme 2) in humans.While bats are probably the host of 2019-nCoV, researchers suspect that animal from the ocean sold at the seafood market was an intermediate host. RSCU analysis proposes that the 2019-nCoV is a recombinant within the viral spike glycoprotein between the bat coronavirus and an unknown coronavirus.

Interleukin-1 ra is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.

Prolactin is a lactogenic hormone secreted by the adenohypophysis .Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation.Prolactin has been shown also to have cytokine-like activities and to have important immunoregulatory activities. It contributes to the development of lymphoid tissues and the maintenance of physiological immune function and also modulates a variety of T-cell immune responses. Prolactin has been reported to activate cellular proliferation in nonreproductive tissue, such as liver, spleen, and thymus. It induces significant proliferation in aortic smooth muscle cells and also enhances proliferation of these cells induced by PDGF . Prolactin also appears to be directly mitogenic for pancreatic beta cells. Prolactin is also mitogenic for cultured astrocytes.

AKT Serine/Threonine Kinase 3 (Akt3) is a member of the Akt subfamily of serine/threonine protein kinases. Akt3is 1/3 closely related serine/threonine-protein kinases (Akt1, Akt2 and Akt3) called the Akt kinase and which regulate various processes including proliferation, metabolism, cell survival, growth and angiogenesis. The mentioned above is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Akt3 takes part in brain development and is critical for the viability of malignant glioma cells.

Cathepsin S (CTSS) belongs to the peptidase C1 family. CTSS is a lysosomal cysteine proteinase that participates in the degradation of antigenic proteins to peptides for presentation on MHC class II molecules. CTSS functions as an elastase over a broad pH range in alveolar macrophages.

PLAUR is one of 2 activators which convert the extracellular zymogen plasminogen to plasmin, a serine protease involved in a various normal and pathological processes that require cell migration and/or tissue destruction. PLAUR protein is synthesized and released from cells as a single-chain proenzyme with narrow enzymatic activity and is converted to an active two-chain disulfide-linked active enzyme by plasmin and other specific proteinases.

Glycoprotein Nmb (GPNMB) is a member of the PMEL/NMB family. GPNMB is a type I transmembrane glycoprotein which exhibits homology to the pMEL17 precursor, a melanocyte-specific protein. GPNMB is expressed in the lowly metastatic human melanoma cell lines and xenografts but has no expression in the highly metastatic cell lines. GPNMB might be involved in growth delay and reduction of metastatic potential. GPNMB is up-regulated in a number of cancer cells, including in glioblastoma multiforme. GPNMB is expressed in many melanoma cells, as well as in tissue macrophages, including liver Kuppfer cells and lung alveolar macrophages, in podocytes and in some cells of the ciliary body of the eye (at protein level). GPNMB is hardly detectable in the healthy brain.

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 that have been identified in mammals. The 14-3-3gamma, a subtype of the 14-3-3 family of proteins, was thought to be brain and neuron-specific. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways.

SQSTM1 is an adapter protein which binds ubiquitin and mediates the activation of NFKB1 by TNF-a, NGF and IL-1. SQSTM1 is involved in titin/TTN downstream signaling in muscle cells. SQSTM1 controls signaling cascades through ubiquitination. SQSTM1 participates in cell differentiation, apoptosis, immune response and regulation of K(+) channels. Mutations in UBA domain of the SQSTM1 protein cause Paget’s disease because the UBA is essential for aggregate sequestration and cell survival.

Syntaxin 4 (STX4) is a member of the syntaxin/epimorphin family of proteins. The Syntaxin family is cellular receptors for transport vesicles which participate in exocytosis in neutrophils. Syntaxin 4 is vital for normal regulation of glucose metabolism uptake in skeletal muscle and decline in STX4 protein levels lead to reduction of whole-body hormone-stimulated glucose metabolism. STX4 is expressed in neutrophils and neutrophil-differentiated HL-60 cells. The STX4 expression in neutrophils increases with differentiation.

BSND is a vital beta subunit for CLC chloride channels. These heteromeric channels are restricted to basolateral membranes of renal tubules and of potassium-secreting epithelia of the inner ear. BSND gene mutations are linked with Bartter syndrome with sensorineural deafness.

Peptidyl-tRNA hydrolase 2 (PTRH2) is a mitochondrial protein. PTRH2 is released during apoptosis from the mitochondria to the cytoplasm. When in the cytoplasm, PTRH2 regulates the function of 2 transcriptional regulators, TLE5 and TLE1, thus promoting caspase-independent cell death. Natural substrates for PTRH2 may be petidyl-tRNAs which drop off the ribosome during protein synthesis.

TRIAP1 has a p53-binding site in its second exon. TRIAP1 expression is reduced by small interfering RNA enhanced apoptosis, while overexpression of TRIAP1 protects cells from apoptosis triggered by DNA damage. TRIAP1 is highly induced when cells have low levels of genotoxic stresses, but not when DNA damage is severe. TRIAP1 is able to control apoptotic pathways by interacting with Hsp70 which inhibits activity of apoptosis protease activating factor-1.

C-type lectin domain family 7 member A 1 or CLEC7A is a protein, that in the innate immune system, acts against fungal pathogens. CLEC7A can be found in the immune system response cells such as monocytes, macrophages & neutrophils, or in dendritic and T cells. The protein is enhanced by macrophages by using GM-CSF, IL-4, or IL-13, or diminishes by dexamethasone, IL-10 and LPS.

Syntaxin-2 (STX2) is a member of the syntaxin/epimorphin family of proteins. Syntaxin family members are cellular receptors for transport vesicles which participate in exocytosis in neutrophils. STX2 regulates epithelial-mesenchymal interactions and epithelial cell morphogenesis and activation. STX2 is a t-SNARE which localizes to the apical plasma membrane and intracellular vesicular structures. In addition, STX2, along with SNAP-23, is essential for regulated surfactant secretion.