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FLASH GENE

Symbol

NME1

contributors: mct/npt/pgu - updated : 17-01-2013

HGNC name	non-metastatic cells 1, protein (NM23A) expressed in
HGNC id	7849

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_198175 6 - 1031 NP_937818 - 177 - 2008 18635542 NME1IA isoform soluble NM_000269 5 - 811 NP_000260 - 152 - 2008 18635542 NME1IB associated with the soluble as well as membranous fraction NM23-H4 - - - NM23-H4 - - - 2008 18635542 mitochondrial isoform ,in the pancreatic beta cell mitochondrial subfraction NME1L - splicing - - - - - 24811176 only NME1L interacts with IKBKB is a potent antimetastatic protein and may be a useful weapon in the fight against cancers

EXPRESSION

Type	ubiquitous

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 Digestive liver       highly   pharynx       highly   salivary gland       highly Reproductive female system breast mammary gland   highly Skin/Tegument skin       highly Visual eye       highly

cell lineage
cell lines	lung carcinoma cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	putative leucine-zipper domain
	a Kpn (Drosophila Killer of prune) loop
	a RGD domain
	a C terminal extension preceded by the YEEEEP motifs

HOMOLOGY

Homologene

FAMILY

NM23 nucleoside diphosphate kinase gene family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	pyrimidine biosynthetic pathway, involved in the phosphorylation of nucleoside diphosphates
	selectively regulates the PRKAA1, independently of the AMP concentration such that the manipulation of NME1 nucleotide trans-phosphorylation activity to generate ATP enhanced the activity of PRKAA1
	involved in the regulation of many cellular processes as well as in tumor metastasis
	involved in epidermal homeostasis which depends on a tight regulation of the levels of NME1 isoforms
	can negatively regulate cell migration and tumor metastasis by modulating the activity of CDC42 and possibly other Rho family members through interaction with MCF2
	having a 3prime-5prime exonuclease activity necessary for metastasis suppressor function
	tumor metastasis suppressor, which functions as a nucleoside-diphosphate kinase converting nucleoside diphosphates to nucleoside triphosphates with an expense of ATP
	may have a role in the regulation of cell cycle and apoptosis in human B-cells
	loss of NME1, an event suspected to promote metastasis, may additionally function at an earlier stage of tumor development to drive the acquisition of chromosomal instability
	critical for control of cell-cell adhesion and cell migration at early stages of the invasive program in epithelial cancers, orchestrating a barrier against conversion of in situ carcinoma into invasive malignancy
	critical role for NME1 isoforms in limiting mutagenesis and suppressing UV radiation -induced melanomagenesis
	exists in a functional cellular complex with PRKAA1 and CFTR in airway epithelia, and its catalytic function is required for the PRKAA1-dependent regulation of CFTR

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

complexing with SCS(succinyl-coA-synthetase)

INTERACTION

DNA

RNA

small molecule

protein	MEN1, SCS
	interacting with TUBB, TUBG1, VIM
	interaction partner of PRUNE
	IFI16 and NME1 are simultaneously bound to the same DNA fragments, suggesting their common involvement in the reduced development of some tumors
	TXNRD1 is an interacting protein of NME1, and it binds specifically to oxidized NME1
	TSLP might downregulate NME1 expression via STAT3 signaling pathway, affecting TIMP1 expression in influencing trophoblast invasion
	NME1 enhanced ALDOC transcription, evidenced by increased expression of ALDOC pre-mRNA and activity of an ALDOC promoter-luciferase module

cell & other

REGULATION

inhibited by

of NME1 expression by TSLP was completely abrogated by STAT3 inhibitor

Other

key enzymatic and metastasis suppressor functions of NME1 are regulated by oxido-reduction of its Cys109

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral somatic mutation       mutated in agressive neuroblastoma with a reduced expression in tumor progression to the metastatic phenotype tumoral     --over   in neuroblastoma tumoral     --low   associated with aggressive forms of multiple cancers tumoral     --other   its expression is associated with poor prognosis in peripheral T-cell lymphoma

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS