adrenal

Transcriptional activator. Essential for sexual differentiation and formation of the primary steroidogenic tissues. Binds to the Ad4 site found in the promoter region of steroidogenic P450 genes such as CYP11A, CYP11B and CYP21B. Also regulates the AMH Muellerian inhibiting substance gene as well as the AHCH and STAR genes. 5'-YCAAGGYC-3' and 5'-RRAGGTCA-3' are the consensus sequences for the recognition by NR5A1. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. Binds phosphatidylcholine. Binds phospholipids with a phosphatidylinositol (PI) headgroup, in particular PI(3,4)P2 and PI(3,4,5)P3. Activated by the phosphorylation of NR5A1 by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.

Essential for the synthesis of various steroid hormones. Participates in the reduction of mitochondrial cytochrome P450 for steroidogenesis. Transfers electrons from adrenodoxin reductase to CYP11A1, a cytochrome P450 that catalyzes cholesterol side-chain cleavage to produce pregnenolone, the precursor of most steroid hormones. Does not form a ternary complex with adrenodoxin reductase and CYP11A1 but shuttles between the two enzymes to transfer electrons. Adrenodoxin, mitochondrial Protein, Bovine, Recombinant (His) is expressed in E. coli expression system with N-10xHis tag. The predicted molecular weight is 19.5 kDa and the accession number is P00257.

CD254, also known as RANKL, TNFSF11, TRANCE, OPGL and ODF, is a type II membrane protein of the tumor necrosis factor (TNF) superfamily, and affects the immune system and control bone regeneration and remodeling. RANKL is the ligand of nuclear factor (NF)-κB (RANK). When RANKL binds to RANK, it will undergo trimerization and then bind to an adaptor molecule TNF receptor-associated factor 6 (TRAF6). This results in the activation of several downstream signaling cascades, including the NFκB, mitogen-activated protein kinases (MAPK), activating protein 1 (AP-1), and nuclear factor of activated T cells (NFATc1), resulting in the formation of multinucleated bone-resorbing osteoclasts. RANKL is widely expressed in skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoblast, mammary gland epithelial cells, prostate and pancreas.

Malate dehydrogenase, mitochondrial is a 338 amino acids protein that belongs to the LDH MDH superfamily. MDH type 1 family. MDH2 catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD NADH cofactor system in the citric acid cycle. MDH2 is localized to the mitochondria and takes part in the malate-aspartate shuttle that functions in the metabolic coordination between cytosol and mitochondria. MDH2 is highly expressed in the adrenal system, small intestine, heart and pancreas.

Serves as the first electron transfer protein in all the mitochondrial P450 systems including cholesterol side chain cleavage in all steroidogenic tissues, steroid 11-beta hydroxylation in the adrenal cortex, 25-OH-vitamin D3-24 hydroxylation in the kidney, and sterol C-27 hydroxylation in the liver. Adrenodoxin reductase Protein, Bovine, Recombinant (His) is expressed in yeast with N-10xHis tag. The predicted molecular weight is 52.8 kDa and the accession number is P08165.

Neuroendocrine convertase 1, also known as Prohormone convertase 1, Proprotein convertase 1, PCSK1 and NEC1, is an enzyme which belongs to the peptidase S8 family and Furin subfamily. PCSK1 is an enzyme that performs the proteolytic cleavage of prohormones to their intermediate (or sometimes completely cleaved) forms. It is present only in neuroendocrine cells such as brain, pituitary and adrenal, and most often cleaves after a pair of basic residues within prohormones but can occasionally cleave after a single arginine. It binds to a protein known as proSAAS, which also represents its endogenous inhibitor. PCSK1 is involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. PCSK1 substrates include POMC, renin, enkephalin, dynorphin, somatostatin and insulin. Defects in PCSK1 are the cause of proprotein convertase 1 deficiency (PC1 deficiency). PC1 deficiency is characterized by obesity, hypogonadism, hypoadrenalism, reactive hypoglycemia as well as marked small-intestinal absorptive dysfunction. It is due to impaired processing of prohormones.

