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Q62433 (NDRG1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Protein NDRG1
Alternative name(s):
N-myc downstream-regulated gene 1 protein
Short name=Protein Ndr1
Gene names
Name:Ndrg1
Synonyms:Ndr1, Ndrl, Tdd5
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length394 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53-mediated caspase activation and apoptosis. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy By similarity. Has a role in cell trafficking notably of the Schwann cell and is necessary for the maintenance and development of the peripheral nerve myelin sheath. Ref.5 Ref.9

Subunit structure

Interacts with RAB4A (membrane-bound form); the interaction involves NDRG1 in vesicular recycling of CDH1. Interacts with APOA1, APOA2, PRA1 and RTN1 By similarity.

Subcellular location

Cytoplasmcytosol. Cytoplasmcytoskeletoncentrosome. Nucleus. Cell membrane By similarity. Note: Mainly cytoplasmic but differentially localized to other regions. Associates with the plasma membrane in intestinal epithelia and lactating mammary gland. Translocated to the nucleus in a p53/TP53-dependent manner. In prostate epithelium and placental chorion, located in both the cytoplasm and in the nucleus. No nuclear localization in colon epithelium cells. In intestinal mucosa, prostate and renal cortex, located predominantly adjacent to adherens junctions. Cytoplasmic with granular staining in proximal tubular cells of the kidney and salivary gland ducts. Recruits to the membrane of recycling/sorting and late endosomes via binding to phosphatidylinositol 4-phosphate. Associates with microtubules. Colocalizes with TUBG1 in the centrosome. Cytoplasmic location increased with hypoxia. Phosphorylated form found associated with centromeres during S-phase of mitosis and with the plasma membrane By similarity. Ref.1 Ref.4 Ref.5 Ref.9

Tissue specificity

Widely expressed, with highest levels in kidney followed by brain, pancreas, small intestine, colon and spleen (at protein level). Also detected in heart and preputial gland, and in much smaller quantities in other tissues. Not detected in duodenum and prostate. Highly expressed in Schwann cells. Ref.2 Ref.4 Ref.5 Ref.8

Developmental stage

In early stages of embryo development, expression low when MYCN expression is high. Later, when MYCN levels diminish, levels increase. Ref.1

Induction

Repressed by testosterone and also to a lesser extent by dihydrotestosterone. Down-regulated by MYCN. Ref.1 Ref.2

Post-translational modification

Under stress conditions, phosphorylated in the C-terminal on many serine and threonine residues. Phosphorylated in vitro by PKA. Phosphorylation enhanced by increased intracellular cAMP levels. Homocysteine induces dephosphorylation. Phosphorylation by SGK1 is cell cycle dependent By similarity. Ref.4

Disruption phenotype

Mutant mice exhibit defects in peripheral nerve development. Initial hind limb weakness developed around age 12 weeks, and significant functional impairment (dragging of hind legs) and muscle atrophy became apparent at age 1 year. After about 5 weeks extensive demyelination of nerve fibers is observed. In later life, large inclusions were seen in the adaxonal Schwann cell cytoplasm. There is no evidence of apoptotic response. Ref.5 Ref.9

Sequence similarities

Belongs to the NDRG family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 394394Protein NDRG1
PRO_0000159574

Regions

Repeat339 – 348101
Repeat349 – 358102
Repeat359 – 368103
Region339 – 368303 X 10 AA tandem repeats of G-[PST]-R-S-R-S-H-T-S-E

Amino acid modifications

Modified residue21Phosphoserine Ref.7
Modified residue3261Phosphoserine By similarity
Modified residue3281Phosphothreonine; by SGK1 Ref.6
Modified residue3301Phosphoserine; by SGK1 Ref.6
Modified residue3321Phosphoserine; by SGK1 By similarity
Modified residue3331Phosphoserine By similarity
Modified residue3351Phosphothreonine Ref.6
Modified residue3361Phosphoserine Ref.6
Modified residue3461Phosphothreonine; by SGK1 Ref.4 Ref.7
Modified residue3561Phosphothreonine; by SGK1 By similarity
Modified residue3621Phosphoserine Ref.7
Modified residue3641Phosphoserine By similarity
Modified residue3661Phosphothreonine; by SGK1 By similarity
Modified residue3751Phosphothreonine By similarity

Experimental info

Sequence conflict33 – 353QEQ → LEE in AAB58249. Ref.2
Sequence conflict891F → P in AAB58249. Ref.2
Sequence conflict103 – 1097APSFPVG → PLPSQW in AAB58249. Ref.2
Sequence conflict141 – 1488AGAYILTR → PWXLHPDP in AAB58249. Ref.2
Sequence conflict191 – 20818VVSHL…NVEVV → CVPPLRXGGDTQQRGGM in AAB58249. Ref.2
Sequence conflict2411R → A in AAB58249. Ref.2
Sequence conflict298 – 35053PAKLA…TSEGP → RPSLLRPSSTLCRHGIHAFC QHDSPDRVPHPVWLQCHILE GT in AAB58249. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q62433 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 905CA71ECF4C87C2

FASTA39443,009
        10         20         30         40         50         60 
MSRELHDVDL AEVKPLVEKG ESITGLLQEF DVQEQDIETL HGSLHVTLCG TPKGNRPVIL 

