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Transcription elongation factor A protein-like 1 (TCEAL1) is a member of the transcription elongation factor A (SII)-like (TCEAL) family, which may function as nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. TCEAL1 is involved in transcriptional regulation. TCEAL1 is expressed in all tissues, especially highly expressed in the heart, ovary, prostate and skeletal muscle.

C8, a component of the complement system consists of three polypeptides C8A, C8B and C8G and takes part in the formation of Membrane Attack Complex (MAC). Patients with C8 deficiency are exposed to several bacteria infections. C8G, a member of the lipocalin family and calycin superfamily, is a secreted protein that can bind retinol. C8G is created in the liver, monocytes and fibroblast and has a role in clearing pathogens from an infected host.

CCL25 (Teck) is a novel CC chemokine, which is distantly related (about 20% amino acid sequence identity) to other CC chemokines. The mouse CCL25 cDNA has also been cloned and shown to encode a 144 a.a. protein, which exhibits 49% a.a. sequence identity to the human CCL25. Human and mouse CCL25 expression was shown to be greatly restricted to the thymus and small intestine. While dendritic cells are identified as the source of CCL25 production in the thymus, dendritic cells derived from bone marrow do not express CCL25. CCL25 signals through the CCR9 receptor. Teck is possibly involved in T-cell development.
Recombinant human and mouse Teck were shown to be chemotactic for activated macrophages, dendritic cells and thymocytes. The recombinant protein demonstrates chemotactic activity on thymocytes, macrophages, THP-1 cells, and dendritic cells but is inactive on peripheral blood lymphocytes and neutrophils.

Profilin1 (PFN1) is a ubiquitous actin monomer-binding protein which is a member of the profilin family. PFN1 significantly boosts skin wound healing in-vitro and in-vivo which may be mediated by purinergic receptors. PFN1 is also active in endothelial cell migration and vessel sprouting. PFN1 is thought to control actin polymerization in response to extracellular signals. PFN1 binds to actin and affects the formation of the cytoskeleton. In addition, PFN1 has an important role in the regulation of epithelial cell-cell adhesion. At high concentrations, profilin averts the polymerization of actin, while at low concentrations it enhances the polymerization. PFN1 gene deletion is linked to Miller-Dieker syndrome.

FHIT enzyme cleaves adenosine 5'' PPP 5'' A to yield AMP and ADP. FHIT gene includees the regular fragile site FRA3B on chromosome 3. Alterations and deletions of the FHIT gene are highly linked to the genesis and establishment of human tumors of the lung, cervix, breast, colon, stomach and pancreas. In normal cells, FHIT functions as a tumor suppressor and physically relates with ubiquitin conjugating enzyme 9.

CCL28 is part of the subfamily of small cytokine CC genes. CCL28 shows chemotactic activity for resting CD4 or CD8 T cells and eosinophils. CCL28 binds to chemokine receptors CCR3 and CCR10. CCL28 is involved in the physiology of extracutaneous epithelial tissues, including diverse mucosal organs. CCL28 mediates mucosal immunity in HIV exposure and infection. CCL28 is involved in the pathogenesis of inflammatory skin diseases.
Human CCL28 cDNA encodes a 127 amino acid residue precursor protein with a putative 22 amino acid residue signal peptide that is cleaved to produce the 105 amino acid residue mature protein. Human and mouse CCL28 are highly conserved, sharing 83% amino acid identity in their mature regions. CCL28 shares the most homology with CCL27/CTACK. Human and mouse CCL28 RNA expression was found to be highest in normal and pathologic colon with the protein being expressed by epithelial cells. Human CCL28 RNA was also present in normal and asthmatic lung tissues.

KLRB1 has an inhibitory role on natural killer (NK) cells cytotoxicity which are lymphocytes who facilitate cytotoxicity and secrete cytokines subsequent to immune stimulation. Some genes of the C-type lectin superfamily, like the rodent NKRP1 family of glycoproteins, are expressed by NK cells and take part in NK cell function regulation. KLRB1 holds an extracellular domain with a few characteristic motifs of C-type lectins, a transmembrane domain, and a cytoplasmic domain. Due to its external C terminus KLRB1 is considered to be a type II membrane protein.

Killer Cell lectin-Like Receptor Subfamily K, Member 1 (KLRK1) is an activating receptor which has recently generated considerable interest. The most fascinating of these, are a couple of closely related proteins known as MICA and MICB. These are cell-surface molecules distantly related to MHC class I proteins, and their genes have elements of heat shock promoters. Thus, MICA and MICB are expressed in the course of cell stress and are up-regulated in tumor cells and during viral infections. This receptor-ligand combination has a crucial role in the immune response to various pathologies.

