dbPTM

KS6B1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KS6B1_HUMAN
UniProt AC	P23443
Protein Name	Ribosomal protein S6 kinase beta-1
Gene Name	RPS6KB1
Organism	Homo sapiens (Human).
Sequence Length	525
Subcellular Localization	Cell junction, synapse, synaptosome. Mitochondrion outer membrane. Mitochondrion. Colocalizes with URI1 at mitochondrion. Isoform Alpha I: Nucleus. Cytoplasm. Isoform Alpha II: Cytoplasm.
Protein Description	Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR. [PubMed: 11500364]
Protein Sequence	MRRRRRRDGFYPAPDFRDREAEDMAGVFDIDLDQPEDAGSEDELEEGGQLNESMDHGGVGPYELGMEHCEKFEISETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSGGELFMQLEREGIFMEDTACFYLAEISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLCKESIHDGTVTHTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKKTIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHPFFRHINWEELLARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTLSESANQVFLGFTYVAPSVLESVKEKFSFEPKIRSPRRFIGSPRTPVSPVKFSPGDFWGRGASASTANPQTPVEYPMETSGIEQMDVTMSGEASAPLPIRQPNSGPYKKQAFPMISKRPEHLRMNL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
11	Phosphorylation	RRRRDGFYPAPDFRD CCCCCCCCCCCCCCC	12.19	27642862
32	Ubiquitination	AGVFDIDLDQPEDAG CCCEECCCCCCCCCC	7.23	29967540
40	Phosphorylation	DQPEDAGSEDELEEG CCCCCCCCHHHHHHC	43.53	27251275
46	Ubiquitination	GSEDELEEGGQLNES CCHHHHHHCCCCCCC	79.74	-
46	Ubiquitination	GSEDELEEGGQLNES CCHHHHHHCCCCCCC	79.74	29967540
51	Ubiquitination	LEEGGQLNESMDHGG HHHCCCCCCCCCCCC	31.26	29967540
51	Ubiquitination	LEEGGQLNESMDHGG HHHCCCCCCCCCCCC	31.26	-
53	Phosphorylation	EGGQLNESMDHGGVG HCCCCCCCCCCCCCC	28.56	12023960
62	Ubiquitination	DHGGVGPYELGMEHC CCCCCCHHHHCHHHH	20.18	29967540
65	Ubiquitination	GVGPYELGMEHCEKF CCCHHHHCHHHHCEE	13.90	29967540
75	Phosphorylation	HCEKFEISETSVNRG HHCEEECCCCCCCCC	27.85	28555341
76	Ubiquitination	CEKFEISETSVNRGP HCEEECCCCCCCCCC	51.25	29967540
81	Ubiquitination	ISETSVNRGPEKIRP CCCCCCCCCCHHHCH	60.94	29967540
82	Ubiquitination	SETSVNRGPEKIRPE CCCCCCCCCHHHCHH	29.52	24816145
85	Ubiquitination	SVNRGPEKIRPECFE CCCCCCHHHCHHHHH	47.34	29967540
95	Ubiquitination	PECFELLRVLGKGGY HHHHHHHHHHCCCCC	33.95	29967540
99	Ubiquitination	ELLRVLGKGGYGKVF HHHHHHCCCCCCCEE	45.03	29967540
