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Protein

Wee1-like protein kinase

Gene

WEE1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

Enzyme 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

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS09406-MONOMER.
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 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

HGNCiHGNC:12761. WEE1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: Ensembl
  • nucleolus Source: HPA
  • nucleoplasm Source: Reactome
  • nucleus Source: ProtInc
Complete GO annotation...

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.

PTM databases

iPTMnetiP30291.
PhosphoSitePlusiP30291.

Miscellaneous databases

PMAP-CutDBP30291.

Expressioni

Gene expression databases

BgeeiENSG00000166483.
CleanExiHS_WEE1.
ExpressionAtlasiP30291. baseline and differential.
GenevisibleiP30291. HS.

Organism-specific databases

HPAiCAB004619.
HPA068845.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
BTRCQ9Y2972EBI-914695,EBI-307461
FBXW11Q9UKB13EBI-914695,EBI-355189
YWHAZP631043EBI-914695,EBI-347088

Protein-protein interaction databases

BioGridi113303. 32 interactors.
DIPiDIP-37969N.
IntActiP30291. 18 interactors.
MINTiMINT-129561.
STRINGi9606.ENSP00000402084.

Chemistry databases

BindingDBiP30291.

Structurei

Secondary structure

1646
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi294 – 298Combined sources5
Beta strandi299 – 308Combined sources10
Beta strandi311 – 318Combined sources8
Turni319 – 321Combined sources3
Beta strandi324 – 331Combined sources8
Beta strandi335 – 337Combined sources3
Helixi338 – 352Combined sources15
Beta strandi362 – 368Combined sources7
Beta strandi371 – 377Combined sources7
Helixi384 – 394Combined sources11
Helixi400 – 419Combined sources20
Helixi429 – 431Combined sources3
Beta strandi432 – 435Combined sources4
Beta strandi458 – 461Combined sources4
Helixi464 – 466Combined sources3
Helixi480 – 482Combined sources3
Helixi485 – 488Combined sources4
Helixi495 – 510Combined sources16
Beta strandi518 – 520Combined sources3
Helixi521 – 527Combined sources7
Helixi540 – 549Combined sources10
Helixi554 – 556Combined sources3
Helixi560 – 564Combined sources5
Helixi567 – 569Combined sources3

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[»]
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
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR017164. Wee1-like_protein_kinase.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF037281. Wee1-like_protein_kinase. 1 hit.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

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 → C.1 PublicationCorresponds to variant rs34412975dbSNPEnsembl.1
Natural variantiVAR_041303472S → I.1 PublicationCorresponds to variant rs56411856dbSNPEnsembl.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

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[»]
DisProtiDP00611.
ProteinModelPortaliP30291.
SMRiP30291.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113303. 32 interactors.
DIPiDIP-37969N.
IntActiP30291. 18 interactors.
MINTiMINT-129561.
STRINGi9606.ENSP00000402084.

Chemistry databases

BindingDBiP30291.
ChEMBLiCHEMBL5491.
GuidetoPHARMACOLOGYi2278.

PTM databases

iPTMnetiP30291.
PhosphoSitePlusiP30291.

Polymorphism and mutation databases

BioMutaiWEE1.
DMDMi1351419.

Proteomic databases

EPDiP30291.
MaxQBiP30291.
PaxDbiP30291.
PeptideAtlasiP30291.
PRIDEiP30291.

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.
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

BioCyciZFISH:HS09406-MONOMER.
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 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-CutDBP30291.
PROiP30291.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166483.
CleanExiHS_WEE1.
ExpressionAtlasiP30291. baseline and differential.
GenevisibleiP30291. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR017164. Wee1-like_protein_kinase.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF037281. Wee1-like_protein_kinase. 1 hit.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiWEE1_HUMAN
AccessioniPrimary (citable) accession number: P30291
Secondary accession number(s): B3KVE1, D3DQV0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: February 1, 1996
Last modified: November 2, 2016
This is version 182 of the entry and version 2 of the sequence. [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 chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.