NUP98 (nucleoporin 98 kDa)

2002-03-01   Lyndal Kearney 

Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK

Identity

HGNC
LOCATION
11p15.4
LOCUSID
ALIAS
ADIR2,NUP196,NUP96,Nup98-96
FUSION GENES

DNA/RNA

Transcription

3.6, 6.5 , 7.0 kb mRNA

Proteins

Atlas Image
NUP98 protein; NUP98 contains a Gly-Leu-Phe-Gly (GLFG and FG) repeat in N-term (aa 1-156), a GLEBS-like motif (which binds RAE1, aa 157-213), another FG motif (aa 214-480) and a RNA binding motif in C-term (aa 738-880). NUP98 is involved in nuclear import/export, mitotic progression, and regulation of gene expression

Description

920 amino acids; 97 kDa; contains repeated motifs (GLFG and FG) in N-term and a RNA binding motif in C-term

Expression

wide

Localisation

nuclear membrane localisation

Function

nucleoporin: associated with the nuclear pore complex; role in nucleocytoplasmic transport processes

Homology

member of the GLFG nucleoporins

Implicated in

Entity name
inv (11)(p15q22)/ myelodysplasic syndrome (MDS) or acute non lymphocytic leukemia (AML) --> NUP98-DDX10
Disease
therapy related MDS (t-MDS) and AML; de novo AML
Hybrid gene
5 NUP98 - 3 DDX10
Fusion protein
fuses the GLFG repeat domains of NUP98 to the acidic domain of DDX10
Entity name
t(1;11)(q23;p15.5) / t-MDS orAML --> NUP98 -PMX1
Disease
One case of t-AML
Hybrid gene
5 NUP98 - 3 PMX1
Fusion protein
fuses the GLFG repeat domains of NUP98 to the homeodomain of PMX1
Entity name
t(2;11)(q31;p15)/treatment related leukaemia --> NUP98 -HOXD13
Disease
so far, only 1 case of treatment related myelodysplasia evolving towards M6 acute myeloid leukemia
Hybrid gene
5 NUP98 - 3 HOXD13
Fusion protein
fuses the GLFG repeat domains of NUP98 to the HOXD13 homeodomain
Entity name
t(4;11)(q21;p15.5)/ T- acute lymphoblastic leukemia (ALL) --> NUP98 -RAP1GDS1
Disease
3 cases of adult T-ALL
Hybrid gene
5 NUP98 - 3 RAP1GDS1
Fusion protein
fuses the GLFG repeat domains of NUP98 to the entire coding region of RAP1GDS1. The product, rap1gds, has guanine nucleotide exchange factor activity.
Entity name
Disease
AML. 5 cases reported to date. All were children or young adults (age range 3-18 years). Note that the t(5;11)(q35;p15.5) is not detectable by G-banding. Three cases were reported as cryptic t(5;11) associated with del(5q); a further two cases were identified in apparently normal karyotypes.
Hybrid gene
5 NUP98 - 3 NSD1
Fusion protein
fuses the GLFG repeat domains of NUP98 to the conserved SET, SAC and PHD finger domains of the NSD1 gene.
Entity name
Disease
M2-M4 AML mostly; occasionally: CML-like cases
Prognosis
mean survival: 15 mths
Cytogenetics
sole anomaly most often
Hybrid gene
5 NUP98 - 3 HOXA9
Fusion protein
fuses the GLFG repeat domains of NUP98 to the HOXA9 homeobox
Entity name
Disease
One case of de novo AML
Hybrid gene
5 NUP98 - 3 LEDGF
Fusion protein
fuses the GLFG repeat domains of NUP98 to the COOH terminal of the LEDGF gene (encoding transcriptional activators p52 and p75)
Entity name
t(11;12)(p15;q13)/treatment related leukemia (t-AML/MDS)
Disease
1patient with t-MDS/AML
Hybrid gene
5; NUP98 - 3; unknown
Entity name
Disease
1 patient with t-MDS/AML
Hybrid gene
5 NUP98 - 3 unknown
Entity name
t(11;20)(p15.5;q11)/AML, t-MDS/AML--> NUP98 -TOP1
Disease
AML, t-MDS/AML
Hybrid gene
5 NUP98 - 3 TOP1
Fusion protein
fuses the GLFG repeat domains of NUP98 to the catalytic domain of TOP1

