ID NDRG1_HUMAN Reviewed; 394 AA. AC Q92597; B3KR80; B7Z446; O15207; Q6IBG2; Q9NYR6; Q9UK29; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 27-MAR-2024, entry version 211. DE RecName: Full=Protein NDRG1; DE AltName: Full=Differentiation-related gene 1 protein; DE Short=DRG-1; DE AltName: Full=N-myc downstream-regulated gene 1 protein; DE AltName: Full=Nickel-specific induction protein Cap43; DE AltName: Full=Reducing agents and tunicamycin-responsive protein; DE Short=RTP; DE AltName: Full=Rit42; GN Name=NDRG1; Synonyms=CAP43, DRG1, RTP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, AND TISSUE SPECIFICITY. RC TISSUE=Umbilical vein endothelial cell; RX PubMed=8939898; DOI=10.1074/jbc.271.47.29659; RA Kokame K., Kato H., Miyata T.; RT "Homocysteine-respondent genes in vascular endothelial cells identified by RT differential display analysis. GRP78/BiP and novel genes."; RL J. Biol. Chem. 271:29659-29665(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, SUBCELLULAR LOCATION, RP AND TISSUE SPECIFICITY. RX PubMed=9251681; RA van Belzen N., Dinjens W.N.M., Diesveld M.P.G., Groen N.A., RA van der Made A.C.J., Nozawa Y., Vlietstra R., Trapman J., Bosman F.T.; RT "A novel gene which is up-regulated during colon epithelial cell RT differentiation and down-regulated in colorectal neoplasms."; RL Lab. Invest. 77:85-92(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INDUCTION. RC TISSUE=Lung; RX PubMed=9605764; RA Zhou D., Salnikow K., Costa M.; RT "Cap43, a novel gene specifically induced by Ni2+ compounds."; RL Cancer Res. 58:2182-2189(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INDUCTION. RX PubMed=10395947; DOI=10.1016/s0167-4889(99)00056-7; RA Piquemal D., Joulia D., Balaguer P., Basset A., Marti J., Commes T.; RT "Differential expression of the RTP/Drg1/Ndr1 gene product in proliferating RT and growth arrested cells."; RL Biochim. Biophys. Acta 1450:364-373(1999). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Brain, and Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-21 (ISOFORM 1). RC TISSUE=Brain; RA Angelicheva D., Kalaydjieva L.; RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases. RN [11] RP PROTEIN SEQUENCE OF 4-19; 54-70; 133-148; 199-212; 286-300; 307-322; RP 328-341 AND 364-388, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Fetal brain cortex; RA Lubec G., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [12] RP FUNCTION, AND INDUCTION. RX PubMed=9766676; RA Kurdistani S.K., Arizti P., Reimer C.L., Sugrue M.M., Aaronson S.A., RA Lee S.W.; RT "Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 RT and DNA damage."; RL Cancer Res. 58:4439-4444(1998). RN [13] RP INVOLVEMENT IN CMT4D. RX PubMed=10831399; DOI=10.1086/302978; RA Kalaydjieva L., Gresham D., Gooding R., Heather L., Baas F., de Jonge R., RA Blechschmidt K., Angelicheva D., Chandler D., Worsley P., Rosenthal A., RA King R.H.M., Thomas P.K.; RT "N-myc downstream-regulated gene 1 is mutated in hereditary motor and RT sensory neuropathy-Lom."; RL Am. J. Hum. Genet. 67:47-58(2000). RN [14] RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION. RX PubMed=10860807; DOI=10.1006/bbrc.2000.2833; RA Agarwala K.L., Kokame K., Kato H., Miyata T.; RT "Phosphorylation of RTP, an ER stress-responsive cytoplasmic protein."; RL Biochem. Biophys. Res. Commun. 