104	Ubiquitination	LGKGGYGKVFQVRKV HCCCCCCCEEEEEEE	31.24	29967540
112	Ubiquitination	VFQVRKVTGANTGKI EEEEEEECCCCCCHH	33.34	24816145
118	Ubiquitination	VTGANTGKIFAMKVL ECCCCCCHHHHHHHH	32.39	29967540
135	Ubiquitination	AMIVRNAKDTAHTKA HHHHHCCCHHHCCHH	60.19	24816145
137	Phosphorylation	IVRNAKDTAHTKAER HHHCCCHHHCCHHHH	21.45	22210691
235	Phosphorylation	HQGHVKLTDFGLCKE CCCCEEECCCCCCCC	24.46	26074081
243	Phosphorylation	DFGLCKESIHDGTVT CCCCCCCCCCCCCCE	15.66	22322096
248	Phosphorylation	KESIHDGTVTHTFCG CCCCCCCCCEEEECC	28.43	22322096
250	Phosphorylation	SIHDGTVTHTFCGTI CCCCCCCEEEECCEE	18.29	22322096
251	Acetylation	IHDGTVTHTFCGTIE CCCCCCEEEECCEEH	16.77	-
251	Acetylation	IHDGTVTHTFCGTIE CCCCCCEEEECCEEH	16.77	19608861
252	Phosphorylation	HDGTVTHTFCGTIEY CCCCCEEEECCEEHH	15.97	22322096
256	Phosphorylation	VTHTFCGTIEYMAPE CEEEECCEEHHHCHH	16.30	22322096
278	Phosphorylation	NRAVDWWSLGALMYD CCCCCHHHHHHHHHH	16.81	-
281	Acetylation	VDWWSLGALMYDMLT CCHHHHHHHHHHHHH	8.41	19608861
304	Acetylation	NRKKTIDKILKCKLN CHHHHHHHHHHCCCC	46.19	23749302
304	Malonylation	NRKKTIDKILKCKLN CHHHHHHHHHHCCCC	46.19	26320211
311	Ubiquitination	KILKCKLNLPPYLTQ HHHHCCCCCCHHCCH	35.68	29967540
317	Ubiquitination	LNLPPYLTQEARDLL CCCCHHCCHHHHHHH	20.65	29967540
341	Ubiquitination	SRLGAGPGDAGEVQA HHCCCCCCCHHHHCC	36.16	29967540
347	Ubiquitination	PGDAGEVQAHPFFRH CCCHHHHCCCHHHCC	29.65	29967540
355	Phosphorylation	AHPFFRHINWEELLA CCHHHCCCCHHHHHH	5.82	33259812
358	Phosphorylation	FFRHINWEELLARKV HHCCCCHHHHHHHHC	33.99	32645325
363	Phosphorylation	NWEELLARKVEPPFK CHHHHHHHHCCCCCH	43.45	32142685
364	Phosphorylation	WEELLARKVEPPFKP HHHHHHHHCCCCCHH	45.39	33259812
364	Ubiquitination	WEELLARKVEPPFKP HHHHHHHHCCCCCHH	45.39	29967540
367	Phosphorylation	LLARKVEPPFKPLLQ HHHHHCCCCCHHHCC	42.49	32645325
370	Phosphorylation	RKVEPPFKPLLQSEE HHCCCCCHHHCCCHH	40.30	33259812
370	Ubiquitination	RKVEPPFKPLLQSEE HHCCCCCHHHCCCHH	40.30	29967540
372	Phosphorylation	VEPPFKPLLQSEEDV CCCCCHHHCCCHHHH	7.57	32142685
372	Ubiquitination	VEPPFKPLLQSEEDV CCCCCHHHCCCHHHH	7.57	29967540
373	Phosphorylation	EPPFKPLLQSEEDVS CCCCHHHCCCHHHHH	7.75	32645325
378	Phosphorylation	PLLQSEEDVSQFDSK HHCCCHHHHHHCCHH	41.12	32142685
380	Phosphorylation	LQSEEDVSQFDSKFT CCCHHHHHHCCHHHC	37.13	28555341
387	Phosphorylation	SQFDSKFTRQTPVDS HHCCHHHCCCCCCCC	26.13	20068231
