Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

NUP98

contributors: mct/pgu - updated : 05-06-2015

HGNC name	nucleoporin 98kDa
HGNC id	8068

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	AMLT2 acute myeloid leukemia, with limited differentiation (FAB M2 and M4)
Location	11p15.4      Physical location : 3.696.240 - 3.819.022
Synonym name	GLFG-repeat containing nucleoporin
	nuclear pore complex protein Nup98-Nup96
Synonym symbol(s)	ADIR2, NUP196, HXAD, NU98, Nup98-Nup96, ADAR2, NUP96

DNA

TYPE	functioning gene
STRUCTURE	126.71 kb     33 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_139131 20 - 3908 NP_624357 96.1 920 - 2010 20237156 NM_139132 32 splicing 6758 NP_624358 - 1726 - 2010 20237156 NM_016320 33 splicing 6980 NP_057404 195.8 1800 - 2010 20237156 NM_005387 20 splicing 3959 NP_005378 97.8 937 - 2010 20237156

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine pancreas       highly Lymphoid/Immune lymph node       highly   thymus       moderately Nervous brain         Reproductive female system uterus     highly   male system testis     highly Respiratory lung       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal docking site, which contains the nucleoporin FG/GLFG repeat motifs , a GLFG domain functioning in pore targeting through binding to NUP93, positioning the GLFG domain in the center of the nuclear pore complex and supporting a role for this nucleoporin in the permeability barrier
	multiple FG repeats that function in nucleocytoplasmic transport
	a Gle2-binding sequence (GLEBS), for interaction with RAE1

HOMOLOGY

interspecies

homolog to C.elegans ZK328.5B

Homologene

FAMILY

GLFG nucleoporin family

CATEGORY

RNA associated , transport carrier

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,nucleus,nucleoplasm
	intracellular,nuclear envelope,pore

basic FUNCTION	multiple RNA export pathway
	playing a role in the bidirectional transport across the nucleoporin complex
	plays roles in several important biological events such as gene expression, mitotic checkpoint, and pathogenesis
	nucleoporin characterized by multiple FG repeats that function in nucleocytoplasmic transport by interacting with import and export carriers
	in germ cells, the function of NUP98 extends beyond transport at the nuclear pore (NPC) to include mRNA regulation in the cytoplasm
	functions as a novel shuttling cofactor for XPO1-mediated nuclear export in conjunction with RANBP3
	contribution of the nucleoporin NUP98 to mitotic spindle assembly through regulation of microtubule dynamics
	mitotic phosphorylation of NUP98 is a rate-limiting step in mitotic NPC disassembly
	major determinant of the permeability barrier of NPCs
	function in regulating select TP53 target genes that is distinct from the well-characterized oncogenic properties of NUP98 fusion proteins
	dynamically associates with the human genome during differentiation, revealing a role of a nuclear pore protein in regulating developmental gene expression programs (PMID
	NUP98 binding to recently expressed promoters plays potentially a conserved role in promoting epigenetic transcriptional memory

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	essential component of the nuclear pore complex
	RAE1/NUP98 complex has distinct and versatile roles at different stages of the cell cycle, including the nuclear export of mRNAs and the regulation of the cell cycle progression

INTERACTION

DNA

RNA

small molecule

protein	KPNB2 (can dissociate from its substrate)
	interaction with RAE1
	only two of more than 20 nuclear pore core structure components, namely NUP93 and NUP98, are caspase targets
	NUP98-IQCG fusion protein may play an essential role in leukemogenesis, but by itself may not be sufficient to induce leukemia
	predominantly interacted with transcriptionally active genes inside the nucleoplasm, in particular those involved in developmental regulation and the cell cycle
	combined action of CDK1, NEK6, NEK7, and likely other kinases contributes to hyperphosphorylation of NUP98 during mitosis
	specifically regulates nucleus-cytoplasm transport of galectin-3, which is a beta-galactoside-binding protein affecting adhesion, migration, and cancer progression, and controls cell growth through the CTNNB1 signaling pathway in cancer cells
	highly selective targeting of NUP98-fusion proteins to HOX cluster regions via prebound XPO1 induces the formation of higher order chromatin structures that causes aberrant HOX gene regulation (pMID: 26740045)

cell & other

REGULATION

Other	its phosphorylation presents a crucial step during nuclear pore complexes disassembly

ASSOCIATED DISORDERS

corresponding disease(s)

AMLT2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion       t(6;11)(q24.1;p15.5) resulting in a NUP98-CCDC28A fusion in acute megakaryoblastic leukemia tumoral fusion       fused with HOXD11 in t(5;11)(q35;p15.5) in acute myeloid leukemia tumoral fusion       fused with TOP1 in t(11;20)(p15;q11) in therapy related myelodysplastic syndrome, and with HOXA13 int (7;11) (p15;p15) tumoral fusion       fused with WHSC1L1 in t(8;11) (p11.2-p15) in acute myeloid leukemia, with ADD3 in t(10;11)(q25;p15) in T-cell acute lymphoblastic leukemia tumoral fusion       with DDX10 in de novo or therapy related myeloid malignancies,with HOXD13 or FN1 in translocation t(2;11) (q35;p15) or t(2;11) (q31;p15) in acute myelomonocytic leukemia with inv11(p15-q22) tumoral fusion       with PMX1 in translocation t(1;11) (q23;p15),with RAP1GDS1 in t(4;11)(q21;p15) in T cell acute lymphocitic leukemia,with PSIP1 in t (9;11) (p22;p15) in acute myeloid leukemia tumoral fusion       to KDM5A in acute lymphoblastic leukemia tumoral     --over   of NUP98-HOXA9 represses myeloid-specific gene transcription, thereby contributing to differentiation block in leukemogenesis tumoral fusion       NUP98-HOXD13 (NHD13) fusion in patients with myelodysplastic syndrome (MDS) and acute nonlymphocytic leukemia (ANLL) tumoral   translocation     t(3;11)(q12;p15)/NUP98-LNP1 fusion transcript in acute myeloid leukemia tumoral fusion       NUP98/NSD1 identifies a previously unrecognized group of young acute myeloid leukemia with a distinct HOX gene expression pattern tumoral fusion       POU1F1 is a fusion partner of NUP98 in acute myeloid leukemia with t(3;11)(p11;p15) ( tumoral fusion       of NUP98 to KDM5A (t(11;15)(p15;q35)in acute megakaryoblastic leukemia (AMKL)

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS