secreted glycoprotein

Follistatin-like 3 (FLRG Fstl3) is a secreted glycoprotein of the follistatin-module-protein family. It may have a role in leukemogenesis. FLRG Fstl3 is a recently described member of the FST family having an overall structure and activity profile similar to that of FST, including binding and neutralization of activin. FLRG Fstl3 is expressed in a wide range of adult tissues, not detected in hematopoietic cells except in patients with a B cell chronic leukemia and a translocation. Isoform 1 or the secreted form is a binding and antagonizing protein for members of the TGF-beta family, such us activin, BMP2 and MSTN. Inhibits activin A-, activin B-, BMP2- and MSDT-induced cellular signaling; more effective on activin A than on activin B. Involved in bone formation; inhibits osteoclast differentiation. Involved in hematopoiesis; involved in differentiation of hemopoietic progenitor cells, increases hematopoietic cell adhesion to fibronectin and seems to contribute to the adhesion of hematopoietic precursor cells to the bone marrow stroma. Isoform 2 of FLRG Fstl3 or the nuclear form of FLRG Fstl3 is probably involved in transcriptional regulation via interaction with MLLT10. Modulation of activin and other TGFβ superfamily signaling is the primary mechanism of action for both follistatin (FS) and FS-like 3 (FSTL-3). FLRG Fstl3 is likely to be a local regulator of activin action in gonadal development and gametogenesis and, further, that activin appears to have important actions in gonadal development and function that are critical for normal reproduction.

Zaire ebolavirus (strain Kikwit-95) Glycoprotein GP Protein (His & Myc) is expressed in HEK293 mammalian cells with N-10xHis and C-Myc tag. The predicted molecular weight is 34.7 kDa and the accession number is P0C773.

Pregnancy-specific beta-1-glycoprotein 9(PSG9) is a secreted protein and contains 3 Ig-like C2-type (immunoglobulin-like) domains, 1 Ig-like V-type (immunoglobulin-like) domain. It is a member of the PSG family, a group of closely related secreted glycoproteins that are highly expressed in fetal placental syncytiotrophoblast cells. The members of the PSG protein family all have a characteristic N-terminal domain that is homologous to the immunoglobulin variable region. PSGs become detectable in serum during the first two to three weeks of pregnancy and increase as the pregnancy progresses, eventually representing the most abundant fetal protein in the maternal blood at term. PSGs function to stimulate secretion of TH2-type cytokines from monocytes, and they may also modulate the maternal immune system during pregnancy, thereby protecting the semi-allotypic fetus from rejection. PSGs are commonly expressed in trophoblast tumors. Eleven human PSG proteins (PSG1-PSG11) have been described.

Angiopoietin-like 3 (ANGPTL3) is a secreted glycoprotein that is structurally related to the angiopoietins. Mature human ANGPTL3 contains an N-terminal coiled coil domain and a C-terminal fibrinogen-like domain. ANGPTL3 is expressed in the liver from early in development through adulthood. Full length ANGPTL3 circulates in the plasma as do the proteolytically separated N-and C-terminal segments containing the coiled coil domain and fibrinogen-like domains,respectively. ANGPTL3 directly inhibits lipoprotein lipase (LPL) and endothelial lipase (EL), enzymes responsible for hydrolyzing circulating triglycerides and HDL phospholipids. ANGPTL3 promotes an increase in circulating triglyceride levels without altering VLDL or HDL secretion or uptake. ANGPTL3 expression in vivo is up-regulated by LXR agonists and down-regulated by insulin, leptin, and agonists of TRβ or PPARβ.

Pregnancy-specific beta-1-glycoprotein 5, is a secreted protein which belongs to the immunoglobulin superfamily, CEA family. It contains 2 Ig-like C2-type (immunoglobulin-like) domains and 1 Ig-like V-type (immunoglobulin-like) domain.

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.