272:641-647(2000). RN [15] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=12432451; DOI=10.1007/s00418-002-0460-9; RA Lachat P., Shaw P., Gebhard S., van Belzen N., Chaubert P., Bosman F.T.; RT "Expression of NDRG1, a differentiation-related gene, in human tissues."; RL Histochem. Cell Biol. 118:399-408(2002). RN [16] RP PHOSPHORYLATION AT THR-328; SER-330; THR-346; THR-356 AND THR-366. RX PubMed=15461589; DOI=10.1042/bj20041057; RA Murray J.T., Campbell D.G., Morrice N., Auld G.C., Shpiro N., Marquez R., RA Peggie M., Bain J., Bloomberg G.B., Grahammer F., Lang F., Wulff P., RA Kuhl D., Cohen P.; RT "Exploitation of KESTREL to identify NDRG family members as physiological RT substrates for SGK1 and GSK3."; RL Biochem. J. 384:477-488(2004). RN [17] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=15247272; DOI=10.1074/jbc.m400781200; RA Kim K.T., Ongusaha P.P., Hong Y.K., Kurdistani S.K., Nakamura M., Lu K.P., RA Lee S.W.; RT "Function of Drg1/Rit42 in p53-dependent mitotic spindle checkpoint."; RL J. Biol. Chem. 279:38597-38602(2004). RN [18] RP FUNCTION. RX PubMed=15377670; DOI=10.1074/jbc.m400386200; RA Stein S., Thomas E.K., Herzog B., Westfall M.D., Rocheleau J.V., RA Jackson R.S. II, Wang M., Liang P.; RT "NDRG1 is necessary for p53-dependent apoptosis."; RL J. Biol. Chem. 279:48930-48940(2004). RN [19] RP INTERACTION WITH APOA1; APOA2; PRA1 AND RTN1, AND POSSIBLE FUNCTION. RX PubMed=15922294; DOI=10.1016/j.bbrc.2005.05.050; RA Hunter M., Angelicheva D., Tournev I., Ingley E., Chan D.C., Watts G.F., RA Kremensky I., Kalaydjieva L.; RT "NDRG1 interacts with APO A-I and A-II and is a functional candidate for RT the HDL-C QTL on 8q24."; RL Biochem. Biophys. Res. Commun. 332:982-992(2005). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-330 AND SER-333, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Prostate cancer; RX PubMed=17487921; DOI=10.1002/elps.200600782; RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.; RT "Toward a global characterization of the phosphoproteome in prostate cancer RT cells: identification of phosphoproteins in the LNCaP cell line."; RL Electrophoresis 28:2027-2034(2007). RN [23] RP SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=17316623; DOI=10.1016/j.febslet.2007.01.080; RA Sibold S., Roh V., Keogh A., Studer P., Tiffon C., Angst E., RA Vorburger S.A., Weimann R., Candinas D., Stroka D.; RT "Hypoxia increases cytoplasmic expression of NDRG1, but is insufficient for RT its membrane localization in human hepatocellular carcinoma."; RL FEBS Lett. 581:989-994(2007). RN [24] RP INTERACTION WITH RAB4A, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=17786215; DOI=10.1371/journal.pone.0000844; RA Kachhap S.K., Faith D., Qian D.Z., Shabbeer S., Galloway N.L., Pili R., RA Denmeade S.R., DeMarzo A.M., Carducci M.A.; RT "The N-Myc down regulated Gene1 (NDRG1) is a Rab4a effector involved in RT vesicular recycling of E-cadherin."; RL PLoS ONE 2:E844-E844(2007). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-326; SER-330; SER-333; RP SER-336; SER-364 AND THR-375, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [26] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [27] RP PHOSPHORYLATION AT THR-346; THR-356 AND THR-366. RX PubMed=18787837; DOI=10.1007/s00424-008-0587-1; RA Inglis S.K., Gallacher M., Brown S.G., McTavish N., Getty J., Husband E.M., RA Murray J.T., Wilson S.M.; RT "SGK1 activity in Na+ absorbing airway epithelial cells monitored by RT assaying NDRG1-Thr346/356/366 phosphorylation."; RL Pflugers Arch. 457:1287-1301(2009). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-328 AND SER-330, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [30] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [31] RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION. RX PubMed=21708134; DOI=10.1016/j.bbrc.2011.06.092; RA McCaig C., Potter L., Abramczyk O., Murray J.T.; RT "Phosphorylation of NDRG1 is temporally and spatially controlled during the RT cell cycle."; RL Biochem. Biophys. Res. Commun. 411:227-234(2011). