dbPTM

STK3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	STK3_HUMAN
UniProt AC	Q13188
Protein Name	Serine/threonine-protein kinase 3
Gene Name	STK3
Organism	Homo sapiens (Human).
Sequence Length	491
Subcellular Localization	Cytoplasm. Nucleus. The caspase-cleaved form cycles between nucleus and cytoplasm (By similarity). Phosphorylation at Thr-117 leads to inhibition of nuclear translocation.
Protein Description	Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38..
Protein Sequence	MEQPPAPKSKLKKLSEDSLTKQPEEVFDVLEKLGEGSYGSVFKAIHKESGQVVAIKQVPVESDLQEIIKEISIMQQCDSPYVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLIEDEIATILKSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVKKCLVKNPEQRATATQLLQHPFIKNAKPVSILRDLITEAMEIKAKRHEEQQRELEEEEENSDEDELDSHTMVKTSVESVGTMRATSTMSEGAQTMIEHNSTMLESDLGTMVINSEDEEEEDGTMKRNATSPQVQRPSFMDYFDKQDFKNKSHENCNQNMHEPFPMSKNVFPDNWKVPQDGDFDFLKNLSLEELQMRLKALDPMMEREIEELRQRYTAKRQPILDAMDAKKRRQQNF

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Sulfoxidation	-------MEQPPAPK -------CCCCCCCH	11.02	28465586
1	Acetylation	-------MEQPPAPK -------CCCCCCCH	11.02	19413330
13	Ubiquitination	APKSKLKKLSEDSLT CCHHHHHHCCHHHCC	68.62	-
15	Phosphorylation	KSKLKKLSEDSLTKQ HHHHHHCCHHHCCCC	48.51	29255136
18	Phosphorylation	LKKLSEDSLTKQPEE HHHCCHHHCCCCHHH	33.61	29255136
20	Phosphorylation	KLSEDSLTKQPEEVF HCCHHHCCCCHHHHH	31.42	20873877
21	Ubiquitination	LSEDSLTKQPEEVFD CCHHHCCCCHHHHHH	69.97	-
32	Ubiquitination	EVFDVLEKLGEGSYG HHHHHHHHHCCCCCH	58.60	-
37	Phosphorylation	LEKLGEGSYGSVFKA HHHHCCCCCHHHHHH	23.24	22167270
38	Phosphorylation	EKLGEGSYGSVFKAI HHHCCCCCHHHHHHH	25.03	22167270
40	Phosphorylation	LGEGSYGSVFKAIHK HCCCCCHHHHHHHHC	19.02	22167270
43	Phosphorylation	GSYGSVFKAIHKESG CCCHHHHHHHHCCCC	44.25	27251275
43	Ubiquitination	GSYGSVFKAIHKESG CCCHHHHHHHHCCCC	44.25	-
43	Acetylation	GSYGSVFKAIHKESG CCCHHHHHHHHCCCC	44.25	25953088
46	Phosphorylation	GSVFKAIHKESGQVV HHHHHHHHCCCCCEE	32.46	27251275
47	Ubiquitination	SVFKAIHKESGQVVA HHHHHHHCCCCCEEE	47.68	-
49	Ubiquitination	FKAIHKESGQVVAIK HHHHHCCCCCEEEEE	39.05	-
49	Phosphorylation	FKAIHKESGQVVAIK HHHHHCCCCCEEEEE	39.05	29396449
56	Ubiquitination	SGQVVAIKQVPVESD CCCEEEEEEECCCCC	35.19	21906983
72	Phosphorylation	QEIIKEISIMQQCDS HHHHHHHHHHHHCCC	17.07	20068231
79	Phosphorylation	SIMQQCDSPYVVKYY HHHHHCCCCEEEEEE	26.25	30576142
81	Phosphorylation	MQQCDSPYVVKYYGS HHHCCCCEEEEEECC	23.10	30576142
84	Ubiquitination	CDSPYVVKYYGSYFK CCCCEEEEEECCCCC	23.78	22053931
84	Ubiquitination	CDSPYVVKYYGSYFK CCCCEEEEEECCCCC	23.78	-
116	Ubiquitination	DIIRLRNKTLIEDEI HHHHHHCCCCCHHHH	37.97	21906983
117	Phosphorylation	IIRLRNKTLIEDEIA HHHHHCCCCCHHHHH	36.20	19060867
125	Phosphorylation	LIEDEIATILKSTLK CCHHHHHHHHHHHHH	32.29	30622161
128	Ubiquitination	DEIATILKSTLKGLE HHHHHHHHHHHHHHH	37.23	-
144	Ubiquitination	LHFMRKIHRDIKAGN HHHHHHHHCCHHHCC	25.13	-
144	Ubiquitination	LHFMRKIHRDIKAGN HHHHHHHHCCHHHCC	25.13	22053931
148	Ubiquitination	RKIHRDIKAGNILLN HHHHCCHHHCCEEEC	55.31	-
161	Ubiquitination	LNTEGHAKLADFGVA ECCCCCHHHHHCCCC	38.23	-