CCN4 Wnt-induced secreted protein 1 (WISP1) is a secreted, cysteine-rich, heparin-binding glycoprotein, belonging to the CCN (CTGF CYR61 NOV) family of growth factors, and is involved in diverse biological functions such as cell growth, adhesion, migration, angiogenesis, tissue repair, and regulation of extracellular matrix. Members of the CCN family demonstrate high structural homology sharing four conserved cysteine-rich modular domains: an IGFBP (insulin-like growth factor-binding) domain, a von Willebrand type C domain, a thrombospondin domain and a C-terminal cysteine -knot domain. WISP1 is a putative downstream effector of the Wnt Frizzled pathway that mediates diverse developmental processes, was identified as an oncogene regulated by the Wnt-1-beta-catenin pathway. Thus WISP1 may contribute to Wnt-1-mediated tumorigenesis and malignance. Expression of WISP1 in some cells results in transformation and tumorigenesis. WISP1 acts to block cell death at a late stage in the p53-mediated apoptosis pathway. It was reported that WISP1 interacts with sulfated glycoconjugates, decorin and biglycan in the ECM of connective tissue, and possibly prevents their inhibitory activity in tumor cell proliferation.

Mannose-Binding Protein C (MBP-C) belongs to the Collectin family of innate immune defense proteins. MBL binds to an array of carbohydrate patterns on pathogen surfaces. Collectin family members share common structural features: a cysteine rich amino-terminal domain, a collagen-like region, an α-helical coiled-coil neck domain and a carboxy terminal C-type Lectin or carbohydrate recognition domain (CRD). MBL homotrimerizes to form a structural unit joined by N-terminal disulfide bridges. These homotrimers further associates into oligomeric structures of up to 6 units. Whereas two forms of MBL proteins exist in rodents and other animals. Human MBL-2 is 25 kDa. Human MBL-2 is a secreted glycoprotein that is synthesized as a 248 amino acid (aa) precursor that contains a 20 aa signal sequence, a 21 aa cysteine-rich region, a 58 aa collagen-like segment and a 111 aa C-type lectin domain that binds to neutral bacterial carbohydrates.

Erythropoietin (EPO) is a glycoprotein hormone that is principally known for its role in erythropoiesis, where it is responsible for stimulating proliferation and differentiation of erythroid progenitor cells. Erythropoietin is a member of the EPO TPO family. It is a secreted, glycosylated cytokine composed of four alpha helical bundles. The differentiation of CFU-E (Colony Forming Unit-Erythroid) cells into erythrocytes can only be accomplished in the presence of EPO. Physiological levels of EPO in adult mammals are maintained primarily by the kidneys, whereas levels in fetal or neonatal mammals are maintained by the liver. EPO also can exert various non-hematopoietic activities, including vascularization and proliferation of smooth muscle, neural protection during hypoxia, and stimulation of certain B cells. Genetic variation in erythropoietin is associated with susceptbility to microvascular complications of diabetes type 2. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy.

Interleukin 25 (IL-25) belongs to the Interleukin 17 (IL-17) family of proteins, which is comprised of six members (IL-17, IL-17B through IL-17F). These proteins are secreted and are structurally related by sharing a conserved cysteine-knot fold near the C-terminus, but have considerable sequence divergence at the N-terminus. With the exception of IL-17B, which exists as a non-covalently linked dimer, all IL-17 family members are disulfide-linked dimers. IL-17 family proteins are pro-inflammatory cytokines that induce local cytokine production and are involved in the regulation of immune functions. Human interleukin-17E (IL17E), also referred to as Interleukin-25 (IL25), is a distinct member of the IL17 cytokine family comprised of at least six members sharing a conserved cysteine-knot structure but divergent at the N-terminus. IL25 is a glycoprotein secreted as dimers by innate effector eosinophils and basophils, and present at very low levels in various peripheral tissues. IL25, together with IL17B, are ligands for the cytokine receptor IL17BR, and the cross-linking induces NF-κB activation and production of the proinflammatory chemokine IL-8, as well as ERK, JNK, and p38 activation. Overexpression of IL25 gene in transgenic mice suggested that this cytokine can regulate hematopoietic and immune functions, and additionally is identified as a proinflammatory cytokine favoring Th2-type immune responses possibly by enhancing the maintenance and functions of adaptive Th2 memory cells.

Microfibril-associated glycoprotein 4(MFAP4) is a secreted protein and contains 1 fibrinogen C-terminal domain, similarity to a bovine microfibril-associated protein. The protein has binding specificities for both collagen and carbohydrate. It is thought to be an extracellular matrix protein which is involved in calcium-dependent cell adhesion or intercellular interactions. The gene is located within the Smith-Magenis syndrome region.

