Q66JT0 (WEE2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Wee1-like protein kinase 2
EC=2.7.10.2

Alternative name(s):
Wee1-like protein kinase 1B
Wee1B kinase
Short name=mWee1B

Gene names

Name:	Wee2
Synonyms:	Wee1b

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	555 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Oocyte-specific protein tyrosine kinase that phosphorylates and inhibits CDK1 and acts as a key regulator of meiosis during both prophase I and metaphase II. Required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, by phosphorylating CDK1 at 'Tyr-15', leading to inhibit CDK1 activity and prevent meiotic reentry. Also required for metaphase II exit during egg activation by phosphorylating CDK1 at 'Tyr-15', to ensure exit from meiosis in oocytes and promote pronuclear formation. Ref.1 Ref.5 Ref.6
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subcellular location	Cytoplasm. Nucleus. Note: Localizes mainly in the nucleus. Exported from the nucleus to the cytoplasm before germinal vesicle breakdown (GVBD), allowing meiosis resumption. Ref.4 Ref.5
Tissue specificity	Ovary-specific. Ref.1
Developmental stage	Detected only in the oocytes at all developmental stages of the follicle including primary, secondary, preantral, and antral follicles with an increase in signal during development. Readily detectable at the mature oocyte, but disappears at E2.5. Detected in germinal vesicle (GV) and metaphase II-stage oocyte (at protein level). Ref.1 Ref.6
Post-translational modification	Phosphorylated by PKA at Ser-15 in vitro, leading to activate kinase activity. Phosphorylation at Ser-15 by CaMK2, leading to increase its activity and promote metaphase II exit during egg activation. Ref.1 Ref.6
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Meiosis
Cellular component	Cytoplasm Nucleus
Domain	Coiled coil
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	female meiosis Inferred from mutant phenotype Ref.1. Source: UniProtKB female pronucleus assembly Inferred from mutant phenotype Ref.6. Source: UniProtKB mitosis Inferred from electronic annotation. Source: InterPro negative regulation of cyclin-dependent protein serine/threonine kinase activity Inferred from mutant phenotype Ref.6. Source: UniProtKB negative regulation of oocyte maturation Inferred from mutant phenotype Ref.1Ref.6. Source: UniProtKB regulation of meiosis I Inferred from mutant phenotype Ref.1. Source: UniProtKB
Cellular_component	centrosome Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay Ref.5. Source: UniProtKB nucleus Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: InterPro non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Inferred from electronic annotation. Source: InterPro protein tyrosine kinase activity Traceable author statement Ref.1Ref.6. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 555	555	Wee1-like protein kinase 2		PRO_0000248080
Regions
	Domain	208 – 485	278	Protein kinase
	Nucleotide binding	214 – 222	9	ATP By similarity
	Coiled coil	488 – 514	27	Potential
	Motif	167 – 169	3	Nuclear localization signal
	Motif	310 – 324	15	Nuclear export signal
Sites
	Active site	334	1	Proton acceptor By similarity
	Metal binding	339	1	Magnesium; via carbonyl oxygen By similarity
	Metal binding	375	1	Magnesium; via carbonyl oxygen By similarity
	Binding site	237	1	ATP Probable
Amino acid modifications
	Modified residue	15	1	Phosphoserine; by CaMK2 and PKA Ref.1 Ref.6
	Modified residue	71	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	15	1	S → A: Abolishes phosphorylation and impairs ability to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage and metaphase II exit during egg activation. Ref.1 Ref.6
	Mutagenesis	15	1	S → D: Mimicks phosphorylation state, lesading to enhance kinase activity and promote pronuclear formation. Ref.1 Ref.6
	Mutagenesis	167 – 169	3	Missing: Abolishes nuclear localization. Ref.5
	Mutagenesis	237	1	K → M: Loss of function. Ref.5 Ref.6
	Mutagenesis	311	1	L → A: Abolishes the cytoplasmic localization; when associated with A-316; A-320 and A-322. Ref.5
	Mutagenesis	316	1	L → A: Abolishes the cytoplasmic localization; when associated with A-311; A-320 and A-322. Ref.5
	Mutagenesis	320	1	L → A: Abolishes the cytoplasmic localization; when associated with A-311; A-316 and A-322. Ref.5