172	Phosphorylation	FGVAGQLTDTMAKRN CCCCCHHHHHHHHHC	22.87	29255136
174	Phosphorylation	VAGQLTDTMAKRNTV CCCHHHHHHHHHCCC	17.50	29255136
176	Ubiquitination	GQLTDTMAKRNTVIG CHHHHHHHHHCCCCC	15.11	22053931
176	Ubiquitination	GQLTDTMAKRNTVIG CHHHHHHHHHCCCCC	15.11	-
177	Ubiquitination	QLTDTMAKRNTVIGT HHHHHHHHHCCCCCC	35.05	21906983
180	Phosphorylation	DTMAKRNTVIGTPFW HHHHHHCCCCCCCCC	19.96	12554736
184	Phosphorylation	KRNTVIGTPFWMAPE HHCCCCCCCCCCCHH	12.28	12223493
202	Phosphorylation	EIGYNCVADIWSLGI HHCCCHHHHHHHCCC	12.55	27251275
205	Ubiquitination	YNCVADIWSLGITSI CCHHHHHHHCCCEEE	6.51	-
205	Ubiquitination	YNCVADIWSLGITSI CCHHHHHHHCCCEEE	6.51	22053931
235	Phosphorylation	RAIFMIPTNPPPTFR EEEEEEECCCCCCCC	49.81	20068231
240	Phosphorylation	IPTNPPPTFRKPELW EECCCCCCCCCCCCC	41.67	20068231
243	Ubiquitination	NPPPTFRKPELWSDD CCCCCCCCCCCCCCH	38.36	21906983
256	Ubiquitination	DDFTDFVKKCLVKNP CHHHHHHHHHHCCCH	37.45	-
271	Ubiquitination	EQRATATQLLQHPFI HHHHHHHHHHHCHHH	37.40	22053931
271	Ubiquitination	EQRATATQLLQHPFI HHHHHHHHHHHCHHH	37.40	-
282	Ubiquitination	HPFIKNAKPVSILRD CHHHCCCCCCHHHHH	56.18	-
284	Ubiquitination	FIKNAKPVSILRDLI HHCCCCCCHHHHHHH	5.68	-
298	Ubiquitination	ITEAMEIKAKRHEEQ HHHHHHHHHHHHHHH	34.25	2190698
316	Phosphorylation	LEEEEENSDEDELDS HHHHHHCCCHHHHHH	45.73	29255136
323	Phosphorylation	SDEDELDSHTMVKTS CCHHHHHHHHCEEEE	33.22	23927012
325	Phosphorylation	EDELDSHTMVKTSVE HHHHHHHHCEEEEHH	27.84	23927012
326	Ubiquitination	DELDSHTMVKTSVES HHHHHHHCEEEEHHH	2.14	22053931
326	Ubiquitination	DELDSHTMVKTSVES HHHHHHHCEEEEHHH	2.14	-
329	Phosphorylation	DSHTMVKTSVESVGT HHHHCEEEEHHHHCC	26.96	30278072
330	Phosphorylation	SHTMVKTSVESVGTM HHHCEEEEHHHHCCE	20.40	30278072
333	Phosphorylation	MVKTSVESVGTMRAT CEEEEHHHHCCEEEE	24.56	25850435
336	Phosphorylation	TSVESVGTMRATSTM EEHHHHCCEEEEECC	11.00	25159151
337	Sulfoxidation	SVESVGTMRATSTMS EHHHHCCEEEEECCC	1.95	21406390
344	Phosphorylation	MRATSTMSEGAQTMI EEEEECCCHHHHHHH	32.73	27251275
364	Phosphorylation	MLESDLGTMVINSED EEEHHCCCEEECCCC	18.63	28348404
369	Phosphorylation	LGTMVINSEDEEEED CCCEEECCCCHHCCC	34.99	30624053
378	Phosphorylation	DEEEEDGTMKRNATS CHHCCCCCCCCCCCC	31.66	-
384	Phosphorylation	GTMKRNATSPQVQRP CCCCCCCCCCCCCCC	44.48	25159151
385	Phosphorylation	TMKRNATSPQVQRPS CCCCCCCCCCCCCCH	15.78	25159151
392	Phosphorylation	SPQVQRPSFMDYFDK CCCCCCCHHHHHCCH	35.08	23401153
396	Phosphorylation	QRPSFMDYFDKQDFK CCCHHHHHCCHHHHC	11.24	27794612
397	Phosphorylation	RPSFMDYFDKQDFKN CCHHHHHCCHHHHCC	9.13	27251275
406	Phosphorylation	KQDFKNKSHENCNQN HHHHCCCCCCCCCCC	45.48	28985074
412	Phosphorylation	KSHENCNQNMHEPFP CCCCCCCCCCCCCCC	51.31	27251275
413	Phosphorylation	SHENCNQNMHEPFPM CCCCCCCCCCCCCCC	21.56	27251275
430	Ubiquitination	NVFPDNWKVPQDGDF CCCCCCCCCCCCCCC	50.74	-
434	Phosphorylation	DNWKVPQDGDFDFLK CCCCCCCCCCCHHHH	53.19	27251275
444	Phosphorylation	FDFLKNLSLEELQMR CHHHHCCCHHHHHHH	43.03	22617229
450	Sulfoxidation	LSLEELQMRLKALDP CCHHHHHHHHHHHCH	9.41	21406390
453	Ubiquitination	EELQMRLKALDPMME HHHHHHHHHHCHHHH	36.22	-
472	Phosphorylation	ELRQRYTAKRQPILD HHHHHHHHHHCHHHH	8.97	27251275