Cerberus 1 is a secreted glycoprotein that forms disulfide-linked homodimers. It is a cytokine member of the DAN domain family of BMP antagonists that includes DAN (DAND1), Gremlin Drm (DAND2), PRDC (Protein Related to Dan and Cerberus, DAND3), and COCO Dante (DAND5). DAN family members contain a cysteine knot domain that is homologous to that found in other TGF-beta superfamily ligands. At the onset of gastrulation, Cerberus 1 is transiently expressed in anterior endodermal structures in response to Nodal and Shh. Cerberus 1 binds BMP-4 and Nodal and inhibits their activities. The inhibitory functions of Cerberus favor mesodermal development in the anterior region of the gastrula and suppresses posterior mesodermal differentiation. In chick and Xenopus, Cerberus 1 also regulates, but is not required for embryonic left-right polarization, neurulation, and head and heart induction.

Noggin is a secreted homodimeric glycoprotein that is an antagonist of bone morphogenetic proteins (BMPs). Mouse Noggin cDNA encodes a 232 amino acid (aa) residue precursor protein with 19 aa residue putative signal peptide that is cleaved to generate the 213 aa residue mature protein which is secreted as a homodimeric glycoprotein. Secreted Noggin probably remains close to the cell surface due to its binding of heparin-containing proteoglycans. Noggin binds some BMPs such as BMP4 with high affinity and others such as BMP7 with lower affinity. It antagonizes BMP bioactivities by blocking epitopes on BMPs that are needed for binding to both type I and type II receptors. Noggin is expressed in defined areas of the adult central nervous system and peripheral tissues such as lung, skeletal muscle and skin. During culture of human embryonic stem cells (hESC) or neural stem cells under certain conditions, addition of Noggin to antagonize BMP activity may allow stem cells to proliferate while maintaining their undifferentiated state, or alternatively, to differentiate into dopaminergic neurons.

Dickkopf-related protein 3 (DKK3) belongs to the DKK protein family including Dkk-1, 2, 3 and -4. DKK3 is a 350 amino acid secreted glycoprotein which is comprised of an N-terminal signal peptide and 2 conserved cysteine-rich domains that are separated by a 12 amino acid linker region. Dkk-3 also have one prokineticin domain. DKK3 is involved in embryonic development through its inhibition of the WNT signaling pathway. The Dkk family also includes Soggy, which is homologous to Dkk-3 but not to the other family members. Soggy has not been shown to inhibit Wnt signaling, and its role in the pathway is unclear.

Angiopoietin-2 (Ang-2; also ANGPT2) is a secreted glycoprotein that plays a complex role in angiogenesis and inflammation. Mature Ang-2 is 478 amino acids in length.Ang2 is widely expressed during development, but it is restricted postnatally to highly angiogenic tissues such as the placenta, ovaries, and uterus. It is particularly abundant in vascular endothelial cells (EC) where it is stored in intracellular Weibel Palade bodies..

Deleted in malignant brain tumors 1 protein, also known as glycoprotein 34, surfactant pulmonary-associated D-binding protein, DMBT1 and GP34, is a secreted protein which belongs to theDMBT1 family. DMBT1 contains 2CUB domains, 14SRCR domains and 1ZP domain. It is highly expressed in alveolar and macrophage tissues. In some macrophages, expression is detected on the membrane, and in other macrophages, it is strongly expressed in the phagosome phagolysosome compartments. Defects in DMBT1 are involved in the development of glioma (GLM). Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas , and ependymomas. DMBT1 may be considered as a candidate tumor suppressor for brain, lung, esophageal, gastric, and colorectal cancers. It may play roles in mucosal defense system, cellular immune defense and epithelial differentiation. DMBT1 may play a role as an opsonin receptor for SFTPD and SPAR in macrophage tissues throughout the body, including epithelial cells lining the gastrointestinal tract. It may be an important factor in fate decision and differentiation of transit-amplifying ductular (oval) cells within the hepatic lineage. DMBT1 may function as a binding protein in saliva for the regulation of taste sensation. It binds to HIV-1 envelope protein and has been shown to both inhibit and facilitate viral transmission.

