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Protein

Wee1-like protein kinase

Gene

WEE1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on 'Tyr-15'. Specifically phosphorylates and inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase and a minimum as cells enter M phase. Phosphorylation of cyclin B1-CDK1 occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDK1 does not occur. Its activity increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated. A correlated decrease in protein level occurs at M/G1 phase, probably due to its degradation.

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Cofactori

Mg2+Note: Binds 2 magnesium ions per subunit.

Activity regulationi

Synthesis is increased during S and G2 phases, presumably by an increase in transcription; activity is decreased by phosphorylation during m phase. Protein levels fall in M phase as a result of decreased synthesis combined with degradation. Activity seems to be negatively regulated by phosphorylation upon entry into mitosis, although N-terminal phosphorylation might also regulate the protein stability via protection from proteolysis or might regulate the subcellular location.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei328ATPPROSITE-ProRule annotation1
Active sitei426Proton acceptorPROSITE-ProRule annotation1
Metal bindingi431Magnesium; via carbonyl oxygen1 Publication1
Metal bindingi463Magnesium; via carbonyl oxygen1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi305 – 313ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processCell cycle, Cell division, Mitosis
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-156711 Polo-like kinase mediated events
R-HSA-69202 Cyclin E associated events during G1/S transition
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-69478 G2/M DNA replication checkpoint
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
R-HSA-983231 Factors involved in megakaryocyte development and platelet production
SignaLinkiP30291
SIGNORiP30291

Names & Taxonomyi

Protein namesi
Recommended name:
Wee1-like protein kinase (EC:2.7.10.2)
Short name:
WEE1hu
Alternative name(s):
Wee1A kinase
Gene namesi
Name:WEE1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000166483.10
HGNCiHGNC:12761 WEE1
MIMi193525 gene
neXtProtiNX_P30291

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi53S → A: Abolishes phosphorylation by PLK1 and CDK1 and binding of the SCF(BTRC) complex, leading to stabilization of the protein; when associated with A-123. 1 Publication1
Mutagenesisi116 – 117EE → AA: Impairs binding of the SCF(BTRC) complex. 1 Publication2
Mutagenesisi123S → A: Abolishes phosphorylation by PLK1 and CDK1 and binding of the SCF(BTRC) complex, leading to stabilization of the protein; when associated with A-53. 1 Publication1
Mutagenesisi328K → R: Abolishes activity. 1 Publication1
Mutagenesisi642S → A: Abolishes phosphorylation by BRSK1 and BRSK2. 1 Publication1

Organism-specific databases

DisGeNETi7465
OpenTargetsiENSG00000166483
PharmGKBiPA366

Chemistry databases

ChEMBLiCHEMBL5491
GuidetoPHARMACOLOGYi2278

Polymorphism and mutation databases

BioMutaiWEE1
DMDMi1351419

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000868101 – 646Wee1-like protein kinaseAdd BLAST646

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei53Phosphoserine; by PLK11 Publication1
Modified residuei78PhosphoserineBy similarity1
Modified residuei85PhosphoserineCombined sources1
Modified residuei123Phosphoserine; by CDK11 Publication1
Modified residuei127PhosphoserineCombined sources1
Modified residuei137PhosphoserineCombined sources1
Modified residuei139PhosphoserineCombined sources1
Modified residuei150PhosphoserineCombined sources1
Modified residuei165PhosphoserineBy similarity1
Modified residuei187PhosphothreonineCombined sources1
Modified residuei190PhosphothreonineCombined sources1
Modified residuei239Phosphothreonine1 Publication1
Modified residuei270PhosphoserineCombined sources1
Modified residuei307PhosphoserineCombined sources1
Modified residuei312PhosphoserineCombined sources1
Modified residuei642Phosphoserine; by BRSK1 and BRSK22 Publications1

Post-translational modificationi

Phosphorylated during M and G1 phases. Also autophosphorylated. Phosphorylation at Ser-642 by BRSK1 and BRSK2 in post-mitotic neurons, leads to down-regulate WEE1 activity in polarized neurons. Phosphorylated at Ser-53 and Ser-123 by PLK1 and CDK1, respectively, generating an signal for degradation that can be recognized by the SCF(BTRC) complex, leading to its ubiquitination and degradation at the onset of G2/M phase.4 Publications
Dephosphorylated at Thr-239 by CTDP1.
Ubiquitinated and degraded at the onset of G2/M phase.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP30291
MaxQBiP30291
PaxDbiP30291
PeptideAtlasiP30291
PRIDEiP30291
ProteomicsDBi54650

PTM databases

iPTMnetiP30291
PhosphoSitePlusiP30291

Miscellaneous databases

PMAP-CutDBiP30291

Expressioni

Gene expression databases

BgeeiENSG00000166483 Expressed in 203 organ(s), highest expression level in female gonad
CleanExiHS_WEE1
ExpressionAtlasiP30291 baseline and differential
GenevisibleiP30291 HS

