ID NDRG1_MOUSE Reviewed; 394 AA.
AC Q62433; P97862;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 01-MAY-2013, entry version 104.
DE RecName: Full=Protein NDRG1;
DE AltName: Full=N-myc downstream-regulated gene 1 protein;
DE Short=Protein Ndr1;
GN Name=Ndrg1; Synonyms=Ndr1, Ndrl, Tdd5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muroidea; Muridae; Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP AND INDUCTION.
RC TISSUE=Embryo;
RX PubMed=10381566; DOI=10.1016/S0925-4773(99)00025-8;
RA Shimono A., Okuda T., Kondoh H.;
RT "N-myc-dependent repression of ndr1, a gene identified by direct
RT subtraction of whole mouse embryo cDNAs between wild type and N-myc
RT mutant.";
RL Mech. Dev. 83:39-52(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Hybridoma;
RX PubMed=9144177; DOI=10.1073/pnas.94.10.4988;
RA Lin T.-M., Chang C.;
RT "Cloning and characterization of TDD5, an androgen target gene that is
RT differentially repressed by testosterone and dihydrotestosterone.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:4988-4993(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PHOSPHORYLATION AT THR-346; THR-356 AND THR-366, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND MASS SPECTROMETRY.
RX PubMed=15461589; DOI=10.1042/BJ20041057;
RA Murray J.T., Campbell D.G., Morrice N., Auld G.C., Shpiro N.,
RA Marquez R., Peggie M., Bain J., Bloomberg G.B., Grahammer F., Lang F.,
RA Wulff P., Kuhl D., Cohen P.;
RT "Exploitation of KESTREL to identify NDRG family members as
RT physiological substrates for SGK1 and GSK3.";
RL Biochem. J. 384:477-488(2004).
RN [5]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP FUNCTION.
RX PubMed=15082788; DOI=10.1128/MCB.24.9.3949-3956.2004;
RA Okuda T., Higashi Y., Kokame K., Tanaka C., Kondoh H., Miyata T.;
RT "Ndrg1-deficient mice exhibit a progressive demyelinating disorder of
RT peripheral nerves.";
RL Mol. Cell. Biol. 24:3949-3956(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-328; SER-330; THR-335
RP AND SER-336, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; THR-346 AND SER-362,
RP AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=19367708; DOI=10.1021/pr800599n;
RA Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J.,
RA Faessler R., Mann M.;
RT "Solid tumor proteome and phosphoproteome analysis by high resolution
RT mass spectrometry.";
RL J. Proteome Res. 7:5314-5326(2008).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=21636852; DOI=10.1074/jbc.M111.256446;
RA Yamamoto H., Kokame K., Okuda T., Nakajo Y., Yanamoto H., Miyata T.;
RT "NDRG4 protein-deficient mice exhibit spatial learning deficits and
RT vulnerabilities to cerebral ischemia.";
RL J. Biol. Chem. 286:26158-26165(2011).
RN [9]
RP DISRUPTION PHENOTYPE, CHARACTERISTICS OF A MOUSE MODEL OF CMT4D,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21303696; DOI=10.1016/j.nbd.2011.01.030;
RA King R.H., Chandler D., Lopaticki S., Huang D., Blake J., Muddle J.R.,
RA Kilpatrick T., Nourallah M., Miyata T., Okuda T., Carter K.W.,
RA Hunter M., Angelicheva D., Morahan G., Kalaydjieva L.;
RT "Ndrg1 in development and maintenance of the myelin sheath.";
RL Neurobiol. Dis. 42:368-380(2011).
CC -!- FUNCTION: Stress-responsive protein involved in hormone responses,
CC cell growth, and differentiation. Acts as a tumor suppressor in
CC many cell types. Necessary but not sufficient for p53/TP53-
CC mediated caspase activation and apoptosis. Required for vesicular
CC recycling of CDH1 and TF. May also function in lipid trafficking.
CC Protects cells from spindle disruption damage. Functions in
CC p53/TP53-dependent mitotic spindle checkpoint. Regulates
CC microtubule dynamics and maintains euploidy (By similarity). Has a
CC role in cell trafficking notably of the Schwann cell and is
CC necessary for the maintenance and development of the peripheral
CC nerve myelin sheath.
