dbPTM

WEE1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	WEE1_HUMAN
UniProt AC	P30291
Protein Name	Wee1-like protein kinase
Gene Name	WEE1
Organism	Homo sapiens (Human).
Sequence Length	646
Subcellular Localization	Nucleus.
Protein Description	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..
Protein Sequence	MSFLSRQQPPPPRRAGAACTLRQKLIFSPCSDCEEEEEEEEEEGSGHSTGEDSAFQEPDSPLPPARSPTEPGPERRRSPGPAPGSPGELEEDLLLPGACPGADEAGGGAEGDSWEEEGFGSSSPVKSPAAPYFLGSSFSPVRCGGPGDASPRGCGARRAGEGRRSPRPDHPGTPPHKTFRKLRLFDTPHTPKSLLSKARGIDSSSVKLRGSSLFMDTEKSGKREFDVRQTPQVNINPFTPDSLLLHSSGQCRRRKRTYWNDSCGEDMEASDYELEDETRPAKRITITESNMKSRYTTEFHELEKIGSGEFGSVFKCVKRLDGCIYAIKRSKKPLAGSVDEQNALREVYAHAVLGQHSHVVRYFSAWAEDDHMLIQNEYCNGGSLADAISENYRIMSYFKEAELKDLLLQVGRGLRYIHSMSLVHMDIKPSNIFISRTSIPNAASEEGDEDDWASNKVMFKIGDLGHVTRISSPQVEEGDSRFLANEVLQENYTHLPKADIFALALTVVCAAGAEPLPRNGDQWHEIRQGRLPRIPQVLSQEFTELLKVMIHPDPERRPSAMALVKHSVLLSASRKSAEQLRIELNAEKFKNSLLQKELKKAQMAKAAAEERALFTDRMATRSTTQSNRTSRLIGKKMNRSVSLTIY

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
5	Phosphorylation	---MSFLSRQQPPPP ---CCCCCCCCCCCC	26.49	24719451
14	Methylation	QQPPPPRRAGAACTL CCCCCCCCCCCCCCH	43.05	115920049
20	Phosphorylation	RRAGAACTLRQKLIF CCCCCCCCHHHHHCC	21.90	23917254
31	Phosphorylation	KLIFSPCSDCEEEEE HHCCCCCCCCCHHHH	48.99	28348404
45	Phosphorylation	EEEEEEGSGHSTGED HHHHHCCCCCCCCCC	36.29	28348404
48	Phosphorylation	EEEGSGHSTGEDSAF HHCCCCCCCCCCCCC	41.45	28348404
49	Phosphorylation	EEGSGHSTGEDSAFQ HCCCCCCCCCCCCCC	38.63	28348404
53	Phosphorylation	GHSTGEDSAFQEPDS CCCCCCCCCCCCCCC	27.04	16085715
67	Phosphorylation	SPLPPARSPTEPGPE CCCCCCCCCCCCCCC	37.98	30266825
69	Phosphorylation	LPPARSPTEPGPERR CCCCCCCCCCCCCCC	56.93	29255136
78	Phosphorylation	PGPERRRSPGPAPGS CCCCCCCCCCCCCCC	32.18	18691976
85	Phosphorylation	SPGPAPGSPGELEED CCCCCCCCCCCCCCC	28.77	17192257
121	Phosphorylation	WEEEGFGSSSPVKSP CCCCCCCCCCCCCCC	25.94	16085715
122	Phosphorylation	EEEGFGSSSPVKSPA CCCCCCCCCCCCCCC	38.75	26699800
123	Phosphorylation	EEGFGSSSPVKSPAA CCCCCCCCCCCCCCC	35.10	16085715
127	Phosphorylation	GSSSPVKSPAAPYFL CCCCCCCCCCCCCCC	21.72	21945579
132	Phosphorylation	VKSPAAPYFLGSSFS CCCCCCCCCCCCCCC	13.50	21945579
136	Phosphorylation	AAPYFLGSSFSPVRC CCCCCCCCCCCCCCC	30.29	21945579
137	Phosphorylation	APYFLGSSFSPVRCG CCCCCCCCCCCCCCC	28.13	21945579
139	Phosphorylation	YFLGSSFSPVRCGGP CCCCCCCCCCCCCCC	25.16	25159151
150	Phosphorylation	CGGPGDASPRGCGAR CCCCCCCCCCCCCCC	21.62	29255136
165	Phosphorylation	RAGEGRRSPRPDHPG CCCCCCCCCCCCCCC	24.73	23401153
173	Phosphorylation	PRPDHPGTPPHKTFR CCCCCCCCCCCCCCC	37.79	23401153
178	Phosphorylation	PGTPPHKTFRKLRLF CCCCCCCCCCCEECC	26.16	28111955