481	Ubiquitination	RQPILDAMDAKKRRQ HCHHHHHHHHHHHHH	5.27	-

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
15	S	Phosphorylation	Kinase	PLK1	P53350	PSP
18	S	Phosphorylation	Kinase	PLK1	P53350	PSP
81	Y	Phosphorylation	Kinase	ABL1	P00519	GPS
117	T	Phosphorylation	Kinase	AKT1	P31749	Uniprot
180	T	Phosphorylation	Kinase	STK3	Q13188	GPS
316	S	Phosphorylation	Kinase	PLK1	P53350	PSP
378	T	Phosphorylation	Kinase	STK3	Q13188	GPS
384	T	Phosphorylation	Kinase	AKT1	P31749	Uniprot
385	S	Phosphorylation	Kinase	CDK1	P06493	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
117	T	Phosphorylation	20086174
Phosphorylation at Thr-117 and Thr-384 by PKB/AKT1, leads to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation, and increase in its binding to RAF1.
180	T	Phosphorylation	20086174
Phosphorylation at Thr-117 and Thr-384 by PKB/AKT1, leads to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation, and increase in its binding to RAF1.
384	T	Phosphorylation	20086174
Phosphorylation at Thr-117 and Thr-384 by PKB/AKT1, leads to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation, and increase in its binding to RAF1.

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 STK3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
STK4_HUMAN	STK4	physical	20562859
SAV1_HUMAN	SAV1	physical	20562859
ATG4B_HUMAN	ATG4B	physical	20562859
PLK1_HUMAN	PLK1	physical	20562859
CYBP_HUMAN	CACYBP	physical	20562859
RASF2_HUMAN	RASSF2	physical	20562859
FREM1_HUMAN	FREM1	physical	20562859
FUBP2_HUMAN	KHSRP	physical	21900206
DDAH2_HUMAN	DDAH2	physical	21900206
PHAX_HUMAN	PHAX	physical	21900206
SYQ_HUMAN	QARS	physical	21900206
EM55_HUMAN	MPP1	physical	21900206
GBP2_HUMAN	GBP2	physical	21900206
LATS1_HUMAN	LATS1	physical	22195963
PHOCN_HUMAN	MOB4	physical	19797269
MOB1A_HUMAN	MOB1A	physical	18362890
RASF1_HUMAN	RASSF1	physical	17379520
SAV1_HUMAN	SAV1	physical	17379520
LATS1_HUMAN	LATS1	physical	17379520
LATS1_HUMAN	LATS1	physical	19962312
SAV1_HUMAN	SAV1	physical	15688006
LATS1_HUMAN	LATS1	physical	15688006
MBP_HUMAN	MBP	physical	20212043
MOB1B_HUMAN	MOB1B	physical	19919647
4EBP1_HUMAN	EIF4EBP1	physical	20090955
RASF1_HUMAN	RASSF1	physical	17889669
RAF1_HUMAN	RAF1	physical	17889669
RAF1_HUMAN	RAF1	physical	15618521
STK3_HUMAN	STK3	physical	15618521
RAF1_HUMAN	RAF1	physical	20086174
AKT1_HUMAN	AKT1	physical	20086174
STK3_HUMAN	STK3	physical	20086174
AKT1_HUMAN	AKT1	physical	20231902
RASF1_HUMAN	RASSF1	physical	20086174
Z3H7A_HUMAN	ZC3H7A	physical	21988832
ST2A1_HUMAN	SULT2A1	physical	21988832
RASF3_HUMAN	RASSF3	physical	24255178
AURKB_HUMAN	AURKB	physical	24255178
ERLN2_HUMAN	ERLIN2	physical	24255178
STRP1_HUMAN	STRIP1	physical	24255178
FGOP2_HUMAN	FGFR1OP2	physical	24255178
KIF2C_HUMAN	KIF2C	physical	24255178
MAP1S_HUMAN	MAP1S	physical	24255178
MOB1A_HUMAN	MOB1A	physical	24255178
PHOCN_HUMAN	MOB4	physical	24255178
PLK1_HUMAN	PLK1	physical	24255178
P52K_HUMAN	PRKRIR	physical	24255178
RAE1L_HUMAN	RAE1	physical	24255178
RASF1_HUMAN	RASSF1	physical	24255178