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; THR-328; SER-330; SER-333; RP SER-336; SER-364; THR-366 AND THR-375, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-328; SER-332 AND SER-333, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Stress-responsive protein involved in hormone responses, cell CC growth, and differentiation. Acts as a tumor suppressor in many cell CC types. Necessary but not sufficient for p53/TP53-mediated caspase CC activation and apoptosis. Has a role in cell trafficking, notably of CC the Schwann cell, and is necessary for the maintenance and development CC of the peripheral nerve myelin sheath. Required for vesicular recycling CC of CDH1 and TF. May also function in lipid trafficking. Protects cells CC from spindle disruption damage. Functions in p53/TP53-dependent mitotic CC spindle checkpoint. Regulates microtubule dynamics and maintains CC euploidy. {ECO:0000269|PubMed:15247272, ECO:0000269|PubMed:15377670, CC ECO:0000269|PubMed:17786215, ECO:0000269|PubMed:9766676}. CC -!- SUBUNIT: Interacts with RAB4A (membrane-bound form); the interaction CC involves NDRG1 in vesicular recycling of CDH1. CC {ECO:0000269|PubMed:15922294, ECO:0000269|PubMed:17786215}. CC -!- INTERACTION: CC Q92597; P27824: CANX; NbExp=2; IntAct=EBI-716486, EBI-355947; CC Q92597; Q9H6J7-2: CSTPP1; NbExp=3; IntAct=EBI-716486, EBI-13328871; CC Q92597; P35222: CTNNB1; NbExp=3; IntAct=EBI-716486, EBI-491549; CC Q92597; Q9H816: DCLRE1B; NbExp=3; IntAct=EBI-716486, EBI-3508943; CC Q92597; Q3SYB3: FOXD4L6; NbExp=3; IntAct=EBI-716486, EBI-6425864; CC Q92597; Q9BYZ2: LDHAL6B; NbExp=3; IntAct=EBI-716486, EBI-1108377; CC Q92597; Q9H204: MED28; NbExp=3; IntAct=EBI-716486, EBI-514199; CC Q92597; Q9Y3D2: MSRB2; NbExp=3; IntAct=EBI-716486, EBI-9092052; CC Q92597; Q6ZNA4-2: RNF111; NbExp=3; IntAct=EBI-716486, EBI-21535400; CC Q92597; Q8N488: RYBP; NbExp=3; IntAct=EBI-716486, EBI-752324; CC Q92597; O75446: SAP30; NbExp=3; IntAct=EBI-716486, EBI-632609; CC Q92597; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-716486, EBI-11959123; CC Q92597; Q8IUW3: SPATA2L; NbExp=3; IntAct=EBI-716486, EBI-2510414; CC Q92597; Q6PID6: TTC33; NbExp=3; IntAct=EBI-716486, EBI-2555404; CC Q92597; P12956: XRCC6; NbExp=2; IntAct=EBI-716486, EBI-353208; CC Q92597; Q96NC0: ZMAT2; NbExp=3; IntAct=EBI-716486, EBI-2682299; CC Q92597-3; Q9Y3D8: AK6; NbExp=3; IntAct=EBI-10278703, EBI-2896123; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cytoplasm, cytoskeleton, CC microtubule organizing center, centrosome. Nucleus. Cell membrane. CC Note=Mainly cytoplasmic but differentially localized to other regions. CC Associates with the plasma membrane in intestinal epithelia and CC lactating mammary gland. Translocated to the nucleus in a p53/TP53- CC dependent manner. In prostate epithelium and placental chorion, located CC in both the cytoplasm and in the nucleus. No nuclear localization in CC colon epithelium cells. In intestinal mucosa, prostate and renal CC cortex, located predominantly adjacent to adherens junctions. CC Cytoplasmic with granular staining in proximal tubular cells of the CC kidney and salivary gland ducts. Recruits to the membrane of CC recycling/sorting and late endosomes via binding to CC phosphatidylinositol 4-phosphate. Associates with microtubules. CC Colocalizes with TUBG1 in the centrosome. Cytoplasmic location CC increased with hypoxia. Phosphorylated form found associated with CC centromeres during S-phase of mitosis and with the plasma membrane. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q92597-1; Sequence=Displayed; CC Name=2; CC IsoId=Q92597-2; Sequence=VSP_045038; CC Name=3; CC IsoId=Q92597-3; Sequence=VSP_045037; CC -!- TISSUE SPECIFICITY: Ubiquitous; expressed most prominently in placental CC membranes and prostate, kidney, small intestine, and ovary tissues. CC Also expressed in heart, brain, skeletal muscle, lung, liver and CC pancreas. Low levels in peripheral blood leukocytes and in tissues of CC the immune system. Expressed mainly in epithelial cells. Also found in CC Schwann cells of peripheral neurons. Reduced expression in CC adenocarcinomas compared to normal tissues. In colon, prostate and CC placental membranes, the cells that border the lumen show the highest CC expression. {ECO:0000269|PubMed:12432451, ECO:0000269|PubMed:8939898, CC ECO:0000269|PubMed:9251681, ECO:0000269|PubMed:9605764}. CC -!