salivary

Kallikrein-1 (KLK1) is a member of human tissue Kallikrein family. Human KLK1 precursor contains a singal peptide (residues 1 to 18), a short pro peptide (residues 19 to 24) and a mature chain (residues 25 to 262). The function of KLK1 is to cleave Kininogen in order to release the vasoactive Kinin peptide (Lysyl-Bradykinin or Bradykinin). The Kinin peptide controls blood pressure reduction, vasodilation, smooth muscle relaxation and contraction, pain induction and inflammation. KLK1 also plays a role in angiogensis and tumorigenesis.

PRB1 Protein, Human, Recombinant (GST & His) is expressed in E. coli.

Antimicrobial agent which utilizes hydrogen peroxide and thiocyanate (SCN) to generate the antimicrobial substance hypothiocyanous acid (HOSCN). May contribute to airway host defense against infection.

Gel-forming mucin that is thought to contribute to the lubricating and viscoelastic properties of whole saliva and cervical mucus. Mucin-5B/MUC5B Protein, Human, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 18.9 kDa and the accession number is Q9HC84.

HTN3 belongs to the histatin/statherin family. Histatins are salivary proteins that are considered to be major precursors of the protective proteinaceous structure on tooth surfaces (enamel pellicle). In addition, histatins exhibit antibacterial and antifungal activities. Post-translational proteolytic processing results in many histatins: e.g., histatins 4-6 are derived from histatin 3 by proteolysis. Histatins 1 and 3 are primary products of HIS1and HIS2 alleles, respectively. Histatins are believed to have important non-immunological, anti-microbial function in the oral cavity.

Renin is a highly specific endopeptidase, related to pepsin, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney. Its function in the salivary gland is not understood. Renin-2 Protein, Mouse, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 35.0 kDa and the accession number is P00796.

Fibroblast growth factor 10 (FGF10) is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF10 exhibits mitogenic activity for keratinizing epidermal cells, but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7. FGF10 plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. FGF10 is required for normal branching morphogenesis. It may play a role in wound healing. Defects in FGF10 are the cause of autosomal dominant aplasia of lacrimal and salivary glands (ALSG). ALSG has variable expressivity, and affected individuals may have aplasia or hypoplasia of the lacrimal, parotid, submandibular and sublingual glands and absence of the lacrimal puncta. The disorder is characterized by irritable eyes, recurrent eye infections, epiphora (constant tearing) and xerostomia (dryness of the mouth), which increases the risk of dental erosion, dental caries, periodontal disease and oral infections.

Cystatin-S, also known as Cystatin-4, Salivary acidic protein 1, Cystatin-SA-III and CST4, is a secreted protein which belongs to thecystatin family. Cystatin-4 / CST4 is expressed in submandibular and sublingual saliva but not in parotid saliva (at protein level). It is also expressed in saliva, tears, urine and seminal fluid. The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions. Cystatin-4 / CST4 strongly inhibits papain and ficin, partially inhibits stem bromelain and bovine cathepsin C, but does not inhibit porcine cathepsin B or clostripain. Papain is inhibited non-competitively. Cystatin-4 / CST4 is an S-type cystatin, based on its high level of expression in saliva, tears and seminal plasma. The specific role in these fluids is unclear but antibacterial and antiviral activity is present, consistent with a protective function.

β-Defensin 4A is a membrane-active cationic peptide that functions in inflammation and innate immune responses. There are at least 30 β-Defensins, which are distinguished from α-Defensins by the connectivity pattern of their three intermolecular disulfide bonds. Members of the Defensin family are highly similar in protein sequence. This gene encodes Defensin, DEFB4;, which has broad-spectrum antimicrobial activity and may play an important role in innate epithelial defense. They are highly expressed in skin and tonsils, and to a lesser extent in trachea, uterus, kidney, thymus, adenoid, pharynx and tongue. β-Defensin 4A has low expression in salivary gland, bone marrow, colon, stomach, polyp and larynx. No expression in small intestine. The 45 amino acid mature human BD3 shares 38% and 33% amino acid sequence identity with mouse and rat BD3, respectively.

