dbPTM

STK4_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	STK4_MOUSE
UniProt AC	Q9JI11
Protein Name	Serine/threonine-protein kinase 4
Gene Name	Stk4
Organism	Mus musculus (Mouse).
Sequence Length	487
Subcellular Localization	Cytoplasm. Nucleus. The caspase-cleaved form cycles between nucleus and cytoplasm..
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 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes (By similarity)..
Protein Sequence	METVQLRNPPRRQLKKLDEDSLTKQPEEVFDVLEKLGEGSYGSVYKAIHKETGQIVAIKQVPVESDLQEIIKEISIMQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDNFMDFVKQCLVKSPEQRATATQLLQHPFVKSAKGVSILRDLINEAMDVKLKRQEAQQREVDQDDEENSEEDEMDSGTMVRAAGDEMGTVRVASTMSGGANTMIEHGDTLPSQLGTMVINTEDEEEEGTMKRRDETMQPAKPSFLEYFEQKEKENQINSFGKNVSGSLKNSSDWKIPQDGDYEFLKSWTVEDLQKRLLALDPMMEQEMEEIRQKYRSKRQPILDAIEAKKRRQQNF

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------METVQLRN -------CCCCCCCC	9.82	-
3	Phosphorylation	-----METVQLRNPP -----CCCCCCCCCC	16.56	-
41	Phosphorylation	EKLGEGSYGSVYKAI HHHCCCCCHHHHHHH	25.03	24719451
43	Phosphorylation	LGEGSYGSVYKAIHK HCCCCCHHHHHHHHC	17.65	24719451
120	Phosphorylation	IIRLRNKTLTEDEIA HHHHHCCCCCHHHHH	42.32	-
175	Phosphorylation	FGVAGQLTDTMAKRN CCCCCHHHHHHHHHC	22.87	28066266
177	Phosphorylation	VAGQLTDTMAKRNTV CCCHHHHHHHHHCCC	17.50	26824392
183	Phosphorylation	DTMAKRNTVIGTPFW HHHHHHCCCCCCCCC	19.96	22817900
265	Phosphorylation	VKQCLVKSPEQRATA HHHHHCCCHHHHHHH	26.62	-
288	Phosphorylation	VKSAKGVSILRDLIN HHCCHHHHHHHHHHH	25.27	24719451
320	Phosphorylation	DQDDEENSEEDEMDS CCCCHHCCHHHHHCC	45.72	25521595
327	Phosphorylation	SEEDEMDSGTMVRAA CHHHHHCCCCEEECC	34.55	25619855
329	Phosphorylation	EDEMDSGTMVRAAGD HHHHCCCCEEECCCC	19.22	25619855
340	Phosphorylation	AAGDEMGTVRVASTM CCCCCCCCEEEEEEC	12.11	25521595
346	Phosphorylation	GTVRVASTMSGGANT CCEEEEEECCCCCCE	12.96	-
367	Phosphorylation	TLPSQLGTMVINTED CCCHHCCEEEEECCC	19.50	-
372	Phosphorylation	LGTMVINTEDEEEEG CCEEEEECCCCCCCC	33.42	21183079
380	Phosphorylation	EDEEEEGTMKRRDET CCCCCCCCCCCCHHH	23.85	22817900
387	Phosphorylation	TMKRRDETMQPAKPS CCCCCHHHCCCCCHH	25.95	22817900
410	Phosphorylation	EKENQINSFGKNVSG HHHHCCCCCCCCCCC	36.68	26824392
416	Phosphorylation	NSFGKNVSGSLKNSS CCCCCCCCCCCCCCC	31.87	28833060
418	Phosphorylation	FGKNVSGSLKNSSDW CCCCCCCCCCCCCCC	28.76	25521595
422	Phosphorylation	VSGSLKNSSDWKIPQ CCCCCCCCCCCCCCC	28.25	29176673
423	Phosphorylation	SGSLKNSSDWKIPQD CCCCCCCCCCCCCCC	57.81	29176673
433	Phosphorylation	KIPQDGDYEFLKSWT CCCCCCCCHHHHHCC	17.70	20438120
438	Phosphorylation	GDYEFLKSWTVEDLQ CCCHHHHHCCHHHHH	30.08	22817900
440	Phosphorylation	YEFLKSWTVEDLQKR CHHHHHCCHHHHHHH	22.55	18846507

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
177	T	Phosphorylation	Kinase	STK4	Q9JI11	PhosphoELM
183	T	Phosphorylation	Kinase	STK4	Q9JI11	GPS
327	S	Phosphorylation	Kinase	STK4	Q13043	GPS
387	T	Phosphorylation	Kinase	AKT1	P31750	Uniprot
387	T	Phosphorylation	Kinase	STK4	Q9JI11	PhosphoELM
433	Y	Phosphorylation	Kinase	SRC	P12931	PSP
438	S	Phosphorylation	Kinase	MTOR	P42345	PSP
438	S	Phosphorylation	Kinase	MTOR	Q9JLN9	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
183	T	Phosphorylation	-
Phosphorylation at Thr-387 by PKB/AKT1, leads to inhibition of its: kinase activity, nuclear translocation and autophosphorylation at Thr-183.
387	T	Phosphorylation	-
Phosphorylation at Thr-387 by PKB/AKT1, leads to inhibition of its: kinase activity, nuclear translocation and autophosphorylation at Thr-183.

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 STK4_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
Oops, there are no PPI records of STK4_MOUSE !!

Drug and Disease Associations

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

Regulatory Network of STK4_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Phosphoproteomic analysis of the developing mouse brain."; Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.; Mol. Cell. Proteomics 3:1093-1101(2004). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, AND MASSSPECTROMETRY.	15345747 [Abstract]
"Quantitative time-resolved phosphoproteomic analysis of mast cellsignaling."; Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,Kawakami T., Salomon A.R.; J. Immunol. 179:5864-5876(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-433, AND MASSSPECTROMETRY.	17947660 [Abstract]

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