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Clusterin also named Apolipoprotein J (APO-J) is a 75-80 kD disulfide-linked heterodimeric protein containing about 30% of N-linked carbohydrate rich in sialic acid but truncated forms targeted to the nucleus have also been identified.
The precursor polypeptide chain is cleaved proteolytically to remove the 22-mer secretory signal peptide and subsequently between residues 227/228 to generate the a and b chains. These are assembled in anti-parallel to give a heterodimeric molecule in which the cysteine-rich centers are linked by five disulfide bridges and are flanked by two predicted coiled-coil a-helices and three predicted amphipathic a-helices.
Across a broad range of species clusterin shows a high degree of sequence homology ranging from 70% to 80%. It is nearly ubiquitously expressed in most mammalian tissues and can be found in plasma, milk, urine, cerebrospinal fluid and semen.
It is able to bind and form complexes with numerous partners such as immunoglobulins, lipids, bacteria, complement components, paraoxonase, beta amyloid, leptin and others. Clusterin has been ascribed a plethora of functions such as phagocyte recruitment, aggregation induction, complement attack prevention, apoptosis inhibition, membrane remodeling, lipid transport, hormone transport and/or scavenging, matrix metalloproteinase inhibition.
A genuine function of clusterin has not been defined. One tempting hypothesis says that clusterin is an extracellular chaperone protecting cells from stress induced insults caused by degraded and misfolded protein precipitates.
Clusterin is up- or down regulated on the mRNA or protein level in many pathological and clinically relevant situations including cancer, organ regeneration, infection, Alzheimer disease, retinitis pigmentosa, myocardial infarction, renal tubular damage, autoimmunity and others.

Galectin-4 is a member of the subfamily of galectins composed of two carbohydrate recognition domains having similar peptide chains. The galectins are a family of beta-galactoside-binding proteins having a role in modulating cell-cell and cell-matrix interactions, which inhibits chronic inflammations, GVHD, and allergic responses. LGALS4 expression is limited to small intestine, colon, and rectum, and it is underexpressed in colorectal cancer. LGALS4 binds as an endogenous ligand to glycosphingolipids having 3-O-sulfated Gal residues and bind as well to cholesterol-3-sulfate. LGALS4 takes part in cell adhesion. LGALS4 plays a role in crosslinking the lateral cell membranes of the surface-lining epithelial cells, thus supporting epithelial integrity against mechanical stress exerted by the bowel lume. LGALS4 is in charge of intestinal inflammation via selective regulation of peripheral and mucosal T-cell cell cycle, in addition to cell death by apoptosis of T-cells by a pathway independent of the activation of caspases. LGALS4 blockade decreases TNF-alpha inhibitor induced T-cell death. LGALS4 decreases pro-inflammatory cytokine secretion including IL-6 & IL-17.

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.

APIP catalyzes the dehydration of methylthioribulose-1-phosphate (MTRu-1-P) into 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P). APIP has an anti-apoptotic function and inhibits muscle ischemic impairment. APIP inhibits the cytochrome c-dependent and APAF1-mediated cell death.

IL-28B is a cytokine remotely related to type I interferons and the IL-10 family. Interleukin-28B, interleukin 28A (IL28A), and interleukin 29 (IL29) are 3 closely related cytokine genes which form a cytokine gene cluster on a chromosomal region mapped to 19q13. Expression of the cytokines encoded by these 3 genes can be induced by viral infection. All 3 cytokines interact with a heterodimeric class II cytokine receptor which consists of interleukin 10 receptor, beta (IL10RB) and interleukin 28 receptor, alpha (IL28RA).

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.

GCSF is a cytokine that controls the production, differentiation, and function of granulocytes. The active protein is found extracellularly. Three transcript variants encoding three different isoforms have been found for the GCSF gene. Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This csf induces granulocytes.

