dbPTM

KS6A1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KS6A1_MOUSE
UniProt AC	P18653
Protein Name	Ribosomal protein S6 kinase alpha-1
Gene Name	Rps6ka1
Organism	Mus musculus (Mouse).
Sequence Length	724
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, 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 pre-initiation 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). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB. [PubMed: 10635333 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 (By similarity Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (By similarity]
Protein Sequence	MPLAQLKEPWPLMELVPLDPENGQTSGEEAGLQPSKDEAILKEISITHHVKAGSEKADPSQFELLKVLGQGSFGKVFLVRKVTRPDSGHLYAMKVLKKATLKVRDRVRTKMERDILADVNHPFVVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELALGLDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKEAIDHEKKAYSFCGTVEYMAPEVVNRQGHTHSADWWSYGVLMGKDRKETMTLILKAKLGMPQFLSTEAQSLLRALFKRNPANRLGSGPDGAEEIKRHIFYSTIDWNKLYRREIKPPFKPAVAQPDDTFYFDTEFTSRTPRDSPGIPPSAGAHQLFRGFSFVATGLMEDDGKPRTTQAPLHSVVQQLHGKNLVFSDGYVVKETIGVGSYSVCKRCVHKATNMEYAVKVIDKSKRDPSEEIEILLRYGQHPNIITLKDVYDDGKHVYLVTELMRGGELLDKILRQKFFSEREASFVLHTISKTVEYLHSQGVVHRDLKPSNILYVDESGNPECLRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDEGCDIWSLGILLYTMLAGYTPFANGPSDTPEEILTRIGSGKFTLSGGNWNTVSETAKDLVSKMLHVDPHQRLTAKQVLQHPWITQKDKLPQSQLSHQDLQLVKGAMAATYSALNSSKPTPQLKPIESSILAQRRVRKLPSTTL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
45	Phosphorylation	EAILKEISITHHVKA HHHHHHHCEEEEECC	23.64	23684622
54	Phosphorylation	THHVKAGSEKADPSQ EEEECCCCCCCCHHH	40.56	-
72	Phosphorylation	LKVLGQGSFGKVFLV HHHHCCCCCCEEEEE	23.96	25338131
75	Ubiquitination	LGQGSFGKVFLVRKV HCCCCCCEEEEEEEE	28.01	-
186	Methylation	HSLGIIYRDLKPENI HHCCEEECCCCHHHE	32.17	30988765
209	Phosphorylation	KLTDFGLSKEAIDHE EECCCCCCHHHHCCC	28.91	23737553
220	Phosphorylation	IDHEKKAYSFCGTVE HCCCHHHHHCCCCCE	15.91	22322096
221	Phosphorylation	DHEKKAYSFCGTVEY CCCHHHHHCCCCCEE	20.94	25521595
225	Phosphorylation	KAYSFCGTVEYMAPE HHHHCCCCCEECCHH	16.02	22322096
228	Phosphorylation	SFCGTVEYMAPEVVN HCCCCCEECCHHHHC	8.34	22322096
275	Phosphorylation	LGMPQFLSTEAQSLL HCCCHHHCHHHHHHH	26.03	23140645
276	Phosphorylation	GMPQFLSTEAQSLLR CCCHHHCHHHHHHHH	37.17	23140645
280	Phosphorylation	FLSTEAQSLLRALFK HHCHHHHHHHHHHHH	36.10	23140645
296	Phosphorylation	NPANRLGSGPDGAEE CHHHCCCCCCCCHHH	52.31	-
348	Phosphorylation	DTEFTSRTPRDSPGI CCCCCCCCCCCCCCC	23.57	20710027
352	Phosphorylation	TSRTPRDSPGIPPSA CCCCCCCCCCCCCCC	26.72	25521595
358	Phosphorylation	DSPGIPPSAGAHQLF CCCCCCCCCCHHHHH	33.70	25521595
369	Phosphorylation	HQLFRGFSFVATGLM HHHHCCCEEEEECCC	22.95	25521595
373	Phosphorylation	RGFSFVATGLMEDDG CCCEEEEECCCCCCC	26.08	28833060
376	Oxidation	SFVATGLMEDDGKPR EEEEECCCCCCCCCC	5.85	17242355
455	Phosphorylation	EIEILLRYGQHPNII HHHHHHHHCCCCCEE	22.55	21454597
463	Phosphorylation	GQHPNIITLKDVYDD CCCCCEEEEEECCCC	24.77	21454597
478	Phosphorylation	GKHVYLVTELMRGGE CCEEEEEEEHHHCHH	22.32	26239621
551	Ubiquitination	ICDFGFAKQLRAENG ECCHHHHHHHHHHCC	47.83	-
562	Phosphorylation	AENGLLMTPCYTANF HHCCCEECCCEECCC	15.35	14647453
564	Glutathionylation	NGLLMTPCYTANFVA CCCEECCCEECCCCC	3.29	24333276
565	Phosphorylation	GLLMTPCYTANFVAP CCEECCCEECCCCCH	15.30	25266776
566	Phosphorylation	LLMTPCYTANFVAPE CEECCCEECCCCCHH	23.11	25777480
665	Phosphorylation	VLQHPWITQKDKLPQ HHCCCCCCCCCCCCH	26.20	26370283
676	Phosphorylation	KLPQSQLSHQDLQLV CCCHHHCCHHHHHHH	16.09	26370283
721	Phosphorylation	RRVRKLPSTTL---- HHHHCCCCCCC----	44.45	22942356
722	Phosphorylation	RVRKLPSTTL----- HHHCCCCCCC-----	30.12	29895711
723	Phosphorylation	VRKLPSTTL------ HHCCCCCCC------	34.50	29895711

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
221	S	Phosphorylation	Kinase	PDPK1	Q9Z2A0	Uniprot
369	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
369	S	Phosphorylation	Kinase	MAPK3	Q63844	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
221	S	Phosphorylation	-
Activated by phosphorylation at Ser-221 by PDPK1.
348	T	Phosphorylation	-
May be phosphorylated at Thr-348 and Ser-352 by MAPK1/ERK2 and MAPK3/ERK1 (By similarity).
352	S	Phosphorylation	-
May be phosphorylated at Thr-348 and Ser-352 by MAPK1/ERK2 and MAPK3/ERK1 (By similarity).
369	S	Phosphorylation	17242355
Autophosphorylated on Ser-369, as part of the activation process.

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 KS6A1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
Oops, there are no PPI records of KS6A1_MOUSE !!

Drug and Disease Associations

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

Regulatory Network of KS6A1_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large-scale phosphorylation analysis of mouse liver."; Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-721, AND MASSSPECTROMETRY.	17242355 [Abstract]

show

show

show

show