NDRG1_MOUSE
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 03-AUG-2022, entry version 170.
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; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND
RP 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 project:
RT 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 IDENTIFICATION BY MASS SPECTROMETRY.
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 [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 SER-330 AND SER-336, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-319; SER-326; THR-328;
RP SER-330; SER-332; SER-333; THR-335; SER-336; THR-340 AND SER-342, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
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 [10]
RP DISRUPTION PHENOTYPE, CHARACTERISTICS OF A MOUSE MODEL OF CMT4D, FUNCTION,
RP 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., Hunter M.,
RA 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, 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. Required for vesicular recycling of CDH1 and
CC TF. May also function in lipid trafficking. Protects cells from spindle
CC disruption damage. Functions in p53/TP53-dependent mitotic spindle
CC checkpoint. Regulates microtubule dynamics and maintains euploidy (By
CC similarity). Has a role in cell trafficking notably of the Schwann cell
CC and is necessary for the maintenance and development of the peripheral
CC nerve myelin sheath. {ECO:0000250, ECO:0000269|PubMed:15082788,
CC ECO:0000269|PubMed:21303696}.
CC -!- SUBUNIT: Interacts with RAB4A (membrane-bound form); the interaction
CC involves NDRG1 in vesicular recycling of CDH1. Interacts with APOA1,
CC APOA2, PRA1 and RTN1 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome. Nucleus. Cell membrane
CC {ECO:0000250}. Note=Mainly cytoplasmic but differentially localized to
CC other regions. Associates with the plasma membrane in intestinal
CC epithelia and 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 nuclear
CC localization in colon epithelium cells. In intestinal mucosa, prostate
CC and renal 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 (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in kidney
CC followed by brain, pancreas, small intestine, colon and spleen (at
CC protein level). Also detected in heart and preputial gland, and in much
CC smaller quantities in other tissues. Not detected in duodenum and
CC prostate. Highly expressed in Schwann cells.
CC {ECO:0000269|PubMed:15082788, ECO:0000269|PubMed:15461589,
CC ECO:0000269|PubMed:21636852, ECO:0000269|PubMed:9144177}.
CC -!- DEVELOPMENTAL STAGE: In early stages of embryo development, expression
CC low when MYCN expression is high. Later, when MYCN levels diminish,
CC levels increase. {ECO:0000269|PubMed:10381566}.
CC -!- INDUCTION: Repressed by testosterone and also to a lesser extent by
CC dihydrotestosterone. Down-regulated by MYCN.
CC {ECO:0000269|PubMed:10381566, ECO:0000269|PubMed:9144177}.
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 (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice exhibit defects in peripheral nerve
CC development. Initial hind limb weakness developed around age 12 weeks,
CC and significant functional impairment (dragging of hind legs) and
CC muscle atrophy became apparent at age 1 year. After about 5 weeks
CC extensive demyelination of nerve fibers is observed. In later life,
CC large inclusions were seen in the adaxonal Schwann cell cytoplasm.
CC There is no evidence of apoptotic response.
CC {ECO:0000269|PubMed:15082788, ECO:0000269|PubMed:21303696}.
CC -!- SIMILARITY: Belongs to the NDRG family. {ECO:0000305}.
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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 CCDS; CCDS37092.1; -.
DR RefSeq; NP_032707.2; NM_008681.2.
DR AlphaFoldDB; Q62433; -.
DR SMR; Q62433; -.
DR BioGRID; 201714; 20.
DR IntAct; Q62433; 1.
DR STRING; 10090.ENSMUSP00000005256; -.
DR ESTHER; mouse-ndr1; Ndr_family.
DR MEROPS; S33.988; -.
DR iPTMnet; Q62433; -.
DR PhosphoSitePlus; Q62433; -.
DR SwissPalm; Q62433; -.
DR EPD; Q62433; -.
DR jPOST; Q62433; -.
DR MaxQB; Q62433; -.
DR PaxDb; Q62433; -.
