KS6A3_MOUSE - dbPTM
KS6A3_MOUSE - PTM Information in dbPTM
Basic Information of Protein
UniProt ID KS6A3_MOUSE
UniProt AC P18654
Protein Name Ribosomal protein S6 kinase alpha-3
Gene Name Rps6ka3
Organism Mus musculus (Mouse).
Sequence Length 740
Subcellular Localization Nucleus. Cytoplasm.
Protein Description Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1. Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation. [PubMed: 22827337 Phosphorylates EPHA2 at 'Ser-897',the RPS6KA-EPHA2 signaling pathway controls cell migration (By similarity]
Protein Sequence MPLAQLADPWQKMAVESPSDSAENGQQIMDEPMGEEEINPQTEEGSIKEIAITHHVKEGHEKADPSQFELLKVLGQGSFGKVFLVKKISGSDARQLYAMKVLKKATLKVRDRVRTKMERDILVEVNHPFIVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKESIDHEKKAYSFCGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGTLPFQGKDRKETMTMILKAKLGMPQFLSPEAQSLLRMLFKRNPANRLGAGPDGVEEIKRHSFFSTIDWNKLYRREIHPPFKPATGRPEDTFYFDPEFTAKTPKDSPGIPPSANAHQLFRGFSFVAITSDDESQAMQTVGVHSIVQQLHRNSIQFTDGYEVKEDIGVGSYSVCKRCIHKATNMEFAVKIIDKSKRDPTEEIEILLRYGQHPNIITLKDVYDDGKYVYVVTELMKGGELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYVDESGNPESIRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDAACDIWSLGVLLYTMLTGYTPFANGPDDTPEEILARIGSGKFSLSGGYWNSVSDTAKDLVSKMLHVDPHQRLTAALVLRHPWIVHWDQLPQYQLNRQDAPHLVKGAMAATYSALNRNQSPVLEPVGRSTLAQRRGIKKITSTAL
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 Orthologous
Protein Cluster
17PhosphorylationWQKMAVESPSDSAEN
HHHHCCCCCCCCHHH		24.0927087446
19PhosphorylationKMAVESPSDSAENGQ
HHCCCCCCCCHHHCC		54.1827087446
21PhosphorylationAVESPSDSAENGQQI
CCCCCCCCHHHCCCC		41.6525777480
42PhosphorylationEEEINPQTEEGSIKE
CCCCCCCCCCCCEEE		36.9425777480
46PhosphorylationNPQTEEGSIKEIAIT
CCCCCCCCEEEEEEE		33.4925777480
53PhosphorylationSIKEIAITHHVKEGH
CEEEEEEEEEHHCCC		9.2622871156
78PhosphorylationLKVLGQGSFGKVFLV
HHHHCCCCCCEEEEE		23.9625338131
192MethylationHSLGIIYRDLKPENI
HHCCCEECCCCHHHE		32.1730989265
215PhosphorylationKLTDFGLSKESIDHE
EECCCCCCHHHCCCC		34.4523737553
226PhosphorylationIDHEKKAYSFCGTVE
CCCCHHHHHCCCCHH		15.9122322096
227PhosphorylationDHEKKAYSFCGTVEY
CCCHHHHHCCCCHHH		20.9422322096
231PhosphorylationKAYSFCGTVEYMAPE
HHHHCCCCHHHHCHH		16.0222322096
234PhosphorylationSFCGTVEYMAPEVVN
HCCCCHHHHCHHHHC		8.3422322096
248PhosphorylationNRRGHTQSADWWSFG
CCCCCCCCCCHHHHH		29.3821183079
274UbiquitinationPFQGKDRKETMTMIL
CCCCCCHHHHHHHHH		68.61-
282UbiquitinationETMTMILKAKLGMPQ
HHHHHHHHHHHCCCC		32.33-
284AcetylationMTMILKAKLGMPQFL
HHHHHHHHHCCCCCC		43.9419854261
325PhosphorylationVEEIKRHSFFSTIDW
HHHHHHHCCCCCCCH		31.8322817900
328PhosphorylationIKRHSFFSTIDWNKL
HHHHCCCCCCCHHHH		23.5721183079
348PhosphorylationHPPFKPATGRPEDTF
CCCCCCCCCCCCCCE		42.1023684622
354PhosphorylationATGRPEDTFYFDPEF
CCCCCCCCEECCHHH		20.6926060331
356PhosphorylationGRPEDTFYFDPEFTA
CCCCCCEECCHHHCC		14.7925367039
362PhosphorylationFYFDPEFTAKTPKDS
EECCHHHCCCCCCCC		26.1125367039
365PhosphorylationDPEFTAKTPKDSPGI
CHHHCCCCCCCCCCC		32.8627087446
369PhosphorylationTAKTPKDSPGIPPSA
CCCCCCCCCCCCCCC		31.0227087446
375PhosphorylationDSPGIPPSANAHQLF
CCCCCCCCCCHHHHH		28.8827087446
386PhosphorylationHQLFRGFSFVAITSD
HHHHCCCEEEEEECC		22.9522322096
391PhosphorylationGFSFVAITSDDESQA
CCEEEEEECCCHHHH		19.1623984901
392PhosphorylationFSFVAITSDDESQAM
CEEEEEECCCHHHHH		36.6326745281
396PhosphorylationAITSDDESQAMQTVG
EEECCCHHHHHHHHC		30.1823984901
401PhosphorylationDESQAMQTVGVHSIV
CHHHHHHHHCHHHHH		13.2223984901
406PhosphorylationMQTVGVHSIVQQLHR
HHHHCHHHHHHHHHH		23.2723984901
415PhosphorylationVQQLHRNSIQFTDGY
HHHHHHCCCCCCCCC		20.0925521595
419PhosphorylationHRNSIQFTDGYEVKE
HHCCCCCCCCCEECC		16.4928464351
470PhosphorylationEIEILLRYGQHPNII
HHHHHHHHCCCCCEE		22.5521454597
478PhosphorylationGQHPNIITLKDVYDD
CCCCCEEEEEEECCC		24.7721454597
483PhosphorylationIITLKDVYDDGKYVY
EEEEEEECCCCCEEE		20.60-
488PhosphorylationDVYDDGKYVYVVTEL
EECCCCCEEEEEEEC		11.53-
490PhosphorylationYDDGKYVYVVTELMK
CCCCCEEEEEEECHH		6.01-
529PhosphorylationTITKTVEYLHAQGVV
EHHHHHHHHHHCCCC		10.2317785202
556PhosphorylationDESGNPESIRICDFG
CCCCCCCCEEECCHH		20.58-
566UbiquitinationICDFGFAKQLRAENG
ECCHHHHHHHHHHCC		47.83-
577PhosphorylationAENGLLMTPCYTANF
HHCCCEECCCEECCC		15.3526824392
580PhosphorylationGLLMTPCYTANFVAP
CCEECCCEECCCCCH		15.3025266776
581PhosphorylationLLMTPCYTANFVAPE
CEECCCEECCCCCHH		23.1125777480
688PhosphorylationHWDQLPQYQLNRQDA
CHHHCCHHCCCCCCC		17.0229514104
706PhosphorylationVKGAMAATYSALNRN
HHHHHHHHHHHHHCC		14.4229176673
707PhosphorylationKGAMAATYSALNRNQ
HHHHHHHHHHHHCCC		6.2929514104
708PhosphorylationGAMAATYSALNRNQS
HHHHHHHHHHHCCCC		23.1729176673
715PhosphorylationSALNRNQSPVLEPVG
HHHHCCCCCCCCCCC		22.1126824392
724PhosphorylationVLEPVGRSTLAQRRG
CCCCCCHHHHHHHHC		23.1129514104
737PhosphorylationRGIKKITSTAL----
HCCCHHHHCCC----		18.3718779572
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
227SPhosphorylationKinaseMAPKAPK2P49137
PSP
227SPhosphorylationKinaseMAPK1P28482
GPS
227SPhosphorylationKinasePDK1O15530
PSP
227SPhosphorylationKinasePDK1Q9Z2A0
PSP
369SPhosphorylationKinasePDPK1Q9Z2A0
GPS
386SPhosphorylationKinaseRPS6KA3P18654
GPS
386SPhosphorylationKinaseMAPKAPK2P49137
PSP
386SPhosphorylationKinaseMAPKAPK2P49138
Uniprot
386SPhosphorylationKinaseMAPK1P28482
GPS
386SPhosphorylationKinaseMAPK3Q63844
GPS
386SPhosphorylationKinasePDK1O15530
PSP
386SPhosphorylationKinasePDPK1Q9Z2A0
GPS
529YPhosphorylationKinaseFGFR3Q61851
Uniprot
577TPhosphorylationKinaseMAPK1P28482
GPS
577TPhosphorylationKinasePDK1O15530
PSP
577TPhosphorylationKinasePDPK1Q9Z2A0
PhosphoELM
Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference
227SPhosphorylation

