NDRG1_HUMAN
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 03-AUG-2022, entry version 202.
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; Q9H6J7-2: C11orf49; NbExp=3; IntAct=EBI-716486, EBI-13328871;
CC Q92597; P27824: CANX; NbExp=2; IntAct=EBI-716486, EBI-355947;
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="http://atlasgeneticsoncology.org/Genes/NDRG1ID41512ch8q24.html";
CC ---------------------------------------------------------------------------
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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; CCDS59112.1; -. [Q92597-3]
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; 220.
DR IntAct; Q92597; 105.
DR MINT; Q92597; -.
DR STRING; 9606.ENSP00000404854; -.
DR ChEMBL; CHEMBL4295916; -.
DR ESTHER; human-NDRG1; Ndr_family.
DR MEROPS; S33.988; -.
DR GlyGen; Q92597; 1 site, 1 O-linked glycan (1 site).
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; Q92597; -.
DR PeptideAtlas; Q92597; -.
DR PRIDE; Q92597; -.
DR ProteomicsDB; 3585; -.
DR ProteomicsDB; 6569; -.
DR ProteomicsDB; 75343; -. [Q92597-1]
DR TopDownProteomics; Q92597-1; -. [Q92597-1]
DR Antibodypedia; 1521; 648 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 CTD; 10397; -.
DR DisGeNET; 10397; -.
DR GeneCards; NDRG1; -.
DR GeneReviews; NDRG1; -.
DR HGNC; HGNC:7679; NDRG1.
DR HPA; ENSG00000104419; Tissue enhanced (brain).
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; MFIDSYI; -.
DR OrthoDB; 854690at2759; -.
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 1087 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 203 other tissues.
DR ExpressionAtlas; Q92597; baseline and differential.
DR Genevisible; Q92597; HS.
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; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR004142; NDRG.
DR InterPro; IPR030693; NDRG1.
DR PANTHER; PTHR11034; PTHR11034; 1.
DR PANTHER; PTHR11034:SF18; PTHR11034:SF18; 1.
DR Pfam; PF03096; Ndr; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
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