390	Phosphorylation	DSKFTRQTPVDSPDD CHHHCCCCCCCCCCC	23.22	27362937
391	Phosphorylation	SKFTRQTPVDSPDDS HHHCCCCCCCCCCCC	21.41	33259812
394	Phosphorylation	TRQTPVDSPDDSTLS CCCCCCCCCCCCCCC	30.38	20459645
397	Ubiquitination	TPVDSPDDSTLSESA CCCCCCCCCCCCHHH	47.08	-
398	Phosphorylation	PVDSPDDSTLSESAN CCCCCCCCCCCHHHH	38.33	20068231
399	Phosphorylation	VDSPDDSTLSESANQ CCCCCCCCCCHHHHH	41.10	20068231
401	Phosphorylation	SPDDSTLSESANQVF CCCCCCCCHHHHHHE	29.59	20068231
402	Ubiquitination	PDDSTLSESANQVFL CCCCCCCHHHHHHEE	57.91	29967540
403	Phosphorylation	DDSTLSESANQVFLG CCCCCCHHHHHHEEE	29.19	12023960
408	Phosphorylation	SESANQVFLGFTYVA CHHHHHHEEEEEEEC	3.88	33259812
411	Phosphorylation	ANQVFLGFTYVAPSV HHHHEEEEEEECHHH	4.91	32645325
412	Phosphorylation	NQVFLGFTYVAPSVL HHHEEEEEEECHHHH	18.45	19934253
413	Phosphorylation	QVFLGFTYVAPSVLE HHEEEEEEECHHHHH	7.73	20068231
416	Phosphorylation	LGFTYVAPSVLESVK EEEEEECHHHHHHHH	18.22	32142685
417	Phosphorylation	GFTYVAPSVLESVKE EEEEECHHHHHHHHH	29.60	20068231
421	Phosphorylation	VAPSVLESVKEKFSF ECHHHHHHHHHHCCC	34.04	33259812
424	Phosphorylation	SVLESVKEKFSFEPK HHHHHHHHHCCCCCC	58.12	32645325
425	Ubiquitination	VLESVKEKFSFEPKI HHHHHHHHCCCCCCC	40.36	29967540
427	Phosphorylation	ESVKEKFSFEPKIRS HHHHHHCCCCCCCCC	39.50	23401153
429	Phosphorylation	VKEKFSFEPKIRSPR HHHHCCCCCCCCCCC	44.48	32142685
434	Phosphorylation	SFEPKIRSPRRFIGS CCCCCCCCCCCCCCC	26.65	11914378
441	Phosphorylation	SPRRFIGSPRTPVSP CCCCCCCCCCCCCCC	13.34	22322096
441 (in isoform 4)	Phosphorylation	-	13.34	22210691
444	Phosphorylation	RFIGSPRTPVSPVKF CCCCCCCCCCCCCCC	31.27	22322096
447	Phosphorylation	GSPRTPVSPVKFSPG CCCCCCCCCCCCCCC	25.77	22322096
447 (in isoform 4)	Phosphorylation	-	25.77	22210691
448 (in isoform 4)	Phosphorylation	-	33.29	22210691
450	Ubiquitination	RTPVSPVKFSPGDFW CCCCCCCCCCCCCCC	43.43	-
452	Phosphorylation	PVSPVKFSPGDFWGR CCCCCCCCCCCCCCC	23.43	22322096
462	Phosphorylation	DFWGRGASASTANPQ CCCCCCCCCCCCCCC	26.10	-
470	Phosphorylation	ASTANPQTPVEYPME CCCCCCCCCCCCCCC	30.47	22817900
487	Phosphorylation	GIEQMDVTMSGEASA CCCEEEEEECCEECC	11.01	29759185
503	Phosphorylation	LPIRQPNSGPYKKQA CCCCCCCCCCCCCCC	48.07	28674419
506	Phosphorylation	RQPNSGPYKKQAFPM CCCCCCCCCCCCCCC	34.05	28985074
