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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.

Ubiquitin-conjugating enzyme E2S (UBE2S) belongs to the ubiquitin-conjugating enzyme family. UBE2S is able to form a thiol ester linkage with ubiquitin in a ubiquitin activating enzyme-dependent manner, a typical property of ubiquitin carrier proteins. UBE2S catalyzes the covalent attachment of ubiquitin to other proteins. UBE2S acts as a crucial factor of the anaphase promoting complex/cyclosome (APC/C), which is a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. UBE2S acts by purposely elongating ''Lys-11''-linked polyubiquitin chains initiated by the E2 enzyme UBE2C/UBCH10 on APC/C substrates, augmenting the degradation of APC/C substrates by the proteasome and promoting mitotic exit. UBE2S also acts by elongating ubiquitin chains initiated by the E2 enzyme UBE2D1/UBCH5 in vitro; it is nevertheless uncertain whether UBE2D1/UBCH5 acts as an E2 enzyme for the APC/C in vivo. UBE2S is also involved in ubiquitination and consequent degradation of VHL, resu

Chlamydia is a common term for infection with any bacterium belonging to the phylum Chlamydiae. This term derives from the name of the bacterial genusChlamydiain the family Chlamydiaceae, order Chlamydiales, class and phylum Chlamydiae. There are two genera in Chlamydiaceae: Chlamydia and Chlamydophila. The genus Chlamydia includes three species: C. trachomatis, C. muridarum, and C. suis.

Inhibitor of Growth Family Member 1, also known as ING1 is a tumor suppressor protein which is able to induce cell growth arrest and apoptosis. ING1 is a nuclear protein which physically act together with the tumor suppressor protein TP53 and is a component of the p53 signaling pathway. In addition, Reduced expression and rearrangement of ING1 have been identified in various cancers. Multiple alternatively spliced transcript variants encoding distinct isoforms have been described for ING1.

KLK2 is a part of the grandular kallikrein protein family whose Members are engaged in a diverse array of biological functions. Kallikreins are a subgroup of serine proteases which are clustered on chromosome 19. KLK2 is a highly active trypsin-like serine protease which selectively cleaves at arginine remains. KLK2 is mostly expressed in prostatic tissue and is accountable for cleaving pro-prostate-specific antigen into its enzymatically active form. KLK2 is greatly expressed in prostate tumor cells and may possibly be a prognostic maker for prostate cancer risk.

KLK7 catalyzes the degradation of intercellular cohesive structures in the cornified layer of the skin in the continuous shedding of cells from the skin surface. Specific for amino acid residues with aromatic side chains in the P1 position. KLK7 cleaves insulin B chain at ''6-Leu- -Cys-7'', ''16-Tyr- -Leu-17'', ''25-Phe- -Tyr-26'' and ''26-Tyr--Thr-27''. KLK7 is involved in the activation of precursors to inflammatory cytokines.

SERPINA1 is secreted and is a serine protease inhibitor which its targets include elastase, plasmin, collagenase, thrombin, leucocytic proteases, trypsin, chymotrypsin, and plasminogen activator. Defects in SERPINA1 gene can cause emphysema or liver disease. Antral SERPINA1 expression is particularly induced by H. pylori infection. lung and prostate cancers have shown a significant increase in SERPINA1 serum levels compared with healthy controls though breast cancers did not show a significant change. SERPINA1 is an endogenous inhibitor of serine proteases and inhibits the catalytic domain of human recombinant matriptase in vitro. Rise in SERPINA1 occurs as an acute phase response to tissue necrosis and inflammation. mutations in SERPINA1 and SLC11A1 genes change the balance between elastase produced by leukocytes during phagocytosis.