Midkine (MK or MDK) also known as neurite growth-promoting factor 2 (NEGF2) is a basic heparin-binding growth factor of low molecular weight, and forms a family with pleiotrophin. Midkine is a retinoic acid-responsive, heparin-binding growth factor expressed in various cell types during embryogenesis. It promotes angiogenesis, cell growth, and cell migration. Midkine is also expressed in several carcinomas, suggesting that it may play a role in tumorigenesis, perhaps through its effects on angiogenesis. Midkine binds anaplastic lymphoma kinase (ALK) which induces ALK activation and subsequent phosphorylation of the insulin receptor substrate (IRS1), followed by the activation of mitogen-activated protein kinase (MAPK) and PI3-kinase and the induction of cell proliferation. Midkine is involved in neointima formation after arterial injury, possibly by mediating leukocyte recruitment. Also involved in early fetal adrenal gland development. Midkine exhibited increased expression in the breast carcinomas but showed much lower expression in the normal breast tissue. Thus, it can be used as a breast carcinomas marker.

Adrenomedullin consists of 52 amino acids and is a member of the adrenomedullin family. It s a a hypotensive peptide and has 1 intramolecular disulfide bond. It seems that adrenomedullin has a slight homology with the calcitonin gene-related peptide. Adrenomedullin has a highly expression in pheochromocytoma and adrenal medulla. It also can be detected in lung, ventricle and kidney tissues. Adrenomedullin and PAMP are potent hypotensive and vasodilatator agents. Numerous actions have been reported most related to the physiologic control of fluid and electrolyte homeostasis. In the kidney, adrenomedullin is diuretic and natriuretic, and both adrenomedullin and PAMP inhibit aldosterone secretion by direct adrenal actions. In pituitary gland, both peptides at physiologically relevant doses inhibit basal ACTH secretion. Both peptides appear to act in brain and pituitary gland to facilitate the loss of plasma volume, actions which complement their hypotensive effects in blood vessels. It is believed that adrenomedullin functions through combinations of the calcitonin receptor like receptor and receptor activity-modifying proteins complexes, as well as CGRP receptors.

FGF-basic is a members of the Fibroblast Growth Factors (FGFs) family. The family constitutes a large family of proteins involved in many aspects of development including cell proliferation, growth, and differentiation. They act on several cell types to regulate diverse physiologic functions including angiogenesis, cell growth, pattern formation, embryonic development, metabolic regulation, cell migration, neurotrophic effects, and tissue repair. FGF-basic is a non-glycosylated heparin binding growth factor that is expressed in the brain, pituitary, kidney, retina, bone, testis, adrenal gland liver, monocytes, epithelial cells and endothelial cells. FGF-basic signals through FGFR 1b, 1c, 2c, 3c and 4.

Serves as the first electron transfer protein in all the mitochondrial P450 systems including cholesterol side chain cleavage in all steroidogenic tissues, steroid 11-beta hydroxylation in the adrenal cortex, 25-OH-vitamin D3-24 hydroxylation in the kidney, and sterol C-27 hydroxylation in the liver. Adrenodoxin reductase Protein, Bovine, Recombinant (E. coli, His) is expressed in E. coli expression system with N-10xHis tag. The predicted molecular weight is 55.8 kDa and the accession number is P08165.

Serves as the first electron transfer protein in all the mitochondrial P450 systems including cholesterol side chain cleavage in all steroidogenic tissues, steroid 11-beta hydroxylation in the adrenal cortex, 25-OH-vitamin D3-24 hydroxylation in the kidney, and sterol C-27 hydroxylation in the liver. FDXR Protein, Human, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 61.6 kDa and the accession number is P22570.

A cytochrome P450 monooxygenase that plays a major role in adrenal steroidogenesis. Catalyzes the hydroxylation at C-21 of progesterone and 17alpha-hydroxyprogesterone to respectively form 11-deoxycorticosterone and 11-deoxycortisol, intermediate metabolites in the biosynthetic pathway of mineralocorticoids and glucocorticoids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).

Serpins are the largest and most diverse family of serine protease inhibitors which are involved in a number of fundamental biological processes such as blood coagulation, complement activation, fibrinolysis, angiogenesis, inflammation and tumor suppression and are expressed in a cell-specific manner.Mouse SerpinB8, also known as Cytoplasmic antiproteinase 2, Peptidase inhibitor 8, SerpinB8, PI-8, SERPINB8 and CAP2, is a member of the Serpin superfamily. SERPINB8 was broadly expressed. In normal neuroendocrine tissues, strongest SerpinB8 expression was detected in islets of Langerhans of the pancreas. Moderate SerpinB8 expression was observed in neuroendocrine cells of the thyroid, adrenal cortex, colon, and pituitary gland. In the pancreas, SerpinB8 is specifically expressed by insulin-producing beta cells, and can be used as an additional diagnostic immunohistochemical marker. Mouse SerpinB8 distribution alters during kidney regeneration, possibly to control a prohormone convertase involved in inflammation or tissue repair.