DR PRIDE; Q62433; -.
DR ProteomicsDB; 286160; -.
DR Antibodypedia; 1521; 648 antibodies from 43 providers.
DR DNASU; 17988; -.
DR Ensembl; ENSMUST00000005256; ENSMUSP00000005256; ENSMUSG00000005125.
DR GeneID; 17988; -.
DR KEGG; mmu:17988; -.
DR UCSC; uc007wax.1; mouse.
DR CTD; 10397; -.
DR MGI; MGI:1341799; Ndrg1.
DR VEuPathDB; HostDB:ENSMUSG00000005125; -.
DR eggNOG; KOG2931; Eukaryota.
DR GeneTree; ENSGT00950000182872; -.
DR HOGENOM; CLU_035361_1_0_1; -.
DR InParanoid; Q62433; -.
DR OMA; MFIDSYI; -.
DR OrthoDB; 854690at2759; -.
DR PhylomeDB; Q62433; -.
DR TreeFam; TF313168; -.
DR BioGRID-ORCS; 17988; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Ndrg1; mouse.
DR PRO; PR:Q62433; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q62433; protein.
DR Bgee; ENSMUSG00000005125; Expressed in sciatic nerve and 290 other tissues.
DR ExpressionAtlas; Q62433; baseline and differential.
DR Genevisible; Q62433; MM.
DR GO; GO:0005912; C:adherens junction; ISO:MGI.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; ISO:MGI.
DR GO; GO:0045296; F:cadherin binding; ISO:MGI.
DR GO; GO:0043015; F:gamma-tubulin binding; ISO:MGI.
DR GO; GO:0008017; F:microtubule binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IEA:Ensembl.
DR GO; GO:0045576; P:mast cell activation; IDA:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:CACAO.
DR GO; GO:0032287; P:peripheral nervous system myelin maintenance; IMP:UniProtKB.
DR GO; GO:0099173; P:postsynapse organization; ISO:MGI.
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 Acetylation; Cell membrane; Cytoplasm; Cytoskeleton; Membrane; Microtubule;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q92597"
FT CHAIN 2..394
FT /note="Protein NDRG1"
FT /id="PRO_0000159574"
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-[PST]-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:0000250|UniProtKB:Q92597"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92597"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 328
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 330
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 332
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 335
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 336
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 340
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 342
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 346
FT /note="Phosphothreonine; by SGK1"
FT /evidence="ECO:0000269|PubMed:15461589"
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:0000250|UniProtKB:Q92597"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6JE36"
FT MOD_RES 364
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92597"
FT MOD_RES 366
FT /note="Phosphothreonine; by SGK1"
FT /evidence="ECO:0000250|UniProtKB:Q92597"
FT MOD_RES 375
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q92597"
FT CONFLICT 33..35
FT /note="QEQ -> LEE (in Ref. 2; AAB58249)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="F -> P (in Ref. 2; AAB58249)"
FT /evidence="ECO:0000305"
FT CONFLICT 103..109
FT /note="APSFPVG -> PLPSQW (in Ref. 2; AAB58249)"
FT /evidence="ECO:0000305"
FT CONFLICT 141..148
FT /note="AGAYILTR -> PWXLHPDP (in Ref. 2; AAB58249)"
FT /evidence="ECO:0000305"
FT CONFLICT 191..208
FT /note="VVSHLFGKEEIHNNVEVV -> CVPPLRXGGDTQQRGGM (in Ref. 2;
FT AAB58249)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="R -> A (in Ref. 2; AAB58249)"
FT /evidence="ECO:0000305"
FT CONFLICT 298..350
FT /note="PAKLAEAFKYFVQGMGYMPSASMTRLMRSRTASGSSVTSLEGTRSRSHTSEG
FT P -> RPSLLRPSSTLCRHGIHAFCQHDSPDRVPHPVWLQCHILEGT (in Ref. 2;
FT AAB58249)"
FT /evidence="ECO:0000305"
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