Virulence factor that contributes to intimate adherence of enterohemorrhagic E.coli (EHEC) O157:H7 to host cells. Is able to cleave the secreted human mucin 7 (MUC7) and the glycoprotein 340 (DMBT1/GP340). Also cleaves human C1 inhibitor (SERPING1), a regulator of multiple inflammatory pathways, and binds and localizes it to bacterial and host cell surfaces, protecting them from complement-mediated lysis. Therefore, the current model proposes two roles for StcE during infection: it acts first as a mucinase, allowing passage of EHEC through the oral cavity by cleaving the salivary glycoproteins that are responsible for bacterial aggregation. Similarly, in the colon, StcE cleaves the glycoproteins that protect the intestinal epithelial surface, allowing EHEC to come into close contact with host cell membranes. Secondly, it acts as an anti-inflammatory agent by localizing SERPING1 to cell membranes.

Cystatin-SN, also known as Cystain-SA-I, Cystatin-1, Salivary cystatin-SA-1 and CST1, is a secreted protein which belongs to thecystatin family. The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. Cystatin-SN / CST1 is expressed in submandibular and sublingual saliva but not in parotid saliva (at protein level). Cystatin-SN / CST1 is also expressed in saliva, tears, urine and seminal fluid. Human saliva appears to contain several cysteine proteinase inhibitors that are immunologically related to cystatin S but that differ in their specificity due to amino acid sequence differences. Human salivary cystatins include Cystatin-S, Cystatin-S1, Cystatin-S2, Cystatin- SA, Cystatin-SN, Cystatin-C and Cystatin-D. Cystatin-SN is a much better inhibitor of papain and dipeptidyl peptidase I than is cystatin-S, although both inhibit ficin equally well.

Thymic stromal lymphopoietin (TSLP) is a novel member of the hemopoietic cytokine family that promotes the development of B cells and shares overlapping activity with IL-7. The human TSLP protein comprises a 28 amino acids (aa) signal sequence and 131 aa mature region. Human TSLP has two isoforms lfTSLP and sfTSLP produced by alternative splicing . lfTSLP is expressed in a number of tissues including heart, liver and prostate, and sfTSLP (63aa) is predominantly expressed in keratinocytes of oral mucosa, skin and in salivary glands. In aa sequence level, Human TSLP displays about 43% identity with mouse TSLP.TSLP is a cytokine that functions mainly on myeloid cells; it induces the release of T cell-attracting chemokines from monocytes and enhances the maturation of CD11c(+) dendritic cells.TSLP has proliferative effects on the myeloid cell line and may initiate asthma or atopic dermatitis responses by directly activating mast cells . TSLP signals cells via the interleukin-7 receptor-α chain (IL-7Rα),shared with IL-7, together with the TSLP receptor (TSLPR) subunit. Recent studies indicate that TSLP and its receptor are novel therapeutic targets for rheumatoid arthritis,for increased intraarticular TSLP concentrations in patients has caused chemotaxis and activation of arthritogenic T cells.

Tissue kallikrein 13 (hK13), also known as KLK-L4 (kallikrein-like gene 4), is a member of the human tissue kallikrein family of serine proteases having diverse physiological functions in many tissues. The KLK13 gene resides on chromosome 19q13.3-4 along with other 14 members in a gene cluster and shares a high degree of homology. KLK13 is a trypsin-like, secreted serine protease expressed specifically in the testicular tissue including prostate, salivary gland, breast, and testis. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and may play a role in metastasis. KLK13 may be involved in the pathogenesis and/or progression of breast and ovary cancers and is regarded as a novel cancer biomarker. Besides, KLK13 interacts and forms complexes with several serum protease inhibitors, such as alpha2-macroglobulin, and its expression is regulated by steroid hormones.

Statherin, also known as STATH, belongs to the histatin/statherin family. Statherin may play an important role in the maintenance of oral health. It prevents calcium phospate precipitation in saliva, so maintaining a high calcium level in saliva and preventing teeth from dissolving. Statherin also inhibits spontaneous precipitation of calcium phosphate salts. Thus, statherin and PRPs may prevent build-up of harmful deposits in the salivary glands and on the tooth surfaces. Statherin is a highly stable salivary protein of low molecular mass (5,380).

Wnt Inhibitory Factor 1 (WIF1) is a secreted protein, which binds WNT proteins and inhibits their activities. WNT proteins are extracellular signaling molecules involved in the control of embryonic development. WIF1 contains a WNT inhibitory factor (WIF) domain and 5 epidermal growth factor (EGF)-like domains. is found to be present in fish, amphibia and mammals. WIF1 is a recurrent target in human salivary gland oncogenesis.WIF1 may be involved in mesoderm segmentation. WIF1 is a tumor suppressor, specifically in nonfunctioning pituitary tumors.

