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Endothelial cells express three different vascular endothelial growth factor (VEGF) receptors, belonging to the family of receptor tyrosine kinases (RTKs). They are named VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). Their expression is almost exclusively restricted to endothelial cells, but VEGFR-1 can also be found on monocytes. All VEGF-receptors have seven immunoglobulin-like extracellular domains, a single transmembrane region and an intracellular split tyrosine kinase domain. VEGFR-2 has a lower affinity for VEGF than the Flt-1 receptor, but a higher signalling activity. Mitogenic activity in endothelial cells is mainly mediated by VEGFR-2 leading to their proliferation. Differential splicing of the flt-1 gene leads to the formation of a secreted, soluble variant of VEGFR-1 (sVEGFR-1). No naturally occurring, secreted forms of VEGFR-2 have so far been reported. The binding of VEGF165 to VEGFR-2 is dependent on heparin.

TNFR1 belongs to the TNF-receptor superfamily. TNFR1 is a receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha.
There are 2 types of soluble TNF receptors: sTNFR-I and sTNFR-II, which act to neutralize the biological activities of TNF alpha and TNF beta. The levels of these soluble receptors seem to increase as a result of shedding of the extracellular domains of the membrane bound receptors. TNF-a, TNFR1 and TNFR2 have roles in cellular differentiation. TNFR1 and TNFR2 function in cell type-specific renal injury.
TNFR1 is capable of signaling both cell survival and apoptosis. TNFR1-induced apoptosis requires 2 sequential signaling complexes. TNFR1 is capable of activating NF-kappaB, mediate apoptosis, and function as a regulator of inflammation. Oxidative stress promotes TNFR1 and TNFR2 self-interaction, ligand-independent and enhanced ligand-dependent TNF signaling. TNFR1 contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase. Human TNFR1 has a major region which controls cell surface expression. High levels of soluble TNF receptors are found in the amniotic fluid of pregnant women.
Germline mutations of the extracellular domains of TNFR1 are linked to the autosomal dominant periodic fever syndrome. The impaired receptor clearance is believed to be a mechanism of the disease. Familial hibernian fever (FHF) is caused by defects in TNFRSF1A gene.

Pro-opiomelanocortin preproprotein (POMC) is a polypeptide hormone precursor which experiences extensive, tissue-specific, post-translational processing via cleavage by subtilisin-like enzymes known as prohormone convertases. POMC regulates the corticosteroid production in the adrenal cortex. Furthermore, POMC is cleaved into ten hormone chains named NPP, g-MSH, ACTH, a-MSH, CLIP, Lipotropin b, Lipotropin g, b-MSH,b endorphin and Met-enkephalin. POMC gene defects are the cause of POMC deficiency, which is characterized by red hair and adrenal insufficiency.

CD68 encodes a 110-kD transmembrane glycoprotein that is highly expressed by human monocytes and tissue macrophages. It is a member of the lysosomal/endosomal-associated membrane glycoprotein (LAMP) family. The protein primarily localizes to lysosomes and endosomes with a smaller fraction circulating to the cell surface. It is a type I integral membrane protein with a heavily glycosylated extracellular domain and binds to tissue- and organ-specific lectins or selectins. The protein is also a member of the scavenger receptor family. Scavenger receptors typically function to clear cellular debris, promote phagocytosis, and mediate the recruitment and activation of macrophages. Alternative splicing results in multiple transcripts encoding different isoforms.

Cadherin 11 (CDH11) belongs to the cadherin superfamily (integral membrane proteins) which mediate calcium-dependent cell-cell adhesion. CDH11 is defined based on lacking a HAV cell adhesion recognition sequence specific to type I cadherins. CDH11 protein’s expression in osteoblastic cell lines, and its upregulation during differentiation, suggests a specific function in bone development and maintenance. CDH11 contributes to the sorting of heterogeneous cell types.

