Search results

The protein encoded by this gene is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamily. The superfamily includes large families of growth and differentiation factors. Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site. This particular family member plays an important role in the onset of endochondral bone formation in humans, and a reduction in expression has been associated with a variety of bone diseases, including the heritable disorder Fibrodysplasia Ossificans Progressiva. Alternative splicing in the 5' untranslated region of this gene has been described and three variants are described, all encoding an identical protein.

FGF-basic is a member of the fibroblast growth factor (FGF) family. FGF family members bind and possess broad mitogenic and angiogenic activities. This protein has been implicated in diverse biological processes, such as limb and nervous system development, wound healing, and tumor growth. The mRNA for this gene contains multiple polyadenylation sites, and is alternatively translated from AUG and non-AUG (CUG) initiation codons resulting in five different isoforms with distinct properties. The CUG-initiated isoforms are localized in the nucleus and are responsible for the intracrine effect, whereas, the AUG-initiated form is mostly cytosolic and is responsible for the paracrine and autocrine effects of this FGF.
The binding growth factors are angiogenic agents in vivo and are potent mitogens for a variety of cell types in vitro. there are differences in the tissue distribution and concentration of these 2 growth factors.

GDF15 is part of the TGF-Beta superfamily that is involved in regulating inflammatory and apoptotic pathways in injured tissues and throughout disease processes. GDF15 is most abundant in the liver. Its expression in liver can be considerably up-regulated in during injury of organs such as liver, kidney, heart and lung. GDF-15 promotes proliferation or growth arrest and differentiation due to differences in cellular differentiation. GDF15 prevents apoptosis in cerebellar granule neurons by activating Akt and inhibiting endogenously active ERK. GDF15 is a novel autocrine/endocrine factor that antagonizes the hypertrophic response and loss of ventricular performance.

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. DKK3 is involved in embryonic development through its inhibition of the WNT signaling pathway. DKK3 gene expression is decreased in a variety of cancer cell lines and it may act as a tumor suppressor gene.

Transforming growth factor betas (TGFBetas) mediate many cell-cell interactions that occur during embryonic development. Three TGFBetas have been identified in mammals. TGFBeta1, TGFBeta2 and TGFBeta3 are each synthesized as precursor proteins that are very similar in that each is cleaved to yield a 112 amino acid polypeptide that remains associated with the latent portion of the molecule.

The somatomedins, or insulin-like growth factors (IGFs), comprise a family of peptides that play important roles in mammalian growth and development. IGF1 mediates many of the growth-promoting effects of growth hormone (GH; MIM 139250). Early studies showed that growth hormone did not directly stimulate the incorporation of sulfate into cartilage, but rather acted through a serum factor, termed 'sulfation factor,' which later became known as 'somatomedin' (Daughaday et al., 1972). Three main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2; MIM 147470), and somatomedin B (MIM 193190) (Rotwein, 1986; Rosenfeld, 2003).

Podoplanin is a small mucin-like type-1 transmembrane protein, typically expressed in various specialized cell types throughout the body. Podoplanin is a type-I integral membrane glycoprotein with diverse distribution in human tissues. PDPN physiological function is related to its mucin-type character. The homologous protein in other species has been described as a differentiation antigen and influenza-virus receptor.
PDPN is expressed in lymphatic progenitor cells and afterwards during mouse development in lymphatic endothelial cells. Podoplanin is a specific marker for lymph vessel endothelial cells. Over-expression of podoplanin significantly elevates endothelial cell adhesion, migration, and tube formation. Inhibition of Podoplanin expression decreases cell adhesion in human dermal lymphatic endothelial cells. Podoplanin is used as a specific marker for lymphatic endothelium in histopathology.
Podoplanin expression is increased in nearly all human colon, rectum, and small intestine tumors. AGGRUS may serve as a diagnostic marker that distinguishes seminomas, the majority of which over express the protein, from embryonal carcinoma in testicular germ cell tumors.

PGK1 is an X-linked enzyme that has a major role in the glycolytic pathway. PGK1 is a glycolytic enzyme which catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate, generating an ATP molecule. PGK1 may also act as a cofactor for polymerase alpha. Defects in the PGK1 gene are usually associated with chronic hemolytic anemia, though it can be accompanied by either mental retardation or muscular disease (rhabdomyolysis). Overexpression of PGK1 and its signalling targets are possibly an expression-pathway in diffuse primary gastric carcinomas promoting peritoneal dissemination. It was shown that PGK1 is differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia.