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a member of the IGF-II mRNA-binding protein (IMP) family. IGF2BP2 is a member of a family of mRNA binding proteins that, collectively, have been shown to bind to several different mRNAs in mammalian cells, including one of the mRNAs encoding insulin-like growth factor-2. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is involved in the stimulation of insulin action. IGF2BP2 / IMP2 is expressed in oocytes, granulosa cells of small and growing follicles, Leydig cells, spermatogonia, and semen (at protein level). It is also expressed in testicular cancer (at protein level). It is expressed weakly in the heart, placenta, skeletal muscle, bone marrow, colon, kidney, salivary glands, testis, and pancreas. IGF2BP2 binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs. This binding is isoform-specific. IGF2BP2 may regulate the translation of target mRNAs.

Beta-defensin 3 is a member of the defensin family. Defensin family is comprised by microbicidal and cytotoxic peptides made by neutrophils. Members of the beta-defensin 3 family are highly similar in protein sequence. Beta-defensin 3 shows antimicrobial activity against Gram-positive bacteria S.aureus and S.pyogenes, Gram-negative bacteria P.aeruginosa and E.coli and the yeast C.albicans. Beta-defensin 3 is abundantly expressed in skin and tonsils, and to a lesser extent in trachea, uterus, kidney, thymus, adenoid, pharynx and tongue. It is also expressed in salivary gland, bone marrow, colon, stomach, polyp and larynx. However, in small intestine, it cannot be detected. Defensin has broad spectrum antimicrobial activity and may play an important role in innate epithelial defense. Beta-defensin 3 kills multiresistant S.aureus and vancomycin-resistent E.faecium. It has no significant hemolytic activity.

Tyrosine-protein kinase Blk, also known as B lymphocyte kinase, p55-Blk and BLK, is a member of theprotein kinase superfamily, Tyr protein kinase family and SRC subfamily. BLK / p55-Blk is expressed in lymphatic organs, pancreatic islets, Leydig cells, striate ducts of salivary glands and hair follicles. BLK / p55-Blk is a src-family protein tyrosine kinase specifically expressed in B-lineage cells of mice. The early onset of Blk expression during B-cell development in the bone marrow and the high expression levels of Blk in mature B cells suggest a possible important role of Blk in B-cell physiology. It is a modulator of beta-cells function, acting through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose. Defects in BLK are a cause of maturity-onset diabetes of the young type 11 which is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.

FZD2 may be a tumor suppressor gene in salivary adenoid cystic carcinomas (SACCs) that inhibits cell growth and migration. OMOD2 is a rare skeletal dysplasia and characterized by facial dysmorphism and shortness of the upper extremities and first metacarpal bones, and heterozygous FZD2 mutations may be disease-causing for OMOD2. heterozygous de novo mutation (G434V) in the frizzled class receptor 2 (FZD2) gene in a patient with distinct facial features including hypertelorism, bilateral cleft lip/palate, short nose with a broad nasal bridge, microretrognathia, and bilateral shortness of the upper limbs,

Carbonic anhydrase 7, also known as carbonate dehydratase VII, carbonic anhydrase VII, CA-VII and CA7, is a cytoplasm protein which belongs to thealpha-carbonic anhydrase family. Carbonic anhydrases are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. Carbonic anhydrases show extensive diversity in tissue distribution and in their subcellular localization. CA7 / CA-VII is predominantly expressed in the salivary glands. Alternative splicing in the coding region results in multiple transcript variants encoding different isoforms.

WIF1, also known as WIF-1 and wnt inhibitory factor 1, is a secreted protein that binds WNT proteins and inhibits their activities. It contains a WNT inhibitory factor (WIF) domain and 5 epidermal growth factor (EGF)-like domains. WNT proteins are extracellular signaling molecules involved in the control of embryonic development. WIF1 may be involved in mesoderm segmentation and can be detected in fish, amphibia and mammals. WIF-1 is a recurrent target in human salivary gland oncogenesis. Downregulation of WIF1 takes part in the development and progression of pleomorphic adenomas. WIF1 also is a tumor suppressor, and has been found to be epigenetically silenced in various cancers, specifically in nonfunctioning pituitary tumors. WIF1 are expected to have molecular function (protein tyrosine kinase activity) and to localize in various compartments (extracellular space, extracellular region).