RASF2_HUMAN	RASSF2	physical	24255178
RASF4_HUMAN	RASSF4	physical	24255178
RASF5_HUMAN	RASSF5	physical	24255178
RUN3B_HUMAN	RUNDC3B	physical	24255178
SAV1_HUMAN	SAV1	physical	24255178
SLMAP_HUMAN	SLMAP	physical	24255178
STK4_HUMAN	STK4	physical	24255178
STRN_HUMAN	STRN	physical	24255178
STRN3_HUMAN	STRN3	physical	24255178
STRN4_HUMAN	STRN4	physical	24255178
TSYL1_HUMAN	TSPYL1	physical	24255178
NEBU_HUMAN	NEB	physical	23455922
MAP1B_HUMAN	MAP1B	physical	23455922
RASF2_HUMAN	RASSF2	physical	23455922
CDK3_HUMAN	CDK3	physical	23455922
DYST_HUMAN	DST	physical	23455922
STK4_HUMAN	STK4	physical	23455922
ACACA_HUMAN	ACACA	physical	23455922
MAP1S_HUMAN	MAP1S	physical	23455922
RASF3_HUMAN	RASSF3	physical	23455922
RASF5_HUMAN	RASSF5	physical	23455922
RASF4_HUMAN	RASSF4	physical	23455922
SAV1_HUMAN	SAV1	physical	23455922
RASF1_HUMAN	RASSF1	physical	23455922
VAPA_HUMAN	VAPA	physical	23455922
TRAF1_HUMAN	TRAF1	physical	25416956
SLMAP_HUMAN	SLMAP	physical	25416956
RASF2_HUMAN	RASSF2	physical	25416956
TFPT_HUMAN	TFPT	physical	25416956
GMCL1_HUMAN	GMCL1	physical	25416956
RASF4_HUMAN	RASSF4	physical	25416956
FAM9B_HUMAN	FAM9B	physical	25416956
STK3_HUMAN	STK3	physical	18082144
MAP1B_HUMAN	MAP1B	physical	24366813
MAP1S_HUMAN	MAP1S	physical	24366813
STK4_HUMAN	STK4	physical	24366813
RASF1_HUMAN	RASSF1	physical	24366813
RASF2_HUMAN	RASSF2	physical	24366813
RASF3_HUMAN	RASSF3	physical	24366813
RASF5_HUMAN	RASSF5	physical	24366813
RM40_HUMAN	MRPL40	physical	24366813
SAV1_HUMAN	SAV1	physical	24366813
NSUN5_HUMAN	NSUN5	physical	26344197
CASP3_HUMAN	CASP3	physical	25241761
LATS2_HUMAN	LATS2	physical	26898830
KIF3B_HUMAN	KIF3B	physical	27173435

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 STK3_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.	19413330 [Abstract]
Phosphorylation
Reference	PubMed
"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-316, AND MASSSPECTROMETRY.	19690332 [Abstract]
"Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15; SER-316; SER-323;THR-325; THR-336; THR-384; SER-385; SER-392 AND SER-444, AND MASSSPECTROMETRY.	19369195 [Abstract]
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, AND MASSSPECTROMETRY.	18669648 [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-15; SER-316; SER-385 ANDSER-444, AND MASS SPECTROMETRY.	18691976 [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-316, AND MASSSPECTROMETRY.	17081983 [Abstract]
"Regulation of proapoptotic mammalian ste20-like kinase MST2 by theIGF1-Akt pathway."; Kim D., Shu S., Coppola M.D., Kaneko S., Yuan Z.Q., Cheng J.Q.; PLoS ONE 5:E9616-E9616(2010). Cited for: PHOSPHORYLATION AT THR-117, AND INTERACTION WITH PKB/AKT1.	20231902 [Abstract]
"Proapoptotic kinase MST2 coordinates signaling crosstalk betweenRASSF1A, Raf-1, and Akt."; Romano D., Matallanas D., Weitsman G., Preisinger C., Ng T., Kolch W.; Cancer Res. 70:1195-1203(2010). Cited for: PHOSPHORYLATION AT THR-117 AND THR-384, AND INTERACTION WITH PKB/AKT1.	20086174 [Abstract]

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