STK3_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: STK3_MOUSE
• UniProt AC: Q9JI10
• Protein Name: Serine/threonine-protein kinase 3
• Gene Name: Stk3
• Organism: Mus musculus (Mouse).
• Sequence Length: 497
• Subcellular Localization: Cytoplasm. Nucleus. The caspase-cleaved form cycles between nucleus and cytoplasm. Phosphorylation at Thr-117 leads to inhibition of nuclear translocation (By similarity)..
• 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. Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, 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 (By similarity)..
• Protein Sequence: MEQPPASKSKLKKLSEDSLTKQPEEVFDVLEKLGEGSYGSVFKAIHKESGQVVAIKQVPVESDLQEIIKEISIMQQCDSPYVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLTEDEIATILKSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVKKCLVKSPEQRATATQLLQHPFIKNAKPVSILRDLIAEAMEIKAKRHEEQQRELEEEEENSDEDELDSHTMVKTSSESVGTMRATSTMSEGAQTMIEHNSTMLESDLGTMVINSEEEEEEEEEEEEDGTMKRNATSPQVQRPSFMDYFDKQDFKNKSHENCDQSMREPGPMSNSVFPDNWRVPQDGDFDFLKNLSLEELQMRLKALDPMMEREIEELHQRYSAKRQPILDAMDAKKRRQQNF

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MEQPPASK -------CCCCCCCH	11.02	-
15	Phosphorylation	KSKLKKLSEDSLTKQ HHHHHHHCCCCCCCC	48.51	28418008
18	Phosphorylation	LKKLSEDSLTKQPEE HHHHCCCCCCCCHHH	33.61	28066266
81	Phosphorylation	MQQCDSPYVVKYYGS HHHCCCCEEEEEECC	23.10	22590567
117	Phosphorylation	IIRLRNKTLTEDEIA HHHHHCCCCCHHHHH	42.32	-
172	Phosphorylation	FGVAGQLTDTMAKRN CCCCCHHHHHHHHHC	22.87	28066266
174	Phosphorylation	VAGQLTDTMAKRNTV CCCHHHHHHHHHCCC	17.50	26824392
180	Phosphorylation	DTMAKRNTVIGTPFW HHHHHHCCCCCCCCC	19.96	22817900
246 (in isoform 2)	Phosphorylation	-	7.81	19144319
316	Phosphorylation	LEEEEENSDEDELDS HHHHHHCCCHHHHHH	45.73	27087446
323	Phosphorylation	SDEDELDSHTMVKTS CCHHHHHHCCEEEEC	33.22	25619855
325	Phosphorylation	EDELDSHTMVKTSSE HHHHHHCCEEEECCC	27.84	25619855
330	Phosphorylation	SHTMVKTSSESVGTM HCCEEEECCCCCCCE	26.79	28973931
336	Phosphorylation	TSSESVGTMRATSTM ECCCCCCCEEEEECC	11.00	25266776
369	Phosphorylation	LGTMVINSEEEEEEE HCCEEECCHHHHHHH	34.95	25338131
390	Phosphorylation	GTMKRNATSPQVQRP CCCCCCCCCCCCCCC	44.48	26824392
391	Phosphorylation	TMKRNATSPQVQRPS CCCCCCCCCCCCCCH	15.78	27087446
398	Phosphorylation	SPQVQRPSFMDYFDK CCCCCCCHHHHHCCH	35.08	25266776
402	Phosphorylation	QRPSFMDYFDKQDFK CCCHHHHHCCHHHHC	11.24	26745281
412	Phosphorylation	KQDFKNKSHENCDQS HHHHCCCCCCCCCHH	45.48	26643407
419	Phosphorylation	SHENCDQSMREPGPM CCCCCCHHHCCCCCC	13.42	26643407
450	Phosphorylation	FDFLKNLSLEELQMR CHHHHCCCHHHHHHH	43.03	26643407
477	Phosphorylation	EELHQRYSAKRQPIL HHHHHHHHHHHCHHH	29.51	25338131

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
117	T	Phosphorylation	Kinase	AKT1	P31750	Uniprot
390	T	Phosphorylation	Kinase	AKT1	P31750	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
117	T	Phosphorylation	Phosphorylation at Thr-117 and Thr-390 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	Phosphorylation at Thr-117 and Thr-390 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.	-
390	T	Phosphorylation	Phosphorylation at Thr-117 and Thr-390 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.

Oops, there are no SNP-PTM records of STK3_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MOB1A_HUMAN	MOB1A	physical	18328708

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"The phagosomal proteome in interferon-gamma-activated macrophages.";
Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,Thibault P.;
Immunity 30:143-154(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, AND MASSSPECTROMETRY.
PubMed: 19144319

"Solid tumor proteome and phosphoproteome analysis by high resolutionmass spectrometry.";
Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J.,Faessler R., Mann M.;
J. Proteome Res. 7:5314-5326(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, AND MASSSPECTROMETRY.
PubMed: 19367708