CC -!- SUBUNIT: Interacts with RAB4A (membrane-bound form); the
CC interaction involves NDRG1 in vesicular recycling of CDH1.
CC Interacts with APOA1, APOA2, PRA1 and RTN1 (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cytoplasm, cytoskeleton,
CC centrosome. Nucleus. Cell membrane (By similarity). Note=Mainly
CC 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
CC p53/TP53-dependent manner. In prostate epithelium and placental
CC chorion, located in both the cytoplasm and in the nucleus. No
CC nuclear localization in colon epithelium cells. In intestinal
CC mucosa, prostate and renal cortex, located predominantly adjacent
CC to adherens junctions. Cytoplasmic with granular staining in
CC proximal tubular cells of the kidney and salivary gland ducts.
CC Recruits to the membrane of recycling/sorting and late endosomes
CC via binding to phosphatidylinositol 4-phosphate. Associates with
CC microtubules. Colocalizes with TUBG1 in the centrosome.
CC Cytoplasmic location increased with hypoxia. Phosphorylated form
CC found associated with centromeres during S-phase of mitosis and
CC with the plasma membrane (By similarity).
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in
CC kidney followed by brain, pancreas, small intestine, colon and
CC spleen (at protein level). Also detected in heart and preputial
CC gland, and in much smaller quantities in other tissues. Not
CC detected in duodenum and prostate. Highly expressed in Schwann
CC cells.
CC -!- DEVELOPMENTAL STAGE: In early stages of embryo development,
CC expression low when MYCN expression is high. Later, when MYCN
CC levels diminish, levels increase.
CC -!- INDUCTION: Repressed by testosterone and also to a lesser extent
CC by dihydrotestosterone. Down-regulated by MYCN.
CC -!- PTM: Under stress conditions, phosphorylated in the C-terminal on
CC many serine and threonine residues. Phosphorylated in vitro by
CC PKA. Phosphorylation enhanced by increased intracellular cAMP
CC levels. Homocysteine induces dephosphorylation. Phosphorylation by
CC SGK1 is cell cycle dependent (By similarity).
CC -!- DISRUPTION PHENOTYPE: Mutant mice exhibit defects in peripheral
CC nerve development. Initial hind limb weakness developed around age
CC 12 weeks, and significant functional impairment (dragging of hind
CC legs) and muscle atrophy became apparent at age 1 year. After
CC about 5 weeks extensive demyelination of nerve fibers is observed.
CC In later life, large inclusions were seen in the adaxonal Schwann
CC cell cytoplasm. There is no evidence of apoptotic response.
CC -!- SIMILARITY: Belongs to the NDRG family.
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DR EMBL; U60593; AAB03484.1; -; mRNA.
DR EMBL; U52073; AAB58249.1; -; mRNA.
DR EMBL; BC015282; AAH15282.1; -; mRNA.
DR EMBL; BC071235; AAH71235.1; -; mRNA.
DR IPI; IPI00125960; -.
DR RefSeq; NP_032707.2; NM_008681.2.
DR UniGene; Mm.30837; -.
DR ProteinModelPortal; Q62433; -.
DR SMR; Q62433; 33-315.
DR IntAct; Q62433; 1.
DR MEROPS; S33.987; -.
DR PhosphoSite; Q62433; -.
DR PaxDb; Q62433; -.
DR PRIDE; Q62433; -.
DR DNASU; 17988; -.
DR Ensembl; ENSMUST00000005256; ENSMUSP00000005256; ENSMUSG00000005125.
DR GeneID; 17988; -.
DR KEGG; mmu:17988; -.
DR CTD; 10397; -.
DR MGI; MGI:1341799; Ndrg1.
DR eggNOG; NOG310435; -.
DR GeneTree; ENSGT00390000001874; -.
DR HOGENOM; HOG000230891; -.
DR HOVERGEN; HBG052591; -.
DR InParanoid; Q62433; -.
DR OMA; LHGSIHV; -.
DR OrthoDB; EOG4QC15K; -.
DR ChiTaRS; NDRG1; mouse.
DR NextBio; 292963; -.
DR ArrayExpress; Q62433; -.
DR Bgee; Q62433; -.
DR CleanEx; MM_NDRG1; -.
