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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.

Activin A Receptor Type 1 (ACVR1) is a member of TGF-beta serine/threonine kinase receptor family. ACVR1 forms a receptor complex contains2 type II and 2 type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate,bind and activate SMAD transcriptional regulators. ACVR1 takes part in left-right pattern formation during embryogenesis and is also essential in the BMP pathway which is responsible for the development and repair of the skeletal system.ACVR1 is linked to Fibrodysplasia Ossificans Progressiva which isknown for the formation of heterotopic bone throughout the body.

Leukemia Inhibitory Factor also called LIF is a lymphoid factor that promotes long-term maintenance of embryonic stem cells by suppressing spontaneous differentiation. Leukemia Inhibitory Factor has several functions such as cholinergic neuron differentiation, control of stem cell pluripotency, bone & fat metabolism, mitogenesis of factor dependent cell lines & promotion of megakaryocyte production in vivo. Human and mouse LIF exhibit a 78% identity in its amino acid sequence.

CDKN2C is a member of the CDKN2 cyclin-dependent kinase inhibitor family. CDKN2C cooperates with CDK4 or CDK6, and inhibits the activation of the CDK kinases, therefore acts as a cell growth regulator which regulates cell cycle G1 progression. CDKN2C suppresses the cell growth and proliferation with a correlated dependency on endogenous retinoblastoma protein RB. Studies in the knockout mice show CDKN2C takes part in regulating spermatogenesis, in addition to suppressing tumorigenesis.

Ornithine aminotransferase is a key enzyme in the pathway that converts arginine and ornithine into the major excitatory and inhibitory neurotransmitters glutamate and GABA. Ornithine aminotransferase (OAT) is a 49kDa nucleus-encoded protein imported into mitochondria to give the mature 48kDa OAT polypeptide. It is found in humans, animals, insects, plants and microorganisms. The OAT has a sex-differential expression in the mouse kidney. OAT plays central physiological roles in amino acid metabolism. OAT shows a large structural and mechanistic similarity to other enzymes from the subgroup III of aminotransferases that transfer an amino group from a carbon atom which doesn’t carry a carboxyl function. OAT is vital for nitrogen recycling from arginine but not for the stress-induced proline accumulation. OAT enzyme deficiency causes the autosomal recessive eye disease Gyrate Atrophy.

Pyridoxine-5'-phosphate oxidase (PNPO) is the rate-limiting enzyme in vitamin B6 synthesis. Vitamin B6 (Pyridoxal 5-prime-phosphate or PLP) is vital for normal cellular function, and some cancer cells have notable differences in vitamin B6 metabolism compared to their normal counterparts.Vitamin B6 is an essential co-factor for enzymes involved in both homocysteine metabolism and synthesis of neurotransmitters such as catecholamine. Mutations in the PNPO gene result in PNPO deficiency, a form of neonatal epileptic encephalopathy.

Chromgranin-A is part of the neuroendocrine secretory protein family. CHGA is located in secretory vesicles of neurons and endocrine cells. Chromgranin-A is a precursor to three biologically active peptides; vasostatin, pancreastatin, and parastatin. These peptides act as autocrine or paracrine negative modulators of the neuroendocrine system. Other peptides, including chromostatin, beta-granin, WE-14 and GE-25, are also derived from the full-length protein. Chromgranin-A has numerous biological activities on some tissues and organs and exerts a large spectrum of homeostatic actions, including antifungal and antimicrobial effect, modulation of cell adhesion, and inhibition of parathyroid hormone secretion.

PRPS1 catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis. PRPS1 catalyzes the phosphoribosylation of ribose 5-phosphate to 5-phosphoribosyl-1-pyrophosphate, which is essential for purine metabolism and nucleotide biosynthesis. Defects in PRPS1 result in phosphoribosylpyrophosphate synthetase superactivity, Charcot-Marie-Tooth disease X-linked recessive type 5 and Arts Syndrome.

Oncostatin M is a member of a cytokine family that includes leukemia-inhibitory factor, granulocyte colony-stimulating factor, and interleukin 6. This gene encodes a growth regulator which inhibits the proliferation of a number of tumor cell lines. It regulates cytokine production, including IL-6, G-CSF and GM-CSF from endothelial cells.

Cathepsin D is synthesized as a 54kDa precursor, which is proteolytically processed to an intermediate 48kDa single chain, which matures into more stable 34kDa and 14kDa two chain form. It is an estrogen-regulated lysosomal protease that has been suggested to facilitate cancer cell migration and invasion by digesting the basement membrane, extracellular matrix, and xonnective tissue. Because of its mitogenic and proteolytic activities, it has been implicated as a prognostic marker in many tumor types. Cathepsin D is expressed in epithelial cells as well as in macrophages.

Cathepsin-Z (CTSZ) is a lysosomal cysteine proteinase and member of the peptidase C1 family. CTSZ, which has been also known as cathepsin X and cathepsin P, exhibits carboxy-monopeptidase and carboxy-dipeptidase activities. CTSZ is expressed ubiquitously in cancer cell lines and primary tumors and, similar to other members of this family, takes part in tumorigenesis.