Breakpoints

Atlas Image

Bibliography

Pubmed IDLast YearTitleAuthors
109590882000Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations.Ahuja HG et al
111037742000t(9;11)(p22;p15) in acute myeloid leukemia results in a fusion between NUP98 and the gene encoding transcriptional coactivators p52 and p75-lens epithelium-derived growth factor (LEDGF).Ahuja HG et al
91668301997The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10.Arai Y et al
118957892002A cryptic t(5;11)(q35;p15.5) in 2 children with acute myeloid leukemia with apparently normal karyotypes, identified by a multiplex fluorescence in situ hybridization telomere assay.Brown J et al
104777371999The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia.Hussey DJ et al
114934822001A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia.Jaju RJ et al
103977451999A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. The UK Cancer Cytogenetics Group (UKCCG)Jaju RJ et al
116814082001NUP98 gene fusions in hematologic malignancies.Lam DH et al
103977411999NUP98 is fused to PMX1 homeobox gene in human acute myelogenous leukemia with chromosome translocation t(1;11)(q23;p15).Nakamura T et al
90152971997The vertebrate GLFG nucleoporin, Nup98, is an essential component of multiple RNA export pathways.Powers MA et al
97666501998NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia.Raza-Egilmez SZ et al

Other Information

Locus ID:

NCBI: 4928
MIM: 601021
HGNC: 8068
Ensembl: ENSG00000110713

Variants:

dbSNP: 4928
ClinVar: 4928
TCGA: ENSG00000110713
COSMIC: NUP98

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000110713ENST00000324932P52948
ENSG00000110713ENST00000355260P52948
ENSG00000110713ENST00000359171P52948
ENSG00000110713ENST00000397004P52948
ENSG00000110713ENST00000397007P52948
ENSG00000110713ENST00000397013H7BYP8
ENSG00000110713ENST00000429801H7C3P6
ENSG00000110713ENST00000524563H0YDF4
ENSG00000110713ENST00000527104H0YEN4
ENSG00000110713ENST00000529063H0YDA1
ENSG00000110713ENST00000529379H0YCR0
ENSG00000110713ENST00000532475E9PNN0
ENSG00000110713ENST00000533346H0YCT1
ENSG00000110713ENST00000650171A0A3B3ITD8