Legumain, also known as LGMN is a lysosomal cysteine protease which is found in all mouse tissues, however it was mainly abundant in the kidney as well as placenta. LGMN plays an essential role in the endosomal/lysosomal degradation system as the Legumain deficiency causes the accumulation of pro cathepsins B, H & L, another group of lysosomal cysteine proteases. Furthermore, over expression of LGMN in tumors is important for invasion/metastasis.

ULBP2 is a member of the MHC class I family. ULBP2 is ligand for the NKG2D receptor, composed with at least ULBP1 and ULBP3. ULBPs promote multiple signaling pathways in primary NK cells, triggering the production of cytokines and chemokines. Binding of ULBPs ligands to NKG2D encourages calcium mobilization and activation of the JAK2, STAT5, ERK and PI3K kinase/Akt signal transduction pathway. In CMV infected cells, ULBP2 cooperates with soluble CMV glycoprotein UL16. This cooperation is blocked with the NKG2D receptor, providing a mechanism in which CMV infected cells can escape the immune system. Additionally, UL16 causes ULBP2 to be held in the ER and cis-Golgi apparatus so that it does not reach the cell surface.

COMMD1 is accountable for inhibition of TNF-induced NFκB p50 and n facilitats of biliary copper excretion within hepatocytes. High expression of COMMD1 is localized in liver tissue, with lower expressions in lung, heart, kidney and brain tissue. COMMD1 interacts directly with COMMD6 and ATP7B, and indirectly with IκB-β and COMMD7.

HAUS augmin-like complex subunit 1 (HAUS1) is 1 of 8 subunits of the 390kDa human augmin complex/ HAUS complex. The augmin complex is a microtubule-binding complex required in microtubule generation within the mitotic spindle and is imperative to mitotic spindle compilation. HAUS1 contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. HAUS1 is broadly expressed, especially in the pancreas, kidney, skeletal muscle, liver and heart. However it is weakly expressed in the lung, brain and placenta. HAUS1-depleted cells hold functional cell cycle checkpoints, but the depletion reduces the G2/M cell cycle compartment and stimulates apoptosis. The HAUS1 protein level remains constant through the cell cycle.

Regulated upon Activation, Normal T-cell Expressed, and Secreted or RANTES is an 8 kDa protein classified as a chemotactic cytokine or chemokine. It has recently been renamed CCL5. RANTES is chemotactic for T cells, eosinophils and basophils and plays an active role in recruiting leukocytes into inflammatory sites. With the help of particular cytokines (i.e. IL-2 and IFN-?) that are released by T cells, RANTES also induces the proliferation and activation of certain natural killer (NK) cells to form CHAK (CC-Chemokine-activated killer) cells. It is also a HIV-suppressive factor released from CD8+ T cells. This chemokine has been localized to chromosome 17 in humans.

A 16-kDa peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores.

A 16-kDa peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores.

CRYGD is a member of the beta/gamma-crystallin family. Crystallins are the principal structural components of the vertebrate eye lens. The mammalian lens crystallins are divided into alpha, beta, and gamma families. Gamma-crystallins are involved in cataract formation. Defects in the CRYGD gene are responsible for cataract autosomal dominant (ADC), cataract congenital non-nuclear polymorphic autosomal dominant (CCP), cataract congenital cerulean type 3 (CCA3) and cataract crystalline aculeiform (CACA).

Mannoside Acetylglucosaminyltransferase 2 (MGAT2) is a golgi enzyme catalyzing an vital step in the conversion of oligomannose to complex N-glycans. MGAT2 enzyme has the characteristic glycosyltransferase domains: a short N-terminal cytoplasmic domain, a hydrophobic non-cleavable signal-anchor domain, and a C-terminal catalytic domain. MGAT2 gene mutations may lead to carbohydrate-deficient glycoprotein syndrome, type II.