OPTN (Optineurin) is a Protein Coding gene. The Optineurin gene encodes the coiled-coil containing protein optineurin. Optineurin is a multifunctional adaptor protein intimately involved in various vesicular trafficking pathways. Through interactions with an array of proteins, such as myosin VI, huntingtin, Rab8, and Tank-binding kinase 1, as well as via its oligomerization, optineurin can act as an adaptor, scaffold, or signal regulator to coordinate many cellular processes associated with the trafficking of membrane-delivered cargo. It is widely expressed in fat, adrenal, and other tissues. Certain mutations in OPTN (gene OPTN) are associated with primary open-angle glaucoma, a leading cause of irreversible blindness, and amyotrophic lateral sclerosis, a fatal motor neuron disease.

Calcium Calmodulin-Dependent Protein Kinase Type 1 (CAMK1) belongs to the protein kinase superfamily, CAMK Ser Thr protein kinase family, and CaMK subfamily. CAMK1 contains one protein kinase domain and widely expressed. CAMK1 is phosphorylated by CaMKK1 and CaMKK2 on Thr-177. CAMK1 regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization, and neurite outgrowth. CAMK1 plays a role in K+ and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex.

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.

TINAGL1 is a secreted protein and contains one SMB (somatomedin-B) domain. TINAGL1 is expressed in aorta, lymph nodes, heart, bone marrow, placenta, lung, kidney, skeletal muscle, pancreas, thyroid, adrenal gland and so on. TINAGL1 may be implicated in the adrenocortical zonation and in mechanisms for repressing the CYP11B1 gene expression in adrenocortical cells.

A cytochrome P450 monooxygenase that plays a major role in adrenal steroidogenesis. Catalyzes the hydroxylation at C-21 of progesterone and 17alpha-hydroxyprogesterone to respectively form 11-deoxycorticosterone and 11-deoxycortisol, intermediate metabolites in the biosynthetic pathway of mineralocorticoids and glucocorticoids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).

MRAP (Melanocortin 2 Receptor Accessory Protein) is a Protein Coding gene. This gene encodes a melanocortin receptor-interacting protein. It belongs to the MRAP family. MRAP, which contains a single transmembrane domain, has a unique structure, an antiparallel homodimer. MRAP is a single transmembrane domain accessory protein and a critical component of the hypothamo pituitary-adrenal axis. MRAP is highly expressed in the adrenal gland and is essential for adrenocorticotropin hormone (ACTH) receptor expression and function. In adrenal cells, MRAP is essential for adrenocorticotropic hormone (ACTH)-induced activation of the cAMP protein kinase A (PKA) pathway by melanocortin 2 receptor (MC2R), leading to glucocorticoid production and secretion. Diseases associated with MRAP include Glucocorticoid Deficiency 2 and Glucocorticoid Deficiency 1.

Endothelin-converting enzyme 1, also known as ECE-1, is a single-pass type II membrane protein which belongs to thepeptidase M13 family. ECE-1 converts big endothelin-1 to endothelin-1. ECE-1 is a membrane metalloprotease that generates endothelin from its direct precursor big endothelin. Four isoforms of ECE-1 are produced from a single gene through the use of alternate promoters. These isoforms share the same extracellular catalytic domain and contain unique cytosolic tails, which results in their specific subcellular targeting.All isoforms of ECE-1 are expressed in umbilical vein endothelial cells, polynuclear neutrophils, fibroblasts, atrium cardiomyocytes and ventricles. Isoforms A, B and C of ECE-1 are also expressed in placenta, lung, heart, adrenal gland and phaeochromocytoma; isoforms A and C of ECE-1 in liver, testis and small intestine; isoform B, C and D of ECE-1 in endothelial cells and umbilical vein smooth muscle cells; isoforms C and D in saphenous vein cells, and isoform C in kidney. Defects in ECE1 are a cause of Hirschsprung disease, cardiac defects and autonomic dysfunction. It is a form of Hirschsprung disease with skip-lesions defects, craniofacial abnormalities and other dysmorphic features, and autonomic dysfunction.