Recombinant Human Lipocalin-2 also called Neutrophil Gelatinase Associated Lipocalin (NGAL) belongs to a family of lipocans which include 25 proteins (including a1-microglobulin and b-lactoglobulin), which are characterized by their ability to bind small lipophilic substances in their hydrophobic core.
They thereby serve as transporters of substances like retinal, biliverdins & prostaglandins. There are indications that NGAL is involved in modulation of the inflammatory response and is found in the plasma of patients after stroke.

CDC37 is an essential protein in Saccharomyces cerevisiae and is a molecular chaperone with precise function in cell signal transduction. CDC37 forms a complex/associates with Hsp90 molecular chaperone as one of several auxiliary proteins that are collectively referred to as Hsp90 co-chaperones. CDC37 also forms complex with a number of protein kinases such as CDK4, CDK6, SRC, RAF-1, MOK, as well as eIF2 alpha kinases. CDC34 is involved in directing Hsp90 to its target kinases. CDC37 up-regulation is a common early event in some localized human cancers. CDC37 is necessary for maintaining prostate tumor cell growth and represents a novel target in the exploration for multitargeted therapies. CDC37 plays a role in regulating Hsp90 ATPase activity. CDC37 binds to Akt and HSP90 in the signal transduction pathway in human tumor cells. Tnf-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90. CDC37 and heat shock protein 90 bind specifically to the kinase domain of LKB1.

Thioredoxins are small disulphide-containing redox proteins (within the conserved Cys-Gly-Pro-Cys active site) that have been found in all the kingdoms of living organisms. Thioredoxin contains a single disulfide active site and serves as a general protein disulphide oxidoreductase. Thioredoxins are involved in the first unique step in DNA synthesis. It interacts with a broad range of proteins by a redox mechanism based on reversible oxidation of two cysteine thiol groups to a disulphide, accompanied by the transfer of two electrons and two protons. The net result is the covalent interconversion of a disulphide and a dithiol. It has been suggested that thioredoxin may catalyze the formation of correct disulfides during protein folding because of its ability to act as an efficient oxidoreductant. Trx also provides control over a number of transcription factors affecting cell proliferation and death through a mechanism referred to as redox regulation.

Geminin is a 25 kDa nuclear protein, which inhibits DNA replication and is degraded during the mitotic phase of the cell cycle. Geminin controls replication by binding to the licensing factor Cdt1, and is involved in neural differentiation. In addition, Geminin directly interacts with Six3 and Hox homeodomain proteins during embryogenesis and inhibits their functions. Geminin can also promote DNA replication. Geminin has 2 roles in 2 different stages of the cell cycle: Geminin is a negative regulator of DNA replication during the “S phase” of the cell cycle. Inhibition of Geminin during the “S phase” (by RNAi) results in an additional round of replication of portions of the genome. During the “M phase” of the cell cycle (mitosis) Geminin stabilizes the replication factor Cdt1 promoting DNA replication during the next cell cycle. Moreover, inhibition of Geminin during mitosis (by RNAi) causes destabilization of Cdt1 protein and impairment of DNA replication during the next cell cycle. Geminin thus guarantees that only one round of replication occurs during each cell cycle. It was discovered that Geminin is overexpressed in a number of malignancies and cancer cell lines. This maintains the concept that Geminin has also a positive role in DNA replication and cell cycle progression. Geminin accumulates through S, G2 and M phases of the cell cycle but is absent during the G1 phase. During the metaphase/anaphase transition of mitosis Geminin levels decrease.

Chondrolectin (CHODL) is a type I membrane protein with a carbohydrate recognition domain characteristic of C-type lectins in its extracellular portion. In other proteins, this domain is involved in endocytosis of glycoproteins and exogenous sugar-bearing pathogens. The CHODL protein localizes mainly to the perinuclear region.

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.

Vaspin (visceral adipose-specific SERPIN), a newly identified adipokine, which is a member of serine protease inhibitor family. Vaspin is also a unique insulin sensitizing adipocytokine in obesity. A recent publication indicates that induction of human vaspin mRNA expression in adipose tissue is regulated in a fat depot-specific manner and could be associated with parameters of obesity, insulin resistance, and glucose metabolism.

Coactosin-like protein (COTL1) is one of the numerous actin-binding proteins which regulate the actin cytoskeleton. COTL1 binds F-actin, it also interacts with 5-lipoxygenase, which is the first committed enzyme in leukotriene biosynthesis. COTL1 binds to F-actin in a calcium-independent way and has no direct effect on actin depolymerization.

