Search results

ATPase inhibitory factor 1 (ATPIF1) attaches to the C-terminal region of a beta subunit of the F1-ATPase at low pH values and, through interference of the beta and gamma subunit interaction, ATPIF1 controls the activity of the F1 (the hydrophilic catalytic core), F0 (the membrane embedded protein channel) ATPase. ATPIF1 overexpression in a number of human carcinomas additionally reinforces its participation in oncogenesis and offers insight into the transformed metabolism of cancer cells, including the reprogramming of energy metabolism in relation to glycolysis. Endogenous F1F(o)-ATPase inhibitor curbing ATP depletion when the mitochondrial membrane potential drops below a threshold and the F1F(o)-ATP synthase begins hydrolyzing ATP to pump protons out of the mitochondrial matrix.

Inhibitor of DNA Binding 2 (ID2) is a part of the inhibitor of DNA binding family, whose members are transcriptional regulators that contain a helix-loop-helix (HLH) domain but not a basic domain. Members of the ID family inhibit the functions of basic helix-loop-helix transcription factors in a dominant-negative way by suppressing their heterodimerization partners through the HLH domains. ID2 play a role in negatively regulating cell differentiation and may be an inhibitor of tissue-specific gene expression.

SPINT2 is a transmembrane protein acts as an inhibitor of HGF activator. SPINT2 inhibits plasmin, plasma and tissue kallikrein, and factor XIa. SPINT2 has two extracellular Kunitz domains that inhibit few serine proteases. SPINT2 is assumed tumor suppressor, mutations in SPINT2 leads to a congenital sodium diarrhea.

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.

Inhibitor of DNA Binding 1 (ID1) is a helix-loop-helix protein which can form heterodimers with members of the basic HLH family of transcription factors. ID1 is lacking DNA binding activity and thus can inhibit the DNA binding and transcriptional activation ability of basic HLH proteins with which it interacts. ID1 participates in cell growth, senescence, and differentiation.

GDP Dissociation Inhibitor 1 (GDI1) is expressed mainly in neural and sensory tissues. GDI1 regulates the GDP/GTP exchange reaction of nearly all Rab proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. GDI1 is also promoting the dissociation of GDP-bound Rab proteins from the membrane and inhibits their activation. Mutations in GDI1 have been associated with X-linked nonspecific mental retardation.

SPINT2 is a transmembrane protein acts as an inhibitor of HGF activator. SPINT2 inhibits plasmin, plasma and tissue kallikrein, and factor XIa. SPINT2 has two extracellular Kunitz domains that inhibit few serine proteases. SPINT2 is assumed tumor suppressor, mutations in SPINT2 leads to a congenital sodium diarrhea.

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).

cAMP-dependent protein kinase inhibitor beta (PKIB) belongs to the cAMP-dependent protein kinase inhibitor family. PKIB may interact with the catalytic subunit of cAMP-dependent protein kinase and function as a competitive inhibitor.

PSMF1 is a protein which hinders the activation of the proteasome by the 11S and 19S regulators. The 26S proteasome is a multicatalytic proteinase complex with an extremely ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is comprised of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits.

CARD18 belongs to the death-domain-fold superfamily which is induced by proinflammatory stimuli. CARD18 contains basically only a Caspase recruitment domain, inhibits generation of IL-1b by cooperating with caspase-1 and inhibiting connotation with RIP 2. The connotation of CARD18 to caspase-1 is enabled by the charge-charge interactions between the prodomain of caspase-1 and the surface charge of CARD18.

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).

The somatomedins, or insulin-like growth factors (IGFs), comprise a family of peptides that takes part in mammalian growth and development. IGF1 mediates various 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). 3 main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2; MIM 147470), and somatomedin B (MIM 193190) (Rotwein, 1986; Rosenfeld, 2003).

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.

The 14-3-3 family of proteins plays a key regulatory role in signal transduction, checkpoint control, apoptotic and nutrient-sensing pathways. 14-3-3 proteins are highly conserved and ubiquitously expressed. There are at least seven isoforms that have been identified in mammals. The 14-3-3gamma, a subtype of the 14-3-3 family of proteins, was thought to be brain and neuron-specific. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways.

Insulin-like growth factor-binding protein 4 (IGFBP-4) is a part of the insulin-like growth factor binding protein (IGFBP) family. IGFBP4 includes an IGFBP domain and a thyroglobulin type-I domain. IGFBP4 binds both insulin-like growth factors (IGFs) I and II. IGFBP-4 circulates in the plasma in both glycosylated and non-glycosylated forms. IGFBPs can either inhibit or enhance the biological activities of IGF, or act in an IGF independent manner. IGFBP-4 is consistently inhibits several cancer cells in vivo and in vitro, suggesting that it may function as an apoptotic factor. IGFBP4 is produced by all colon cancer cells. Binding of IGFBP-4 prolongs the half-life of the IGFs and changes their interaction with cell surface receptors.

The somatomedins, or IGFs, comprise a family of peptides that play important roles in mammalian growth and development. IGF1 mediates many of the growth-promoting effects of GH. Early studies showed that GH 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. Three main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2), and somatomedin B.

IGFBP6 plays a role in lipoprotein assembly and dietary cholesterol absorption. in addition to its acyltransferase activity, it may act as a ligase. may provide cholesteryl esters for lipoprotein secretion from hepatocytes and intestinal mucosa.

IGF-2 is a member of the insulin family of polypeptide growth factors that is involved in development and growth. It is an imprinted gene and is expressed only from the paternally inherited allele. It is a candidate gene for eating disorders. There is a read-through, INS-IGF2, which aligns to this gene at the 3' region and to the upstream INS gene at the 5' region. Two alternatively spliced transcript variants encoding the same protein have been found for this gene.

Insulin-like growth factor II (IGF-II) is an important foetal growth hormone.IGF-II is made by theca cells during gestation. IGF-II binds the sink IGF-II receptor (IGF2R) which results in IGF-II degradation.IGF-II also engages the IGF-I receptor (IGF1R) to arbitrate embryonic growth.

NFKBIA belongs to the I-kappa-B family of proteins which is separated into four groups (IkB-a, IkB-b, IkB-g, IkB-e). NFKBIA inhibits the NFkB complex by binding and impounding it in the cytoplasm. When stimulated, NFKBIA is phosphorylated on serine residues targeting it for degradation by the ubiquitin pathway.

NF-kappa-B inhibitor beta (NFKBIB) is a member of the NF-kappa-B inhibitor family, which inhibit NF-kappa-B by complexing with, and trapping it in the cytoplasm. Phosphorylation of serine residues on these proteins by kinases marks them for destruction via the ubiquitination pathway, thus allowing activation of the NF-kappa-B, which translocates to the nucleus to act as a transcription factor.

IGFBP3 is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

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.