DR Genevestigator; Q62433; -.
DR GermOnline; ENSMUSG00000005125; Mus musculus.
DR GO; GO:0005913; C:cell-cell adherens junction; IEA:Compara.
DR GO; GO:0005813; C:centrosome; IEA:Compara.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:Compara.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Compara.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IEA:Compara.
DR GO; GO:0045576; P:mast cell activation; IDA:MGI.
DR GO; GO:0032287; P:peripheral nervous system myelin maintenance; IMP:UniProtKB.
DR GO; GO:0090232; P:positive regulation of spindle checkpoint; IEA:Compara.
DR InterPro; IPR004142; Ndr.
DR PANTHER; PTHR11034; PTHR11034; 1.
DR Pfam; PF03096; Ndr; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton; Membrane;
KW Microtubule; Nucleus; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1 394 Protein NDRG1.
FT /FTId=PRO_0000159574.
FT REPEAT 339 348 1.
FT REPEAT 349 358 2.
FT REPEAT 359 368 3.
FT REGION 339 368 3 X 10 AA tandem repeats of G-[PST]-R-S-
FT R-S-H-T-S-E.
FT MOD_RES 2 2 Phosphoserine.
FT MOD_RES 326 326 Phosphoserine (By similarity).
FT MOD_RES 328 328 Phosphothreonine; by SGK1.
FT MOD_RES 330 330 Phosphoserine; by SGK1.
FT MOD_RES 332 332 Phosphoserine; by SGK1 (By similarity).
FT MOD_RES 333 333 Phosphoserine (By similarity).
FT MOD_RES 335 335 Phosphothreonine.
FT MOD_RES 336 336 Phosphoserine.
FT MOD_RES 346 346 Phosphothreonine; by SGK1.
FT MOD_RES 356 356 Phosphothreonine; by SGK1 (By
FT similarity).
FT MOD_RES 362 362 Phosphoserine.
FT MOD_RES 364 364 Phosphoserine (By similarity).
FT MOD_RES 366 366 Phosphothreonine; by SGK1 (By
FT similarity).
FT MOD_RES 375 375 Phosphothreonine (By similarity).
FT CONFLICT 33 35 QEQ -> LEE (in Ref. 2; AAB58249).
FT CONFLICT 89 89 F -> P (in Ref. 2; AAB58249).
FT CONFLICT 103 109 APSFPVG -> PLPSQW (in Ref. 2; AAB58249).
FT CONFLICT 141 148 AGAYILTR -> PWXLHPDP (in Ref. 2;
FT AAB58249).
FT CONFLICT 191 208 VVSHLFGKEEIHNNVEVV -> CVPPLRXGGDTQQRGGM
FT (in Ref. 2; AAB58249).
FT CONFLICT 241 241 R -> A (in Ref. 2; AAB58249).
FT CONFLICT 298 350 PAKLAEAFKYFVQGMGYMPSASMTRLMRSRTASGSSVTSLE
FT GTRSRSHTSEGP -> RPSLLRPSSTLCRHGIHAFCQHDSP
FT DRVPHPVWLQCHILEGT (in Ref. 2; AAB58249).
SQ SEQUENCE 394 AA; 43009 MW; 905CA71ECF4C87C2 CRC64;
MSRELHDVDL AEVKPLVEKG ESITGLLQEF DVQEQDIETL HGSLHVTLCG TPKGNRPVIL
TYHDIGMNHK TCYNPLFNSE DMQEITQHFA VCHVDAPGQQ DGAPSFPVGY MYPSMDQLAE
MLPGVLHQFG LKSVIGMGTG AGAYILTRFA LNNPEMVEGL VLMNVNPCAE GWMDWAASKI
SGWTQALPDM VVSHLFGKEE IHNNVEVVHT YRQHILNDMN PSNLHLFISA YNSRRDLEIE
RPMPGTHTVT LQCPALLVVG DNSPAVDAVV ECNSKLDPTK TTLLKMADCG GLPQISQPAK
LAEAFKYFVQ GMGYMPSASM TRLMRSRTAS GSSVTSLEGT RSRSHTSEGP RSRSHTSEGS
RSRSHTSEDA RLNITPNSGA TGNNAGPKSM EVSC
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