Poly(rC)-binding protein 1, also known as Heterogeneous nuclear ribonucleoprotein E1, Alpha-CP1, Nucleic acid-binding protein SUB2.3 and PCBP1, is a family member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that belong to RNA-binding proteins and bear three KH domains. PCBP1 is loosely bound in the nucleus. It may shuttle between the nucleus and the cytoplasm. It is abundantly expressed in skeletal muscle, thymus and peripheral blood leukocytes while a lower expression is observed in prostate, spleen, testis, ovary, small intestine, heart, liver, adrenal and thyroid glands. PCBP1 is widely expressed in many human tissues and involved in the regulation of transcription, transportation process, and function of RNA molecules. PCBP1 plays a pivotal role in post-transcriptional regulation for RNA metabolism and RNA function in gene expression. PCBP1 acts as a negative regulator of CD44 variants splicing in HepG2 cells, and loss of PCBP1 in human hepatic tumor contributes to the formation of a metastatic phenotype.

NUDC (Nuclear Distribution C, Dynein Complex Regulator) is a Protein Coding gene. NUDC consists of at least 9 exons ranging from 66 bp to 266 bp in size and 8 introns from 92 bp to 2.0 kb in length, and the total genomic region spans about 8 kb. NUDC was mapped to 1p34-p35 by fluorescence in situ hybridization. This gene encodes a nuclear distribution protein that plays an essential role in mitosis and cytokinesis. Nuclear migration is essential for the growth, development, and cellular function of eukaryotes. NUDC protein plays an important role in nuclear migration. It is widely expressed in the testis, adrenal, and other tissues. NUDC protein is expressed highly in CNE-2 and HNE-2 cells. Anti-NUDC antibody could inhibit the growth of CNE-2 and HNE-2 cells.

Pro-Neuropeptide Y (NPY) is a member of the NPY family. NPY is a secreted protein and is one of the most abundant peptides in the nervous system. It also can be found in some chromaffin cells of the adrenal medulla. NPY can be cleaved into Neuropeptide Y and C-flanking peptide of NPY chain, which regulates energy usage, and it is involved in learning, memory processing, and epilepsy. NPY is implicated in the control of feeding and in secretion of gonadotrophin-release hormone. In addition, NPY increases the proportion of energy stored as fat and blocks nociceptive signals to the brain.

Ketohexokinase, also known as Hepatic fructokinase, is a member of the carbohydrate kinase PfkB family. It exits as a homodimer and most abundant in liver, kidney, gut, spleen and pancreas. Low levels also found in adrenal, muscle, brain and eye.This enzyme catalyzes conversion of fructose to fructose-1-phosphate. It is the first enzyme with a specialized pathway that catabolizes dietary fructose. Defects in KHK are the cause of fructosuria.

Receptor Activator of Nuclear Factor κ B (RANK), also known as CD265, TRANCE Receptor or TNFRSF11A, is member of the tumor necrosis factor receptor (TNFR) molecular superfamily. RANK is the receptor for RANK-Ligand (RANKL) and part of the RANK RANKL OPG signaling pathway that regulates osteoclast differentiation and activation. It plays a vital role in bone remodeling and repair, immune cell function, lymph node development, thermal regulation, and mammary gland development. RANK is constitutively expressed in skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoclast, mammary gland epithelial cells, prostate, vascular cell, and pancreas.

Protein Delta Homolog 1 (DLK-1) is a transmembrane protein which contains a signal peptide, an extracellular domain with six tandem epidermai growth factor (EGF)-like domains, a single pass transmembrane domain, and a short cytoplasmic tail. It is found within the stromal cells in close contact to the vascular structure of placental villi, yolk sac, fetal liver, adrenal cortex and pancreas and in the beta cells of the islets of Langerhans in the adult pancreas. In addition, it is detected in some forms of neuroendocrine lung tumor tissue. DLK-1 may have a improtant role in neuroendocrine differentiation.

AKR1C3, is an enzyme which belongs to the aldo keto reductase family. It is expressed in many tissues including adrenal gland, brain, kidney, liver, lung, mammary gland, placenta, small intestine, colon, spleen, prostate and testis. AKR1C3 catalyzes the conversion of aldehydes and ketones to alcohols. It catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2,which functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. It can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites.

