KS6B1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: KS6B1_MOUSE
• UniProt AC: Q8BSK8
• Protein Name: Ribosomal protein S6 kinase beta-1
• Gene Name: Rps6kb1
• Organism: Mus musculus (Mouse).
• Sequence Length: 525
• Subcellular Localization: Cytoplasm. Cell junction, synapse, synaptosome. Mitochondrion outer membrane . Mitochondrion. Colocalizes with URI1 at mitochondrion..
• 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 RMP leading to dissociation of a RMP: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 (By similarity). [PubMed: 11493700]
• Protein Sequence: MRRRRRRDGFYLAPDFRHREAEDMAGVFDIDLDQPEDAGSEDELEEGGQLNESMDHGGVGPYELGMEHCEKFEISETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSGGELFMQLEREGIFMEDTACFYLAEISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLCKESIHDGTVTHTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKKTIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHPFFRHINWEELLARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTLSESANQVFLGFTYVAPSVLESVKEKFSFEPKIRSPRRFIGSPRTPVSPVKFSPGDFWGRGASASTANPQTPVEYPMETSGIEQMDVTVSGEASAPLPIRQPNSGPYKKQAFPMISKRPEHLRMNL

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
53	Phosphorylation	EGGQLNESMDHGGVG HCCCCCCCCCCCCCC	28.56	12023960
104	Ubiquitination	LGKGGYGKVFQVRKV HCCCCCCEEEEEEEE	31.24	-
123	Acetylation	TGKIFAMKVLKKAMI CCHHHHHHHHHHHHH	40.77	7719667
126	Acetylation	IFAMKVLKKAMIVRN HHHHHHHHHHHHHHC	41.28	7719681
140	Phosphorylation	NAKDTAHTKAERNIL CCCHHHCCHHHHHHH	29.50	23567750
217	Methylation	HQKGIIYRDLKPENI HHCCCEECCCCHHHE	32.17	30988753
243	Phosphorylation	DFGLCKESIHDGTVT CCCCEECCCCCCCCE	15.66	22322096
248	Phosphorylation	KESIHDGTVTHTFCG ECCCCCCCCEEEECC	28.43	22322096
250	Phosphorylation	SIHDGTVTHTFCGTI CCCCCCCEEEECCEE	18.29	22322096
252	Phosphorylation	HDGTVTHTFCGTIEY CCCCCEEEECCEEHH	15.97	22322096
256	Phosphorylation	VTHTFCGTIEYMAPE CEEEECCEEHHHCHH	16.30	22322096
375	Phosphorylation	PFKPLLQSEEDVSQF CCHHHCCCHHHHHHC	42.81	29899451
387	Phosphorylation	SQFDSKFTRQTPVDS HHCCHHHCCCCCCCC	26.13	26643407
390	Phosphorylation	DSKFTRQTPVDSPDD CHHHCCCCCCCCCCC	23.22	15799971
394	Phosphorylation	TRQTPVDSPDDSTLS CCCCCCCCCCCCCCC	30.38	12023960
398	Phosphorylation	PVDSPDDSTLSESAN CCCCCCCCCCCHHHH	38.33	12023960
399	Phosphorylation	VDSPDDSTLSESANQ CCCCCCCCCCHHHHH	41.10	26643407
401	Phosphorylation	SPDDSTLSESANQVF CCCCCCCCHHHHHHE	29.59	26643407
403	Phosphorylation	DDSTLSESANQVFLG CCCCCCHHHHHHEEE	29.19	12023960
412	Phosphorylation	NQVFLGFTYVAPSVL HHHEEEEEEECHHHH	18.45	18851840
427	Phosphorylation	ESVKEKFSFEPKIRS HHHHHHCCCCCCCCC	39.50	26824392
434	Phosphorylation	SFEPKIRSPRRFIGS CCCCCCCCCCCCCCC	26.65	19106089
441	Phosphorylation	SPRRFIGSPRTPVSP CCCCCCCCCCCCCCC	13.34	22322096
444	Phosphorylation	RFIGSPRTPVSPVKF CCCCCCCCCCCCCCC	31.27	25521595
447	Phosphorylation	GSPRTPVSPVKFSPG CCCCCCCCCCCCCCC	25.77	25521595
452	Phosphorylation	PVSPVKFSPGDFWGR CCCCCCCCCCCCCCC	23.43	22322096
470	Phosphorylation	ASTANPQTPVEYPME CCCCCCCCCCCCCCC	30.47	7489717
507	Acetylation	QPNSGPYKKQAFPMI CCCCCCCCCCCCCCC	41.35	66675615
508	Acetylation	PNSGPYKKQAFPMIS CCCCCCCCCCCCCCC	40.80	66675617
516	Acetylation	QAFPMISKRPEHLRM CCCCCCCCCHHHHCC	62.13	29579813

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	Q9ES70	PhosphoELM
53	S	Phosphorylation	Kinase	NEK6	Q9ES70	GPS
252	T	Phosphorylation	Kinase	PDPK1	Q9Z2A0	Uniprot
394	S	Phosphorylation	Kinase	NEK6	Q9ES70	PhosphoELM
398	S	Phosphorylation	Kinase	NEK6	Q9ES70	PhosphoELM
403	S	Phosphorylation	Kinase	NEK6	Q9ES70	PhosphoELM
412	T	Phosphorylation	Kinase	MTOR	P42345	PSP
412	T	Phosphorylation	Kinase	MTOR	Q9JLN9	Uniprot
412	T	Phosphorylation	Kinase	NEK6	Q9ES70	Uniprot
412	T	Phosphorylation	Kinase	NEK7	Q9ES74	Uniprot
412	T	Phosphorylation	Kinase	PIK3C2A	O00443	PSP

Functions of PTM Sites

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

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of KS6B1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
IRS1_MOUSE	Irs1	physical	15249583
RS6_MOUSE	Rps6	physical	18851840
DDT4L_MOUSE	Ddit4l	physical	15988001

Drug and Disease Associations

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