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FLASH GENE

Symbol

WEE1

contributors: mct/ - updated : 02-07-2016

HGNC name	WEE1 homolog (S. pombe)
HGNC id	12761

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	16.09 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	SP1/CPBP motif located between -252 bp and the start codon of the promoter

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_003390 11 - 3374 NP_003381 - 646 - - NM_001143976 11 - 3234 NP_001137448 - 432 - 2005 PMID: 158044 also called WWE1 I uses Met215 of WEE1 as its initiation codon provide constitutive WEE1-like kinase activity to inhibit mitotic cell proliferation may play an important role in differentiation and in tumor suppression

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 Cardiovascular heart       highly   vessel       moderately Digestive mouth tongue     moderately Reproductive female system placenta     moderately   female system breast mammary gland   highly   female system uterus     moderately Urinary bladder       highly Visual eye       moderately

tissue

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

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

cell cycle

cell cycle, interphase, S, G2

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal 214 residues facilitating its ubiquitin-dependent degradation to trigger mitotic entry
	a protein kinase domain

HOMOLOGY

interspecies	homolog to yeast wee1
	homolog to murine Wee1

Homologene

FAMILY	protein kinase superfamily
	SER/THR family of protein kinases
	WEE1 subfamily

CATEGORY

enzyme , regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,nucleoplasm

basic FUNCTION	negative regulator of cell cycle
	phosphorylation cyclin dependent kinases
	insuring the completion of DNA replication prior to mitosis
	playing a critical role in controlling the transition into mitosis when it involved in the Swe1-Cdk1 complex
	inhibiting mitosis entry by phosphorylating cyclin B1/CDC2 (M phase promoting factor (MPF))
	repression of WEE1 by Kruppel-like factor 2 (KLF2) is involved in DNA damage-induced apoptosis
	cell-cycle checkpoint kinase that regulates the entry into mitosis in dividing cells
	plays a key role in cell cycle progression at the onset of mitosis by phosphorylating CDK1 at the inhibitory Tyr15 AA residue
	major regulator of the G(2) checkpoint in glioblastoma cells
	protein kinase that negatively regulates mitotic entry in G2 phase by suppressing cyclin B-CDC2 activity
	regulator of genomic stability
	specifically protects the stability of stalled replication forks
	may have important role in hypoxia- induced pathophysiological situations in endothelial cells
	cell-cycle checkpoint regulator

CELLULAR PROCESS	cell cycle, division, mitosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	phosphorylating Y15 in CDC2 and other CDKs
	CDK1
	regulation of WEE1 by BRSK2 and BRSK1 is essential for the differentiation of polarized neurons
	interacting with CSNK2B (participates in PLK1-WEE1 complex formation interacting directly with WEE1 and thereby contributing to the regulation of G2-M cell cycle transition)
	USP50 may act through a HSP90AA1-dependent mechanism to counteract CDC25B mitotic inducing activity and prevent WEE1 degradation
	WEE1 interacting with MUS81 (novel role of WEE1 in controlling MUS81 and DNA replication in human cells)
	plays an important role in the regulation of WEE1 stability
	CDC14A counteracts CDK1-CCNB1 activity through WEE1 dephosphorylation
	both WEE1 and MYT1 can phosphorylate CDK1
	ERRFI1 controls mitotic progression and the G2/M DNA damage checkpoint by stabilizing the WEE1 Kinase

cell & other

regulator of both HIV type 1 Vpr and gamma irradiation-induced apoptosis

REGULATION

activated by	transactivated by and increased in association with FOS/JUN (AP1)
	Cdk1 Phosphorylation

inhibited by

inactivated in phase M and G1 by autophosphorylation and protein degradation

repressed by

KLF2, by directly binding to an SP1/CPBP motif located between -252 bp and the start codon of the WEE1 promoter

Phosphorylated by

BRSK2, BRSK1 that are required to initiate its downregulation in polarized neurons

Other

regulation of its localization around the SPB (spindle pole body) during the G2/M transition is important for proper mitotic entry and progression

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in hepatocellular carcinoma constitutional     --over   in rheumatoid cells inducing aberrant mitosis constitutional     --over   with PKMYT1 induced the phosphorylation of CDC2 leading to G2/M arrest constitutional     --low   caused a block in DNA replication, resulting in accumulation of cells in S phase

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     combination of WEE1 inhibitor and TNFSF10 could provide a novel combination for the treatment of basal/triple-negative breast cancer cancer brain glioma/neuroblstoma inhibition of WEE1 kinase holds potential as a therapeutic approach in treatment of glioblastoma

ANIMAL & CELL MODELS