A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis. Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol (Probable). Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione. Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA. Also 16-alpha hydroxylates androgens, relevant for estriol synthesis. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).

Hydroxysteroid sulfotransferase ( SULT2A1 ) is a key enzyme in the testicular and hepatic metabolism of 5alpha-androstenone, which is a major component of the off-odor and off-flavor in pork known as boar taint. Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. SULT2A1 is a sulfo-conjugating phase II enzyme expressed at very high levels in the liver and intestine, the two major first-pass metabolic tissues, and in the steroidogenic adrenal tissue. SULT2A1 acts preferentially on the hydroxysteroids dehydroepiandrosterone, testosterone dihydrotestosterone, and pregnenolone and on cholesterol-derived amphipathic sterol bile acids.

Secretagogin, also known as SCGN, is a secreted protein that is detectable in human serum after ischemic neuronal damage. It is a recently described calcium-binding protein. Secretagogin SCGN is expressed at high levels in the pancreatic islets of Langerhans and to a much lesser extent in the gastrointestinal tract (stomach, small intestine and colon), the adrenal medulla and cortex and the thyroid C-cells. In the brain, the expression of Secretagogin SCGN is restricted to distinct subtypes of neurons with highest expression in the molecular layer of the cerebellum (stellate and basket cells), in the anterior part of the pituitary gland, in the thalamus, in the hypothalamus and in a subgroup of neocortical neurons. Secretagogin SCGN is widely expressed in prostatic adenocarcinoma as opposed to adenocarcinomas in other organs. The function of Secretagogin SCGN is unknown, but it has been suggested in beta-cells to influence calcium-influx and has been observed downregulated in diabetes-prone BB rat islets exposed to cytokines. Secretagogin SCGN is involved in the calcium metabolism of tumour cells and endothelial cells in a subset of neoplasms of the brain and its coverings. Secretagogin SCGN is also a novel marker for neuroendocrine differentiation.

Glutamate decarboxylase 1, also known as 67 kDa glutamic acid decarboxylase, Glutamate decarboxylase 67 kDa isoform and GAD1, is a member of thegroup II decarboxylase family. GAD1 is expressed in benign and malignant prostatic tissue and may serve as a highly prostate-specific tissue biomarker. GAD1 isoform3 is expressed in pancreatic islets, testis, adrenal cortex, and perhaps other endocrine tissues, but not in brain. Tissue-specific markers are useful for identification of tumour type in advanced cancers of unknown origin. In plants, as in most eukaryotes, glutamate decarboxylase catalyses the synthesis of GABA. Root-specific calcium calmodulin-regulated GAD1 plays a major role in GABA synthesis in plants under normal growth conditions and in response to stress. Defects in GAD1 are the cause of cerebral palsy spastic quadriplegic type 1 (CPSQ1)which is a non-progressive disorder of movement and or posture resulting from defects in the developing central nervous system. Affected individuals manifest symmetrical, non-progressive spasticity and no adverse perinatal history or obvious underlying alternative diagnosis.

EG-VEGF, also known as prokineticin-1, is a member of the AVIT (prokineticin) family. Prokineticins are secreted proteins that can promote angiogenesis and induce strong gastrointestinal smooth muscle contraction. EG-VEGF can be detected in the steroidogenic glands, ovary, testis, adrenal and placenta. EG-VEGF has little or no effect on a variety of other endothelial and non-endothelial cell types. It induces proliferation, migration and fenestration (the formation of membrane discontinuities) in capillary endothelial cells derived from endocrine glands. It directly influences neuroblastoma progression by promoting the proliferation and migration of neuroblastoma cells. EG-VEGF may play a role in placentation. It may also function in normal and pathological testis angiogenesis. It positively regulates PTGS2 expression and prostaglandin synthesis.

DBH is a 29 kDa copper-containing oxygenase. It can be detected in noradrenergic nerve terminals of the central and peripheral nervous systems, and is also expressed in chromaffin cells of the adrenal medulla. DBH contains our identical subunits, and its activity requires ascorbate as a cofactor. It functions in in the synthesis of small-molecule neurotransmitters that is membrane-bound, making norepinephrine the only transmitter synthesized inside vesicles. DBH has been shown to be associated with decision making and addictive behaviors such as alcohol and smoking, attention deficit hyperactivity disorder, and also with neurological diseases such as Schizophrenia and Alzheimer's.