Organism-specific databases

HPAiCAB004619
HPA068845

Interactioni

Binary interactionsi

Protein-protein interaction databases

BioGridi113303, 76 interactors
CORUMiP30291
DIPiDIP-37969N
IntActiP30291, 21 interactors
MINTiP30291
STRINGi9606.ENSP00000402084

Chemistry databases

BindingDBiP30291

Structurei

Secondary structure

1646
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00611
ProteinModelPortaliP30291
SMRiP30291
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30291

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini299 – 569Protein kinasePROSITE-ProRule annotationAdd BLAST271

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi9 – 12Poly-Pro4
Compositional biasi34 – 43Poly-Glu10

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0601 Eukaryota
ENOG410XS1M LUCA
GeneTreeiENSGT00530000063230
HOGENOMiHOG000004824
HOVERGENiHBG005050
InParanoidiP30291
KOiK06632
OMAiWNDSCGE
OrthoDBiEOG091G049H
PhylomeDBiP30291
TreeFamiTF101088

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR017164 Wee1-like_protein_kinase
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PIRSFiPIRSF037281 Wee1-like_protein_kinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P30291-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSFLSRQQPP PPRRAGAACT LRQKLIFSPC SDCEEEEEEE EEEGSGHSTG
60 70 80 90 100
EDSAFQEPDS PLPPARSPTE PGPERRRSPG PAPGSPGELE EDLLLPGACP
110 120 130 140 150
GADEAGGGAE GDSWEEEGFG SSSPVKSPAA PYFLGSSFSP VRCGGPGDAS
160 170 180 190 200
PRGCGARRAG EGRRSPRPDH PGTPPHKTFR KLRLFDTPHT PKSLLSKARG
210 220 230 240 250
IDSSSVKLRG SSLFMDTEKS GKREFDVRQT PQVNINPFTP DSLLLHSSGQ
260 270 280 290 300
CRRRKRTYWN DSCGEDMEAS DYELEDETRP AKRITITESN MKSRYTTEFH
310 320 330 340 350
ELEKIGSGEF GSVFKCVKRL DGCIYAIKRS KKPLAGSVDE QNALREVYAH
360 370 380 390 400
AVLGQHSHVV RYFSAWAEDD HMLIQNEYCN GGSLADAISE NYRIMSYFKE
410 420 430 440 450
AELKDLLLQV GRGLRYIHSM SLVHMDIKPS NIFISRTSIP NAASEEGDED
460 470 480 490 500
DWASNKVMFK IGDLGHVTRI SSPQVEEGDS RFLANEVLQE NYTHLPKADI
510 520 530 540 550
FALALTVVCA AGAEPLPRNG DQWHEIRQGR LPRIPQVLSQ EFTELLKVMI
560 570 580 590 600
HPDPERRPSA MALVKHSVLL SASRKSAEQL RIELNAEKFK NSLLQKELKK
610 620 630 640
AQMAKAAAEE RALFTDRMAT RSTTQSNRTS RLIGKKMNRS VSLTIY
Length:646
Mass (Da):71,597
Last modified:February 1, 1996 - v2
Checksum:iDB00623D304562A0
GO
Isoform 2 (identifier: P30291-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-214: Missing.

Note: No experimental confirmation available.
Show »
Length:432
Mass (Da):49,072
Checksum:i48F8E9EC16E4184A
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PRI3E9PRI3_HUMAN
Wee1-like protein kinase
WEE1
99Annotation score:
E9PRU3E9PRU3_HUMAN
Wee1-like protein kinase
WEE1
214Annotation score:
H0YEJ2H0YEJ2_HUMAN
Wee1-like protein kinase
WEE1
145Annotation score:
E9PQ51E9PQ51_HUMAN
Wee1-like protein kinase
WEE1
162Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti65A → E in CAA43979 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041302210G → C1 PublicationCorresponds to variant dbSNP:rs34412975Ensembl.1
Natural variantiVAR_041303472S → I1 PublicationCorresponds to variant dbSNP:rs56411856Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0449591 – 214Missing in isoform 2. 1 PublicationAdd BLAST214

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U10564 mRNA Translation: AAB60401.1
AJ277546 Genomic DNA Translation: CAC14173.1
AK122837 mRNA Translation: BAG53753.1
AC011979 Genomic DNA No translation available.
AC122179 Genomic DNA No translation available.
CH471064 Genomic DNA Translation: EAW68586.1
CH471064 Genomic DNA Translation: EAW68587.1
CH471064 Genomic DNA Translation: EAW68588.1
X62048 mRNA Translation: CAA43979.1
CCDSiCCDS44536.1 [P30291-2]
CCDS7800.1 [P30291-1]
PIRiS55048
RefSeqiNP_001137448.1, NM_001143976.1 [P30291-2]
NP_003381.1, NM_003390.3 [P30291-1]
UniGeneiHs.249441

