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Protein

Protein NDRG1

Gene

NDRG1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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. 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.4 Publications

GO - Molecular functioni

  • cadherin binding Source: UniProtKB
  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • gamma-tubulin binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • Rab GTPase binding Source: UniProtKB

GO - Biological processi

  • cellular response to hypoxia Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
  • mast cell activation Source: Ensembl
  • negative regulation of cell proliferation Source: Ensembl
  • peripheral nervous system myelin maintenance Source: Ensembl
  • positive regulation of spindle checkpoint Source: UniProtKB
  • regulation of apoptotic process Source: Reactome
  • response to metal ion Source: ProtInc
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000104419-MONOMER.
ReactomeiR-HSA-6803205. TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain.
SIGNORiQ92597.

Protein family/group databases

ESTHERihuman-NDRG1. Ndr_family.
MEROPSiS33.988.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein NDRG1
Alternative name(s):
Differentiation-related gene 1 protein
Short name:
DRG-1
N-myc downstream-regulated gene 1 protein
Nickel-specific induction protein Cap43
Reducing agents and tunicamycin-responsive protein
Short name:
RTP
Rit42
Gene namesi
Name:NDRG1
Synonyms:CAP43, DRG1, RTP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:7679. NDRG1.

Subcellular locationi

  • Cytoplasmcytosol
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome
  • Nucleus
  • Cell membrane

  • 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.

GO - Cellular componenti

  • cell-cell adherens junction Source: UniProtKB
  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • microtubule Source: UniProtKB
  • microtubule cytoskeleton Source: HPA
  • myelin sheath Source: Ensembl
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • recycling endosome membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Microtubule, Nucleus

Pathology & Biotechi

Involvement in diseasei

Charcot-Marie-Tooth disease 4D (CMT4D)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4.
See also OMIM:601455

Keywords - Diseasei

Charcot-Marie-Tooth disease, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi10397.
MalaCardsiNDRG1.
MIMi601455. phenotype.
OpenTargetsiENSG00000104419.
Orphaneti99950. Charcot-Marie-Tooth disease type 4D.
PharmGKBiPA31482.

Polymorphism and mutation databases

BioMutaiNDRG1.
DMDMi6166568.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001595732 – 394Protein NDRG1Add BLAST393

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei2PhosphoserineCombined sources1
Modified residuei319PhosphoserineBy similarity1
Modified residuei326PhosphoserineCombined sources1
Modified residuei328Phosphothreonine; by SGK1Combined sources1 Publication1
Modified residuei330Phosphoserine; by SGK1Combined sources1 Publication1
Modified residuei332Phosphoserine; by SGK1Combined sources1
Modified residuei333PhosphoserineCombined sources1
Modified residuei335PhosphothreonineBy similarity1
Modified residuei336PhosphoserineCombined sources1
Modified residuei340PhosphothreonineBy similarity1
Modified residuei342PhosphoserineBy similarity1
Modified residuei346Phosphothreonine; by SGK12 Publications1
Modified residuei352PhosphoserineBy similarity1
Modified residuei356Phosphothreonine; by SGK12 Publications1
Modified residuei362PhosphoserineBy similarity1
Modified residuei364Phosphoserine; by SGK1Combined sources1
Modified residuei366Phosphothreonine; by SGK1Combined sources2 Publications1
Modified residuei375PhosphothreonineCombined sources1

Post-translational modificationi

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.4 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ92597.
MaxQBiQ92597.
PaxDbiQ92597.
PeptideAtlasiQ92597.
PRIDEiQ92597.
TopDownProteomicsiQ92597-1. [Q92597-1]

PTM databases

iPTMnetiQ92597.
PhosphoSitePlusiQ92597.
SwissPalmiQ92597.

Expressioni

Tissue specificityi

Ubiquitous; expressed most prominently in placental membranes and prostate, kidney, small intestine, and ovary tissues. Also expressed in heart, brain, skeletal muscle, lung, liver and pancreas. Low levels in peripheral blood leukocytes and in tissues of the immune system. Expressed mainly in epithelial cells. Also found in Schwann cells of peripheral neurons. Reduced expression in adenocarcinomas compared to normal tissues. In colon, prostate and placental membranes, the cells that border the lumen show the highest expression.4 Publications

Inductioni

By homocysteine, 2-mercaptoethanol, tunicamycin in endothelial cells. Induced approximately 20-fold during in vitro differentiation of the colon carcinoma cell lines HT-29-D4 and Caco-2. Induced by oxidative stress in colon cancers. Decreased expression in colon adenomas and adenocarcinomas. Induced by nickel compounds in all tested cell lines. The primary signal for its induction is an elevation of free intracellular calcium ion caused by nickel ion exposure. Okadaic acid, a serine/threonine phosphatase inhibitor, induced its expression more rapidly and more efficiently than nickel.6 Publications

Gene expression databases

BgeeiENSG00000104419.
CleanExiHS_DRG1.
HS_NDRG1.
ExpressionAtlasiQ92597. baseline and differential.
GenevisibleiQ92597. HS.