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90
100

Pathways

PathwaySourceExternal ID
RNA transportKEGGko03013
RNA transportKEGGhsa03013
Influenza AKEGGko05164
Influenza AKEGGhsa05164
Nuclear pore complexKEGGhsa_M00427
Nuclear pore complexKEGGM00427
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
SUMOylationREACTOMER-HSA-2990846
SUMO E3 ligases SUMOylate target proteinsREACTOMER-HSA-3108232
SUMOylation of DNA damage response and repair proteinsREACTOMER-HSA-3108214
DiseaseREACTOMER-HSA-1643685
Infectious diseaseREACTOMER-HSA-5663205
HIV InfectionREACTOMER-HSA-162906
HIV Life CycleREACTOMER-HSA-162587
Late Phase of HIV Life CycleREACTOMER-HSA-162599
Rev-mediated nuclear export of HIV RNAREACTOMER-HSA-165054
Host Interactions of HIV factorsREACTOMER-HSA-162909
Interactions of Vpr with host cellular proteinsREACTOMER-HSA-176033
Vpr-mediated nuclear import of PICsREACTOMER-HSA-180910
Interactions of Rev with host cellular proteinsREACTOMER-HSA-177243
Nuclear import of Rev proteinREACTOMER-HSA-180746
Influenza InfectionREACTOMER-HSA-168254
Influenza Life CycleREACTOMER-HSA-168255
Transport of Ribonucleoproteins into the Host NucleusREACTOMER-HSA-168271
Influenza Viral RNA Transcription and ReplicationREACTOMER-HSA-168273
Viral Messenger RNA SynthesisREACTOMER-HSA-168325
Export of Viral Ribonucleoproteins from NucleusREACTOMER-HSA-168274
NEP/NS2 Interacts with the Cellular Export MachineryREACTOMER-HSA-168333
Host Interactions with Influenza FactorsREACTOMER-HSA-168253
NS1 Mediated Effects on Host PathwaysREACTOMER-HSA-168276
Immune SystemREACTOMER-HSA-168256
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Interferon SignalingREACTOMER-HSA-913531
Antiviral mechanism by IFN-stimulated genesREACTOMER-HSA-1169410
ISG15 antiviral mechanismREACTOMER-HSA-1169408
Signal TransductionREACTOMER-HSA-162582
Signaling by Rho GTPasesREACTOMER-HSA-194315
RHO GTPase EffectorsREACTOMER-HSA-195258
RHO GTPases Activate ForminsREACTOMER-HSA-5663220
Gene ExpressionREACTOMER-HSA-74160
Processing of Capped Intron-Containing Pre-mRNAREACTOMER-HSA-72203
Transport of Mature Transcript to CytoplasmREACTOMER-HSA-72202
Transport of Mature mRNA derived from an Intron-Containing TranscriptREACTOMER-HSA-159236
Transport of Mature mRNAs Derived from Intronless TranscriptsREACTOMER-HSA-159234
Transport of the SLBP Dependant Mature mRNAREACTOMER-HSA-159230
Transport of the SLBP independent Mature mRNAREACTOMER-HSA-159227
Transport of Mature mRNA Derived from an Intronless TranscriptREACTOMER-HSA-159231
Gene Silencing by RNAREACTOMER-HSA-211000
Transcriptional regulation by small RNAsREACTOMER-HSA-5578749
Metabolism of non-coding RNAREACTOMER-HSA-194441
snRNP AssemblyREACTOMER-HSA-191859
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
M PhaseREACTOMER-HSA-68886
Mitotic ProphaseREACTOMER-HSA-68875
Nuclear Envelope BreakdownREACTOMER-HSA-2980766
Nuclear Pore Complex (NPC) DisassemblyREACTOMER-HSA-3301854
Mitotic PrometaphaseREACTOMER-HSA-68877
Resolution of Sister Chromatid CohesionREACTOMER-HSA-2500257
Mitotic Metaphase and AnaphaseREACTOMER-HSA-2555396
Mitotic AnaphaseREACTOMER-HSA-68882
Separation of Sister ChromatidsREACTOMER-HSA-2467813
Transmembrane transport of small moleculesREACTOMER-HSA-382551
SLC-mediated transmembrane transportREACTOMER-HSA-425407
Hexose transportREACTOMER-HSA-189200
Glucose transportREACTOMER-HSA-70153
Regulation of Glucokinase by Glucokinase Regulatory ProteinREACTOMER-HSA-170822
MetabolismREACTOMER-HSA-1430728
Metabolism of carbohydratesREACTOMER-HSA-71387
Cellular responses to stressREACTOMER-HSA-2262752
Cellular response to heat stressREACTOMER-HSA-3371556
Regulation of HSF1-mediated heat shock responseREACTOMER-HSA-3371453
tRNA processingREACTOMER-HSA-72306
tRNA processing in the nucleusREACTOMER-HSA-6784531
SUMOylation of RNA binding proteinsREACTOMER-HSA-4570464
SUMOylation of DNA replication proteinsREACTOMER-HSA-4615885

References

Pubmed IDYearTitleCitations
175894992007NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis.136
119509392002Nup98 is a mobile nucleoporin with transcription-dependent dynamics.94
213352362011Phosphorylation of Nup98 by multiple kinases is crucial for NPC disassembly during mitotic entry.93
219482992011NUP98 gene fusions and hematopoietic malignancies: common themes and new biologic insights.93
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
180459342008Differential targeting of nuclear pore complex proteins in poliovirus-infected cells.68
125890572003Nup98 localizes to both nuclear and cytoplasmic sides of the nuclear pore and binds to two distinct nucleoporin subcomplexes.66
218134472011NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern.65
118099372002Role of nucleoporin induction in releasing an mRNA nuclear export block.61
234686462013Dynamic association of NUP98 with the human genome.61

Citation

Lyndal Kearney

NUP98 (nucleoporin 98 kDa)

Atlas Genet Cytogenet Oncol Haematol. 2002-03-01

Online version: http://atlasgeneticsoncology.org/gene/63/nup98-(nucleoporin-98-kda)

Historical Card

2000-02-01 NUP98 (nucleoporin 98 kDa) by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

1998-11-01 NUP98 (nucleoporin 98 kDa) by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

1998-01-01 NUP98 (nucleoporin 98 kDa) by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France