NDRG2 (NDRG family member 2)

2005-06-01   Libo Yao , Lifeng Wang , Jiang Zhang , Na Liu 

Department of Biochemistry, Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xian, Shaanxi 710032, P.R. China

Identity

HGNC
LOCATION
14q11.2
LOCUSID
ALIAS
SYLD
FUSION GENES

DNA/RNA

Description

The gene encompasses 9013 bp of DNA; 16 or 17 exons (the first and second are non-coding).

Transcription

Eight splicing mRNAs are found.
  • 2142 bp mRNA; CDS: 174-1289bp ;1113 bp open reading frame
  • 2100 bp mRNA; CDS: 174-1247bp ;1071 bp open reading frame
  • 2033 bp mRNA; CDS: 107-1180bp ;1071 bp open reading frame
  • 2075 bp mRNA; CDS: 107-1222bp ;1113 bp open reading frame
  • 2010 bp mRNA; CDS: 84-1157bp ;1071 bp open reading frame
  • 2052 bp mRNA; CDS: 84-1199bp ;1113 bp open reading frame
  • 2119 bp mRNA; CDS: 151-1266bp ;1113 bp open reading frame
  • 2077 bp mRNA; CDS: 151-1224bp ;1071 bp open reading frame.
  • Proteins

    Description

    357 amino acids ; another isoform has 371 amino acids ; 40 or 43 kDa ; Thr348 is a Akt phosphorylation site, Ser332 is a PKC teta-phosphorylation site. NDRG2 has the alpha/beta hydrolase fold motif.

    Expression

    Widely expressed, especially in brain, heart, skeletal muscle and kidney.

    Localisation

    cytosol

    Function

    A candidate tumor suppressor gene. Ndrg2 expressed much higher in normal tissues than the tumors (brain, liver, pancreas tissues etc) . Overexpression of ndrg2 can inhibit the proliferation of glioblastoma U373 and U138 cells. NDRG2 upregulation is associated with disease pathogenesis in the human brain. Ndrg2 is expressed during the differentiation of DCs, and the expression is differentially regulated by maturation-inducing stimuli such as LPS and CD40. The expression of ndrg2 in rat frontal cortex was decreased by chronic antidepressant treatment.

    Homology

    At the amino acid level, human NDRG2 shows 57% identical to NDRG1 and NDRG3, 65% identical to NDRG4-B, 63% identical to NDRG4-Bvar and 61% identical to NDRG4-H respectively. Also human NDRG2 shows 92% identical to mouse NDRG2.

    Implicated in

    Entity name
    Alzheimers disease
    Disease
    Alzheimers disease is the most common cause of dementia. Dementia is a collective name for progressive degenerative brain syndromes, which affect memory, thinking, behavior and emotion. Symptoms may include: 1) lose of memory ; 2) difficulty in finding the right words or understanding what people are saying; 3) difficulty in performing previously routine tasks; 4) personality and mood changes.
    Prognosis
    The probable outcome is poor. The disorder is usually not acute, but progresses steadily. Total disability is common. Death normally occurs within 15 years, usually from an infection or a failure of other body systems. The duration of illness, from onset of symptoms to death, averages 8 to 10 years
    Hybrid gene
    NDRG2 is upregulated at both the RNA and protein levels in AD brains. Expression of NDRG2 in affected brains was revealed in : (1) cortical pyramidal neurons, (2) senile plaques and (3) cellular processes of dystrophic neurons. NDRG2 upregulation is associated with disease pathogenesis in the human brain
    Entity name
    Liver cancers
    Disease
    Liver cancers are primary liver tumors (hepatoma/hepatocellular carcinoma, bile duct cancer/cholangio-carcinoma) or metastatic liver tumor.
    Oncogenesis
    Compared with adjacent normal tissues, the expression levels of NDRG2 mRNA in liver cancer tissues reduced significantly, but the mutation in the whole coding region of NDRG2 was not found.
    Entity name
    Glioblastoma
    Disease
    Glioblastoma multiforme (GBM) is the most aggressive form of the primary brain tumors known collectively as gliomas. These tumors arise from the supporting, glial cells of the brain during childhood and in adults. These growths do not spread throughout the body like other forms of cancer, but cause symptoms by invading the brain.NDRG2 gene was first found in this tissue by using subtraction cloning.
    Oncogenesis
    Ndrg2 is present at low levels in human GBM tissues and glioblastoma cell lines comparing with normal tissue and cells. Transient transfection exogenous NDRG2 gene will inhibits glioblastoma U373 and U138 cells proliferation.
    Entity name
    Gastric cancer
    Disease
    Gastric cancer is the result of cell changes in the lining of the stomach. The most common types of stomach cancer start in the glandular cells of the stomach lining and are known as adenocarcinomas. These are rare cancers that usually start from the cells of the muscle layer of the stomach. The most common type of sarcoma to affect the stomach is a leiomyosarcoma. Another type of sarcoma is a gastrointestinal stromal tumour (GIST).
    Oncogenesis
    Ndrg2 is present at low level in some stomach cancer tissue and cell lines.

