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FLASH GENE

Symbol

NEK9

contributors: mct/pgu - updated : 01-06-2016

HGNC name	NIMA (never in mitosis gene a)- related kinase 9
HGNC id	18591

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_033116 22 - 5560 NP_149107 107 979 - 2003 12840024

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 Cardiovascular heart         Digestive liver         Lymphoid/Immune spleen           thymus         Reproductive male system prostate       Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal catalytic domain homologous to the NEK family of protein kinases, protein kinase domain (52-308)
	a nuclear localization signal (306-330)
	central RCC1-like domain (388-726)
	a NEK6 interaction region (732-891)
	a guanine nucleotide exchange factor for the GTPase Ran
	a C-terminal coiled-coil domain, AAs(941-979) are necessary not only for interaction with DYNLL1, but also for NEK6 binding to NEK9

conjugated

PhosphoP

mono polymer

homomer , dimer , oligo

HOMOLOGY

interspecies	ortholog to murine Nek9
	homolog to Drosophila CG10951
	ortholog to C.elegans nekl-1

intraspecies

paralog to NEK2

Homologene

FAMILY	protein kinase superfamily
	NEK Ser/Thr protein kinase family
	NIMA subfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus
text	primarily cytoplasmic with a small portion located in the nucleus
	localized to the spindle poles at the metaphase stages and associated with the midbody at anaphase or telophase stage in both meiotic oocytes and the first mitotic embyros

basic FUNCTION	having a serine/threonine kinase activity and tyrosine kinase activity
	playing a role in association with BICD2 in cell cycle independent microtubule dynamics
	function as a mitotic regulator required for accurate spindle assembly and cell cycle progression, and is recruited to the centrosome in its phosphorylated active form
	serine/threonine kinase that functions as an important regulator of cell-cycle and checkpoint control and is a member of a larger family of NEK proteins that share moderate conservation
	is involved in regulating spindle organization, chromosome alignment, cytokinesis and normal cell cycle progression
	play important roles at the G2-M transition in nuclear envelope breakdown and centromere separation
	regulating chromosome alignment and segregation in mitosis
	tumor associated gene, may be involved in G(2)/M progression
	NIMA-related kinases essential for proper mitotic progression
	role of KIF11, PLK1 and the NIMA-family kinases NEK7 and NEK9 in the control of centrosome separation and normal mitotic progression
	NEK2, NEK6, NEK7 and NEK9 contribute to the establishment of the microtubule-based mitotic spindle, whereas NEK1, NEK10 and NEK11 have been implicated in the DNA damage response
	play a role in spindle assembly and in the control of centrosome separation
	is a crucial regulator of cell-cycle progression in TP53-inactivated cancer cells
	mitotic spindle assembly requires the regulated activities of protein kinases such as NEK7 and NEK9
	is a potential regulator of follicular homeostasis

CELLULAR PROCESS	cell cycle, progression

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

with NEK7 and NEK6 are components of a mitotic spindle-signaling cascade

a component

INTERACTION

DNA

RNA

small molecule	metal binding, nucleotide,
	Mn2+
	ATP
	Mg2+

protein	binding to BICD2, NEK6, Ran GTPase, CDC2
	interaction with NEK6 representing a new signaling pathway that regulates mitotic progression
	interacting partner of NEK6 (phosphorylate NEK6 at S206 within its activation loop)
	potentially as an active enzymatic partner of SSRP1, mediates certain SSRP1-associated cellular processes, which are ultimately essential for interphase progression
	binds to DYNLL1, a highly conserved protein originally described as a component of the dynein complex (binding interferes with the interaction of NEK9 with its downstream partner NEK6 as well as with NEK6 activation, thus controlling both processes)
	DYNLL1 is not absolutely required for NEK9 autoactivation, but binding to NEK9 increases the efficiency of this process
	DYNLL1 binding to NEK9 was regulated by NEK9 autophosphorylation on Ser(944), a AA immediately located N-terminal to the DYNLL1 conserved (K/R)xTQT binding motif
	novel NEK9 network regulates the growth of cancer cells lacking functional TP53
	NEK9 modulate interphase progression via its association with the FACT (Facilitates Chromatin Transcription) complex (pMID: 26908619)

cell & other

REGULATION

activated by

autoactivation by phosphorylation/ATP

Other

regulated by E1A (Adenovirus E1A proteins direct subcellular redistribution of NEK9)

ASSOCIATED DISORDERS

corresponding disease(s)

LCCSR

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   overexpressed in primary breast tumors constitutional somatic mutation       in NC (Nevus Comedonicus) disrupt normal follicular differentiation

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     NEK9 inhibition represents a novel anti-cancer strategy by induction of mitotic catastrophe via impairment of spindle dynamics, cytokinesis and mitotic checkpoint control

ANIMAL & CELL MODELS