dbPTM

BRSK2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	BRSK2_HUMAN
UniProt AC	Q8IWQ3
Protein Name	Serine/threonine-protein kinase BRSK2
Gene Name	BRSK2
Organism	Homo sapiens (Human).
Sequence Length	736
Subcellular Localization	Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, perinuclear region. Endoplasmic reticulum. Detected at centrosomes during mitosis. Localizes to the endoplasmic reticulum in response to stress caused by tunicamycin.
Protein Description	Serine/threonine-protein kinase that plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion. Phosphorylates CDK16, CDC25C, MAPT/TAU, PAK1 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-529' and 'Ser-579'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in postmitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. Plays a role in the regulation of the mitotic cell cycle progress and the onset of mitosis. Plays a role in the regulation of insulin secretion in response to elevated glucose levels, probably via phosphorylation of CDK16 and PAK1. While BRSK2 phosphorylated at Thr-174 can inhibit insulin secretion. [PubMed: 22798068), BRSK2 phosphorylated at Thr-260 can promote insulin secretion]
Protein Sequence	MTSTGKDGGAQHAQYVGPYRLEKTLGKGQTGLVKLGVHCVTCQKVAIKIVNREKLSESVLMKVEREIAILKLIEHPHVLKLHDVYENKKYLYLVLEHVSGGELFDYLVKKGRLTPKEARKFFRQIISALDFCHSHSICHRDLKPENLLLDEKNNIRIADFGMASLQVGDSLLETSCGSPHYACPEVIRGEKYDGRKADVWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHFIPPDCQSLLRGMIEVDAARRLTLEHIQKHIWYIGGKNEPEPEQPIPRKVQIRSLPSLEDIDPDVLDSMHSLGCFRDRNKLLQDLLSEEENQEKMIYFLLLDRKERYPSQEDEDLPPRNEIDPPRKRVDSPMLNRHGKRRPERKSMEVLSVTDGGSPVPARRAIEMAQHGQRSRSISGASSGLSTSPLSSPRVTPHPSPRGSPLPTPKGTPVHTPKESPAGTPNPTPPSSPSVGGVPWRARLNSIKNSFLGSPRFHRRKLQVPTPEEMSNLTPESSPELAKKSWFGNFISLEKEEQIFVVIKDKPLSSIKADIVHAFLSIPSLSHSVISQTSFRAEYKATGGPAVFQKPVKFQVDITYTEGGEAQKENGIYSVTFTLLSGPSRRFKRVVETIQAQLLSTHDPPAAQHLSDTTNCMEMMTGRLSKCGSPLSNFFDVIKQLFSDEKNGQAAQAPSTPAKRSAHGPLGDSAAAGPGPGGDAEYPTGKDTAKMGPPTARREQP

