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ATP-dependent Clp protease proteolytic subunit (CLPP) is a member of the peptidase family S14. CLPP cleaves peptides in a variety of proteins in a manner which requires ATP hydrolysis. CLPP being the catalytic core of the Clp proteolytic complex is commonly involved in many cellular processes via the regulation of intracellular protein quality. CLPP is responsible for a somewhat general and central housekeeping function rather than for the degradation of specific substrates.

Albumin is synthesized in the liver as preproalbumin which has an N-terminal peptide that is removed before the nascent protein is released from the rough endoplasmic reticulum. The product, proalbumin, is in turn cleaved in the Golgi vesicles to produce the secreted albumin. Albumin is a soluble, monomeric protein which comprises about one-half of the blood serum protein. Albumin functions primarily as a carrier protein for steroids, fatty acids, and thyroid hormones and plays a role in stabilizing extracellular fluid volume. Mutations in this gene on chromosome 4 result in various anomalous proteins. Albumin is a globular unglycosylated serum protein of molecular weight 65,000. The human albumin gene is 16,961 nucleotides long from the putative 'cap' site to the first poly (A) addition site. It is split into 15 exons which are symmetrically placed within the 3 domains that are thought to have arisen by triplication of a single primordial domain.
HSA is widely used to stabilize blood volume generally from donors but the fear of contamination such as HIV & Hepatitis has enticed great interest in the recombinant form which is identical to the natural blood.

Sirtuin-1 (SIRT1) belongs to the sirtuin family of proteins, homologs to the yeast Sir2 protein. Sirtuin family members are characterized by a sirtuin core domain and grouped into 4 classes. The functions of human sirtuins have not yet been established; though, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. It has been proposed that the human sirtuins may serve as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity.

Albumin is synthesized in the liver as preproalbumin which has an N-terminal peptide that is removed before the nascent protein is released from the rough endoplasmic reticulum. The product, proalbumin, is in turn cleaved in the Golgi vesicles to produce the secreted albumin. Albumin is a soluble, monomeric protein which comprises about one-half of the blood serum protein. Albumin functions primarily as a carrier protein for steroids, fatty acids, and thyroid hormones and plays a role in stabilizing extracellular fluid volume. Mutations in this gene on chromosome 4 result in various anomalous proteins. Albumin is a globular unglycosylated serum protein of molecular weight 65,000. The human albumin gene is 16,961 nucleotides long from the putative 'cap' site to the first poly (A) addition site. It is split into 15 exons which are symmetrically placed within the 3 domains that are thought to have arisen by triplication of a single primordial domain.
HSA is widely used to stabilize

Calcium/Calmodulin Dependent Protein Kinase II Inhibitor 1 (CAMK2N1), which interacts with CAMK2B, is a part of the CAMK2N family. CAMK2N1 is also interacts with CAMK2A in a way which requires CAMK2A activation by Ca2+. CAMK2N1 is potent and specific inhibitor of CaM-kinase II (CAMK2).

SDSL belongs to the serine/threonine dehydratase family and function as a serinespecific dehydratase. SDSL utilizes pyridoxal phosphate and is one of three key enzymes which take part in the metabolism of Glycine and serine.

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.

Kallikrein-15 (KLK15) is one of the 15 kallikrein subfamily members located in a cluster on chromosome 19. KLK15 contains numerous polyadenylation sites and alternative splicing results in multiple transcript variants encoding different isoforms. KLK15 is over expressed in prostate cancer and therefore uses as a diagnostic or prognostic marker for prostate cancer.

Overexpression of the HIF1AN is linked with tumor aggressiveness in pancreatic endocrine tumors. HIF1AN hydroxylates Notch ICD at two residues that are crucial for the function of Notch ICD as a transactivator within cells and during neurogenesis and myogenesis. HIF1AN is commonly expressed in invasive breast carcinoma. The hypoxic response and survival recommends that tumour regulation of HIF1AN is an additional important mechanism for HIF pathway activation. HIF1AN is an asparaginyl hydroxylase enzyme that controls the transcriptional activity of hypoxia-inducible factor. FIH1 is a part of the Fe2+ and 2-oxoglutarate-dependent dioxygenase superfamily, FIH1 is protein that hydoxylates a specific asparagine residue (Asn-803) within the HIF1A C-terminal transactivation domain. In normoxia, the HIF1AN-mediated hydroxylation of the HIF1? transactivation domain which results in blockage of the HIF1A-p300/CBP interaction and represses transcriptional activity of HIF1A targeted genes.

