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FLASH GENE

Symbol

NEK1

contributors: mct - updated : 11-07-2023

HGNC name	NIMA (never in mitosis gene a)-related kinase 1
HGNC id	7744

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	219.78 kb     34 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_001199397 36 - 5695 NP_001186326 - 1286 - 2023 36443167 NM_012224 34 - 5689 NP_036356 142.7 1258 - 2023 36443167 NM_001199400 36 - 5557 NP_001186329 - 1214 - 2023 36443167 NM_001199398 35 - 5563 NP_001186327 - 1242 - 2023 36443167 NM_001199399 33 - 5404 NP_001186328 - 1189 - 2023 36443167 NM_001374418 35 - 6174 NP_001361347 - 1286 - 2023 36443167 NM_001374421 31 - 5613 NP_001361350 - 1125 - 2023 36443167 NM_001374420 34 - 5961 NP_001361349 - 1241 - 2023 36443167 NM_001374419 35 - 6012 NP_001361348 - 1258 - 2023 36443167

EXPRESSION

Type

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         Nervous brain         Reproductive female system ovary         male system prostate         male system testis     highly Homo sapiens Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow

cells

System Cell Pubmed Species Stage Rna symbol Reproductive germ cell Homo sapiens

cell lineage	germ cells
cell lines	renal cell carcinoma
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an N terminal protein kinase domain, most similar to the catalytic domain of NIMA
	a long basic C terminus (ATP binding and activity site)
	contains functional nuclear localization signals, and is exported from the nucleus via a nuclear export signal-dependent pathway
	FAM189B interaction domain "CID" at the C-terminus of NEK1 is necessary for its association with FAM189B in cells

HOMOLOGY

interspecies	homolog to rattus Nek1 (82.4 pc)
	homolog to murine Nek1 (82.9 pc)

Homologene

FAMILY	protein kinase superfamily
	Ser/Thr family of protein kinases
	NIMA subfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome
text	associated with the centrosomes and translocates from the nucleus during mitosis to the basal body, initiating cilia formation
	accumulates on the chromatin during normal DNA replication
	localize near centrosomes and play a role in centrosomal stability and ciliogenesis

basic FUNCTION	phosphorylation of serines and threonine and having a tyrosine kinase activity
	implicated in the control of meiosis
	may function as a kinase early in the DNA damage response pathway
	involved in cilium control
	CLASP2 and NEK1 proteins are present in a centrosomal complex and participate in cell cycle and cell division mechanisms
	is involved in the beginning of the cellular response to genotoxic stress and plays an important role in preventing cell death induced by DNA damage
	serine/threonine kinase with proposed function in DNA double-strand repair, neuronal development, and coordination of cell-cycle-associated ciliogenesis
	involved early in a DNA damage sensing/repair pathway
	functions independently of canonical DNA damage responses requiring the PI3 kinase-like proteins ATM and ATR
	important for proper checkpoint control
	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
	ATR-associated kinase, NEK1, enhances the stability and activity of ATR–ATRIP before DNA damage, priming ATR–ATRIP for a robust DNA damage response
	required for the phosphorylation of multiple signaling proteins along the ATR pathway, suggesting a role of NEK1 in the initiation of ATR response
	function of NEK1 in DNA damage signaling is critical in specific tissues
	regulate DNA damage response, centrosome duplication and primary cilium formation
	regulatory role for NEK1 in the regulation of spindle architecture and function during meiosis
	serves likely as a hub signalling kinase in response to DNA damage, modulating DNA repair capacity, mitochondrial activity and cell fate determination
	FAM189B like NEK1 is required for homologous recombination

CELLULAR PROCESS	cell cycle,division,meiosis

PHYSIOLOGICAL PROCESS

reproduction/sex

text	cell cycle regulation

PATHWAY

metabolism

signaling

a component

endogenous NEK1 and FAM189B2 form a tight complex in human cells

INTERACTION

DNA

RNA

small molecule	cofactor, nucleotide,
	ATP
	Mg2+

protein	binding to SPERT
	direct interaction between NEK1 and VDAC1 providing a mechanism to explain how NEK1 prevents excessive cell death, as well as the first direct evidence that a specific kinase regulates VDAC1 activity
	NEK1 phosphorylates WWTR1 at a site essential for the ubiquitination and proteasomal degradation of PKD2
	interaction between FKBP6 and the NIMA-related kinase-1, NEK1, and NEK1 is a possible kinase involved in cohesin redistribution in spermatocytes
	possible regulation of VHL by NEK1 that may contribute to ciliary homeostasis and cystogenesis
	NEK1, is critical for initiating the ATR response, and ability of NEK1 to promote ATR activation relies on the kinase activity of NEK1 and its interaction with ATR–ATRIP
	is required for efficient CHEK1 activation in human cells
	NEK1 may facilitate S-phase progression by interacting with XRCC5 and regulating chromatin loading of replication factors
	CFAP410 interact with NEK1
	NEK1 regulates RAD51 removal to orchestrate HR and replication fork stability.
	role for NEK1 in the regulation of WAPL loading during meiotic prophase I, via an interaction between NEK1 and PDS5B
	NEK1 phosphorylates PPP1CC, leading to the dephosphorylation of WAPL, which, in turn, results in its retention on chromosome cores to promote loss of cohesion at the end of prophase I in mammals
	NEK1 competes for binding to CEP104 with the distal centriole-capping protein CCP110
	NEK1 phosphorylation of YAP1 promotes its stabilization and transcriptional output
	NEK1 regulates retromer-mediated endosomal trafficking by phosphorylating VPS26B

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

SRPS2 , ALS24

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional         severely reduces cilia number and alters ciliar morphology constitutional       loss of function Nek1 deficiency leads to disordered kidney maturation, and cysts throughout the nephron constitutional       loss of function disrupts endosomal trafficking of plasma membrane proteins and cerebral proteome homeostasis to promote mitochondrial and lysosomal dysfunction and aggregation of SNCA

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	mutated Nek1 display progressive polycystic kidney disease
	Nek1 is the primary protein inactivated in kat2J mouse models of PKD