Haptoglobin is a glycoprotein which is synthesized in the liver and circulates in the blood. Haptoglobin is produced typically by hepatocytes but also by other tissues: e.g. skin, lung, and kidney. It is a positive acute phase protein that binds free hemoglobin and removes it from the circulation to prevent kidney injury, and iron loss following hemolysis. The haptoglobin-hemoglobin complex is subsequently removed by the reticuloendothelial system (generally the spleen). As the reticuloendothelial system removes the haptoglobin-hemoglobin complex from the body, haptoglobin levels are reduced in hemolytic anaemias. In the course of binding hemoglobin, haptoglobin sequesters the iron inside hemoglobin, preventing iron-utilizing bacteria from benefitting from hemolysis.
Haptoglobin consists of two A- and two B-chains, connected by disulfide bonds. Three major haptoglobin phenotypes are known to exist (Hp 1-1, Hp 2-1, and Hp 2-2). Hp 1-1 is biologically the most effective in binding free hemoglobin and suppressing inflammatory responses associated with free hemoglobin. Hp 2-2 is biologically the least active, and Hp 2-1 is moderately active. Haptoglobin’s molecular mass ranges from 8-200 kDa.
Reduced levels can be seen in haemolysis and impaired liver function. High levels are a marker for acute or chronic inflammation. Ahaptoglobinemia or hypohaptoglobinemia are caused by mutations in the haptoglobin gene and/or its regulatory regions. Haptoglobin is also linked to diabetic nephropathy, the incidence of coronary artery disease in type 1 diabetes, Crohn's disease, inflammatory disease behavior, primary sclerosing cholangitis, susceptibility to idiopathic Parkinson's disease, and a reduced incidence of Plasmodium falciparum malaria.

MCM7 is a highly conserved mini-chromosome maintenance protein (MCM) vital for eukaryotic genome replication initiation. The MCM proteins form a hexameric protein complex which is a key component of the pre-replication complex (pre_RC) which takes part in replication forks formation and in DNA replication related proteins recruitment. The MCM complex is comprised of MCM2, 4, 6 and 7 proteins and possesses DNA helicase activity, such as DNA unwinding.

Chemokine (C-C motif) ligand 7 (CCL7) is a small cytokine known as a chemokine that was previously called monocyte-specific chemokine 3 (MCP3). Due to CCL7 possessing two adjacent N-terminal cysteine residues in its mature protein, it is classified among the subfamily of chemokines known as CC chemokines. CCL7 specifically attracts monocytes, and regulates macrophage function. It is produced by certain tumor cell lines and by macrophages. This chemokine is located on chromosome 17 in humans, in a large cluster containing many other CC chemokines and is most closely related to CCL2(previously called MCP1).

CRCP is a ubiquitous coupling protein for the calcitonin gene-related peptide and adrenomedullin receptors. CRCP controls ligand sensitivity in several tissues and has DNA-directed RNA polymerase activity, catalytic activity and calcitonin receptor activity.

S100A13 is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 family members are localized in the cytoplasm and/or nucleus of a wide range of cells, and are involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100A13 is extensively expressed in various types of tissues with an elevated expression level in the thyroid gland. In smooth muscle cells, S100A13 co-expresses with other family members in the nucleus and in stress fibers, suggesting diverse functions in signal transduction.

Cardiotrophin 1 (CT-1) is a 201 amino acid member of the interleukin-6 superfamily. It was identified by its ability to induce hypertrophic response in cardiac myocytes. CT-1 mRNA levels were found both in cardiac myocytes and in cardiac nonmyocytes. CT 1 was also detected in abundance in normal adult human lung and was expressed in both fetal and adult airway smooth muscle cells. CT 1 activates gp130 dependent signaling and stimulates the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway to transduce hypertrophic and cytoprotective signals in cardiac myocytes.
CT 1 has also a neurotrophic function. CTF1 deficiency causes increased motoneuron cell death in spinal cord and brainstem nuclei of mice during a period between embryonic day 14 and the first postnatal week. Moreover, CT-1 is a hepatocyte survival factor that efficiently reduces hepatocellular damage in animal models of acute liver injury. Cardiotrophin 1 expression is augmented after hypoxic stimulation and it can protect cardiac cells when added either prior to simulated ischaemia or at the time of reoxygenation following simulated ischaemia. Cardiotrophin 1 can induce expression of the protective heat shock proteins (hsps) in cardiac cells.
Cardiotrophin-1 increased ventricular expression of ANP, brain natriuretic peptide (BNP) and angiotensinogen mRNA.
Cardiophin 1 levels were significantly elevated in patients with heart failure, patients with dilatative cardiomyopathy, moderate/severe mitral regurgitation, stable and unstable angina and after acute myocardial infarction.

Sialic acid-binding Ig-like lectin 7 isoform 1, also known as SIGLEC7, is a newly discovered family of sialic acid-binding lectins of the immunoglobulin (Ig) superfamily. The extracellular portion has two Ig-like domains, with the amino-terminal V-set Ig domain containing amino acid residues which known to be implicated in sialic acid recognition by other Siglecs. The combination of an extracellular sialic acid binding site and an intracellular ITIM motif proposes that SIGLEC7 is involved in trans-membrane regulatory signaling reactions. Furthermore, on the cell surface SIGLEC7 exists as a monomer and is expressed on natural killer cells.