- INDUCTION: By homocysteine, 2-mercaptoethanol, tunicamycin in CC endothelial cells. Induced approximately 20-fold during in vitro CC differentiation of the colon carcinoma cell lines HT-29-D4 and Caco-2. CC Induced by oxidative stress in colon cancers. Decreased expression in CC colon adenomas and adenocarcinomas. Induced by nickel compounds in all CC tested cell lines. The primary signal for its induction is an elevation CC of free intracellular calcium ion caused by nickel ion exposure. CC Okadaic acid, a serine/threonine phosphatase inhibitor, induced its CC expression more rapidly and more efficiently than nickel. CC {ECO:0000269|PubMed:10395947, ECO:0000269|PubMed:17316623, CC ECO:0000269|PubMed:8939898, ECO:0000269|PubMed:9251681, CC ECO:0000269|PubMed:9605764, ECO:0000269|PubMed:9766676}. CC -!- PTM: Under stress conditions, phosphorylated in the C-terminal on many CC serine and threonine residues. Phosphorylated in vitro by PKA. CC Phosphorylation enhanced by increased intracellular cAMP levels. CC Homocysteine induces dephosphorylation. Phosphorylation by SGK1 is cell CC cycle dependent. {ECO:0000269|PubMed:10860807, CC ECO:0000269|PubMed:15461589, ECO:0000269|PubMed:18787837, CC ECO:0000269|PubMed:21708134}. CC -!- DISEASE: Charcot-Marie-Tooth disease 4D (CMT4D) [MIM:601455]: A CC recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder CC of the peripheral nervous system, characterized by progressive weakness CC and atrophy, initially of the peroneal muscles and later of the distal CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two CC main groups on the basis of electrophysiologic properties and CC histopathology: primary peripheral demyelinating neuropathies CC (designated CMT1 when they are dominantly inherited) and primary CC peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are CC characterized by severely reduced nerve conduction velocities (less CC than 38 m/sec), segmental demyelination and remyelination with onion CC bulb formations on nerve biopsy, slowly progressive distal muscle CC atrophy and weakness, absent deep tendon reflexes, and hollow feet. By CC convention autosomal recessive forms of demyelinating Charcot-Marie- CC Tooth disease are designated CMT4. {ECO:0000269|PubMed:10831399}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the NDRG family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41512/NDRG1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D87953; BAA13505.1; -; mRNA. DR EMBL; X92845; CAA63430.1; -; mRNA. DR EMBL; AF004162; AAC13419.1; -; mRNA. DR EMBL; AF186190; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CR456842; CAG33123.1; -; mRNA. DR EMBL; AK091147; BAG52292.1; -; mRNA. DR EMBL; AK126924; BAG54400.1; -; mRNA. DR EMBL; AK296794; BAH12432.1; -; mRNA. DR EMBL; AF192304; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471060; EAW92164.1; -; Genomic_DNA. DR EMBL; BC003175; AAH03175.1; -; mRNA. DR EMBL; AF230380; AAF71305.1; -; mRNA. DR CCDS; CCDS34945.1; -. [Q92597-1] DR CCDS; CCDS59113.1; -. [Q92597-2] DR RefSeq; NP_001128714.1; NM_001135242.1. [Q92597-1] DR RefSeq; NP_001245361.1; NM_001258432.1. [Q92597-2] DR RefSeq; NP_001245362.1; NM_001258433.1. [Q92597-3] DR RefSeq; NP_006087.2; NM_006096.3. [Q92597-1] DR PDB; 6ZMM; X-ray; 2.96 A; A/B=31-319. DR PDBsum; 6ZMM; -. DR AlphaFoldDB; Q92597; -. DR SMR; Q92597; -. DR BioGRID; 115669; 230. DR IntAct; Q92597; 110. DR MINT; Q92597; -. DR STRING; 9606.ENSP00000404854; -. DR ChEMBL; CHEMBL4295916; -. DR ESTHER; human-NDRG1; Ndr_family. DR MEROPS; S33.988; -. DR GlyGen; Q92597; 3 sites, 2 O-linked glycans (3 sites). DR iPTMnet; Q92597; -. DR MetOSite; Q92597; -. DR PhosphoSitePlus; Q92597; -. DR SwissPalm; Q92597; -. DR