Parathyroid hormone (PTH), or parathormone, is secreted by the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calciumin the blood, whereas calcitonin (a hormone produced by the parafollicular cells of the thyroid gland) acts to decrease calcium concentration. PTH acts to increase the concentration of calcium in the blood by acting upon parathyroid hormone receptorin three parts of the body: In the bones- It enhances the release of calcium from the large reservoir contained in the bones. Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL, which can bind to osteoclast precursors containing RANK, a receptor for RANKL. The binding of RANKL to RANK stimulates these precursors to fuse, forming new osteoclasts which ultimately enhances the resorption of bone.
In the kidney- It enhances active reabsorption of calcium from distal tubules and the thick ascending limb.
In the intestine- It enhances the absorption of calcium in the intestine by increasing the production of vitamin D and upregulating the enzyme responsible for 1-alpha hydroxylationof 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D) which effects the actual absorption of calcium (as Ca2+ ions) by the intestine via calbindin.
Recombinant Human full length PTH 1-84 has potential as an anti-osteoporotic agent, due to its properties as a bone formation stimulant, it increases bone turnover, stimulating osteoblasts and reducing both vertebral and non vertebral fractures.

IL2 is a secreted cytokine that is important for the proliferation of T and B lymphocytes. The receptor of this cytokine is a heterotrimeric protein complex whose gamma chain is also shared by interleukin 4 (IL4) and interleukin 7 (IL7). The expression of this gene in mature thymocytes is monoallelic, which represents an unusual regulatory mode for controlling the precise expression of a single gene. The targeted disruption of a similar gene in mice leads to ulcerative colitis-like disease, which suggests an essential role of this gene in the immune response to antigenic stimuli.

Thymopentin, also known as TP-5, is a synthetic pentapeptide which is the active site of the naturally occurring hormone thymopoietin with immunomodulating properties (corresponding to the amino acids 32-36 of thymopoietin). Thymopentin enhances the production of thymic T cells and may help restore immunocompetence in immunosuppressed subjects. This agent also augments the effects of ionizing radiation by arresting cancer cells in the G2/M phase of the cell cycle.

Stem cell factor / KIT ligand (SCF) is a cytokine which binds CD117(c-Kit). SCF is also known as "steel factor" or "c-kit ligand". SCF exists in two forms, cell surface bound SCF and soluble (or free) SCF. Soluble SCF is produced by the cleavage of surface bound SCF by metalloproteases. SCF is a growth factor important for the survival, proliferation, and differentiation of hematopoietic stem cells and other hematopoietic progenitor cells. One of its roles is to change the BFU-E (burst-forming unit-erythroid) cells, which are the earliest erythrocyte precursors in the erythrocytic series, into the CFU-E (colony-forming unit-erythroid).

SCGN is a secreted calcium-binding protein which is found in the cytoplasm. It is related to calbindin D-28K and calretinin. Secretagogin is involved in KCL-stimulated calcium flux and cell proliferation.
Secretagogin plays a role in human non-functional pituitary adenomas.

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.

BIRC7 is a part of the inhibitor of apoptosis protein (IAP) family and contains a single copy of a baculovirus IAP repeat (BIR) as well as a RING-type zinc finger domain. The BIR domain is necessary for inhibitory activity & cooperates with caspases, while the RING finger domain sometimes increases anti-apoptotic activity but doesn’t inhibit apoptosis by itself. 2 transcript variants encoding diverse isoforms have been found for this gene. The 2 isoforms have dissimilar antiapoptotic characteristics, with isoform a protecting cells from apoptosis induced by staurosporine and isoform b defending cells from apoptosis induced by etoposide.
BIRC7 has direct contact with several caspases together with caspase-3, caspase-7, & caspase –9. BIRC7 inhibits the activation of caspase-9 induced by Apaf-1, cytochrome c, and dATP.

Endothelial cell-specific molecule 1 (ESM1) is a proteoglycan secreted by endothelial cells (mostly in the human lung and kidney tissues) and its mRNA expression is regulated by inflammatory cytokines. ESM1 has potent implications in lung endothelial cell-leukocyte interactions. In addition, ESM1 expression is detected in various epithelia and in adipocytes. ESM1 is involved in angiogenesis and it also promotes angiogenic sprouting. ESM1 expression is upregulated by TNF alpha, IL1 beta, or lipopolysaccharide and downregulated by IFN gamma. Genetically engineered cells overexpressing ESM1 induce tumor formation, implying that ESM1 might be involved in the pathophysiology of tumor growth in vivo.

