STK11_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: STK11_HUMAN
• UniProt AC: Q15831
• Protein Name: Serine/threonine-protein kinase STK11
• Gene Name: STK11
• Organism: Homo sapiens (Human).
• Sequence Length: 433
• Subcellular Localization: Nucleus. Cytoplasm. Membrane. Mitochondrion. A small fraction localizes at membranes (By similarity). Relocates to the cytoplasm when bound to STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta). Translocates to the mitochond
• Protein Description: Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. In vein endothelial cells, inhibits PI3K/Akt signaling activity and thus induces apoptosis in response to the oxidant peroxynitrite (in vitro). Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair. [PubMed: 25329316; Isoform 2: Has a role in spermiogenesis.]
• Protein Sequence: MEVVDPQQLGMFTEGELMSVGMDTFIHRIDSTEVIYQPRRKRAKLIGKYLMGDLLGEGSYGKVKEVLDSETLCRRAVKILKKKKLRRIPNGEANVKKEIQLLRRLRHKNVIQLVDVLYNEEKQKMYMVMEYCVCGMQEMLDSVPEKRFPVCQAHGYFCQLIDGLEYLHSQGIVHKDIKPGNLLLTTGGTLKISDLGVAEALHPFAADDTCRTSQGSPAFQPPEIANGLDTFSGFKVDIWSAGVTLYNITTGLYPFEGDNIYKLFENIGKGSYAIPGDCGPPLSDLLKGMLEYEPAKRFSIRQIRQHSWFRKKHPPAEAPVPIPPSPDTKDRWRSMTVVPYLEDLHGADEDEDLFDIEDDIIYTQDFTVPGQVPEEEASHNGQRRGLPKAVCMNGTEAAQLSTKSRAEGRAPNPARKACSASSKIRRLSACKQQ

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
24	Phosphorylation	LMSVGMDTFIHRIDS HHEECCCCEEECCCC	18.65	29759185
31	Phosphorylation	TFIHRIDSTEVIYQP CEEECCCCCCCCCCC	24.89	29255136
32	Phosphorylation	FIHRIDSTEVIYQPR EEECCCCCCCCCCCC	30.44	19664994
36	Phosphorylation	IDSTEVIYQPRRKRA CCCCCCCCCCCHHHH	20.03	23927012
44	Acetylation	QPRRKRAKLIGKYLM CCCHHHHHHHHHHHH	44.67	18687677
48	Acetylation	KRAKLIGKYLMGDLL HHHHHHHHHHHHHHH	28.37	18687677
64	Acetylation	EGSYGKVKEVLDSET CCCCCHHHHHCCHHH	45.66	113429603
69	Phosphorylation	KVKEVLDSETLCRRA HHHHHCCHHHHHHHH	28.46	30631047
71	Phosphorylation	KEVLDSETLCRRAVK HHHCCHHHHHHHHHH	34.80	30631047
96	Acetylation	PNGEANVKKEIQLLR CCCCCCHHHHHHHHH	44.49	18687677
97	Acetylation	NGEANVKKEIQLLRR CCCCCHHHHHHHHHH	56.62	18687677
126	Phosphorylation	NEEKQKMYMVMEYCV CHHHHHHHHHHHHHH	8.13	30257219
178	Sumoylation	GIVHKDIKPGNLLLT CCCCCCCCCCCEEEE	57.94	-
178	Sumoylation	GIVHKDIKPGNLLLT CCCCCCCCCCCEEEE	57.94	-
185	Phosphorylation	KPGNLLLTTGGTLKI CCCCEEEECCCEEEE	24.30	22817900
189	Phosphorylation	LLLTTGGTLKISDLG EEEECCCEEEECHHC	26.65	11430832
216	Phosphorylation	TCRTSQGSPAFQPPE CCCCCCCCCCCCCHH	12.86	27050516
240	Phosphorylation	GFKVDIWSAGVTLYN CCEEEEECCCEEEEE	18.58	-
296	Acetylation	MLEYEPAKRFSIRQI HHHCCCCCCCCHHHH	65.77	18687677
299	Phosphorylation	YEPAKRFSIRQIRQH CCCCCCCCHHHHHHC	22.39	29496963
307	Phosphorylation	IRQIRQHSWFRKKHP HHHHHHCHHHHCCCC	21.41	19414597
311	Acetylation	RQHSWFRKKHPPAEA HHCHHHHCCCCCCCC	46.06	18687677
325	Phosphorylation	APVPIPPSPDTKDRW CCCCCCCCCCCHHHH	30.01	27050516
334	Phosphorylation	DTKDRWRSMTVVPYL CCHHHHHHCCHHHHH	16.31	-
336	Phosphorylation	KDRWRSMTVVPYLED HHHHHHCCHHHHHHH	21.43	22817900
363	Phosphorylation	IEDDIIYTQDFTVPG CCCCEEEECCCCCCC	15.97	12234250
399 (in isoform 2)	Phosphorylation	-	42.89	23612973
401	Phosphorylation	GTEAAQLSTKSRAEG CHHHHHHHHHHCCCC	23.00	23186163
402	Phosphorylation	TEAAQLSTKSRAEGR HHHHHHHHHHCCCCC	41.45	22817900
404	Phosphorylation	AAQLSTKSRAEGRAP HHHHHHHHCCCCCCC	36.49	24719451
416	Acetylation	RAPNPARKACSASSK CCCCHHHHHHHHHHH	56.71	18687677
418	S-palmitoylation	PNPARKACSASSKIR CCHHHHHHHHHHHHH	3.81	-
423	Acetylation	KACSASSKIRRLSAC HHHHHHHHHHHHHHH	37.42	18687677
428	Phosphorylation	SSKIRRLSACKQQ-- HHHHHHHHHHHCC--	29.79	18715874
430	Methylation	KIRRLSACKQQ---- HHHHHHHHHCC----	3.53	-
430	Farnesylation	KIRRLSACKQQ---- HHHHHHHHHCC----	3.53	-
431	Acetylation	IRRLSACKQQ----- HHHHHHHHCC-----	51.99	18687677

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
185	T	Phosphorylation	Kinase	STK11	Q15831	GPS
189	T	Phosphorylation	Kinase	STK11	Q15831	PhosphoELM
307	S	Phosphorylation	Kinase	PRKCZ	Q05513	GPS
336	T	Phosphorylation	Kinase	STK11	Q15831	GPS
363	T	Phosphorylation	Kinase	ATM	Q13315	Uniprot
363	T	Phosphorylation	Kinase	STK11	Q15831	GPS
399	S	Phosphorylation	Kinase	PRKCZ	Q05513	GPS
402	T	Phosphorylation	Kinase	STK11	Q15831	GPS
428	S	Phosphorylation	Kinase	PKCZ	Q05513	PSP
428	S	Phosphorylation	Kinase	RPS6KA1	Q15418	Uniprot
428	S	Phosphorylation	Kinase	STK11	Q15831	GPS
428	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
428	S	Phosphorylation	Kinase	RSK-SUBFAMILY	-	GPS
428	S	Phosphorylation	Kinase	PKA	-	Uniprot
428	S	Phosphorylation	Kinase	RSK_GROUP	-	PhosphoELM
-	K	Ubiquitination	E3 ubiquitin ligase	STUB1	Q9UNE7	PMID:21860411
-	K	Ubiquitination	E3 ubiquitin ligase	SKP2	Q13309	PMID:25728766:30250874:32296023

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
48	K	Acetylation	Deacetylation at Lys-48 enhances cytoplasmic localization and kinase activity in vitro.	18687677
363	T	Phosphorylation	Phosphorylated by ATM at Thr-363 following ionizing radiation (IR).	12805220
363	T	Phosphorylation	UV radiation-induced phosphorylation at Thr-363 mediates CDKN1A degradation (By similarity).	12805220
399	S	Phosphorylation	Phosphorylation by PKC/PRKCZ at Ser-399 in isoform 2 promotes metformin (or peroxynitrite)-induced nuclear export of STK11 and activation of AMPK.	23612973
428	S	Phosphorylation	Phosphorylation at Ser-428 by RPS6KA1 and/or some PKA is required to inhibit cell growth.	18854309
428	S	Phosphorylation	Phosphorylation at Ser-428 is also required during neuronal polarization to mediate phosphorylation of BRSK1 and BRSK2 (By similarity).	18854309
428	S	Phosphorylation	Phosphorylation by PKC/PRKCZ at Ser-428 promotes peroxynitrite-induced nuclear export of STK11, leading to PTEN activation and subsequent inhibition of AKT signaling.	18854309