10480933
365TPhosphorylation

21183079
369SPhosphorylation

21183079
386SPhosphorylation

10480933
386SPhosphorylation

10480933
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 KS6A3_MOUSE !!
Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
MK03_HUMANMAPK3physical
12832467
MK01_HUMANMAPK1physical
12832467
FBX5_MOUSEFbxo5physical
15526037
Drug and Disease Associations
Kegg Drug
DrugBank
There are no disease associations of PTM sites.
Regulatory Network of KS6A3_MOUSE

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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"The MAPK-activated kinase Rsk controls an acute Toll-like receptorsignaling response in dendritic cells and is activated through twodistinct pathways.";
Zaru R., Ronkina N., Gaestel M., Arthur J.S., Watts C.;
Nat. Immunol. 8:1227-1235(2007).
Cited for: FUNCTION IN TOLL-LIKE RECEPTOR SIGNALING, AND PHOSPHORYLATION ATSER-386.
"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 THR-365 AND SER-369, ANDMASS SPECTROMETRY.
"90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1.";
Jensen C.J., Buch M.-B., Krag T.O., Hemmings B.A., Gammeltoft S.,Froedin M.;
J. Biol. Chem. 274:27168-27176(1999).
Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-227 AND SER-386, ANDMUTAGENESIS OF SER-227 AND SER-386.
"FGFR3 activates RSK2 to mediate hematopoietic transformation throughtyrosine phosphorylation of RSK2 and activation of the MEK/ERKpathway.";
Kang S., Dong S., Gu T.L., Guo A., Cohen M.S., Lonial S., Khoury H.J.,Fabbro D., Gilliland D.G., Bergsagel P.L., Taunton J.,Polakiewicz R.D., Chen J.;
Cancer Cell 12:201-214(2007).
Cited for: FUNCTION IN HEMATOPOIETIC TRANSFORMATION, PHOSPHORYLATION AT TYR-529,AND MUTAGENESIS OF TYR-529.

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