PSG6 is a pregnancy-specific glycoprotein(PSG). PSGs are secreted proteins produced by the rodent and primate placenta and play a critical role in pregnancy success. The levels of PSGs are highest during the third trimester of pregnancy, a time marked by the most profound suppression of MS disease attacks. PSGs regulate T-cell function. The regulation of T-cell function during pregnancy is likely the result of significant hormonal changes and may well involve immunoregulatory proteins derived from the placenta. Pregnancy specific glycoproteins (PSGs) are the most abundant placentally derived glycoproteins in the maternal serum. PSG1, PSG6, PSG6N, and PSG11 induce dose-dependent secretion of anti-inflammatory cytokines by human monocytes. Human and murine PSGs exhibit cross-species activity.

T-Cell Surface Glycoprotein CD8β Chain (CD8 Antigen) is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. CD8 Antigen, acting as a coreceptor, and the T-cell receptor on the T lymphocyte recognize antigens displayed by an antigen presenting cell (APC) in the context of class I MHC molecules. The functional coreceptor is either a homodimer composed of two alpha chains, or a heterodimer composed of one alpha and one beta chain. Both alpha and beta chains share significant homology to immunoglobulin variable light chains. Multiple alternatively spliced transcript variants encoding distinct membrane associated or secreted isoforms have been described. A pseudogene, also located on chromosome 2, has been identified.

Neuronal Pentraxin (NPTX1, NP1) is a secreted glycoprotein within the Pentraxin family. NPTX1 is co‑expressed and forms heteromultimers with the related secreted protein, NPTX2 NARP, NPTXR (Neuronal Pentraxin Receptor) at excitatory synapses. Mature human NPTX1 shares 97% aa sequence identity with mouse, and rat NPTX1. It is produced by hippocampal, cerebral and cerebellar neurons, retinal ganglia and the inner nuclear layer of the retina. It is enriched on presynaptic axonal membranes where it forms complexes with NPTXR. It may be involved in mediating uptake of synaptic material during synapse remodeling or in mediating the synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses.

Angiopoietin-like 7 (ANGPTL7) is a secreted glycoprotein that is structurally related to the angiopoietins. Members of this protein family contain an N-terminal coiled coil domain and a C-terminal fibrinogen-like domain. ANGPTL7 shares 89% aa sequence identity with mouse and rat ANGPTL7. It is secreted as a 45-50kDa monomer that forms disulfide-linked homotrimers and tetramers via the coiled coil domain. ANGPTL7 is expressed in the corneal stroma, trabecular meshwork, and sclera and is elevated in glaucoma aqueous humor. Its production is up-regulated in trabecular meshwork cells by glucocorticoids and TGF-β and in cartilage by TNF-α. Overexpression of ANGPTL7 in trabecular meshwork cells inhibits the production of collagen and proteoglycans. When overexpressed in tumor cells it promotes collagen and proteoglycan deposition but inhibits tumor xenograft progression and tumor angiogenesis.

Human VEGF121, also known as Vascular endothelial growth factor A, VEGFA, Vascular permeability factor, VPF and VEGF, is a homodimeric, heparin-binding glycoprotein which belongs to the platelet-derived growth factor (PDGF) vascular endothelial growth factor (VEGF) family. VEGF-A is a glycosylated mitogen that specifically acts on endothelial cells and has various effects, including mediating increased vascular permeability, inducing angiogenesis, vasculogenesis, permeabilization of blood vessels and endothelial cell growth, increasing microvascular permeability, promoting cell migration and inhibiting apoptosis. Alternatively spliced transcript variants of VEGF-A encod either secreted or cell-associated isoforms. The lymphangiogenesis may be promoted by upregulation of VEGF121, which may in turn act in part via induction of VEGF-C. It binds to the FLT1 VEGFR1 and KDR VEGFR2 receptors, heparan sulfate and heparin. NRP1 Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.

Amine oxidase copper-containing 1 (AOC1; formerly known as amiloride-binding protein 1) is a secreted glycoprotein that catalyzes the degradation of putrescine and histamine. Polyamines and their diamine precursor putrescine are ubiquitous to all organisms and fulfill pivotal functions in cell growth and proliferation. That the Wilms tumor protein, WT1, which is necessary for normal kidney development, activates transcription of the AOC1 gene. Expression of a firefly luciferase reporter under control of the proximal AOC1 promoter was significantly enhanced by co-transfection of a WT1 expression construct. Binding of WT1 protein to a cis-regulatory element in the AOC1 promoter was confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. WT1-dependent control of polyamine breakdown, which is mediated by changes in AOC1 expression, has a role in kidney organogenesis.