A 88-kDa progranulin, also called proepithelin and PC cell-derived growth factor, is a single precursor protein of granulins which are a family of secreted, glycosylated peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. Granulins are a variety of active, 6 kDa peptides and named granulin A (epithelin 1), granulin B (epithelin 2), granulin C, etc. Both the peptides and intact progranulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on cell growth. Granulin family members are important in normal development, wound healing, and tumorigenesis.

GDF-11 belongs to the bone morphogenetic protein (BMP) family and the TGF-beta superfamily. GDF-11 is a central developmental factor which controls muscular and neural development. In adults, GDF-11 encourages cardiac hypertrophy reverse by the revival of cardiomyocytes.

6PGD is the second dehydrogenase in the pentose phosphate shunt. Pentose is neccesary for nucleic acid biosynthesis. The pentose phosphate cycle is a major source of NADPH 6PGD deficiency is usually asymptomatic, and the inheritance of this disorder is autosomal dominant. PGD deficiency raises the erythrocyte pyruvate kinase levels of activity and decreases glutathione synthetase, resulting in hemolysis.

Vascular endothelial growth factor is an important signaling protein involved in both vasculogenesis and angiogenesis. As its name implies, VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/ macrophagemigration, neurons, cancer cells, kidney epithelial cells ). VEGF mediates increased vascular permeability, induces angiogenesis, vasculogenesis and endothelial cell growth, promotes cell migration, and inhibits apoptosis. In vitro, VEGF has been shown to stimulate endothelial cell mitogenesisand cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor.
Elevated levels of this protein are linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

Developmental Pluripotency Associated 3 (DPPA3) is a protein which in mice may serve as a maternal factor during the preimplantation stage of development. In mice, the DPPA3 protein has a role in transcriptional repression, cell division, and maintenance of cell pluripotentiality. In humans, related intronless loci are found on chromosomes 14 and X. DPPA3 is expressed in embryonic stem and carcinoma cells. DPPA3 has a low expression in the testis, ovary and thymus. DPPA3 is highly expressed in testicular germ cell tumors.

PGK1 is an X-linked enzyme that has a major role in the glycolytic pathway. PGK1 is a glycolytic enzyme which catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate, generating an ATP molecule. PGK1 may also act as a cofactor for polymerase alpha. Defects in the PGK1 gene are usually associated with chronic hemolytic anemia, though it can be accompanied by either mental retardation or muscular disease (rhabdomyolysis). Overexpression of PGK1 and its signalling targets are possibly an expression-pathway in diffuse primary gastric carcinomas promoting peritoneal dissemination. It was shown that PGK1 is differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia.

Transforming growth factor betas (TGFBetas) mediate many cell-cell interactions which occur during embryonic development. Three TGFBetas have been identified in mammals. TGFBeta1, TGFBeta2 and TGFBeta3 are each synthesized as precursor proteins which are very similar in that each is cleaved to yield a 112 amino acid polypeptide which remains associated with the latent portion of the molecule.

Vascular endothelial growth factor is an important signaling protein involved in both vasculogenesis and angiogenesis. As its name implies, VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/ macrophagemigration, neurons, cancer cells, kidney epithelial cells ).VEGF mediates increased vascular permeability, induces angiogenesis, vasculogenesis and endothelial cell growth, promotes cell migration, and inhibits apoptosis. In vitro, VEGF has been shown to stimulate endothelial cell mitogenesisand cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor.
Elevated levels of this protein are linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

PGK2, also known as Phosphoglycerate kinase 2, is a testis-specific form of phosphoglycerate kinase.Originally, it was assumed that PGK2was a pseudogene. However, nowadays it is known that this protein is a functional phosphoglycerate kinase. During the Embden-Meyerhof-Parnas pathway of glycolysis, in thelater stages of spermatogenesis, the protein catalyses the reversible conversion of 1, 3- bisphosphoglycerate to 3-phosphoglycerate.

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. DKK3 is involved in embryonic development through its inhibition of the WNT signaling pathway. DKK3 gene expression is decreased in a variety of cancer cell lines and it may act as a tumor suppressor gene.