BioMuta; NDRG1; -. DR DMDM; 6166568; -. DR EPD; Q92597; -. DR jPOST; Q92597; -. DR MassIVE; Q92597; -. DR MaxQB; Q92597; -. DR PaxDb; 9606-ENSP00000404854; -. DR PeptideAtlas; Q92597; -. DR ProteomicsDB; 3585; -. DR ProteomicsDB; 6569; -. DR ProteomicsDB; 75343; -. [Q92597-1] DR Pumba; Q92597; -. DR TopDownProteomics; Q92597-1; -. [Q92597-1] DR Antibodypedia; 1521; 752 antibodies from 43 providers. DR DNASU; 10397; -. DR Ensembl; ENST00000323851.13; ENSP00000319977.8; ENSG00000104419.17. [Q92597-1] DR Ensembl; ENST00000414097.6; ENSP00000404854.2; ENSG00000104419.17. [Q92597-1] DR Ensembl; ENST00000522476.5; ENSP00000427894.1; ENSG00000104419.17. [Q92597-2] DR GeneID; 10397; -. DR KEGG; hsa:10397; -. DR MANE-Select; ENST00000323851.13; ENSP00000319977.8; NM_006096.4; NP_006087.2. DR UCSC; uc003yug.3; human. [Q92597-1] DR AGR; HGNC:7679; -. DR CTD; 10397; -. DR DisGeNET; 10397; -. DR GeneCards; NDRG1; -. DR GeneReviews; NDRG1; -. DR HGNC; HGNC:7679; NDRG1. DR HPA; ENSG00000104419; Low tissue specificity. DR MalaCards; NDRG1; -. DR MIM; 601455; phenotype. DR MIM; 605262; gene. DR neXtProt; NX_Q92597; -. DR OpenTargets; ENSG00000104419; -. DR Orphanet; 99950; Charcot-Marie-Tooth disease type 4D. DR PharmGKB; PA31482; -. DR VEuPathDB; HostDB:ENSG00000104419; -. DR eggNOG; KOG2931; Eukaryota. DR GeneTree; ENSGT00950000182872; -. DR HOGENOM; CLU_035361_1_0_1; -. DR InParanoid; Q92597; -. DR OMA; DMNQNNL; -. DR OrthoDB; 5352016at2759; -. DR PhylomeDB; Q92597; -. DR TreeFam; TF313168; -. DR PathwayCommons; Q92597; -. DR Reactome; R-HSA-6803205; TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain. DR SignaLink; Q92597; -. DR SIGNOR; Q92597; -. DR BioGRID-ORCS; 10397; 11 hits in 1163 CRISPR screens. DR ChiTaRS; NDRG1; human. DR GeneWiki; NDRG1; -. DR GenomeRNAi; 10397; -. DR Pharos; Q92597; Tbio. DR PRO; PR:Q92597; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q92597; Protein. DR Bgee; ENSG00000104419; Expressed in olfactory bulb and 205 other cell types or tissues. DR ExpressionAtlas; Q92597; baseline and differential. DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005874; C:microtubule; IDA:UniProtKB. DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB. DR GO; GO:0045296; F:cadherin binding; IDA:UniProtKB. DR GO; GO:0043015; F:gamma-tubulin binding; IDA:UniProtKB. DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB. DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB. DR GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB. DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IEP:UniProtKB. DR GO; GO:0045576; P:mast cell activation; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0032287; P:peripheral nervous system myelin maintenance; IEA:Ensembl. DR GO; GO:0010038; P:response to metal ion; TAS:ProtInc. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1. DR InterPro; IPR029058; AB_hydrolase. DR InterPro; IPR004142; NDRG. DR PANTHER; PTHR11034; N-MYC DOWNSTREAM REGULATED; 1. DR PANTHER; PTHR11034:SF18; PROTEIN NDRG1; 1. DR Pfam; PF03096; Ndr; 1. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. DR Genevisible; Q92597; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell membrane; KW Charcot-Marie-Tooth disease; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; Membrane; Microtubule; Neurodegeneration; KW Neuropathy; Nucleus; Phosphoprotein; Reference proteome; Repeat. