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Gankyrin (proteasome 26S subunit) is a multicatalytic proteinase oncoprotein commonly overexpressed in most hepatocellular carcinomas. Proteasomes are found throughout eukaryotic cells at a high concentrations and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. Gankyrin interacts with S6 ATPase of the 19S regulatory particle of the 26S proteasome. Gankyrin is involved in theregulation of the phosphorylation of the retinoblastoma protein by CDK4, and to enhance the ubiquitinylation of p53 by MDM2. Gankyrin consists of 7 ankyrin repeats and is structurally similar to I kappa Bs. Gankyrin acts as a regulatory subunit of the 26s proteasome which is involved in the atp-dependent degradation of ubiquitinated proteins. Gankyrin is involved in progression of esophageal squamous cell carcinoma. gankyrin plays an oncogenic role especially in early stages of human epatocarcinogenesis. Gankyrin binds to NF-kappaB and suppresses its activity at the transcription level by modulating acetylation through SIRT1. Structural comparison between Gankyrin & p16(INK4A) identified numerous residues of gankyrin that are potentially important for CDK4 binding.

The 26S proteasome is a multicatalytic proteinase complex with a well ordered structure composed of two complexes- a 20S core and a 19S regulator. PSMD11 is a non-ATPase subunit of the 19S regulator. The 20S core is composed of four rings of 28 non-identical subunits; two rings are composed of 7 alpha subunits and two rings are composed of 7 beta subunits. The 19S regulator is composed of a base that contains six ATPase subunits and two non-ATPase subunits, and a lid that contains up to ten non-ATPase subunits. Proteasomes are spread throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An indispensable function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides.

Since April 2012, cases of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) have been identified in various countries. Coronaviruses are the cause of the common cold, SARS (severe acute respiratory syndrome) and other severe illnesses with high mortality rates, all are classified into coronavirus family. MERS-CoV is a new type of SARS found in the coronavirus family causing severe pneumonia with sudden and serious respiratory illness with high mortality rates as well. Since January 27th 2015, the WHO has reported 956 human cases, including 351 deaths. More cases of the new coronavirus strain are expected. Like in other coronaviruses, large surface spike glycoprotein is a central structural protein of this virus; it is located above the virion surface to bind and enter into the target cell. Spike protein has 2 domains- S1 and S2. The S1 domain is responsible for cellular tropism and interaction with target cell, while the S2 domain is responsible for membrane fusion. The C-terminal of S1 domain contains a receptor binding domain, and is also a potential target for vaccine development and an antigen for diagnosis.

SARS Coronavirus is an enveloped virus containing three outer structural proteins, namely the membrane (M), envelope (E), and spike (S) proteins. Spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. Accordingly, S-protein plays an important role in virus infection cycle and is the primary target of neutralizing antibodies.

S100A9 is part of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100A9 protein is localized in the cytoplasm and/or nucleus of a wide range of cells, and participates in the regulation of several cellular processes such as cell cycle progression and differentiation. S100 genes include no less than 13 proteins which are localized as a cluster on chromosome 1q21. S100A9 is involved in the inhibition of casein kinase and altered expression of this protein is associated with the disease cystic fibrosis.

4-1BBR is a member of the TNF-receptor superfamily. 4-1BB receptor contributes to the clonal expansion, survival, and development of T cells.4-1BBRcan also induce proliferation in peripheral monocytes, enhance T cell apoptosis induced by TCR/CD3 triggered activation, and regulate CD28 co-stimulation to promote Th1 cell responses. The expression of this receptor is induced by lymphocyte activation. TRAF adaptor proteins have been shown to bind to this receptor and transduce the signals leading to activation of NF-kappaB.