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
8 (in isoform 5)	Phosphorylation	-	36.50	22210691
15	Phosphorylation	GGAQHAQYVGPYRLE CCCCCCEEECCEEEE	14.25	-
23	Sumoylation	VGPYRLEKTLGKGQT ECCEEEEEECCCCCC	54.35	-
48	Ubiquitination	TCQKVAIKIVNREKL ECCEEEEEECCHHHC	30.75	-
174	Phosphorylation	VGDSLLETSCGSPHY CCCHHHHCCCCCCCC	29.32	14976552
178	Phosphorylation	LLETSCGSPHYACPE HHHCCCCCCCCCCCH	16.90	-
245	Phosphorylation	FIPPDCQSLLRGMIE CCCHHHHHHHCCCHH	35.38	24719451
260	Phosphorylation	VDAARRLTLEHIQKH HHHHHHCCHHHHHHH	28.43	16870137
291	Phosphorylation	PRKVQIRSLPSLEDI CCCEEEECCCCHHHC	46.38	23607784
294	Phosphorylation	VQIRSLPSLEDIDPD EEEECCCCHHHCCHH	50.08	29507054
344	Phosphorylation	LLDRKERYPSQEDED CCCCHHHCCCCCCCC	14.34	29759185
346	Phosphorylation	DRKERYPSQEDEDLP CCHHHCCCCCCCCCC	36.95	29759185
367	Phosphorylation	PPRKRVDSPMLNRHG CCCCCCCCHHHCCCC	14.89	25159151
382	Phosphorylation	KRRPERKSMEVLSVT CCCCCCCCEEEEEEC	26.79	25159151
387	Phosphorylation	RKSMEVLSVTDGGSP CCCEEEEEECCCCCC	28.31	27732954
389	Phosphorylation	SMEVLSVTDGGSPVP CEEEEEECCCCCCCC	26.08	29255136
393	Phosphorylation	LSVTDGGSPVPARRA EEECCCCCCCCHHHH	28.40	29255136
409	Methylation	EMAQHGQRSRSISGA HHHHHCCCCCCCCCC	38.33	-
410	Phosphorylation	MAQHGQRSRSISGAS HHHHCCCCCCCCCCC	23.61	-
411	Methylation	AQHGQRSRSISGASS HHHCCCCCCCCCCCC	39.95	-
412	Phosphorylation	QHGQRSRSISGASSG HHCCCCCCCCCCCCC	23.50	29978859
414	Phosphorylation	GQRSRSISGASSGLS CCCCCCCCCCCCCCC	29.56	29978859
416 (in isoform 4)	Phosphorylation	-	8.17	25849741
417	Phosphorylation	SRSISGASSGLSTSP CCCCCCCCCCCCCCC	28.59	21406692
418	Phosphorylation	RSISGASSGLSTSPL CCCCCCCCCCCCCCC	43.13	21406692
421	Phosphorylation	SGASSGLSTSPLSSP CCCCCCCCCCCCCCC	30.29	29978859
422	Phosphorylation	GASSGLSTSPLSSPR CCCCCCCCCCCCCCC	39.13	19958286
423	Phosphorylation	ASSGLSTSPLSSPRV CCCCCCCCCCCCCCC	22.07	25159151
426	Phosphorylation	GLSTSPLSSPRVTPH CCCCCCCCCCCCCCC	41.50	29978859
427	Phosphorylation	LSTSPLSSPRVTPHP CCCCCCCCCCCCCCC	25.14	25159151
431	Phosphorylation	PLSSPRVTPHPSPRG CCCCCCCCCCCCCCC	19.70	20363803
435	Phosphorylation	PRVTPHPSPRGSPLP CCCCCCCCCCCCCCC	24.97	19369195
437	Methylation	VTPHPSPRGSPLPTP CCCCCCCCCCCCCCC	63.66	-
439	Phosphorylation	PHPSPRGSPLPTPKG CCCCCCCCCCCCCCC	25.25	20363803
443	Phosphorylation	PRGSPLPTPKGTPVH CCCCCCCCCCCCCCC	45.36	20363803
443 (in isoform 4)	Phosphorylation	-	45.36	25159151
444 (in isoform 4)	Phosphorylation	-	31.01	25159151
445 (in isoform 4)	Phosphorylation	-	77.29	25159151
447	Phosphorylation	PLPTPKGTPVHTPKE CCCCCCCCCCCCCCC	28.41	27732954
451	Phosphorylation	PKGTPVHTPKESPAG CCCCCCCCCCCCCCC	35.97	28985074
455	Phosphorylation	PVHTPKESPAGTPNP CCCCCCCCCCCCCCC	26.61	27732954
459	Phosphorylation	PKESPAGTPNPTPPS CCCCCCCCCCCCCCC	23.23	27251275
463	Phosphorylation	PAGTPNPTPPSSPSV CCCCCCCCCCCCCCC	55.24	28985074
466	Phosphorylation	TPNPTPPSSPSVGGV CCCCCCCCCCCCCCC	56.96	27732954
467	Phosphorylation	PNPTPPSSPSVGGVP CCCCCCCCCCCCCCC	27.28	27050516
469	Phosphorylation	PTPPSSPSVGGVPWR CCCCCCCCCCCCCHH	35.03	27732954
481	Phosphorylation	PWRARLNSIKNSFLG CHHHHHHHHHHHCCC	39.26	28464451
485	Phosphorylation	RLNSIKNSFLGSPRF HHHHHHHHCCCCCCH	19.49	29396449
489	Phosphorylation	IKNSFLGSPRFHRRK HHHHCCCCCCHHCCC	18.30	22167270
501	Phosphorylation	RRKLQVPTPEEMSNL CCCCCCCCHHHHHCC	44.46	27732954
506	Phosphorylation	VPTPEEMSNLTPESS CCCHHHHHCCCCCCC	31.78	20363803
509	Phosphorylation	PEEMSNLTPESSPEL HHHHHCCCCCCCHHH	29.30	25159151
512	Phosphorylation	MSNLTPESSPELAKK HHCCCCCCCHHHHHH	53.01	25159151
513	Phosphorylation	SNLTPESSPELAKKS HCCCCCCCHHHHHHH	22.26	25159151
520	O-linked_Glycosylation	SPELAKKSWFGNFIS CHHHHHHHCCCCCCC	27.25	30379171
520	Phosphorylation	SPELAKKSWFGNFIS CHHHHHHHCCCCCCC	27.25	29507054
544	Phosphorylation	VIKDKPLSSIKADIV EECCCCHHHCCHHHH	38.25	24719451
608	Phosphorylation	AQKENGIYSVTFTLL HEHHCCEEEEEEEEE	9.85	28509920
609	Phosphorylation	QKENGIYSVTFTLLS EHHCCEEEEEEEEEC	16.86	28509920
611	Phosphorylation	ENGIYSVTFTLLSGP HCCEEEEEEEEECCC	12.64	28509920
613 (in isoform 6)	Phosphorylation	-	19.88	28985074
613	Phosphorylation	GIYSVTFTLLSGPSR CEEEEEEEEECCCCH	19.88	28509920
664	Phosphorylation	GRLSKCGSPLSNFFD CCHHHCCCCHHHHHH	31.94	27050516
673 (in isoform 2)	Phosphorylation	-	2.24	28985074
690	Phosphorylation	GQAAQAPSTPAKRSA CCCCCCCCCCCCCCC	50.46	30631047
695 (in isoform 4)	Phosphorylation	-	40.98	28985074

