ID:NDRG1_HUMAN DESCRIPTION: RecName: Full=Protein NDRG1; AltName: Full=Differentiation-related gene 1 protein; Short=DRG-1; AltName: Full=N-myc downstream-regulated gene 1 protein; AltName: Full=Nickel-specific induction protein Cap43; AltName: Full=Reducing agents and tunicamycin-responsive protein; Short=RTP; AltName: Full=Rit42; FUNCTION: Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53- mediated caspase activation and apoptosis. Has a role in cell trafficking, notably of the Schwann cell, and is necessary for the maintenance and development of the peripheral nerve myelin sheath. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy. SUBUNIT: Interacts with RAB4A (membrane-bound form); the interaction involves NDRG1 in vesicular recycling of CDH1. INTERACTION: P27824:CANX; NbExp=2; IntAct=EBI-716486, EBI-355947; P12956:XRCC6; NbExp=2; IntAct=EBI-716486, EBI-353208; SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cytoplasm, cytoskeleton, centrosome. Nucleus. Cell membrane. Note=Mainly cytoplasmic but differentially localized to other regions. Associates with the plasma membrane in intestinal epithelia and lactating mammary gland. Translocated to the nucleus in a p53/TP53-dependent manner. In prostate epithelium and placental chorion, located in both the cytoplasm and in the nucleus. No nuclear localization in colon epithelium cells. In intestinal mucosa, prostate and renal cortex, located predominantly adjacent to adherens junctions. Cytoplasmic with granular staining in proximal tubular cells of the kidney and salivary gland ducts. Recruits to the membrane of recycling/sorting and 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 and with the plasma membrane. TISSUE SPECIFICITY: Ubiquitous; expressed most prominently in placental membranes and prostate, kidney, small intestine, and ovary tissues. Also expressed in heart, brain, skeletal muscle, lung, liver and pancreas. Low levels in peripheral blood leukocytes and 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 and placental membranes, the cells that border the lumen show the highest expression. INDUCTION: By homocysteine, 2-mercaptoethanol, tunicamycin in endothelial cells. Induced approximately 20-fold during in vitro differentiation of the colon carcinoma cell lines HT29-D4 and Caco-2. Induced by oxidative stress in colon cancers. Decreased expression in colon adenomas and adenocarcinomas. Induced by nickel compounds in all tested cell lines. The primary signal for its induction is an elevation of free intracellular calcium ion caused by nickel ion exposure. Okadaic acid, a serine/threonine phosphatase inhibitor, induced its expression more rapidly and more efficiently than nickel. PTM: Under stress conditions, phosphorylated in the C-terminal on many serine and threonine residues. Phosphorylated in vitro by PKA. Phosphorylation enhanced by increased intracellular cAMP levels. Homocysteine induces dephosphorylation. Phosphorylation by SGK1 is cell cycle dependent. DISEASE: Defects in NDRG1 are the cause of Charcot-Marie-Tooth disease type 4D (CMT4D) [MIM:601455]; also known as hereditary motor and sensory neuropathy Lom type (HMSNL). CMT4D is a recessive form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot- Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy and primary peripheral axonal neuropathy. Demyelinating CMT neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention, autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. SIMILARITY: Belongs to the NDRG family. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NDRG1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q92597
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0008285 negative regulation of cell proliferation GO:0010038 response to metal ion GO:0030330 DNA damage response, signal transduction by p53 class mediator GO:0032287 peripheral nervous system myelin maintenance GO:0042127 regulation of cell proliferation GO:0042981 regulation of apoptotic process GO:0045576 mast cell activation GO:0071456 cellular response to hypoxia GO:0090232 positive regulation of spindle checkpoint
LF210295 - JP 2014500723-A/17798: Polycomb-Associated Non-Coding RNAs. D87953 - Homo sapiens mRNA for RTP, complete cds. LF214025 - JP 2014500723-A/21528: Polycomb-Associated Non-Coding RNAs. AK095649 - Homo sapiens cDNA FLJ38330 fis, clone FCBBF3025280, highly similar to NDRG1 PROTEIN. AF039944 - Homo sapiens TARG1 mRNA, 3' untranslated region. AX229879 - Sequence 5 from Patent WO0162959. BC006260 - Homo sapiens N-myc downstream regulated 1, mRNA (cDNA clone IMAGE:3946764), with apparent retained intron. AK026383 - Homo sapiens cDNA: FLJ22730 fis, clone HSI15793, highly similar to AF004162 Homo sapiens nickel-specific induction protein (Cap43) mRNA. AF004162 - Homo sapiens nickel-specific induction protein (Cap43) mRNA, complete cds. X92845 - H.sapiens mRNA for Drg1 protein. BC003175 - Homo sapiens N-myc downstream regulated 1, mRNA (cDNA clone MGC:4412 IMAGE:2957847), complete cds. AK130985 - Homo sapiens cDNA