Vascular endothelial growth factor (VEGF) is an important signaling protein involved in vessel formation As its name implies, VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/macrophage migration, neurons, cancer cells, kidney epithelial cells ). VEGF mediates increased vascular permeability, induces vasculogenesis and endothelial cell production, promotes cell migration, and inhibits apoptosis. In vitro, VEGF has been shown to stimulate endothelial cell mitogenesis and cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor. VEGF is located in normal cartilage though only osteoarthritic cartilage expresses the VEGF receptors, NP1, VEGFR1 and VEGFR2. The VEGF level in the culture media from OA chondrocytes was more than 3 folds higher than in media from normal chondrocytes

IFN-tau is also known as TP-1 (trophoblast protein-1) is a new class of type I IFN that is secreted by the trophoblast and is the signal for maternal recognition of pregnancy in sheep. IFN- tau has potent immunosuppressive and antiviral activities similar to other type I IFN but is less cytotoxic than IFN-alpha and IFN-beta. The current investigation concerns the effect of recombinant ovine IFN- tau (rOIFN- tau) on the modulation of MHC class I and II expression on cloned mouse cerebrovascular endothelial (CVE) cells.
IFN-tau induced tyrosine phosphorylation of Stat1 and upregulated the expression of MHC class I on CVE. One proposed action by which type I IFN reduces the relapse rate in MS is via interference with IFN-?-induced MHC class II expression. IFN- tau was shown to downregulate IFN-?-induced MHC class II expression on CVE and, hence, may be of potential therapeutic value in downregulating inflammation in the central nervous system (CNS). IFN- tau did not upregulate the expression of MHC class II on CVE. IFN- tau also inhibited the replication of Theiler's virus in CVE.

Krueppel-like factor 12 (KLF12) belongs to the Kruppel-like zinc finger protein family and can repress expression of the AP-2 alpha gene by binding to a particular site in the AP-2 alpha gene promoter. AP-2 alpha (Activator protein-2 alpha) is a developmentally-regulated transcription factor and vital regulator of gene expression during vertebrate development and carcinogenesis. KLF12 gene repression entails binding with a corepressor, CtBP1.

CIAO1 is a vital component of the cytosolic iron-sulfur (Fe/S) protein assembly machinery. CIAO1 protein is required for the maturation of extra mitochondrial Fe/S proteins and seems to specifically modulate the trans-activation activity of WT1. CIAO1 participates in chromosome segregation as a part of the mitotic spindle-associated MMXD complex.

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) induces proliferation, migration, and fenestration in capillary endothelial cells derived from endocrine glands. Its expression is induced by hypoxia and is restricted to the steroidogenic glands (ovary, testis, adrenal, and placenta). Its expression is often complementary to the expression of VEGF (MIM 192240), suggesting that these molecules function in a coordinated manner. EG-VEGF potently contracts gastrointestinal (gi) smooth muscle. Induces proliferation, migration and fenestration (the formation of membrane discontinuities) in capillary endothelial cells derived from endocrine glands. Has little or no effect on a variety of other endothelial and non-endothelial cell types.

Macrophage Scavenger Receptor 1, also known as MSR1 is a member of the class A macrophage scavenger receptors, which comprises three different types 1, 2 and 3 generated by alternative splicing. Furthermore, these receptors or isoforms are macrophage-specific trimeric integral membrane glycoproteins and have been implicated in many macrophage-associated physiological as well as pathological processes which include atherosclerosis, Alzheimer's disease, and host defense.

IL3 is a potent growth promoting cytokine. This cytokine is capable of supporting the proliferation of a broad range of hematopoietic cell types. It is involved in a variety of cell activities such as cell growth, differentiation and apoptosis. This cytokine has been shown to also possess neurotrophic activity, and it may be associated with neurologic disorders.