516	Acetylation	QAFPMISKRPEHLRM CCCCCCCCCHHHHCC	62.13	20599721
522	Methylation	SKRPEHLRMNL---- CCCHHHHCCCC----	17.53	115486225

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
53	S	Phosphorylation	Kinase	NEK6	Q9HC98	PSP
252	T	Phosphorylation	Kinase	PIK3CA	P42336	PSP
252	T	Phosphorylation	Kinase	PDK1	O15530	PSP
252	T	Phosphorylation	Kinase	PDK1	Q15118	GPS
390	T	Phosphorylation	Kinase	MTOR	P42345	PhosphoELM
394	S	Phosphorylation	Kinase	CDK1	P06493	PSP
394	S	Phosphorylation	Kinase	PDK1	O15530	PSP
394	S	Phosphorylation	Kinase	MTOR	Q9JLN9	PSP
394	S	Phosphorylation	Kinase	MTOR	P42345	PSP
403	S	Phosphorylation	Kinase	NEK6	Q9HC98	PSP
412	T	Phosphorylation	Kinase	P70-SUBFAMILY	-	GPS
412	T	Phosphorylation	Kinase	PIK3CA	P42336	PSP
412	T	Phosphorylation	Kinase	PDPK1	O15530	PhosphoELM
412	T	Phosphorylation	Kinase	PDK1	Q15118	GPS
412	T	Phosphorylation	Kinase	NEK7	Q8TDX7	Uniprot
412	T	Phosphorylation	Kinase	NEK6	Q9HC98	Uniprot
412	T	Phosphorylation	Kinase	MTOR	P42345	Uniprot
412	T	Phosphorylation	Kinase	RPS6KB1	P23443	GPS
427	S	Phosphorylation	Kinase	PDK1	Q15118	GPS
427	S	Phosphorylation	Kinase	PDPK1	O15530	PhosphoELM
434	S	Phosphorylation	Kinase	MAPK8	Q91Y86	GPS
434	S	Phosphorylation	Kinase	MAPK3	Q63844	GPS
434	S	Phosphorylation	Kinase	ERK2	P63085	PSP
434	S	Phosphorylation	Kinase	MAPK1	P28482	GPS
434	S	Phosphorylation	Kinase	MAPK9	Q9WTU6	GPS
434	S	Phosphorylation	Kinase	MTOR	P42345	PSP
434	S	Phosphorylation	Kinase	CDK1	P06493	PSP
444	T	Phosphorylation	Kinase	TBK1	Q9UHD2	PSP
444	T	Phosphorylation	Kinase	MAPK3	Q63844	GPS
444	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
444	T	Phosphorylation	Kinase	CDK1	P06493	PhosphoELM
447	S	Phosphorylation	Kinase	CDK1	P06493	PSP
447	S	Phosphorylation	Kinase	TBK1	Q9UHD2	PSP
447	S	Phosphorylation	Kinase	MAPK1	P28482	GPS
447	S	Phosphorylation	Kinase	MAPK3	Q63844	GPS
447	S	Phosphorylation	Kinase	MTOR	P42345	PhosphoELM
-	K	Ubiquitination	E3 ubiquitin ligase	RBX1	P62877	PMID:18279656

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
252	T	Phosphorylation	9445476
Activated by phosphorylation at Thr-252 by PDPK1.
412	T	Phosphorylation	9445476
Dephosphorylation by PPP1CC at Thr-412 in mitochondrion.
412	T	Phosphorylation	9445476
Phosphorylation at Thr-412 is regulated by mTORC1.