The secreted polypeptide noggin, encoded by the NOG gene, binds and inactivates members of the transforming growth factor-beta (TGF-beta) superfamily signaling proteins, such as bone morphogenetic protein-4 (BMP4). By diffusing through extracellular matrices more efficiently than members of the TGF-beta superfamily, noggin may have a principal role in creating morphogenic gradients. Noggin appears to have pleiotropic effect, both early in development as well as in later stages. It was originally isolated from Xenopus based on its ability to restore normal dorsal-ventral body axis in embryos that had been artificially ventralized by UV treatment. The results of the mouse knockout of noggin suggest that it is involved in numerous developmental processes, such as neural tube fusion and joint formation. Recently, several dominant human NOG mutations in unrelated families with proximal symphalangism (SYM1) and multiple synostoses syndrome (SYNS1) were identified; both SYM1 and SYNS1 have multiple joint fusion as their principal feature, and map to the same region (17q22) as NOG. All NOG mutations altered evolutionarily conserved amino acid residues. The amino acid sequence of human noggin is highly homologous to that of Xenopus, rat and mouse.

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) induces proliferation, migration, and fenestration in capillary endothelial cells derived from endocrine glands. Its expression is induced by hypoxia and is restricted to the steroidogenic glands (ovary, testis, adrenal, and placenta). Its expression is often complementary to the expression of VEGF (MIM 192240), suggesting that these molecules function in a coordinated manner. EG-VEGF potently contracts gastrointestinal (gi) smooth muscle. Induces proliferation, migration and fenestration (the formation of membrane discontinuities) in capillary endothelial cells derived from endocrine glands. Has little or no effect on a variety of other endothelial and non-endothelial cell types.

PEDF is a neurotrophic protein that induces extensive neuronal differentiation in retinoblastoma cells. SerpinF1 is a potent inhibitor of angiogenesis. EPC1 doesn’t undergo the stressed to relaxed conformation transition characteristic as of the active serpins since it exhibits no serine protease inhibitory activity.
Aqueous humour level of asymmetric dimethylarginine is correlated with PEDF in humans. ADMA and PEDF levels are increased in response to inflammation in uveitis.
Lack of PEDF expression is a potent factor for the enhancement of tumor growth and angiogenesis in breast cancer.
PEDF & VEGF genes contribute to the development of diabetic retinopathy.
PEDF and VEGF structural changes in blood vessel wall play an important role in the pathophysiology of PD patients.
PEDF-overexpressing tumors exhibited reduced intratumoral angiogenesis.
SerpinF1 is a new promising approach for the treatment of osteosarcoma.
Levels of the natural ocular anti-angiogenic factor SentrinF1 (PEDF) is associated with proliferative retinopathy.
VEGF secreted by retinal pigment epithelial cells upregulates PEDF expression via VEGFR-1 in an autocrine manner.
Sentrin-F1 concentration in the aqueous humor of diabetic patients predicts who will develop progression of retinopathy.
PEDF blocks angiogenic effects of leptin through its anti-oxidative properties.

FGF8 is part of the fibroblast growth factor family. FGF family members have wide mitogenic and cell survival activities, and participate in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF8 supports androgen and anchorage independent growth of mammary tumor cells. FGF8 over expression increases tumor growth and angiogensis. The adult expression of FGF-8 gene is restricted to testes and ovaries. FGF8 functions as an embryonic epithelial factor. FGF8 takes part in midbrain and limb development, organogenesis, embryo gastrulation and left-right axis determination.

FGF12 is part of the Fibroblast Growth Factor (FGF) family which has a vast mitogenic and cell survival functions, and play a role in a range of biological activities, among them are embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. FGF-12 doesn’t obtain the N-terminal signal sequence present in the majority of the FGF family members, but it contains clusters of basic residues that act as a nuclear localization signal. When transfected into mammalian cells, FGF12 accumulated in the nucleus, but was not secreted. FGF12 is involved in nervous system development and function. FGF12 binds to IB2 (islet brain-2), a cellular kinase scaffold, and voltage gated sodium channels and is also involved in intracellular signalling and ion exchange.

PGAM1 is part of the phosphoglycerate mutase family. PGAM1 is an essential component of glucose and 2,3-BPGA (2,3-bisphosphoglycerate) metabolism and catalyzes the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. PGAM1 is a dimeric enzyme containing, in different tissues, different proportions of a slow-migrating muscle (MM) isozyme, a fast-migrating brain (BB) isozyme, and a hybrid form (MB). PGAM1 mutations lead to muscle phosphoglycerate mutase deficiency, a.k.a. glycogen storage disease X.