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of STK11_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CAB39_HUMAN	CAB39	physical	15561763
STRAA_HUMAN	STRADA	physical	15561763
STRAA_HUMAN	STRADA	physical	12805220
SMCA4_HUMAN	SMARCA4	physical	11445556
CAB39_HUMAN	CAB39	physical	20562859
STRAA_HUMAN	STRADA	physical	20562859
FKBP5_HUMAN	FKBP5	physical	20562859
STRAB_HUMAN	STRADB	physical	20562859
CB39L_HUMAN	CAB39L	physical	20562859
CDC37_HUMAN	CDC37	physical	20562859
HS90A_HUMAN	HSP90AA1	physical	14668798
CDC37_HUMAN	CDC37	physical	14668798
STRAB_HUMAN	STRADB	physical	14676191
MARK4_HUMAN	MARK4	physical	14676191
CAB39_HUMAN	CAB39	physical	14676191
HS90A_HUMAN	HSP90AA1	physical	14676191
STRAA_HUMAN	STRADA	physical	14676191
CDC37_HUMAN	CDC37	physical	14676191
FKBP5_HUMAN	FKBP5	physical	14676191
RPAP3_HUMAN	RPAP3	physical	14676191
UBP11_HUMAN	USP11	physical	14676191
LIMS1_HUMAN	LIMS1	physical	14676191
KIF23_HUMAN	KIF23	physical	14676191
SMRC1_HUMAN	SMARCC1	physical	14676191
SMCA4_HUMAN	SMARCA4	physical	14676191
GSK3B_HUMAN	GSK3B	physical	22270359
MARK2_HUMAN	MARK2	physical	16396636
SIK1_HUMAN	SIK1	physical	16396636
HS90A_HUMAN	HSP90AA1	physical	21860411
CDC37_HUMAN	CDC37	physical	21860411
STRAA_HUMAN	STRADA	physical	21860411
CHIP_HUMAN	STUB1	physical	21860411
TNIP2_HUMAN	TNIP2	physical	12595760
TNIP2_HUMAN	TNIP2	physical	12753905
A4_HUMAN	APP	physical	21832049
SNRK_HUMAN	SNRK	physical	15733851
AP2M1_HUMAN	AP2M1	physical	20368287
EI2BA_MOUSE	Eif2b1	physical	20368287
EI2BA_HUMAN	EIF2B1	physical	20368287
AP2M1_MOUSE	Ap2m1	physical	20368287
SIR1_HUMAN	SIRT1	physical	18687677
ETV4_HUMAN	ETV4	physical	16912160
AAPK1_HUMAN	PRKAA1	physical	16912160
SPDEF_HUMAN	SPDEF	physical	16912160
CAB39_HUMAN	CAB39	physical	25852190
CC136_HUMAN	CCDC136	physical	25852190
CSN3_HUMAN	COPS3	physical	25852190
CSN4_HUMAN	COPS4	physical	25852190
FKBP5_HUMAN	FKBP5	physical	25852190
H2AX_HUMAN	H2AFX	physical	25852190
STRAA_HUMAN	STRADA	physical	25852190
WDR6_HUMAN	WDR6	physical	17216128
BCAS3_HUMAN	BCAS3	physical	25640309
CP17A_HUMAN	CYP17A1	physical	25640309
KLK7_HUMAN	KLK7	physical	25640309
LYPD3_HUMAN	LYPD3	physical	25640309
ARY2_HUMAN	NAT2	physical	25640309
RHBT2_HUMAN	RHOBTB2	physical	25640309
S10AE_HUMAN	S100A14	physical	25640309
SPB5_HUMAN	SERPINB5	physical	25640309
ST14_HUMAN	ST14	physical	25640309
THRSP_HUMAN	THRSP	physical	25640309
TRI25_HUMAN	TRIM25	physical	25640309
TSP50_HUMAN	PRSS50	physical	25640309
PAQR1_HUMAN	ADIPOR1	physical	25640309
ARGI2_HUMAN	ARG2	physical	25640309
COF2_HUMAN	CFL2	physical	25640309
CRY2_HUMAN	CRY2	physical	25640309
CATB_HUMAN	CTSB	physical	25640309
D2HDH_HUMAN	D2HGDH	physical	25640309
EF1A2_HUMAN	EEF1A2	physical	25640309
ERLEC_HUMAN	ERLEC1	physical	25640309
LFG2_HUMAN	FAIM2	physical	25640309
GNPI1_HUMAN	GNPDA1	physical	25640309
NU2M_HUMAN	ND2	physical	25640309
MOC2B_HUMAN	MOCS2	physical	25640309
MOC2A_HUMAN	MOCS2	physical	25640309
PLPP_HUMAN	PDXP	physical	25640309
PHF23_HUMAN	PHF23	physical	25640309
PLD3_HUMAN	PLD3	physical	25640309
SEPT9_HUMAN	SEPT9	physical	25640309
STK24_HUMAN	STK24	physical	25640309
THOP1_HUMAN	THOP1	physical	25640309
TS101_HUMAN	TSG101	physical	25640309
TBA1A_HUMAN	TUBA1A	physical	25640309
TBB4A_HUMAN	TUBB4A	physical	25640309
VPS72_HUMAN	VPS72	physical	25640309
CAB39_HUMAN	CAB39	physical	25241761
KS6B1_HUMAN	RPS6KB1	physical	25241761
STRAA_HUMAN	STRADA	physical	25241761
AAPK2_HUMAN	PRKAA2	physical	25241761
SIR1_HUMAN	SIRT1	physical	27259994
HERC2_HUMAN	HERC2	physical	27259994
STRAA_HUMAN	STRADA	physical	28514442
KDM4A_HUMAN	KDM4A	physical	28514442
CAB39_HUMAN	CAB39	physical	28514442
FKBP5_HUMAN	FKBP5	physical	28514442
HS90A_HUMAN	HSP90AA1	physical	28514442
HS90B_HUMAN	HSP90AB1	physical	28514442
ABRX2_HUMAN	FAM175B	physical	28514442
DVL2_HUMAN	DVL2	physical	28514442
IVD_HUMAN	IVD	physical	28514442