Organism-specific databases

HPAiHPA006881.

Interactioni

Subunit structurei

Interacts with RAB4A (membrane-bound form); the interaction involves NDRG1 in vesicular recycling of CDH1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AK6Q9Y3D83EBI-10278703,EBI-2896123
CANXP278242EBI-716486,EBI-355947
XRCC6P129562EBI-716486,EBI-353208

GO - Molecular functioni

  • cadherin binding Source: UniProtKB
  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • gamma-tubulin binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • Rab GTPase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115669. 110 interactors.
IntActiQ92597. 66 interactors.
MINTiMINT-4999487.
STRINGi9606.ENSP00000319977.

Structurei

3D structure databases

ProteinModelPortaliQ92597.
SMRiQ92597.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati339 – 348110
Repeati349 – 358210
Repeati359 – 368310

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni339 – 3683 X 10 AA tandem repeats of G-T-R-S-R-S-H-T-S-EAdd BLAST30

Sequence similaritiesi

Belongs to the NDRG family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2931. Eukaryota.
ENOG410XSPF. LUCA.
GeneTreeiENSGT00390000001874.
HOGENOMiHOG000230891.
HOVERGENiHBG052591.
InParanoidiQ92597.
KOiK18266.
OMAiKTCFNPL.
OrthoDBiEOG091G09VW.
PhylomeDBiQ92597.
TreeFamiTF313168.

Family and domain databases

Gene3Di3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR004142. NDRG.
IPR030693. NDRG1.
[Graphical view]
PANTHERiPTHR11034. PTHR11034. 1 hit.
PTHR11034:SF18. PTHR11034:SF18. 1 hit.
PfamiPF03096. Ndr. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92597-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSREMQDVDL AEVKPLVEKG ETITGLLQEF DVQEQDIETL HGSVHVTLCG
60 70 80 90 100
TPKGNRPVIL TYHDIGMNHK TCYNPLFNYE DMQEITQHFA VCHVDAPGQQ
110 120 130 140 150
DGAASFPAGY MYPSMDQLAE MLPGVLQQFG LKSIIGMGTG AGAYILTRFA
160 170 180 190 200
LNNPEMVEGL VLINVNPCAE GWMDWAASKI SGWTQALPDM VVSHLFGKEE
210 220 230 240 250
MQSNVEVVHT YRQHIVNDMN PGNLHLFINA YNSRRDLEIE RPMPGTHTVT
260 270 280 290 300
LQCPALLVVG DSSPAVDAVV ECNSKLDPTK TTLLKMADCG GLPQISQPAK
310 320 330 340 350
LAEAFKYFVQ GMGYMPSASM TRLMRSRTAS GSSVTSLDGT RSRSHTSEGT
360 370 380 390
RSRSHTSEGT RSRSHTSEGA HLDITPNSGA AGNSAGPKSM EVSC
Length:394
Mass (Da):42,835
Last modified:February 1, 1997 - v1
Checksum:i4C816B9C85E3756F
GO
Isoform 2 (identifier: Q92597-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: Missing.

Note: No experimental confirmation available.
Show »
Length:328
Mass (Da):35,521
Checksum:iB8065321A684117C
GO
Isoform 3 (identifier: Q92597-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-81: Missing.

Note: No experimental confirmation available.
Show »
Length:313
Mass (Da):33,650
Checksum:i33AA0F4A954887BE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti145I → T in CAA63430 (PubMed:9251681).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05023467M → V.Corresponds to variant rs2233319dbSNPEnsembl.1
Natural variantiVAR_050235111M → L.Corresponds to variant rs2233328dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0450371 – 81Missing in isoform 3. 1 PublicationAdd BLAST81
Alternative sequenceiVSP_0450381 – 66Missing in isoform 2. 1 PublicationAdd BLAST66

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D87953 mRNA. Translation: BAA13505.1.
X92845 mRNA. Translation: CAA63430.1.
AF004162 mRNA. Translation: AAC13419.1.
AF186190 Genomic DNA. No translation available.
CR456842 mRNA. Translation: CAG33123.1.
AK091147 mRNA. Translation: BAG52292.1.
AK126924 mRNA. Translation: BAG54400.1.
AK296794 mRNA. Translation: BAH12432.1.
AF192304 Genomic DNA. No translation available.
CH471060 Genomic DNA. Translation: EAW92164.1.
BC003175 mRNA. Translation: AAH03175.1.
AF230380 mRNA. Translation: AAF71305.1.
CCDSiCCDS34945.1. [Q92597-1]
CCDS59112.1. [Q92597-3]
CCDS59113.1. [Q92597-2]
RefSeqiNP_001128714.1. NM_001135242.1. [Q92597-1]
NP_001245361.1. NM_001258432.1. [Q92597-2]
NP_001245362.1. NM_001258433.1. [Q92597-3]
NP_006087.2. NM_006096.3. [Q92597-1]
UniGeneiHs.372914.
Hs.618002.