Genome annotation databases

EnsembliENST00000299613; ENSP00000299613; ENSG00000166483 [P30291-2]
ENST00000450114; ENSP00000402084; ENSG00000166483 [P30291-1]
GeneIDi7465
KEGGihsa:7465
UCSCiuc001mhs.4 human [P30291-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U10564 mRNA Translation: AAB60401.1
AJ277546 Genomic DNA Translation: CAC14173.1
AK122837 mRNA Translation: BAG53753.1
AC011979 Genomic DNA No translation available.
AC122179 Genomic DNA No translation available.
CH471064 Genomic DNA Translation: EAW68586.1
CH471064 Genomic DNA Translation: EAW68587.1
CH471064 Genomic DNA Translation: EAW68588.1
X62048 mRNA Translation: CAA43979.1
CCDSiCCDS44536.1 [P30291-2]
CCDS7800.1 [P30291-1]
PIRiS55048
RefSeqiNP_001137448.1, NM_001143976.1 [P30291-2]
NP_003381.1, NM_003390.3 [P30291-1]
UniGeneiHs.249441

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X8BX-ray1.81A291-575[»]
2IN6X-ray1.90A291-575[»]
2IO6X-ray2.20A291-575[»]
2Z2WX-ray2.22A291-575[»]
3BI6X-ray2.20A291-575[»]
3BIZX-ray2.20A291-575[»]
3CQEX-ray2.50A291-575[»]
3CR0X-ray2.30A291-575[»]
5V5YX-ray1.90A291-575[»]
5VC3X-ray1.97A291-575[»]
5VC4X-ray2.10A291-575[»]
5VC5X-ray1.93A291-575[»]
5VC6X-ray2.00A291-575[»]
5VD2X-ray2.05A291-575[»]
5VD4X-ray2.02A291-575[»]
5VD5X-ray2.05A291-575[»]
5VD7X-ray2.08A291-575[»]
5VD8X-ray1.85A291-575[»]
5VD9X-ray1.87A291-575[»]
5VDAX-ray2.10A291-575[»]
DisProtiDP00611
ProteinModelPortaliP30291
SMRiP30291
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113303, 76 interactors
CORUMiP30291
DIPiDIP-37969N
IntActiP30291, 21 interactors
MINTiP30291
STRINGi9606.ENSP00000402084

Chemistry databases

BindingDBiP30291
ChEMBLiCHEMBL5491
GuidetoPHARMACOLOGYi2278

PTM databases

iPTMnetiP30291
PhosphoSitePlusiP30291

Polymorphism and mutation databases

BioMutaiWEE1
DMDMi1351419

Proteomic databases

EPDiP30291
MaxQBiP30291
PaxDbiP30291
PeptideAtlasiP30291
PRIDEiP30291
ProteomicsDBi54650

Protocols and materials databases

DNASUi7465
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000299613; ENSP00000299613; ENSG00000166483 [P30291-2]
ENST00000450114; ENSP00000402084; ENSG00000166483 [P30291-1]
GeneIDi7465
KEGGihsa:7465
UCSCiuc001mhs.4 human [P30291-1]

Organism-specific databases

CTDi7465
DisGeNETi7465
EuPathDBiHostDB:ENSG00000166483.10
GeneCardsiWEE1
HGNCiHGNC:12761 WEE1
HPAiCAB004619
HPA068845
MIMi193525 gene
neXtProtiNX_P30291
OpenTargetsiENSG00000166483
PharmGKBiPA366
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0601 Eukaryota
ENOG410XS1M LUCA
GeneTreeiENSGT00530000063230
HOGENOMiHOG000004824
HOVERGENiHBG005050
InParanoidiP30291
KOiK06632
OMAiWNDSCGE
OrthoDBiEOG091G049H
PhylomeDBiP30291
TreeFamiTF101088

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-156711 Polo-like kinase mediated events
R-HSA-69202 Cyclin E associated events during G1/S transition
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-69478 G2/M DNA replication checkpoint
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
R-HSA-983231 Factors involved in megakaryocyte development and platelet production
SignaLinkiP30291
SIGNORiP30291

Miscellaneous databases

ChiTaRSiWEE1 human
EvolutionaryTraceiP30291
GeneWikiiWee1-like_protein_kinase
GenomeRNAii7465
PMAP-CutDBiP30291
PROiPR:P30291
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166483 Expressed in 203 organ(s), highest expression level in female gonad
CleanExiHS_WEE1
ExpressionAtlasiP30291 baseline and differential
GenevisibleiP30291 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR017164 Wee1-like_protein_kinase
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PIRSFiPIRSF037281 Wee1-like_protein_kinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiWEE1_HUMAN
AccessioniPrimary (citable) accession number: P30291
Secondary accession number(s): B3KVE1, D3DQV0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: February 1, 1996
Last modified: September 12, 2018
This is version 196 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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