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 KS6B1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
AKT1_HUMAN	AKT1	physical	15149849
CSK2B_HUMAN	CSNK2B	physical	16895915
MTOR_HUMAN	MTOR	physical	15899889
MTOR_HUMAN	MTOR	physical	15905173
MTOR_HUMAN	MTOR	physical	12150926
2ABA_HUMAN	PPP2R2A	physical	10200280
TERT_HUMAN	TERT	physical	15843522
XPO1_HUMAN	XPO1	physical	16895915
EIF3B_HUMAN	EIF3B	physical	16286006
EIF3F_HUMAN	EIF3F	physical	16286006
EF2K_HUMAN	EEF2K	physical	11500364
RPTOR_HUMAN	RPTOR	physical	12150926
RPTOR_HUMAN	RPTOR	physical	12604610
PDIP3_HUMAN	POLDIP3	physical	15341740
XPO1_MOUSE	Xpo1	physical	16895915
RBX1_HUMAN	RBX1	physical	18279656
MDM2_HUMAN	MDM2	physical	20657550
EP300_HUMAN	EP300	physical	19961954
KAT2B_HUMAN	KAT2B	physical	19961954
DPPA4_HUMAN	DPPA4	physical	21900206
TETN_HUMAN	CLEC3B	physical	21900206
MAD1_HUMAN	MXD1	physical	18451027
EIF3H_HUMAN	EIF3H	physical	16286006
RS6_HUMAN	RPS6	physical	21460630
RS6_HUMAN	RPS6	physical	17693255
RPTOR_HUMAN	RPTOR	physical	16837165
PLD2_HUMAN	PLD2	physical	16837165
IRS1_HUMAN	IRS1	physical	23045529
A4_HUMAN	APP	physical	21832049
TAU_HUMAN	MAPT	physical	17512525
RMP_HUMAN	URI1	physical	21397856
TRIB2_HUMAN	TRIB2	physical	24089522
MK08_HUMAN	MAPK8	physical	23816567
RHEB_HUMAN	RHEB	physical	18550814
MTOR_HUMAN	MTOR	physical	15760907
NR1I2_HUMAN	NR1I2	physical	19171678
EIF3B_HUMAN	EIF3B	physical	24396066
EIF3F_HUMAN	EIF3F	physical	24396066
KS6B1_HUMAN	RPS6KB1	physical	24396066
TRAF4_HUMAN	TRAF4	physical	25738361
DPTOR_HUMAN	DEPTOR	physical	22017876
PI42A_HUMAN	PIP4K2A	physical	12747804
RIR2_HUMAN	RRM2	genetic	28319113
VHL_HUMAN	VHL	genetic	28319113
IRS1_HUMAN	IRS1	physical	18498745

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 KS6B1_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-304, AND MASS SPECTROMETRY.	19608861 [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-441; THR-444 ANDSER-447, AND MASS SPECTROMETRY.	19690332 [Abstract]
"Regulation and localization of ribosomal protein S6 kinase 1isoforms."; Kim D., Akcakanat A., Singh G., Sharma C., Meric-Bernstam F.; Growth Factors 27:12-21(2009). Cited for: FUNCTION, ALTERNATIVE SPLICING, PHOSPHORYLATION AT SER-394; THR-412;THR-444 AND SER-447, AND SUBCELLULAR LOCATION.	19085255 [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-441; THR-444 ANDSER-447, AND MASS SPECTROMETRY.	18669648 [Abstract]
"A probability-based approach for high-throughput proteinphosphorylation analysis and site localization."; Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; Nat. Biotechnol. 24:1285-1292(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447, AND MASSSPECTROMETRY.	16964243 [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-441; THR-444 ANDSER-447, AND MASS SPECTROMETRY.	17081983 [Abstract]
"Structural basis of human p70 ribosomal S6 kinase-1 regulation byactivation loop phosphorylation."; Sunami T., Byrne N., Diehl R.E., Funabashi K., Hall D.L., Ikuta M.,Patel S.B., Shipman J.M., Smith R.F., Takahashi I., Zugay-Murphy J.,Iwasawa Y., Lumb K.J., Munshi S.K., Sharma S.; J. Biol. Chem. 285:4587-4594(2010). Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 75-399, AND PHOSPHORYLATIONAT THR-252.	19864428 [Abstract]
"Phosphorylation and activation of p70s6k by PDK1."; Pullen N., Dennis P.B., Andjelkovic M., Dufner A., Kozma S.C.,Hemmings B.A., Thomas G.; Science 279:707-710(1998). Cited for: ENZYME REGULATION, PHOSPHORYLATION AT THR-252, AND MUTAGENESIS OFTHR-412; SER-434; SER-441; THR-444 AND SER-447.	9445476 [Abstract]

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