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
174	T	Phosphorylation	Kinase	STK11	Q15831	PhosphoELM
260	T	Phosphorylation	Kinase	PRKACA	P17612	GPS
260	T	Phosphorylation	Kinase	PKA	-	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
174	T	Phosphorylation	14976552
May be inactivated via dephosphorylation of Thr-174 by PP2C.
174	T	Phosphorylation	14976552
Not phosphorylated at Thr-174 by CaMKK2.
174	T	Phosphorylation	14976552
Phosphorylated at Thr-174 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39.
260	T	Phosphorylation	16870137
Phosphorylated at Thr-260 by PKA.
260	T	Phosphorylation	16870137
Phosphorylation at Thr-260 by PKA was not observed in another study.
260	T	Phosphorylation	16870137
Phosphorylation at Thr-260 seems to play a role in the regulation of insulin secretion.

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 BRSK2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
WEE1_HUMAN	WEE1	physical	15150265
MPIP2_HUMAN	CDC25B	physical	15150265
MPIP3_HUMAN	CDC25C	physical	15150265
TERA_HUMAN	VCP	physical	23907667
CSN5_HUMAN	COPS5	physical	22609399

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 BRSK2_HUMAN

Related Literatures of Post-Translational Modification

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-382; SER-393; SER-412AND THR-509, AND MASS SPECTROMETRY.	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-294; SER-367; SER-382;THR-389; SER-393; THR-422; SER-423; SER-427; SER-435 AND SER-466,PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416 (ISOFORM 4), ANDMASS SPECTROMETRY.	19369195 [Abstract]
"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382; SER-393 ANDSER-423, AND MASS SPECTROMETRY.	19413330 [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-489, AND MASSSPECTROMETRY.	18669648 [Abstract]
"Investigating the regulation of brain-specific kinases 1 and 2 byphosphorylation."; Bright N.J., Carling D., Thornton C.; J. Biol. Chem. 283:14946-14954(2008). Cited for: PHOSPHORYLATION AT THR-174, AND MUTAGENESIS OF THR-174 AND GLY-310.	18339622 [Abstract]
"LKB1 is a master kinase that activates 13 kinases of the AMPKsubfamily, including MARK/PAR-1."; Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A.,Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G.,Alessi D.R.; EMBO J. 23:833-843(2004). Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-174, ANDMUTAGENESIS OF THR-174.	14976552 [Abstract]

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