Cathepsin F ( CTSF) is a member of the peptidase C1 family. Cathepsins are papain familycysteine proteinases which are a main component of the lysosomal proteolytic system. The CTSF gene isubiquitously expressed, and it maps to chromosome 11q13, close to the gene encoding cathepsin W. CTSF plays a role in normal protein catabolism. CTSF involved in some degradative processes occurring in tumor progression since it is highly expressed in some cancer cell lines.

Myozenin 1 (MYOZ1) is a member of the myozenin family. MYOZ1 is mostly expressed in the skeletal muscle. Members of the myozenin family act as calcineurin-interacting proteins which helps tether calcineurin to the sarcomere of cardiac and skeletal muscle. The myozenin family plays a significant role in modulation of calcineurin signaling.

Secreted Frizzled-Related Protein 5, also known as SFRP5, belongs to the SFRP family which includes a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs perform like soluble modulators of Wnt signaling. SFRP5 & SFRP1 are implicated in determining the polarity of photoreceptor cells in the retina. SFRP5 is highly expressed in the retinal pigment epithelium, as well as moderately expressed in the pancreas.

SKP is a 17kDa trimeric periplasmic chaperone that supports outer membrane proteins in their folding and insertion into membranes. SKP protein is necessary for the normal release of ompA from the inner membrane, the maintenance of its solubility in the periplasm, and, in association with lipopolysaccharide (LPS), for the efficient folding and insertion of ompA into the outer membrane.

SLAM family member 6 (SLAMF6) is a member of the SLAM family of immune cell receptors. SLAMF6 is a unique receptor on T cells which, when triggered potentiates T cell expansion in a CD28-independent manner. SLAMF6 has a high expression on NK-, T-, and B cells. SLAMF6 exhibits homotypic interactions and can connect with adaptor molecules such as SAP to alter immune cell function.

ArsA Arsenite Transporter, ATP-Binding, Homolog 1 (ASNA1) is a part of the arsA ATPase family. ASNA1 is the human homolog of the bacterial arsA gene. ArsA ATPase is the catalytic component of a multisubunit oxyanion pump In E.coli, which is in charge for resistance to arsenicals and antimonials. ASNA1 is also a main component of a transmembrane domain (TMD) recognition complex (TRC) which is involved in the post-translational delivery of tail-anchored (TA) proteins from the cytosol to the endoplasmic reticulum (ER).

Isopentenyl-diphosphate Delta-isomerase 2 (IDI2) is a member of the IPP isomerase type 1 family. IDI2 catalyzes the 1,3-allylic reorganization of the homoallylic substrate isopentenyl (IPP) to its extremely electrophilic allylic isomer, dimethylallyl diphosphate (DMAPP).

Eukaryotic translation initiation factor 3, subunit I (EIF3I) is part of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is essential for numerous steps in the initiation of protein synthesis. The eIF-3 complex links with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2: GTP: methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also essential for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. Among the diseases associated with EIF3I are clonorchiasis, and tonsillitis.

Osteoclasts are multinucleated cells that resorb bone and are essential for bone homeostasis. OSCAR plays crucial roles in the regulation of the innate and adaptive immune responses.Unlike the other LRC members, OSCAR expression is found specifically in preosteoclasts or mature osteoclasts. OSCAR is an important bone-specific regulator of osteoclast differentiation. Multiple alternative splicing transcript variants encodes different isoforms have been found for this gene.

Streptavidin is a tetrameric protein secreted by Streptomyces avidinii which binds firmly to biotin. Streptavidin is widely used in molecular biology through its unique high affinity for the vitamin biotin. The dissociation constant (Kd) of the biotin-streptavidin complex is about ~10-15 mol/L. The strong affinity recognition of biotin and biotinylated molecules has made streptavidin one of the most important components in diagnostics and laboratory kits. The streptavidin/biotin system has one of the biggest free energies of association of yet observed for noncovalent binding of a protein and small ligand in aqueous solution (K_assoc = 10**14). The complexes are also extremely stable over a wide range of temperature and pH.