Cartilage Oligomeric Matrix Protein (COMP), also referred to as Thrombospondin-5, is a non-collagenous extracellular matrix (ECM) protein and belongs to the subgroup B of the thrombospondin protein family. This protein is expressed primarily in cartilage, ligament, and tendon, and binds to other ECM proteins such as collagen I, II and IX with high affinities depending on the divalent cations Zn2+ or Ni2+. COMP is a secreted glycoprotein that is important for growth plate organization and function. It is suggested to play a role in cell growth and development, and recent studies have revealed the possible mechanism that it protects cells against death by elevating members of the IAP (inhibitor of apoptosis protein) family of survival proteins. Mutations in COMP cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1), and up-regulated expression of COMP are observed in rheumatoid arthritis and certain carcinomas.

Follistatin 288 is a secreted glycoprotein that was first identified as a follicle-stimulating hormone inhibiting substance in ovarian follicular fluid . Human follistatin 288 cDNA encodes a 317 amino acid (aa) protein with a 29 aa signal sequence, and a 288 aa mature region. Follistatin shows the highest affinity for activins due to its extended configuration. Genetic deletion of follistatin in mice, or expression of only the Follistatin form, is perinatally lethal due to defects of lung, skin and musculoskeletal system. Follistatins also regulate hematopoietic stem cell adhesion to fibronectin via FS2.

Fibroblast growth factor-9 (FGF-9) is an approximately 26 kDa secreted glycoprotein of the FGF family. Secreted mouse FGF-9 lacks the N-terminal 1-3 aa and shares >98% sequence identity with rat, human, equine, porcine and bovine FGF-9. FGF-9 plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. In the mouse embryo the location and timing of FGF-9 expression affects development of the skeleton, cerebellum, lungs, heart, vasculature, digestive tract, and testes .It may have a role in glial cell growth and differentiation during development, gliosis during repair and regeneration of brain tissue after damage, differentiation and survival of neuronal cells, and growth stimulation of glial tumors. Deletion of mouse FGF-9 is lethal at birth due to lung hypoplasia, and causes rhizomelia, or shortening of the proximal skeleton. An unusual constitutive dimerization of FGF 9 buries receptor interaction sites which lowers its activity, and increases heparin affinity which inhibits diffusion. A spontaneous mouse mutant, Eks, interferes with dimerization, resulting monomeric, diffusible FGF-9 that causes elbow and knee synostoses (joint fusions) due to FGF-9 misexpression in developing joints.

Corticotropin-Releasing Factor-Binding Protein (CRHBP) is a 37 kDa secreted glycoprotein that binds both CRH and urocortin in a 42 kDa extracellular complex. The molecule is approximately 300 amino acids in length and demonstrates five intrachain disulfide bonds. Difference between CRHBP from different species exist, human CRHBP is found in plasma while rodent and sheep CRHBP is limited to neuroendocrine tissues. CRHBP may inactivate CRH and may prevent inappropriate pituitary-adrenal stimulation in pregnancy. CRHBP is presumed to either sequester CRH, rendering it unavailable to cells or transport it to target tissues. Although CRF-BP concentration in the human peripheral circulation is normally low, it increases throughout pregnancy and fall back rapidly after parturition.

ANGPTL3 is a secreted glycoprotein that is structurally related to the angiopoietins. Mature human ANGPTL3 contains an N-terminal coiled coil domain and a C‑terminal fibrinogen-like domain. ANGPTL3 is expressed in the liver from early in development through adulthood. Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism. Proposed to play a role in the trafficking of energy substrates to either storage or oxidative tissues in response to food intake. ANGPTL3 Protein, Human, Recombinant (His & Avi), Biotinylated is expressed in HEK293 mammalian cells with C-His-Avi tag. The predicted molecular weight is 26.6 kDa and the accession number is Q9Y5C1.

Limitin, also called IFN-ζ, is a secreted interferon (IFN)-like glycoprotein. Limitin has approximately 30% sequence homology with IFN-α, IFN-β, and IFN-ω and binds to the IFN-α β receptors. Like IFN-α and IFN-β, limitin has antiproliferative, immunomodulatory, and antiviral properties, it is unique in lacking influence on myeloid and erythroid progenitors. Similar dose requirement between limitin and IFN-α was observed for the enhancement of cytotoxic T lymphocyte activity, the augmentation of MHC class I expression, and the growth inhibition of a myelomonocytic leukemia cell line.