Type 1 cystatins are also called stefins which function as intracellular thiol protease inhibitors. Cystatin-B protein is able to form a dimer stabilized by noncovalent forces, inhibiting papain and cathepsins l, h and b. CSTB protein protects proteases leakage from lysosomes. Mutations in Stefin-B gene cause primary defects in patients with progressive myoclonic epilepsy (EPM1), a degenerative disease of the central nervous system. CSTB is overexpressed & elevated in the serum of HCC patients. Cystatin-B in vivo has a polymeric structure which is sensitive to the redox environment. Cystatin-B inhibits bone resorption by down-regulating intracellular cathepsin K activity despite increased osteoclast survival. Protein and mRNA levels of stefin B are significantly lower in atypical benign meningiomas. Stefins-A & Stefin-B which belong to the type-1 Cystatins, are up-regulated in lung tumours and thus able to counteract harmful tumour-associated proteolytic activity. Human stefin-A & Stefin-B form amyloid fibrils. Copper binding by stefin-B reduces amyloid fibril formation. A number of alternatively spliced CSTB isoforms were recognized in patients with progressive myoclonus epilepsy. Decreased CSTB activity in EPM1 pathogenesis is controled by cathepsins through increased activity of cathepsin-S & cathepsin-L.

SNF8 belongs to the SNF8 family of vacuolar sorting proteins and is restricts to both the nucleus and the cytoplasm. SNF8 is a subunit of the endosomal sorting complex essential for transport II (ESCRT-II), which is necessary for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway facilitates transfer of transmembrane proteins into the lumen of the lysosome for degradation. Additionally, the ESCRT-II complex takes part in transcription regulation by contributing to derepression of transcription by RNA polymerase II, probably by its interface with ELL.

SRP14 is a ribonucleoprotein complex which mediates the directing of proteins to the endoplasmic reticulum. The “Alu domain” of SRP is comprised of the heterodimer of the SRP9 and SRP14 proteins that are bound to the 5' and 3' terminal sequences of SRP RNA. SRP9/14 binding may be critical to the transcription, maturation, nucleolus localization and transport of SRP RNA.

SULT2B1 catalyzes the sulfate conjugation of numerous hormones, neurotransmitters, drugs and xenobiotic compounds. Sulfonation enhances the water solubility of molecules, and therefore their renal excretion, however it can also result in bioactivation to form active metabolites. SULT2B1b is localized in the cytosol and nuclei of human cells. SULT2B1b is selective for the sulfation of 3beta-hydroxysteroids such as dehydroepiandrosterone and pregnenolone, and participates in cholesterol sulfation in human skin.

Proline-Serine-Threonine Phosphatase Interacting Protein 1 (PSTPIP1) which is a scaffold protein and a regulator of the actin cytoskeleton binds ABL1, PTPN18, WAS, CD2AP, and PTPN12. PSTPIP1 also binds to the cytoplasmic tail of CD2, an effector of T cell activation and adhesion, negatively affecting CD2-triggered T cell activation. Mutations in PSTPIP1 are a cause of PAPA syndrome.

Parvalbumin alpha (PVALB) is a member of a larger group of EF hand proteins. PVALB is a high affinity calcium ion-binding protein which is structurally and functionally similar to calmodulin and troponin C. Parvalbumin is expressed in a specific population of GABAergic interneurones which are believed to have a role in maintaining the balance between excitation and inhibition in the cortex as well as the hippocampus.

HSP27 or Estrogen-Regulated 24K proteinis a part of the mammalian small heat shock protein family. The protein is expressed constitutively in many tissues and its expression is increased to high levels after different types of stress including high temperatures, toxic metals, drugs and oxidants. Furthermore, Hsp27 is phosphorylated in vivo on three phosphorylation sites (Ser15, Ser78 and Ser82) by protein kinases including MAPKAP kinase 2 and the stress-activated protein kinase SAPK2 (p38).

EFNB1 is a member of the Eph family. The cell-surface proteins Ephrins split into two groups, ephrin-A and ephrin-B, based on their structure and function and perform as ligands for Eph receptors. The transmembrane EFNB1 proteins have conserved cytoplasmic tyrosine residues that are phosphorylated upon interaction with an EphB receptor. In addition, EFNB1 transduces outside-in signals by C-terminal protein interfaces which influence integrin-mediated cell attachment and migration.

