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IID00807
UniprotP51812
ProteinRibosomal protein S6 kinase alpha-3
GeneRPS6KA3
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network 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 39-366 Monomer :
 Evidence X-RAY 5d9k A Reference
       Region 5d9k A 39-61 disorder
       Region 5d9k A 62-216 order
       Region 5d9k A 217-228 disorder
       Region 5d9k A 229-347 order
       Region 5d9k A 348-353 disorder
       Region 5d9k A 354-359 order
       Region 5d9k A 360-366 disorder
 Evidence X-RAY 5d9k B Reference
       Region 5d9k B 39-61 disorder
       Region 5d9k B 62-217 order
       Region 5d9k B 218-228 disorder
       Region 5d9k B 229-346 order
       Region 5d9k B 347-353 disorder
       Region 5d9k B 354-359 order
       Region 5d9k B 360-366 disorder
 Evidence X-RAY 5d9l A Reference
       Region 5d9l A 39-48 disorder
       Region 5d9l A 49-217 order
       Region 5d9l A 218-229 disorder
       Region 5d9l A 230-359 order
 Evidence X-RAY 4nus A Reference
       Region 4nus A 39-52 disorder
       Region 4nus A 53-347 order
       Region 4nus A 348-353 disorder
       Region 4nus A 354-359 order
 Evidence X-RAY 4nw5 A Reference
       Region 4nw5 A 39-50 disorder
       Region 4nw5 A 51-346 order
       Region 4nw5 A 347-353 disorder
       Region 4nw5 A 354-359 order
 Evidence X-RAY 4nw6 A Reference
       Region 4nw6 A 39-50 disorder
       Region 4nw6 A 51-346 order
       Region 4nw6 A 347-353 disorder
       Region 4nw6 A 354-359 order
Seq 399-740 Monomer :
 Evidence X-RAY 4d9t A Reference
       Region 4d9t A 399-414 disorder
       Region 4d9t A 415-713 order
       Region 4d9t A 714-740 disorder
 Evidence X-RAY 4d9u A Reference
       Region 4d9u A 399-407 disorder
       Region 4d9u A 408-714 order
       Region 4d9u A 715-740 disorder
 Evidence X-RAY 4jg8 A Reference
       Region 4jg8 A 399-414 disorder
       Region 4jg8 A 415-714 order
       Region 4jg8 A 715-740 disorder
 Evidence X-RAY 4jg6 A Reference
       Region 4jg6 A 399-405 disorder
       Region 4jg6 A 406-428 order
       Region 4jg6 A 429-433 disorder
       Region 4jg6 A 434-712 order
       Region 4jg6 A 713-740 disorder
 Evidence X-RAY 4jg7 A Reference
       Region 4jg7 A 399-404 disorder
       Region 4jg7 A 405-430 order
       Region 4jg7 A 431-432 disorder
       Region 4jg7 A 433-713 order
       Region 4jg7 A 714-740 disorder
SeqProS possible 696-710 The correspoding region of the fragment RSK1 (Q15418, 80.5% identity) is disordered because of disrupted autoinhibition. :
       Region 4d9u A 408-714 order
       Region 4d9t A 415-713 order
       Region 4jg8 A 415-714 order
       Region 4jg6 A 434-712 order
       Region 4jg7 A 433-713 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 1-58,396-413,721-740
Order 59-370,378-391,414-720
ProS 1-14,42-58,396-413,721-732,737-740
AlphaFold
Disorder 1-62,77-79,161-164,213-215,217-222,348-348,371-371,373-384,390-416,568-595,636-636,710-740
Order 63-76,80-160,165-212,216-216,223-347,349-370,372-372,385-389,417-567,596-635,637-709
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:9770464, PubMed:16223362, PubMed:17360704, PubMed:16213824). 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 (PubMed:9770464, PubMed:10436156). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). 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 (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). 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). 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 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). 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 (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity).
Biological Process
See also
Diagram with PDB data
CREB1/CRBBP/KMT2AAllosteric communication in the KIX domain proceeds through dynamic re-packing of the hydrophobic core