ANGPTL3 is a secreted glycoprotein that is structurally related to the angiopoietins. Mature human ANGPTL3 contains an N-terminal coiled coil domain and a C‑terminal fibrinogen-like domain. ANGPTL3 is expressed in the liver from early in development through adulthood. Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism. Proposed to play a role in the trafficking of energy substrates to either storage or oxidative tissues in response to food intake. ANGPTL3 Protein, Human, Recombinant (His & Avi) is expressed in HEK293 mammalian cells with C-His-Avi tag. The predicted molecular weight is 26.6 kDa and the accession number is Q9Y5C1.

SPARC-like protein 1 (SPARCL1; also known as SC1, high endothelial venule protein, or hevin) is an extracellular matrix-associated, secreted glycoprotein belonging to the secreted protein acidic and rich in cysteine (SPARC) family of matricellular proteins. It contains three conserved structural domains that are implicated in the regulation of cell adhesion, migration, and proliferation. SPARCL1 is expressed during embryogenesis and tissue remodeling and is especially prominent in brain and vasculature. Its down-regulation in a number of cancers and the possibility of its functional compensation by SPARC has led to recent interest in hevin as a tumor suppressor and regulator of angiogenesis. SPARCL1 has antiadhesive properties, and loss of SPARCL1 expression is associated with increased proliferative activity and cell cycle progression. It is suggested that it may influence multiple cellular processes during distinct stages of brain development and function. Besides, SPARCL1 can influence the function of astroglial cells in the developing and mature central nervous system (CNS).

Stanniocalcin-1 (STC1) is a paracrine factor associated with inflammation and carcinogenesis. STC1 is a secreted glycoprotein hormone and involved in various types of human malignancies. Stanniocalcin-1 (STC1), which has myriad functions, including the maintenance of calcium homeostasis, the promotion of early wound healing, uncoupling respiration (aerobic glycolysis), reepithelialization in damaged tissues, the inhibition of vascular leakage, and the regulation of macrophage functions to keep epithelial and endothelial homeostasis, which may adequately cover the myriad therapeutic targets of IPF. STC1 signals through inhibitory G-protein modulates CGRP receptor spatial localization during osteoblastogenesis and may function as a regulatory factor interacting with calcitonin peptide members during bone formation.

KLK3 (Kallikrein Related Peptidase 3) is a Protein Coding gene. The gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. It encodes a single-chain glycoprotein, a protease that is synthesized in the epithelial cells of the prostate gland and is present in seminal plasma. KLK3, also known as Prostate Specific Antigen (PSA), kallikrein-related peptidase 3, Gamma-seminoprotein, is a secreted protein of the glandular kallikrein subfamily of serine proteases. KLK3 contains one peptidase S1 domain. KLK3 is a glycoprotein produced almost exclusively by the prostate gland. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy

Dickkopf-like 1 (DKKL1) or soggy 1, is a glycoprotein unique to mammals that is expressed primarily in developing spermatocytes and localized in the acrosome of mature sperm. It is also expressed in the trophectoderm placental lineage. This glycoprotein is secreted by postmeiotic male germ cells. DKKL1 is a member of the Dickkopf (DKK) family, a group of proteins that are characterized as secreted antagonists of Wnt signal transduction proteins. In mammals, embryos lacking DKKL1 protein developed into viable, fertile adults. DKKL1, either directly or indirectly, facilitates the ability of sperm to penetrate the zona pellucid. DKKL1 is related to the sperm apoptotic procession. Molecular analyses identified the Fas death ligand (FasL) as a target for DkkL1 pro-apoptotic activity in adult mice. DKKL1 is considered as a negative regulator of adult testic homeostasis and identifies a novel, DKKL1 FasL- dependent, regulation that specifically controls the number of postpubertal spermatocytes.

A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in the mammal. NELL2 is an abundant glycoprotein containing an EGF-like domain in the neural tissues where it has multiple physiological functions by interacting with protein kinase C (PKC). There are two different splicing variant forms of NELL2 identified so far. One is secreted NELL2 (sNELL2) which is a neuron-specific variant and the other is cytosolic NELL2 (cNELL2) which is a non-secreted splicing variant of NELL2. NELL2 is strongly expressed in the brain of adults and fetuses but only weakly in the fetal kidney.