Drug and Disease Associations

• Kegg Disease
• H00019: Pancreatic cancer
• H00666: Peutz-Jeghers syndrome
• OMIM Disease
• 175200: Peutz-Jeghers syndrome (PJS)
• 273300: Testicular germ cell tumor (TGCT)
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"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-31, AND MASSSPECTROMETRY.
PubMed: 19690332

"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-31, AND MASSSPECTROMETRY.
PubMed: 19369195

"Characterization of an alternative splice variant of LKB1.";
Denison F.C., Hiscock N.J., Carling D., Woods A.;
J. Biol. Chem. 284:67-76(2009).
Cited for: ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION,PHOSPHORYLATION AT SER-428, AND MUTAGENESIS OF SER-428.
PubMed: 18854309

"Activation of the tumour suppressor kinase LKB1 by the STE20-likepseudokinase STRAD.";
Baas A.F., Boudeau J., Sapkota G.P., Smit L., Medema R., Morrice N.A.,Alessi D.R., Clevers H.C.;
EMBO J. 22:3062-3072(2003).
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STRADA,AUTOPHOSPHORYLATION AT THR-336 AND THR-363, AND CHARACTERIZATION OFVARIANT SPORADIC CANCER TYR-176.
PubMed: 12805220

"The Peutz-Jegher gene product LKB1 is a mediator of p53-dependentcell death.";
Karuman P., Gozani O., Odze R.D., Zhou X.C., Zhu H., Shaw R.,Brien T.P., Bozzuto C.D., Ooi D., Cantley L.C., Yuan J.;
Mol. Cell 7:1307-1319(2001).
Cited for: SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, FUNCTION, MUTAGENESIS OFLYS-78 AND THR-189, AND PHOSPHORYLATION AT THR-189.
PubMed: 11430832