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IID50359
UniprotP18654
ProteinRibosomal protein S6 kinase alpha-3
GeneRps6ka3
OrganismMus musculus
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
740
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 44-367 Monomer :
 Evidence X-RAY 4el9 A Reference
       Region 4el9 A 45-48 disorder
       Region 4el9 A 49-114 order
       Region 4el9 A 115-119 disorder
       Region 4el9 A 120-218 order
       Region 4el9 A 219-221 disorder
       Region 4el9 A 222-346 order
 Evidence X-RAY 3g51 A Reference
       Region 3g51 A 44-46 disorder
       Region 3g51 A 47-110 order
       Region 3g51 A 111-119 disorder
       Region 3g51 A 120-219 order
       Region 3g51 A 220-230 disorder
       Region 3g51 A 231-346 order
       Region 3g51 A 347-367 disorder
 Evidence X-RAY 4gue A Reference
       Region 4gue A 45-47 disorder
       Region 4gue A 48-113 order
       Region 4gue A 114-121 disorder
       Region 4gue A 122-217 order
       Region 4gue A 218-222 disorder
       Region 4gue A 223-346 order
 Evidence X-RAY 3ubd A Reference
       Region 3ubd A 45-48 disorder
       Region 3ubd A 49-113 order
       Region 3ubd A 114-119 disorder
       Region 3ubd A 120-217 order
       Region 3ubd A 218-222 disorder
       Region 3ubd A 223-346 order
Seq 399-740 Monomer :
 Evidence X-RAY 4m8t A Reference
       Region 4m8t A 399-409 disorder
       Region 4m8t A 410-712 order
       Region 4m8t A 713-740 disorder
 Evidence X-RAY 4mao A Reference
       Region 4mao A 399-414 disorder
       Region 4mao A 415-712 order
       Region 4mao A 713-740 disorder
 Evidence X-RAY 2qr7 A Reference
       Region 2qr7 A 399-416 disorder
       Region 2qr7 A 417-714 order
       Region 2qr7 A 715-740 disorder
 Evidence X-RAY 2qr8 A Reference
       Region 2qr8 A 399-416 disorder
       Region 2qr8 A 417-714 order
       Region 2qr8 A 715-740 disorder
 Evidence X-RAY 5o1s A Reference
       Region 5o1s A 400-414 disorder
       Region 5o1s A 415-428 order
       Region 5o1s A 429-433 disorder
       Region 5o1s A 434-579 order
       Region 5o1s A 580-582 disorder
       Region 5o1s A 583-712 order
       Region 5o1s A 713-740 disorder
SeqProS possible 696-710 The coresponding region of the fragment RSK1 (Q15418, 80.6% identity) is disordered because of disrupted autoinhibition. :
       Region 2qr8 A 417-714 order
       Region 2qr7 A 417-714 order
       Region 4m8t A 410-712 order
       Region 4mao A 415-712 order
       Region 5o1s A 583-712 order
Seqphosphorylation
    227-227 Phosphoserine; by PDPK1
    365-365 Phosphothreonine
    369-369 Phosphoserine
    375-375 Phosphoserine
    386-386 Phosphoserine; by autocatalysis and MAPKAPK2
    415-415 Phosphoserine
    529-529 Phosphotyrosine; by FGFR3
    556-556 Phosphoserine
    715-715 Phosphoserine
 
Prediction
NeProc
Disorder 1-59,399-407,721-740
Order 60-370,378-398,408-720
ProS 1-14,44-59,399-407,721-732,737-740
AlphaFold
Disorder 1-62,78-79,161-164,213-215,217-222,348-348,371-371,373-384,390-416,568-595,622-622,636-636,693-694,710-740
Order 63-77,80-160,165-212,216-216,223-347,349-370,372-372,385-389,417-567,596-621,623-635,637-692,695-709
Pfam Hmmer
PF00069 68-327 8.5e-98
PF00433 347-391 6.7e-10
PF00069 422-679 4.1e-110
SEG 174-187 ,480-492
Function
Function in SwissProt
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 (PubMed:10856237, PubMed:15109498). 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 (By similarity). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (By similarity). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (By similarity). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (By similarity). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (By similarity). 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 (By similarity). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (By similarity). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (By similarity). 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 (PubMed:14504289). 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 (PubMed:17785202, PubMed:17906627). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (PubMed:22827337). 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). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (PubMed:15109498).