187	Phosphorylation	RKLRLFDTPHTPKSL CCEECCCCCCCCHHH	15.05	25159151
190	Phosphorylation	RLFDTPHTPKSLLSK ECCCCCCCCHHHHHH	33.35	23401153
193	Phosphorylation	DTPHTPKSLLSKARG CCCCCCHHHHHHHCC	35.43	16964243
196	Phosphorylation	HTPKSLLSKARGIDS CCCHHHHHHHCCCCC	29.57	22496350
199	Methylation	KSLLSKARGIDSSSV HHHHHHHCCCCCCCC	46.46	97795435
203	Phosphorylation	SKARGIDSSSVKLRG HHHCCCCCCCCEECC	23.69	26434776
204	Phosphorylation	KARGIDSSSVKLRGS HHCCCCCCCCEECCC	35.09	23401153
205	Phosphorylation	ARGIDSSSVKLRGSS HCCCCCCCCEECCCC	27.50	26434776
207	Ubiquitination	GIDSSSVKLRGSSLF CCCCCCCEECCCCCE	34.12	-
211	Phosphorylation	SSVKLRGSSLFMDTE CCCEECCCCCEECCC	19.89	15253423
212	Phosphorylation	SVKLRGSSLFMDTEK CCEECCCCCEECCCC	28.57	15253423
217	Phosphorylation	GSSLFMDTEKSGKRE CCCCEECCCCCCCCE	33.26	-
230	Phosphorylation	REFDVRQTPQVNINP CEECCCCCCCCCCCC	12.72	22199227
239	Phosphorylation	QVNINPFTPDSLLLH CCCCCCCCCCCEEEC	27.69	22199227
242	Phosphorylation	INPFTPDSLLLHSSG CCCCCCCCEEECCCC	23.32	22199227
247	Phosphorylation	PDSLLLHSSGQCRRR CCCEEECCCCCCCCC	35.81	22199227
248	Phosphorylation	DSLLLHSSGQCRRRK CCEEECCCCCCCCCC	23.33	22199227
257	Phosphorylation	QCRRRKRTYWNDSCG CCCCCCCCCCCCCCC	35.60	28450419
258	Phosphorylation	CRRRKRTYWNDSCGE CCCCCCCCCCCCCCC	13.27	28450419
262	Phosphorylation	KRTYWNDSCGEDMEA CCCCCCCCCCCCCCC	22.32	30576142
270	Phosphorylation	CGEDMEASDYELEDE CCCCCCCCCCCCCCC	27.67	23898821
272	Phosphorylation	EDMEASDYELEDETR CCCCCCCCCCCCCCC	21.66	30576142
278	Phosphorylation	DYELEDETRPAKRIT CCCCCCCCCCCCEEE	55.03	30576142
289	Phosphorylation	KRITITESNMKSRYT CEEEEECCHHHHCEE	33.31	28555341
292	Ubiquitination	TITESNMKSRYTTEF EEECCHHHHCEEEEE	35.71	-
293	Phosphorylation	ITESNMKSRYTTEFH EECCHHHHCEEEEEE	21.54	20044836
304	Ubiquitination	TEFHELEKIGSGEFG EEEEEEEECCCCCCC	66.06	-
307	Phosphorylation	HELEKIGSGEFGSVF EEEEECCCCCCCHHH	38.33	20044836
312	Phosphorylation	IGSGEFGSVFKCVKR CCCCCCCHHHHHHHH	29.69	25159151
315	Ubiquitination	GEFGSVFKCVKRLDG CCCCHHHHHHHHCCC	35.64	-
444	Phosphorylation	TSIPNAASEEGDEDD CCCCCCCCCCCCCCC	33.50	-
460	Ubiquitination	ASNKVMFKIGDLGHV HHCEEEEEECCCCCE	27.90	-
471	Phosphorylation	LGHVTRISSPQVEEG CCCEEEECCCCCCCC	32.45	18691976
472	Phosphorylation	GHVTRISSPQVEEGD CCEEEECCCCCCCCC	19.58	21815630
480	Phosphorylation	PQVEEGDSRFLANEV CCCCCCCHHHHHHHH	35.47	24667141
547	Ubiquitination	QEFTELLKVMIHPDP HHHHHHHHHHHCCCC	42.24	-
559	Phosphorylation	PDPERRPSAMALVKH CCCCCCCCHHHHHHH	28.94	15253423
571	Phosphorylation	VKHSVLLSASRKSAE HHHHHHHHHCHHCHH	21.75	21712546
576	Phosphorylation	LLSASRKSAEQLRIE HHHHCHHCHHHHHHH	35.61	27251275
588	Ubiquitination	RIELNAEKFKNSLLQ HHHHCHHHHHHHHHH	60.26	-
590	Ubiquitination	ELNAEKFKNSLLQKE HHCHHHHHHHHHHHH	57.61	-