Vascular endothelial growth factor is an important signaling protein involved in both vasculogenesis and angiogenesis. As its name implies, VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/macrophage migration, neurons, cancer cells, kidney epithelial cells ).VEGF mediates increased vascular permeability, induces angiogenesis, vasculogenesis and endothelial cell growth, promotes cell migration, and inhibits apoptosis. In vitro, VEGF has been shown to stimulate endothelial cell mitogenesis and cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor.
Elevated levels of this protein is linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

Glypican 4, also known as GPC4, is part of a family of glycosylphosphatidylinositol (GPI)-anchored heparan sulphate proteoglycans (HSPGs) which take part in the control of cell division and growth regulation. GPC4 is broadly expressed in human tissues, including lung, kidney, heart, placenta, skeletal muscle, and pancreas. In addition, GPC4 has been shown to be present in astrocytes, haematopoietic-progenitor and bone-marrow-stromal cells.

Serpin Peptidase Inhibitor, Clade A Member 9, also known as serpin A9, belongs to the Serpin superfamily of serine protease inhibitors. Serpins are the most extensively distributed superfamily of protease inhibitors which use a conformational modification to inhibit target enzymes. Serpins are known to inhibit serine proteases as well as inhibiting caspases in addition to papain-like cysteine proteases. Serpins are conformational labile and numerous of the disease-linked mutations of serpins outcome in misfolding or in pathogenic, inactive polymers. serpin A9 demonstrates inhibition towards trypsin, thrombin, as well as plasmin and binds DNA and heparin.

KLF4 is a transcription factor that performs as both an activator and repressor. KLF4 is expressed mainly in erythroid tissues and found mostly in gut. KLF4 is takes part in the differentiation of epithelial cells in addition to skeletal and kidney development.

Chemokine (C-X-C motif) ligand (CXCL7) is a small cytokine belonging to the CXC chemokine family. It is a protein that is released in large amounts from platelets following their activation. It stimulates various processes including mitogenesis, synthesis of extracellular matrix, glucose metabolism and synthesis of plasminogen activator.

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.

Epidermal growth factor has a profound effect on the differentiation of specific cells in vivo and is a potent mitogenic factor for a variety of cultured cells of both ectodermal and mesodermal origin. The EGF precursor is believed to exist as a membrane-bound molecule which is proteolytically cleaved to generate the 53-amino acid peptide hormone that stimulates cells to divide. EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture.

Lipophilin is a transmembrane proteolipid protein that is the predominant myelin protein present in the central nervous system. PLP functions in myelination. plays a role in the compaction, stabilization, and maintenance of myelin sheaths, as well as in oligodendrocyte development and axonal survival. Mutations associated with PLP gene cause X-linked Pelizaeus-Merzbacher disease and spastic paraplegia type 2. Two transcript variants encoding distinct isoforms have been identified for PLP gene.
PLP is the major myelin protein from the central nervous system and plays an important role in the formation or maintenance of the multilamellar structure of myelin.

TRAF2 protein is related with transduce signals from members of the TNFR superfamily. TRAF2 is located in the cytoplasm binds to TRAF1, TRAF2, or TRAF3, thus inhibiting TRAF function by sequestering the TRAFs in a suppressed state in the cytoplasm. Overexpression of TANK inhibits TRAF2-mediated NF-Kappa-B activation signaled by CD40 and both TNF receptors and inhibits LMP1-mediated NF-kappa-B activation by blocking the association of TRAF2 with LMP1. TRAF2 is necessary for the cellular response to TNF-alpha by connecting upstream signalling molecules to the IKKs and p65.

Kallikrein-5 (KLK5) is a member of the serine protease family of proteolytic enzymes. KLK5 is expressed in various tissues including the salivary gland, stomach, uterus, lung, thymus, prostate, colon, brain, thyroid, and trachea. KLK5 expression is up-regulated by estrogens and progestins. KLK5 is secreted and may be involved in desquamation in the epidermis. Kallikreins which are a subgroup of serine proteases, have distinct physiological functions. Many kallikreins are associated with carcinogenesis and some have potential as novel cancer and other disease biomarkers. The KLK5 gene is one of the 15 kallikrein subfamily members located in a cluster on chromosome 19.