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NDRG1 protein; differentiation-related gene 1 protein; DRG-1; N-myc downstream-regulated gene 1 protein; nickel-specific induction protein Cap43; reducing agents & tunicamycin-responsive protein; RTP; Rit42 (NDRG1, CAP43, DRG1, RTP)

Function: - stress-responsive protein involved in hormone responses, cell growth, & differentiation - acts as a tumor suppressor protein in many cell types - necessary but not sufficient for p53/TP53-mediated caspase activation & apoptosis. - role in cell trafficking, notably of the Schwann cell - necessary for maintenance & development of the peripheral nerve myelin sheath - required for vesicular recycling of CDH1 & TF - may also function in lipid trafficking - protects cells from spindle disruption damage - functions in p53/TP53-dependent mitotic spindle checkpoint - regulates microtubule dynamics & maintains euploidy - under stress conditions, phosphorylated in the C-terminal on many Ser & Thr - phosphorylated in vitro by PKA - phosphorylation enhanced by increased intracellular cAMP levels - homocysteine induces dephosphorylation - phosphorylation by SGK1 is cell cycle dependent - interacts with RAB4A (membrane-bound form) - the interaction involves NDRG1 in vesicular recycling of CDH1 Structure: belongs to the NDRG family Compartment: - cytoplasm, cytoskeleton, - centrosome, nucleus, cell membrane - mainly cytoplasmic but differentially localized to other cell regions - associates with the plasma membrane in intestinal epithelia & lactating mammary gland - translocated to the nucleus in a p53/TP53-dependent manner - in prostate epithelium & placental chorion, located in both cytoplasm & in the nucleus - no nuclear localization in colon epithelium cells - in intestinal mucosa, prostate & renal cortex, located predominantly adjacent to adherens junctions - cytoplasmic with granular staining in proximal tubular cells of the kidney & salivary gland ducts - recruited to the membrane of recycling/sorting & late endosomes via binding to phosphatidylinositol 4-phosphate - associates with microtubules - colocalizes with TUBG1 in the centrosome - cytoplasmic location increased with hypoxia - phosphorylated form found associated with centromeres during S-phase of mitosis & with the plasma membrane Expression: - ubiquitously expressed - expressed most prominently in placental membranes & prostate, kidney, small intestine, & ovary tissues - also expressed in heart, brain, skeletal muscle, lung, liver & pancreas - low levels in peripheral blood leukocytes & in tissues of the immune system - expressed mainly in epithelial cells - also found in Schwann cells of peripheral neurons - reduced expression in adenocarcinomas compared to normal tissues - in colon, prostate & placental membranes, the cells that border the lumen show the highest expression - induced by homocysteine, 2-mercaptoethanol, tunicamycin in endothelial cells - induced approximately 20-fold during in vitro differentiation of the colon carcinoma cell lines HT29-D4 & Caco-2 - induced by oxidative stress in colon cancers - decreased expression in colon adenomas & adenocarcinomas - induced by nickel compounds in all tested cell lines - the primary signal for its induction is an elevation of free intracellular Ca+2 caused by nickel ion exposure - okadaic acid, a serine/threonine phosphatase inhibitor, induces its expression more rapidly & more efficiently than nickel Pathology: - defects in NDRG1 are the cause of Charcot-Marie-Tooth disease type 4D

Related

N-myc proto-oncogene protein (MYCN, NMYC)

General

anti-oncoprotein (tumor suppressor protein) nuclear protein phosphoprotein

Properties

SIZE: entity length = 394 aa MW = 43 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Ser phosphorylation site {S2} Ser phosphorylation site {S319} Ser phosphorylation site {S326} Thr phosphorylation site {T328} Ser phosphorylation site {S330} Ser phosphorylation site {S332} Ser phosphorylation site {S333} Thr phosphorylation site {T335} Ser phosphorylation site {S336} domain {339-368} MOTIF: consensus repeat {339-348} Thr phosphorylation site {T346} consensus repeat {349-358} Thr phosphorylation site {T356} consensus repeat {359-368} Ser phosphorylation site {S362} Ser phosphorylation site {S364} Thr phosphorylation site {T366} Thr phosphorylation site {T375}

Database Correlations

OMIM correlations MORBIDMAP 605262 UniProt Q92597 Pfam PF03096 Entrez Gene 10397 Kegg hsa:10397

References

  1. UniProt :accession Q92597
  2. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/NDRG1