Serpin Peptidase Inhibitor, Clade C Member 1 (SERPINC1), which is a part of the serpin superfamily, is a plasma protease inhibitor. SERPINC1 inhibits thrombin and other activated serine proteases of the coagulation system, and regulates the blood coagulation cascade. SERPINC1 also inhibits Thrombin and Factors IXa, Xa and XIa. Deficiencies in SERPINC1 can cause ATIII deficiency, an autosomal dominant disease which might lead to a hereditary thrombophilia.

Methionine aminopeptidase 1 (METAP1) is a member of the peptidase M24A family. METAP1 removes the amino-terminal methionine from nascent proteins. METAP1 releases N-terminal amino acids, preferentially methionine, from peptides and arylamides. METAP1 is essential for normal progression through the cell cycle. The active site of METAP1 contains 2 adjacent divalent metal ions linked by a water molecule or hydroxide ion.

Alpha 1-microglobulin (A1M) is a lipocalin superfamily member (kernal lipocalins). A1M is a low molecular weight protein component of plasma. A1M is distributed in plasma and extravascular compartments of all organs. Alpha-1 Microglobulin is found in mammals, birds, amphibians and fish. The primary sites of A1M synthesis are the liver and the kidney. Around the opening of the lipocalin pocket three lysyl residues are situated; those residues carry yellow-brown modification derived from the binding and degradation of heme and kynurenin (a tryptophan metabolite). A1-Microglobulin’s reductase and dehydrogenase have broad biological substrate specificity properties due to its’ free cysteine side-chain which is located in a flexible loop. Alpha-1-microglobulin is glycosylated by three separate carbohydrate chains: two complex carbohydrates which are N-linked to asparagines at residues 17 and 96, and the other simple carbohydrate which is O-linked to threonine at position 5. The carbohydrates comprise 22% of the total molecular mass of the protein. The glycosylation varies between species.
A1M exists in two forms- a free form and complexed to other macromolecules: in humans- complexed to immunoglobulin A (IgA), in rat- complexed to alpha-1-inhibitor-3. Free A1M is exceptionally heterogeneous in charge (therefore also known as protein HC), and is found tightly linked to a chromophore. The free Alpha-1-microglobulin is a monomeric protein composed of one 188 residue polypeptide and contains three cysteines, two of which (residues 75 and 173) form a conserved intra-molecular disulphide link. The chromophoric group is covalently bound to the free cysteine residue at position 34. A1M binds retinol as a major ligand, but this is probably distinct from its covalent chromophore.
Half of all human plasma A1M (approximately 0.03mg/ml) forms a 1:1 complex with about 5% of plasma immunoglobulin A. The resulting macromolecular complexes’ molecular weight is 200000, and a plasma concentration of 0.3mg/ml. The complex can exhibit both antibody activity and affect many of the biological actions of free Alpha-1-microglobulin.
Alpha-1-microglobulin was first discovered in pathological human urine.
It was suggested that A1M might be involved in tissue defense against reactive oxygen species, oxidation by heme and kynurenin. Evidence also suggests that A1M functions in the regulation of the immune system. Other functions include inhibition of stimulation of cultured lymphocytes by protein antigens; induction of cell division of lymphocytes, a mitogenic effect that can either be enhanced or inhibited by the action of other plasma components; inhibition of neutrophil granulocyte migration in vitro; and inhibition of chemotaxis.

SERPINB5 (Maspin) is a tumor suppressor protein of the serine proteinase inhibitor family. Maspin plays a vital role in embryonic development through critical functions in cell adhesion. In addition, Maspin is present in normal breast and prostatic epithelial cells although down regulated in the particular carcinomas. SERPINB5 impedes the growth, invasion, and metastatic properties of mammary tumors as well as the invasive ability of pancreatic ductal adenocarcinoma cells. SERPINB5 being a breast tumor suppressor gene is a significant marker of the disease progression in breast neoplasms. Furthermore, high expression of maspin is linked to squamous cell carcinoma in non-small-cell lung cancer. Moreover, maspin expression has been directly linked with the biological aggressiveness of ovarian carcinoma. Maspin exhibits no serine protease inhibitory activity since it does not undergo the stressed to relaxed conformational transition typical of active serpins.