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..394 FT /note="Protein NDRG1" FT /id="PRO_0000159573" FT REPEAT 339..348 FT /note="1" FT REPEAT 349..358 FT /note="2" FT REPEAT 359..368 FT /note="3" FT REGION 325..394 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 339..368 FT /note="3 X 10 AA tandem repeats of G-T-R-S-R-S-H-T-S-E" FT COMPBIAS 325..343 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 344..368 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 369..394 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 319 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q62433" FT MOD_RES 326 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 328 FT /note="Phosphothreonine; by SGK1" FT /evidence="ECO:0000269|PubMed:15461589, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 330 FT /note="Phosphoserine; by SGK1" FT /evidence="ECO:0000269|PubMed:15461589, FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 332 FT /note="Phosphoserine; by SGK1" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 333 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 335 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q62433" FT MOD_RES 336 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 340 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q62433" FT MOD_RES 342 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q62433" FT MOD_RES 346 FT /note="Phosphothreonine; by SGK1" FT /evidence="ECO:0000269|PubMed:15461589, FT ECO:0000269|PubMed:18787837" FT MOD_RES 352 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6JE36" FT MOD_RES 356 FT /note="Phosphothreonine; by SGK1" FT /evidence="ECO:0000269|PubMed:15461589, FT ECO:0000269|PubMed:18787837" FT MOD_RES 362 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6JE36" FT MOD_RES 364 FT /note="Phosphoserine; by SGK1" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 366 FT /note="Phosphothreonine; by SGK1" FT /evidence="ECO:0000269|PubMed:15461589, FT ECO:0000269|PubMed:18787837, ECO:0007744|PubMed:23186163" FT MOD_RES 375 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..81 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045037" FT VAR_SEQ 1..66 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045038" FT VARIANT 67 FT /note="M -> V (in dbSNP:rs2233319)" FT /id="VAR_050234" FT VARIANT 111 FT /note="M -> L (in dbSNP:rs2233328)" FT /id="VAR_050235" FT CONFLICT 145 FT /note="I -> T (in Ref. 2; CAA63430)" FT /evidence="ECO:0000305" FT STRAND 33..39 FT /evidence="ECO:0007829|PDB:6ZMM" FT STRAND 42..48 FT /evidence="ECO:0007829|PDB:6ZMM" FT STRAND 58..62 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 69..72 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 74..77 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 80..82 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 83..88 FT /evidence="ECO:0007829|PDB:6ZMM" FT STRAND 90..95 FT /evidence="ECO:0007829|PDB:6ZMM" FT TURN 97..99 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 115..120 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 122..128 FT /evidence="ECO:0007829|PDB:6ZMM" FT STRAND 134..139 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 141..152 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 154..156 FT /evidence="ECO:0007829|PDB:6ZMM" FT STRAND 157..164 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 187..195 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 209..217 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 221..232 FT /evidence="ECO:0007829|PDB:6ZMM" FT STRAND 255..260 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 266..274 FT /evidence="ECO:0007829|PDB:6ZMM" FT TURN 278..280 FT /evidence="ECO:0007829|PDB:6ZMM" FT STRAND 281..286 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 293..296 FT /evidence="ECO:0007829|PDB:6ZMM" FT HELIX 298..311 FT /evidence="ECO:0007829|PDB:6ZMM" SQ SEQUENCE 394 AA; 42835 MW; 4C816B9C85E3756F CRC64; MSREMQDVDL AEVKPLVEKG ETITGLLQEF DVQEQDIETL HGSVHVTLCG TPKGNRPVIL TYHDIGMNHK TCYNPLFNYE DMQEITQHFA VCHVDAPGQQ DGAASFPAGY MYPSMDQLAE MLPGVLQQFG LKSIIGMGTG AGAYILTRFA LNNPEMVEGL VLINVNPCAE GWMDWAASKI SGWTQALPDM VVSHLFGKEE MQSNVEVVHT YRQHIVNDMN PGNLHLFINA YNSRRDLEIE RPMPGTHTVT LQCPALLVVG DSSPAVDAVV ECNSKLDPTK TTLLKMADCG GLPQISQPAK LAEAFKYFVQ GMGYMPSASM TRLMRSRTAS GSSVTSLDGT RSRSHTSEGT RSRSHTSEGT RSRSHTSEGA HLDITPNSGA AGNSAGPKSM EVSC //