FLJ27475 fis, clone DMC07108. AK091269 - Homo sapiens cDNA FLJ33950 fis, clone CTONG2018413. AX746885 - Sequence 410 from Patent EP1308459. AK129867 - Homo sapiens cDNA FLJ26357 fis, clone HRT05043, highly similar to NDRG1 PROTEIN. AK124709 - Homo sapiens cDNA FLJ42719 fis, clone BRAMY3010492, highly similar to Protein NDRG1. AK091147 - Homo sapiens cDNA FLJ33828 fis, clone CTONG2003599, highly similar to Protein NDRG1. AK096562 - Homo sapiens cDNA FLJ39243 fis, clone OCBBF2008283, highly similar to Protein NDRG1. AK126924 - Homo sapiens cDNA FLJ44977 fis, clone BRAWH3002513, highly similar to Protein NDRG1. JD245342 - Sequence 226366 from Patent EP1572962. JD331707 - Sequence 312731 from Patent EP1572962. JD382577 - Sequence 363601 from Patent EP1572962. LF336988 - JP 2014500723-A/144491: Polycomb-Associated Non-Coding RNAs. JD225767 - Sequence 206791 from Patent EP1572962. JD518137 - Sequence 499161 from Patent EP1572962. LF336989 - JP 2014500723-A/144492: Polycomb-Associated Non-Coding RNAs. JD423612 - Sequence 404636 from Patent EP1572962. JD459390 - Sequence 440414 from Patent EP1572962. JD400277 - Sequence 381301 from Patent EP1572962. JD204308 - Sequence 185332 from Patent EP1572962. JD476248 - Sequence 457272 from Patent EP1572962. LF336990 - JP 2014500723-A/144493: Polycomb-Associated Non-Coding RNAs. JD193279 - Sequence 174303 from Patent EP1572962. JD530481 - Sequence 511505 from Patent EP1572962. LF336991 - JP 2014500723-A/144494: Polycomb-Associated Non-Coding RNAs. JD145801 - Sequence 126825 from Patent EP1572962. JD138946 - Sequence 119970 from Patent EP1572962. JD183520 - Sequence 164544 from Patent EP1572962. LF336992 - JP 2014500723-A/144495: Polycomb-Associated Non-Coding RNAs. JD225110 - Sequence 206134 from Patent EP1572962. AK299636 - Homo sapiens cDNA FLJ53648 complete cds, highly similar to Protein NDRG1. JD140183 - Sequence 121207 from Patent EP1572962. JD043277 - Sequence 24301 from Patent EP1572962. JD525807 - Sequence 506831 from Patent EP1572962. AK298236 - Homo sapiens cDNA FLJ53637 complete cds, highly similar to Protein NDRG1. JD437293 - Sequence 418317 from Patent EP1572962. JD497581 - Sequence 478605 from Patent EP1572962. AK296794 - Homo sapiens cDNA FLJ55222 complete cds, highly similar to Protein NDRG1. AK223542 - Homo sapiens mRNA for N-myc downstream regulated gene 1 variant, clone: FCC125F02. JD399497 - Sequence 380521 from Patent EP1572962. AY277597 - Homo sapiens transformation-related protein 14 (TRG14) mRNA, complete cds. DQ892952 - Synthetic construct clone IMAGE:100005582; FLH191116.01X; RZPDo839H0876D N-myc downstream regulated gene 1 (NDRG1) gene, encodes complete protein. KJ902098 - Synthetic construct Homo sapiens clone ccsbBroadEn_11492 NDRG1 gene, encodes complete protein. KJ893025 - Synthetic construct Homo sapiens clone ccsbBroadEn_02419 NDRG1 gene, encodes complete protein. DQ896199 - Synthetic construct Homo sapiens clone IMAGE:100010659; FLH191112.01L; RZPDo839H0866D N-myc downstream regulated gene 1 (NDRG1) gene, encodes complete protein. AB529085 - Synthetic construct DNA, clone: pF1KB4166, Homo sapiens NDRG1 gene for N-myc downstream regulated 1, without stop codon, in Flexi system. CR456842 - Homo sapiens full open reading frame cDNA clone RZPDo834C1011D for gene NDRG1, N-myc downstream regulated gene 1; complete cds, incl. stopcodon. AK308117 - Homo sapiens cDNA, FLJ98065. AF147402 - Homo sapiens full length insert cDNA clone YN54B03. CU678420 - Synthetic construct Homo sapiens gateway clone IMAGE:100017172 5' read NDRG1 mRNA. BX648361 - Homo sapiens mRNA; cDNA DKFZp686B09185 (from clone DKFZp686B09185). AK307829 - Homo sapiens cDNA, FLJ97777. AK297342 - Homo sapiens cDNA FLJ59927 complete cds, moderately similar to Protein NDRG1. LF336996 - JP 2014500723-A/144499: Polycomb-Associated Non-Coding RNAs. AF230380 - Homo sapiens N-myc downsteam regulated gene 1 (NDRG1) mRNA, partial cds. LF212607 - JP 2014500723-A/20110: Polycomb-Associated Non-Coding RNAs. JD256419 - Sequence 237443 from Patent EP1572962. JD408865 - Sequence 389889 from Patent EP1572962. JD391997 - Sequence 373021 from Patent EP1572962. MA449602 - JP 2018138019-A/21528: Polycomb-Associated Non-Coding RNAs. MA445872 - JP 2018138019-A/17798: Polycomb-Associated Non-Coding RNAs. MA572565 - JP 2018138019-A/144491: Polycomb-Associated Non-Coding RNAs. MA572566 - JP 2018138019-A/144492: Polycomb-Associated Non-Coding RNAs. MA572567 - JP 2018138019-A/144493: Polycomb-Associated Non-Coding RNAs. MA572568 - JP 2018138019-A/144494: Polycomb-Associated Non-Coding RNAs. MA572569 - JP 2018138019-A/144495: Polycomb-Associated Non-Coding RNAs. MA572573 - JP 2018138019-A/144499: Polycomb-Associated Non-Coding RNAs. MA448184 - JP 2018138019-A/20110: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q92597 (Reactome details) participates in the following event(s):
R-HSA-6803205 TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain R-HSA-5633008 TP53 Regulates Transcription of Cell Death Genes R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)