        70         80         90        100        110        120 
TYHDIGMNHK TCYNPLFNSE DMQEITQHFA VCHVDAPGQQ DGAPSFPVGY MYPSMDQLAE 

       130        140        150        160        170        180 
MLPGVLHQFG LKSVIGMGTG AGAYILTRFA LNNPEMVEGL VLMNVNPCAE GWMDWAASKI 

       190        200        210        220        230        240 
SGWTQALPDM VVSHLFGKEE IHNNVEVVHT YRQHILNDMN PSNLHLFISA YNSRRDLEIE 

       250        260        270        280        290        300 
RPMPGTHTVT LQCPALLVVG DNSPAVDAVV ECNSKLDPTK TTLLKMADCG GLPQISQPAK 

       310        320        330        340        350        360 
LAEAFKYFVQ GMGYMPSASM TRLMRSRTAS GSSVTSLEGT RSRSHTSEGP RSRSHTSEGS 

       370        380        390 
RSRSHTSEDA RLNITPNSGA TGNNAGPKSM EVSC 

« Hide

References

« Hide 'large scale' references
[1]"N-myc-dependent repression of ndr1, a gene identified by direct subtraction of whole mouse embryo cDNAs between wild type and N-myc mutant."
Shimono A., Okuda T., Kondoh H.
Mech. Dev. 83:39-52(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, INDUCTION.
Tissue: Embryo.
[2]"Cloning and characterization of TDD5, an androgen target gene that is differentially repressed by testosterone and dihydrotestosterone."
Lin T.-M., Chang C.
Proc. Natl. Acad. Sci. U.S.A. 94:4988-4993(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION.
Tissue: Hybridoma.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Kidney.
[4]"Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3."
Murray J.T., Campbell D.G., Morrice N., Auld G.C., Shpiro N., Marquez R., Peggie M., Bain J., Bloomberg G.B., Grahammer F., Lang F., Wulff P., Kuhl D., Cohen P.
Biochem. J. 384:477-488(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-346; THR-356 AND THR-366, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MASS SPECTROMETRY.
[5]"Ndrg1-deficient mice exhibit a progressive demyelinating disorder of peripheral nerves."
Okuda T., Higashi Y., Kokame K., Tanaka C., Kondoh H., Miyata T.
Mol. Cell. Biol. 24:3949-3956(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION.
[6]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-328; SER-330; THR-335 AND SER-336, MASS SPECTROMETRY.
Tissue: Liver.
[7]"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry."
Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M.
J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; THR-346 AND SER-362, MASS SPECTROMETRY.
Tissue: Melanoma.
[8]"NDRG4 protein-deficient mice exhibit spatial learning deficits and vulnerabilities to cerebral ischemia."
Yamamoto H., Kokame K., Okuda T., Nakajo Y., Yanamoto H., Miyata T.
J. Biol. Chem. 286:26158-26165(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Ndrg1 in development and maintenance of the myelin sheath."
King R.H., Chandler D., Lopaticki S., Huang D., Blake J., Muddle J.R., Kilpatrick T., Nourallah M., Miyata T., Okuda T., Carter K.W., Hunter M., Angelicheva D., Morahan G., Kalaydjieva L.
Neurobiol. Dis. 42:368-380(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, CHARACTERISTICS OF A MOUSE MODEL OF CMT4D, FUNCTION, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U60593 mRNA. Translation: AAB03484.1.
U52073 mRNA. Translation: AAB58249.1.
BC015282 mRNA. Translation: AAH15282.1.
BC071235 mRNA. Translation: AAH71235.1.
IPIIPI00125960.
RefSeqNP_032707.2. NM_008681.2.
UniGeneMm.30837.

3D structure databases

ProteinModelPortalQ62433.
SMRQ62433. Positions 33-315.
ModBaseSearch...

Protein-protein interaction databases

IntActQ62433. 1 interaction.

Protein family/group databases

MEROPSS33.987.

PTM databases

PhosphoSiteQ62433.

Proteomic databases

PaxDbQ62433.
PRIDEQ62433.

Protocols and materials databases

DNASU17988.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000005256; ENSMUSP00000005256; ENSMUSG00000005125.
GeneID17988.
KEGGmmu:17988.

Organism-specific databases

CTD10397.
MGIMGI:1341799. Ndrg1.

Phylogenomic databases

eggNOGNOG310435.
GeneTreeENSGT00390000001874.
HOGENOMHOG000230891.
HOVERGENHBG052591.
InParanoidQ62433.
OMALHGSIHV.
OrthoDBEOG4QC15K.

Gene expression databases

ArrayExpressQ62433.
BgeeQ62433.
CleanExMM_NDRG1.
GenevestigatorQ62433.
GermOnlineENSMUSG00000005125. Mus musculus.

Family and domain databases

InterProIPR004142. Ndr.
[Graphical view]
PANTHERPTHR11034. PTHR11034. 1 hit.
PfamPF03096. Ndr. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNDRG1. mouse.
NextBio292963.
SOURCESearch...

Entry information

Entry nameNDRG1_MOUSE
AccessionPrimary (citable) accession number: Q62433
Secondary accession number(s): P97862
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: May 1, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families