590	Sumoylation	ELNAEKFKNSLLQKE HHCHHHHHHHHHHHH	57.61	-
590	Sumoylation	ELNAEKFKNSLLQKE HHCHHHHHHHHHHHH	57.61	-
592	Phosphorylation	NAEKFKNSLLQKELK CHHHHHHHHHHHHHH	30.92	28555341
596	Ubiquitination	FKNSLLQKELKKAQM HHHHHHHHHHHHHHH	66.05	-
600	Ubiquitination	LLQKELKKAQMAKAA HHHHHHHHHHHHHHH	57.38	-
617	Methylation	ERALFTDRMATRSTT HHHHHHHHHCCCCCC	17.36	115920053
622	O-linked_Glycosylation	TDRMATRSTTQSNRT HHHHCCCCCCCCCHH	31.30	30379171
640	Phosphorylation	IGKKMNRSVSLTIY- HHHCCCCCEEEEEC-	15.85	29978859
642	Phosphorylation	KKMNRSVSLTIY--- HCCCCCEEEEEC---	22.50	27794612
644	Phosphorylation	MNRSVSLTIY----- CCCCEEEEEC-----	15.66	29978859
646	Phosphorylation	RSVSLTIY------- CCEEEEEC-------	13.78	23025827

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
53	S	Phosphorylation	Kinase	PLK1	P53350	Uniprot
121	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
123	S	Phosphorylation	Kinase	CDK1	P06493	Uniprot
123	S	Phosphorylation	Kinase	CDK-FAMILY	-	GPS
139	S	Phosphorylation	Kinase	CDK1	P06493	PSP
211	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
212	S	Phosphorylation	Kinase	CSNK1D	P48730	GPS
642	S	Phosphorylation	Kinase	AKT1	P31749	PSP
642	S	Phosphorylation	Kinase	BRSK1	Q8TDC3	Uniprot
642	S	Phosphorylation	Kinase	BRSK1	Q8TDC3-2	GPS
642	S	Phosphorylation	Kinase	BRSK2	Q8IWQ3	Uniprot
642	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	BTRC	Q9Y297	PMID:15070733
-	K	Ubiquitination	E3 ubiquitin ligase	FBXW11	Q9UKB1	PMID:15070733
-	K	Ubiquitination	E3 ubiquitin ligase	CDCA3	Q99618	PMID:18032919

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
53	S	Phosphorylation	15070733
Dephosphorylated at Ser-53 and Ser-123 by the serine/threonine-protein phosphatase 2A preventing its ubiquitin-mediated degradation.
53	S	Phosphorylation	15070733
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.
53	S	ubiquitylation	15070733
Dephosphorylated at Ser-53 and Ser-123 by the serine/threonine-protein phosphatase 2A preventing its ubiquitin-mediated degradation.
53	S	ubiquitylation	15070733
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.
123	S	Phosphorylation	15070733
Dephosphorylated at Ser-53 and Ser-123 by the serine/threonine-protein phosphatase 2A preventing its ubiquitin-mediated degradation.
123	S	Phosphorylation	15070733
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.
123	S	ubiquitylation	15070733
Dephosphorylated at Ser-53 and Ser-123 by the serine/threonine-protein phosphatase 2A preventing its ubiquitin-mediated degradation.
123	S	ubiquitylation	15070733
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.
239	T	Phosphorylation	22692537
Dephosphorylated at Thr-239 by CTDP1.