PCK1 is a central regulating point for the regulation of gluconeogenesis. PCK1 has a vital part in this process by stimulating hepatic glucose production. The expression of PCK1 is controlled by cAMP, glucocorticoids, diet etc. Modulation of the signals controlling PCK1 levels offers a possible therapeutic tactic to the treatment of Diabetes and subsequently obesity.

PFDN6 is a subunit of the heteromeric prefoldin complex that chaperones developing actin and alpha- and beta-tubulin chains until they are transferred to the cytosolic chaperonin containing TCP1 (CCT) complex. PFDN6 binds specifically to cytosolic chaperonin (c-CPN), transfers target proteins to it and bind to developing polypeptide chain to promote folding in a setting where there are many competing pathways for nonnative proteins.

PIH1 domain-containing protein 1 (PIH1D1) is a member of the PIH1 family. PIH1D1 is a phylogenetically conserved protein vital for efficient processing of pre-rRNA through its association along with a class of small nucleolar RNAs (snoRNAs) during ribosomal biogenesis. SnoRNAs are linked in ribonucleoprotein particles localized to the nucleolus. PIH1D1 may also act as a novel modulator of apoptosis pathway.

Follistatin is a single-chain gonadal protein that specifically inhibits follicle-stimulating hormone release. The single FST gene encodes two isoforms, FST317 and FST344 containing 317 and 344 amino acids respectively, resulting from alternative splicing of the precursor mRNA. In a study in which 37 candidate genes were tested for linkage and association with polycystic ovary syndrome (PCOS) or hyperandrogenemia in 150 families, evidence was found for linkage between PCOS and follistatin. Follistatin binds directly to activin and functions as an activin antagonist. specific inhibitor of the biosynthesis and secretion of pituitary follicle stimulating hormone (fsh).

TPM1 is a member of the tropomyosin family which consists of a number of extremely conserved, extensively distributed 35-45 kDa actin-binding proteins that are involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosin-1 is composed of 2 alpha-helical chains arranged as a coiled-coil. TPM1 is polymerized end to end alongside the two grooves of actin filaments and provides stability to the filaments. TPM1 binds to actin filaments in muscle and non-muscle cells. TPM1 also functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. In non-muscle cells TPM1 is implicated in stabilizing cytoskeleton actin filaments. Smooth muscle contraction is controlled by interaction with caldesmon.
Alternatively spliced transcript variants encoding a range of isoforms have been described in smooth muscle and non-muscle cells. TPM1 Isoform 1 is expressed in adult and fetal skeletal muscle and cardiac tissues, with higher expression levels in the cardiac tissues, whereas Isoform 10 is expressed in adult and fetal cardiac tissues, but not in skeletal muscle.
Mutations in the TPM1 gene are linked to type 3 familial hypertrophic cardiomyopathy.

GH is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature.

PRKAG1 is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer comprised of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is a vital energy-sensing enzyme which supervises cellular energy status. PRKAG1 is one of the gamma regulatory subunits of AMPK. Alternatively spliced transcript variants encoding dissimilar isoforms were found.

Procalcitonin is a peptide hormone mainly produced by the C cells of the thyroid and certain endocrine cells of the lung. Under normal expression conditions, procalcitonin is immediately cleaved into three specific fragments, an N terminal residue, calcitonin and katacalcin. Levels of unprocessed procalcitonin rise significantly after bacterial infection, trauma or shock.

MAGE belongs to the MAGE gene family, that comprises 12 known genes, of which 6 are expressed in tumors. The Melanoma-associated antigen 3 genes were originally isolated from different kinds of tumors, and based on their virtually limited tumor-specific expression in adult tissues, they were used as targets for cancer immunotherapy. MAGEA3 is a tumor-specific antigen extensively expressed in solid and hematologic malignancies, but not in normal tissues, with the exclusion of testis and placenta. Consequently, MAGEA3 is an outstanding candidate tumor antigen.