Prolactin is a lactogenic hormone secreted by the adenohypophysis .Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation.Prolactin has been shown also to have cytokine-like activities and to have important immunoregulatory activities. It contributes to the development of lymphoid tissues and the maintenance of physiological immune function and also modulates a variety of T-cell immune responses. Prolactin has been reported to activate cellular proliferation in nonreproductive tissue, such as liver, spleen, and thymus. It induces significant proliferation in aortic smooth muscle cells and also enhances proliferation of these cells induced by PDGF . Prolactin also appears to be directly mitogenic for pancreatic beta cells. Prolactin is also mitogenic for cultured astrocytes.

The cytokine Macrophage migration inhibitory factor (MIF) has been identified to be secreted by the pituitary gland and the monocyte/macrophage and to play an important role in endotoxic shock. MIF has the unique property of being released from macrophages and T cells in response to physiological concentrations of glucocorticoids. The secretion of MIF is tightly regulated and decreases at high, anti-inflammatory steroid concentration.

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, heparin, 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.

Kallikrein-3 (KLK3) belongs to the kallikrein-related peptidase family. Kallikreins are a subgroup of serine proteases having various physiological functions. Numerous kallikreins are involved in carcinogenesis and some may be prospective cancer and other disease biomarkers. Kallikrein-3 is 1 of the 15 kallikrein subfamily members located in a cluster on chromosome 19 and is a protease present in seminal plasma. KLK3 hydrolyzes semenogelin-1 consequently leading to the liquefaction of the seminal coagulum. KLK3 is assumed to act normally in the liquefaction of seminal coagulum, probably by hydrolysis of the high molecular mass seminal vesicle protein. Serum level of the KLK3 protein, called PSA in the clinical setting, is beneficial in the diagnosis and monitoring of prostatic carcinoma.

SHMT1 is a member of the SHMT family. SHMT1 is the cellular form of serine hydroxymethyltransferase, a pyridoxal phosphate-containing enzyme which catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and 5 10-methylene tetrahydrofolate. In addition, SHMT1 specifically provides one-carbon units for thymidylate biosynthesis, reduces methylenetetrahydrofolate pools for S-adenosylmethionine (SAM) synthesis by synthesizing serine, sequesters 5-methyltetrahydrofolate and inhibits SAM synthesis.

Carcinoembryonic antigen (CEA) is a glycoprotein present in fetal digestive-tract tissues; it’s involved in cell adhesion. The production of CEA stops before birth. CEA is called tumor marker since its elevated levels are found in the serum from individuals with colorectal, gastric, pancreatic, lung and breast carcinomas and in heavy smokers.
There are also benign conditions that elevate CEA levels such as smoking, infection, inflammatory bowel disease, pancreatitis, cirrhosis of the liver, and some benign tumors (in the equivalent organs which have cancers with elevated CEA). Typically, higher levels of CEA are found in men, smokers, and older individuals.
The presence of CEA assists in screening, in evaluating recurrent or disseminated disease, and in determining the success of surgical removal of malignant tumors.
CEA levels can be used as indicators of treatment success. The normal values range from 0.0 to 2.5 ng/ml of serum (from blood), in non-smokers, a greater amount than that may be suggestive of cancer. Levels above 20 ng/ml before treatment are associated with cancer which has already metastasized. Benign conditions do not usually cause a CEA increase over 10 ng/ml.
The high levels of CEA should return to normal after successful therapy, however if during follow up there’s an elevation in CEA levels it indicates a recurrence of tumor.
Carcinoembryonic antigen family belongs to the immunoglobulin superfamily; it consists of 29 genes, 18 of which are normally expressed.

IL11 is a member of the gp130 family of cytokines. These cytokines drive the assembly of multisubunit receptor complexes, all of which contain at least one molecule of the transmembrane signaling receptor IL6ST (gp130). IL-11 is shown to stimulate the T-cell-dependent development of immunoglobulin-producing B cells. It is also found to support the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells.

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.

Hemoglobin Subunit Zeta (Hbz) or Hba-x is a alpha-like hemoglobin and part of the globin family. The protein is expressed and produced in the the yolk sac in early stages of embryonic development. Hemoglobin subunit zeta has 2 pseudogenes and 5 functional genes.

SEPT2 is a GTPase which is mandatory for cytokinesis and related to exocytosis. Septin-2 protein is able to hetero-oligomerize with Septin6, 7 and in addition takes part in the organization of new growth in organisms. SEPT2 is associated with a Tau-based paired helical filament core and contributes to the creation of neurofibrillary tangle as integral constituents of paired helical filaments.

SET is part of a complex localized to the endoplasmic reticulum however is found in the nucleus. SET inhibits apoptosis following attack by cytotoxic T lymphocytes and can also enhance DNA replication of the adenovirus genome. SET inhibits acetylation of nucleosomes, particularly histone H4, by histone acetylases (HAT). This inhibition is accomplished by masking histone lysines from being acetylated.