Genome annotation databases

EnsembliENST00000323851; ENSP00000319977; ENSG00000104419. [Q92597-1]
ENST00000414097; ENSP00000404854; ENSG00000104419. [Q92597-1]
ENST00000522476; ENSP00000427894; ENSG00000104419. [Q92597-2]
ENST00000537882; ENSP00000437443; ENSG00000104419. [Q92597-3]
GeneIDi10397.
KEGGihsa:10397.
UCSCiuc003yug.3. human. [Q92597-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D87953 mRNA. Translation: BAA13505.1.
X92845 mRNA. Translation: CAA63430.1.
AF004162 mRNA. Translation: AAC13419.1.
AF186190 Genomic DNA. No translation available.
CR456842 mRNA. Translation: CAG33123.1.
AK091147 mRNA. Translation: BAG52292.1.
AK126924 mRNA. Translation: BAG54400.1.
AK296794 mRNA. Translation: BAH12432.1.
AF192304 Genomic DNA. No translation available.
CH471060 Genomic DNA. Translation: EAW92164.1.
BC003175 mRNA. Translation: AAH03175.1.
AF230380 mRNA. Translation: AAF71305.1.
CCDSiCCDS34945.1. [Q92597-1]
CCDS59112.1. [Q92597-3]
CCDS59113.1. [Q92597-2]
RefSeqiNP_001128714.1. NM_001135242.1. [Q92597-1]
NP_001245361.1. NM_001258432.1. [Q92597-2]
NP_001245362.1. NM_001258433.1. [Q92597-3]
NP_006087.2. NM_006096.3. [Q92597-1]
UniGeneiHs.372914.
Hs.618002.

3D structure databases

ProteinModelPortaliQ92597.
SMRiQ92597.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115669. 110 interactors.
IntActiQ92597. 66 interactors.
MINTiMINT-4999487.
STRINGi9606.ENSP00000319977.

Protein family/group databases

ESTHERihuman-NDRG1. Ndr_family.
MEROPSiS33.988.

PTM databases

iPTMnetiQ92597.
PhosphoSitePlusiQ92597.
SwissPalmiQ92597.

Polymorphism and mutation databases

BioMutaiNDRG1.
DMDMi6166568.

Proteomic databases

EPDiQ92597.
MaxQBiQ92597.
PaxDbiQ92597.
PeptideAtlasiQ92597.
PRIDEiQ92597.
TopDownProteomicsiQ92597-1. [Q92597-1]

Protocols and materials databases

DNASUi10397.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000323851; ENSP00000319977; ENSG00000104419. [Q92597-1]
ENST00000414097; ENSP00000404854; ENSG00000104419. [Q92597-1]
ENST00000522476; ENSP00000427894; ENSG00000104419. [Q92597-2]
ENST00000537882; ENSP00000437443; ENSG00000104419. [Q92597-3]
GeneIDi10397.
KEGGihsa:10397.
UCSCiuc003yug.3. human. [Q92597-1]

Organism-specific databases

CTDi10397.
DisGeNETi10397.
GeneCardsiNDRG1.
GeneReviewsiNDRG1.
HGNCiHGNC:7679. NDRG1.
HPAiHPA006881.
MalaCardsiNDRG1.
MIMi601455. phenotype.
605262. gene.
neXtProtiNX_Q92597.
OpenTargetsiENSG00000104419.
Orphaneti99950. Charcot-Marie-Tooth disease type 4D.
PharmGKBiPA31482.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2931. Eukaryota.
ENOG410XSPF. LUCA.
GeneTreeiENSGT00390000001874.
HOGENOMiHOG000230891.
HOVERGENiHBG052591.
InParanoidiQ92597.
KOiK18266.
OMAiKTCFNPL.
OrthoDBiEOG091G09VW.
PhylomeDBiQ92597.
TreeFamiTF313168.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000104419-MONOMER.
ReactomeiR-HSA-6803205. TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain.
SIGNORiQ92597.

Miscellaneous databases

ChiTaRSiNDRG1. human.
GeneWikiiNDRG1.
GenomeRNAii10397.
PROiQ92597.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104419.
CleanExiHS_DRG1.
HS_NDRG1.
ExpressionAtlasiQ92597. baseline and differential.
GenevisibleiQ92597. HS.

Family and domain databases

Gene3Di3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR004142. NDRG.
IPR030693. NDRG1.
[Graphical view]
PANTHERiPTHR11034. PTHR11034. 1 hit.
PTHR11034:SF18. PTHR11034:SF18. 1 hit.
PfamiPF03096. Ndr. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNDRG1_HUMAN
AccessioniPrimary (citable) accession number: Q92597
Secondary accession number(s): B3KR80
, B7Z446, O15207, Q6IBG2, Q9NYR6, Q9UK29
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: February 1, 1997
Last modified: November 2, 2016
This is version 167 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.