TIMP1 is a member of the TIMP family. TIMP1 is an inducible glycoprotein produced by various cell types. The TIMP1 glycoprotein is a natural inhibitor of the matrix metalloproteinases, which a group of peptidases involved in degradation of the extracellular matrix. TIMP1 binds in a reversible mode to MMPs, with regions in the N-terminal domain binding to the MMP substrate-binding site. On top of its inhibitory function against most of the known MMPs, TIMP1 is able to promote cell proliferation in a broad range of cell types, and may also have an anti-apoptotic role. Furthermore, TIMP1 has erthyroid-potentiating activity via translocation to the nucleus and also inhibits apoptosis in B-cells. The TIMP1 gene is situated within intron 6 of the synapsin I gene and is transcribed in the opposite direction. TIMP1 activity is dependent on the existence of disulfide bonds. TIMP1 transcription is extremely inducible in reaction to many cytokines and hormones.
Increased TIMP1 levels are connected with squamous cell laryngeal carcinoma. TIMP1 overexpression is linked to gastric cancer.

SIRT6 is part of the sirtuin family of proteins (Class IV), homologs to the yeast Sir2 protein. SIRT6 is characterized by a sirtuin core domain. Yeast sirtuin proteins are recognized by their ability to regulate epigenetic gene silencing and suppress recombination of rDNA. SIRT6, a chromatin-associated protein is involved in DNA repair. Human Sirtuins function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity.

CST6 belongs to the type 2 cystatin family. Unlike other family members that act as active cysteine protease inhibitors, CST6 restrain the inhibition of cathepsin B but is not active against cathepsin C. CST6 are secretable proteins that influence osteogenesis and bone resorption, regulation of the hepatocyte growth factor receptors, and the response to systemic inflammation.

GADD45GIP1 is a nuclear protein which takes part in apoptosis control. GADD45GIP1 is expressed in several tissues, such as heart, thyroid, trachea, kidney, ovary, pancreas, testis and stomach and acts as a negative regulator of G1 to S phase cell cycle production by collaborating with GADD45 proteins to inhibit the activity of cyclin-dependent kinases.

Caspase 3 Apoptosis-Related Cysteine Peptidase (CASP3) belongs to the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a key role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to generate 2 subunits, large and small, that dimerize to create the active enzyme. CASP3 protein cleaves and activates caspases 6, 7 and 9, and the protein itself is processed by caspases 8, 9 and 10. CASP3 is the leading caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is linked with neuronal death in Alzheimer's disease. In addition, CASP3 is involved in the cleavage of huntingtin. CASP3 also cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. CASP3 initiates cell adhesion in sympathetic neurons through RET cleavage.

Carboxypeptidase B (EC 3.4.17.2) catalyzes hydrolysis of the basic amino acids lysine, arginine and ornithine from the C-terminal end of polypeptides. The Mw was found to be 34.5 kDa, optimun pH-7.9, and pI-6. Carboxypeptidase B is inhibited by arginine, lysine and ornithine. The enzyme is not inhibited by di-isopropylfluorophosphate (DFP), but it is inhibited by metal chelating agents, e.g., EDTA, 1,10-phenanthroline.

Glutamyl endopeptidase (GLU-C) is an enzyme which cleaves peptide bonds on the carboxyl-terminal side of glutamic acid and, less frequently, aspartic acid (for example: Glu-|-Xaa, Asp-|-Xaa). GLU-C is a pathogenic factor involved in the adherence and colonization of human tissue. GLU-C preferentially cleaves peptide bonds on the carboxyl-terminal side of aspartate and glutamate. GLU-C is required for proteolytic maturation of thiol protease SspB and inactivation of SspC, an inhibitor of SspB. GLU-C is the most important protease for degradation of fibronectin-binding protein (FnBP) and surface protein A, which are involved in adherence to host cells. Furthermore, GLU-C protects bacteria against host defense mechanism by cleaving the immunoglobulin classes IgG, IgA and IgM. GLU-C may also be involved in the stability of secreted lipases.

Methionyl Aminopeptidase 1D (METAP1D) is a part of the peptidase M24A family. METAP1D which is overexpressed in colon cancer cell lines participates in tumorigenesis. METAP1D eliminates methionine from the N-terminus of nascent proteins.

Atosiban is the first oxytocin antagonist to be specifically developed for the treatment of preterm labor. Atosiban has a specific mode of action, inhibiting oxytocin-induced uterine contractions by blocking oxytocin receptors in the uterus. Extensive clinical investigations have shown Atosiban to be at least as effective as current tocolytic agents. In addition, due to its novel and specific mode of action, Atosiban has a markedly improved maternal side effects profile compared with conventional therapies.