	Mutagenesis	322	1	L → A: Abolishes the cytoplasmic localization; when associated with A-311; A-316 and A-320. Ref.5
	Sequence conflict	21	1	E → K in AAH80784. Ref.3
	Sequence conflict	70	1	E → G in AAH52883. Ref.3
	Sequence conflict	98	1	L → P in AAH52883. Ref.3
	Sequence conflict	118	1	L → R in AAH80784. Ref.3
	Sequence conflict	138	1	M → V in AAH52883. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q66JT0 [UniParc]. Last modified September 5, 2006. Version 2. Checksum: 0D3FA3972C626693	FASTA	555	62,343
	10 20 30 40 50 60 MADTETDQGL NKKLSFSFCE EDTESEGQMT AQDIGGAQSQ KPGREESEEL EGPVPPTRDE 70 80 90 100 110 120 LHTSLSRDKE SPGPDLWKSV SGPPKCPETP VLHSKSKLPV PTNFSTPKNS LGQPEISLLE 130 140 150 160 170 180 KLSSRSSRHM RLTPASLMDE KTSLSLVNIN PFTPETYRKL LLQSKGKRKT RDYLEETGEE 190 200 210 220 230 240 ESKSVQWLPA KRSILQETNM ASRYEKEFFE IEKIGVGEFG TVYKCIKRLD GCIYAIKRSA 250 260 270 280 290 300 KSFSGLSNEL DLHEVYAHAV LGHHPHVVRY YSSWIEDDHV VIQNEYCNGG SLQAAISENT 310 320 330 340 350 360 ASNNHFQEPK LKDILLQISL GLKYIHNSGM VHLDIKPSNI FICHKMQCDS PVGPEEAESE 370 380 390 400 410 420 ADWFLNASVM YKIGDLGHAT SISKPKVEEG DTRFLANEIL QENYQHLPKA DIFALGLTIA 430 440 450 460 470 480 VAAGAESLPI NGDMWHHIRK GNFPEISQEL SDDFYGLLKN MIHPAPKERP SAAALARSRI 490 500 510 520 530 540 LWPFLEKTDE LQKQLNLEKS KTATLKRELK KARHIQTPQR EVHHCYYQIC KGSRHLLVGG 550 RRKAPSSFTR GTSSV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Wee1B is an oocyte-specific kinase involved in the control of meiotic arrest in the mouse." Han S.J., Chen R., Paronetto M.P., Conti M. Curr. Biol. 15:1670-1676(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, PHOSPHORYLATION AT SER-15, MUTAGENESIS OF SER-15. Strain: C57BL/6J.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Egg and Ovary.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Egg.
[4]	"Identification and characterization of human Wee1B, a new member of the Wee1 family of Cdk-inhibitory kinases." Nakanishi M., Ando H., Watanabe N., Kitamura K., Ito K., Okayama H., Miyamoto T., Agui T., Sasaki M. Genes Cells 5:839-847(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[5]	"Wee1B, Myt1, and Cdc25 function in distinct compartments of the mouse oocyte to control meiotic resumption." Oh J.S., Han S.J., Conti M. J. Cell Biol. 188:199-207(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF 167-LYS--LYS-169; LYS-237; LEU-311; LEU-316; LEU-320 AND LEU-322.
[6]	"Protein tyrosine kinase Wee1B is essential for metaphase II exit in mouse oocytes." Oh J.S., Susor A., Conti M. Science 332:462-465(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE, PHOSPHORYLATION AT SER-15, MUTAGENESIS OF SER-15 AND LYS-237.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	DQ011691 mRNA. Translation: AAY44075.1. AK163344 mRNA. Translation: BAE37310.1. AK143336 mRNA. Translation: BAE25345.1. AK139573 mRNA. Translation: BAE24069.1. BC052883 mRNA. Translation: AAH52883.1. BC080784 mRNA. Translation: AAH80784.1.
IPI	IPI00380459.
RefSeq	NP_958758.2. NM_201370.2.
UniGene	Mm.20593.
3D structure databases
ProteinModelPortal	Q66JT0.
SMR	Q66JT0. Positions 202-510.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000038754.
Proteomic databases
PRIDE	Q66JT0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000038907; ENSMUSP00000038754; ENSMUSG00000037159.
GeneID	381759.
KEGG	mmu:381759.
UCSC	uc009bmq.2. mouse.
Organism-specific databases
CTD	494551.
MGI	MGI:3027899. Wee2.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00530000063230.
HOGENOM	HOG000004824.
HOVERGEN	HBG005050.
InParanoid	Q66JT0.
KO	K06632.
OMA	CEEDTES.
OrthoDB	EOG4FJ88X.
Gene expression databases
ArrayExpress	Q66JT0.
Bgee	Q66JT0.
CleanEx	MM_WEE2.
Genevestigator	Q66JT0.
GermOnline	ENSMUSG00000037159. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. IPR017164. Wee1-like_protein_kinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF037281. Wee1-like_protein_kinase. 1 hit.
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	WEE2. mouse.
NextBio	402507.
SOURCE	Search...

Entry information

Entry name

WEE2_MOUSE

Accession

Primary (citable) accession number: Q66JT0
Secondary accession number(s): Q4U4S4, Q7TPV9

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	September 5, 2006
Last modified:	May 29, 2013
This is version 79 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program