642	S	Phosphorylation	15150265
Phosphorylation at Ser-642 by BRSK1 and BRSK2 in post-mitotic neurons, leads to down-regulate WEE1 activity in polarized neurons.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of WEE1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
1433B_HUMAN	YWHAB	physical	10775038
PIN1_HUMAN	PIN1	physical	9499405
CSK21_HUMAN	CSNK2A1	physical	18560763
CSK2B_HUMAN	CSNK2B	physical	18560763
FBW1A_HUMAN	BTRC	physical	15070733
CNBP_HUMAN	CNBP	physical	25852190
EF2_HUMAN	EEF2	physical	25852190
PCBP1_HUMAN	PCBP1	physical	25852190
SPTB2_HUMAN	SPTBN1	physical	25852190
RUSC2_HUMAN	RUSC2	physical	26496610
CE350_HUMAN	CEP350	physical	26496610
WDFY3_HUMAN	WDFY3	physical	26496610
BRPF3_HUMAN	BRPF3	physical	26496610
CCYL1_HUMAN	CCNYL1	physical	26496610
FBW1B_HUMAN	FBXW11	physical	25241761
KC1A_HUMAN	CSNK1A1	physical	27173435
KCTD3_HUMAN	KCTD3	physical	27173435
UBP15_HUMAN	USP15	physical	27173435
KI13B_HUMAN	KIF13B	physical	27173435
MCM2_HUMAN	MCM2	physical	27173435
MCM4_HUMAN	MCM4	physical	27173435
CING_HUMAN	CGN	physical	27173435
CBY1_HUMAN	CBY1	physical	27173435
CHK1_HUMAN	CHEK1	genetic	27453043
CDC73_HUMAN	CDC73	genetic	27453043
TITIN_HUMAN	TTN	genetic	27453043
RB_HUMAN	RB1	genetic	27453043
ING4_HUMAN	ING4	genetic	27453043
FZR1_HUMAN	FZR1	genetic	27453043
WRN_HUMAN	WRN	genetic	27453043
BLM_HUMAN	BLM	genetic	27453043
ATAD5_HUMAN	ATAD5	genetic	27453043
BRD4_HUMAN	BRD4	genetic	27453043
FUMH_HUMAN	FH	genetic	27453043
WEE1_HUMAN	WEE1	genetic	27453043
CDN1B_HUMAN	CDKN1B	genetic	27453043
XRCC3_HUMAN	XRCC3	genetic	27453043
CDK12_HUMAN	CDK12	genetic	27453043
CDC6_HUMAN	CDC6	genetic	27453043
MTOR_HUMAN	MTOR	genetic	27453043

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of WEE1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Persistence of the cell-cycle checkpoint kinase Wee1 in SadA- andSadB-deficient neurons disrupts neuronal polarity."; Muller M., Lutter D., Puschel A.W.; J. Cell Sci. 123:286-294(2010). Cited for: PHOSPHORYLATION AT SER-642, AND MUTAGENESIS OF SER-642.	20026642 [Abstract]
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions."; Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.; Sci. Signal. 2:RA46-RA46(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, AND MASSSPECTROMETRY.	19690332 [Abstract]
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle."; Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.; Mol. Cell 31:438-448(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-67; SER-127; SER-139;SER-150; THR-173; THR-190 AND SER-312, AND MASS SPECTROMETRY.	18691976 [Abstract]
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT forefficient phosphoproteomic analysis."; Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,Yates J.R. III; J. Proteome Res. 7:1346-1351(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, AND MASSSPECTROMETRY.	18220336 [Abstract]
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry."; Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.; Mol. Cell. Proteomics 6:537-547(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139 AND THR-173, ANDMASS SPECTROMETRY.	17192257 [Abstract]
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127; SER-139 ANDSER-165, AND MASS SPECTROMETRY.	17081983 [Abstract]
"Large-scale characterization of HeLa cell nuclear phosphoproteins."; Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,Li J., Cohn M.A., Cantley L.C., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, AND MASSSPECTROMETRY.	15302935 [Abstract]
"M-phase kinases induce phospho-dependent ubiquitination of somaticWee1 by SCFbeta-TrCP."; Watanabe N., Arai H., Nishihara Y., Taniguchi M., Watanabe N.,Hunter T., Osada H.; Proc. Natl. Acad. Sci. U.S.A. 101:4419-4424(2004). Cited for: PHOSPHORYLATION AT SER-53 AND SER-123, UBIQUITINATION, AND MUTAGENESISOF SER-53; 116-GLU-GLU-117 AND SER-123.	15070733 [Abstract]
"Human SAD1 kinase is involved in UV-induced DNA damage checkpointfunction."; Lu R., Niida H., Nakanishi M.; J. Biol. Chem. 279:31164-31170(2004). Cited for: PHOSPHORYLATION AT SER-642.	15150265 [Abstract]

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