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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
  • 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

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000104419.14.
HGNCiHGNC:7679. NDRG1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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.
GeneReviewsiNDRG1.
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

Show more details

GO - Molecular functioni

  • cadherin binding Source: UniProtKB
  • gamma-tubulin binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • Rab GTPase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115669. 111 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.
OMAiNNVEVVH.
OrthoDBiEOG091G09VW.
PhylomeDBiQ92597.
TreeFamiTF313168.

Family and domain databases

Gene3Di3.40.50.1820. 1 hit.
InterProiView protein in InterPro
IPR029058. AB_hydrolase.
IPR004142. NDRG.
IPR030693. NDRG1.
PANTHERiPTHR11034. PTHR11034. 1 hit.
PTHR11034:SF18. PTHR11034:SF18. 1 hit.
PfamiView protein in Pfam
PF03096. Ndr. 1 hit.
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 dbSNP:rs2233319Ensembl.1
Natural variantiVAR_050235111M → L. Corresponds to variant dbSNP:rs2233328Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiNDRG1_HUMAN
AccessioniPrimary (citable) accession number: Q92597
Secondary accession number(s): B3KR80
, B7Z446, O15207, Q6IBG2, Q9NYR6, Q9UK29
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: February 1, 1997
Last modified: October 25, 2017
This is version 172 of the entry and version 1 of the sequence. See 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