    Bibliography

    Pubmed IDLast YearTitleAuthors
    14594501992Embryonic lethality in mice homozygous for a targeted disruption of the N-myc gene.Charron J et al
    128456712003N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation.Deng Y et al
    155263772004NDRG2 expression and mutation in human liver and pancreatic cancers.Hu XL et al
    89398981996Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes.Kokame K et al
    97666761998Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage.Kurdistani SK et al
    152072612004NDRG2: a novel Alzheimer's disease associated protein.Mitchelmore C et al
    105811911999Identification of new genes ndr2 and ndr3 which are related to Ndr1/RTP/Drg1 but show distinct tissue specificity and response to N-myc.Okuda T et al
    119368452002Characterization and expression of three novel differentiation-related genes belong to the human NDRG gene family.Qu X et al
    103815661999N-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 et al
    14594491992Loss of N-myc function results in embryonic lethality and failure of the epithelial component of the embryo to develop.Stanton BR et al
    113525692001Characterization of the human NDRG gene family: a newly identified member, NDRG4, is specifically expressed in brain and heart.Zhou RH et al
    92516811997A novel gene which is up-regulated during colon epithelial cell differentiation and down-regulated in colorectal neoplasms.van Belzen N et al

    Other Information

    Locus ID:

    NCBI: 57447
    MIM: 605272
    HGNC: 14460
    Ensembl: ENSG00000165795

    Variants:

    dbSNP: 57447
    ClinVar: 57447
    TCGA: ENSG00000165795
    COSMIC: NDRG2

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000165795ENST00000298684Q9UN36
    ENSG00000165795ENST00000298687Q9UN36
    ENSG00000165795ENST00000350792Q9UN36
    ENSG00000165795ENST00000360463Q9UN36
    ENSG00000165795ENST00000397844Q9UN36
    ENSG00000165795ENST00000397847Q9UN36
    ENSG00000165795ENST00000397851Q9UN36
    ENSG00000165795ENST00000397853Q9UN36
    ENSG00000165795ENST00000397856A0A0A0MS87
    ENSG00000165795ENST00000397858Q9UN36
    ENSG00000165795ENST00000403829Q9UN36
    ENSG00000165795ENST00000449431H7C0X0
    ENSG00000165795ENST00000553442G3V271
    ENSG00000165795ENST00000553503Q9UN36
    ENSG00000165795ENST00000553563G3V420
    ENSG00000165795ENST00000553593H0YJT9
    ENSG00000165795ENST00000553784G3V358
    ENSG00000165795ENST00000553867G3V2I9
    ENSG00000165795ENST00000554094G3V5B7
    ENSG00000165795ENST00000554104G3V578
    ENSG00000165795ENST00000554143Q9UN36
    ENSG00000165795ENST00000554379G3V2Y3
    ENSG00000165795ENST00000554398G3V3D5
    ENSG00000165795ENST00000554415G3V5B5
    ENSG00000165795ENST00000554419G3V552
    ENSG00000165795ENST00000554472G3V3P1
    ENSG00000165795ENST00000554483G3V3X3
    ENSG00000165795ENST00000554489G3V5D7
    ENSG00000165795ENST00000554531G3V3L1
    ENSG00000165795ENST00000554561G3V3C3
    ENSG00000165795ENST00000554833G3V5P9
    ENSG00000165795ENST00000554893G3V239
    ENSG00000165795ENST00000555026G3V5H8
    ENSG00000165795ENST00000555142G3V285
    ENSG00000165795ENST00000555158Q9UN36
    ENSG00000165795ENST00000555384G3V383
    ENSG00000165795ENST00000555657G3V5G7
    ENSG00000165795ENST00000555695G3V3P6
    ENSG00000165795ENST00000555733G3V5S0
    ENSG00000165795ENST00000555767G3V4X3
    ENSG00000165795ENST00000555869G3V392
    ENSG00000165795ENST00000556008G3V4S9
    ENSG00000165795ENST00000556147Q9UN36
    ENSG00000165795ENST00000556329G3V5A6
    ENSG00000165795ENST00000556366G3V5L7
    ENSG00000165795ENST00000556420G3V4S2
    ENSG00000165795ENST00000556457G3V2T2
    ENSG00000165795ENST00000556561G3V2S0
    ENSG00000165795ENST00000556688G3V4T9
    ENSG00000165795ENST00000556924G3V280
    ENSG00000165795ENST00000556974G3V5H8
    ENSG00000165795ENST00000557149G3V285
    ENSG00000165795ENST00000557169G3V5G0
    ENSG00000165795ENST00000557182G3V2A6
    ENSG00000165795ENST00000557264G3V3X2
    ENSG00000165795ENST00000557274G3V5G7
    ENSG00000165795ENST00000557353G3V237
    ENSG00000165795ENST00000557616G3V2Y3
    ENSG00000165795ENST00000557633H0YJ56
    ENSG00000165795ENST00000557676G3V5V9
    ENSG00000165795ENST00000635386A0A0U1RR50

    Expression (GTEx)

    0
    100
    200
    300
    400
    500
    600
    700

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    References

    Pubmed IDYearTitleCitations
    154615892004Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3.135
    119368452002Characterization and expression of three novel differentiation-related genes belong to the human NDRG gene family.72
    128456712003N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation.62
    161030612005Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma.51
    185196802008Functional and clinical evidence for NDRG2 as a candidate suppressor of liver cancer metastasis.50
    245697122014Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers.41
    202061602010HIF-1 and NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer Hela cells.35
    152072612004NDRG2: a novel Alzheimer's disease associated protein.34
    208868412010Phosphoproteomic analysis reveals site-specific changes in GFAP and NDRG2 phosphorylation in frontotemporal lobar degeneration.34
    170505362006The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter.33

    Citation

    Libo Yao ; Lifeng Wang ; Jiang Zhang ; Na Liu

    NDRG2 (NDRG family member 2)

    Atlas Genet Cytogenet Oncol Haematol. 2005-06-01

    Online version: http://atlasgeneticsoncology.org/gene/41513/ndrg2-(ndrg-family-member-2)