Vacuolar protein sorting-associated protein 4B (VPS4B) is a member of the AAA (ATPases associated with diverse cellular activities) family. VPS4B is involved in late steps of the endosomal multivesicular bodies (MVB) pathway and recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, probably in combination with membrane fission. A dominant negative mutant of VPS4B inhibits vacuolar protein sorting and also arrest HIV-1 and MLV budding.

Porphobilinogen deaminase (HMBS) belongs to the hydroxymethylbilane synthase superfamily. HMBS is a cytoplasmic enzyme found in the heme synthesis pathway. HMBS is the 3rd enzyme of the heme biosynthetic pathway and catalyzes the head to tail condensation of 4 porphobilinogen molecules into the linear hydroxymethylbilane. HMBS gene mutations cause errors in pyrrole metabolism which in turn lead to the autosomal dominant disease acute intermittent porphyria.

HscB Iron-Sulfur Cluster Co-Chaperone (HSCB) is a member of the hscB family and contains 1 J domain. HSCB is expressed in the lung, brain, stomach, spleen, ovary, testis, liver, muscle and heart and localized to mitochondria and cytoplasm. HSCB may function as a co-chaperone in iron-sulfur cluster assembly in mitochondria, it also interacts with ISCU and HSPA9.

HSF2BP, also known as HSF2 binding protein links with HSF2. This interaction takes place between the trimerization domain of HSF2 and the amino terminal hydrophilic region of HSF2BP which contains two leucine zipper motifs. Therefore, HSF2BP is involved in modulating HSF2 activation.

SARS Coronavirus is an enveloped virus containing three outer structural proteins, namely the membrane (M), envelope (E), and spike (S) proteins. Spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. Accordingly, S-protein plays an important role in virus infection cycle and is the primary target of neutralizing antibodies.

Once Chinese hamster K12 cells are starved from glucose, the synthesis of GRP (glucose-regulated protein) expressed. HSPA5 also called BiP, is part of the HSP70 family and plays a role in the folding and assembly of proteins in the endoplasmic reticulum. HSPA5 plays a key role in monitoring protein transport through the cell.
HSPA5 is a stress response protein which is induced by agents or conditions that adversely affect endoplasmic reticulum function. HSPA5 is crucial for the proper glycosylation, folding as well as for the maintenance of cell homeostasis and the prevention of apoptosis. HSPA5 is differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. HSPA5 guides posttranslational hepatitis B virus large envelope protein import into the mammalian ER. HSPA5 actively regulates multiple malignant phenotypes, including cell growth, migration, and invasion.

SDF-1 (stromal cell-derived factor-1) is small cytokine belonging to the chemokine family that is officially designated Chemokine (C-X-C motif) ligand 12 (CXCL12). It is produced in two forms, SDF-1?/CXCL12a and SDF-1?/CXCL12b, by alternate splicing of the same gene. Chemokines are characterized by the presence of four conserved cysteines, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening amino acid. CXCL12 is strongly chemotactic for lymphocytes and has been implicated as an important cell co-ordinator during development. During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow. Mice which were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life. As another role, CXCL12a alters also the electrophysiology of neurons. CXCL12 was shown to be expressend in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).
The receptor for this chemokine is CXCR4, which was previously called fusin. This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 is also bound by CXCR7 receptor.
The gene for CXCL12 is located on human chromosome 10. In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.

SARS or severe acute respiratory syndrome is a lethal kind of pneumonia generated by coronavirus. Coronaviruses are a family of viruses that causes a mild respiratory tract infection is a large type of creatures such as humans, pigs, cows, mice, cats etc. up to this day, the origin of the coronavirus is still unknown.

SARS Associated Coronavirus Spike is a causative agent of SARS virus. Diseases caused by Coronaviruses are usually controlled by CD8 T cells. The spike antigen is one of the main surface proteins on Coronavirus, therefore one of the main proteins that are candidates for vaccines.

SPON1 is a cell adhesion protein which take part in the regulation of protein binding activity, regulation of protein processing and regulation of amyloid precursor protein catabolic mechanism. SPON1 is found in the extracellular space and it co-localizes with collagen-containing extracellular matrix. SPON1 stimulates the attachment of spinal cord and sensory neuron cells and the outgrowth of neurites in vitro.