Overview
| Uniprot ID | P51812 |
|---|
| Protein Name | Ribosomal protein S6 kinase alpha-3 |
|---|
| Gene Name | RPS6KA3 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 734 |
AQRRGIKKITSTAL* |
Function
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:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). 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:10436156, PubMed:9770464). 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)
Protein Sequence
10
MPLAQLADPW
20
QKMAVESPSD
30
SAENGQQIMD
40
EPMGEEEINP
50
QTEEVSIKEI
60
AITHHVKEGH
70
EKADPSQFEL
80
LKVLGQGSFG
90
KVFLVKKISG
100
SDARQLYAMK
110
VLKKATLKVR
120
DRVRTKMERD
130
ILVEVNHPFI
140
VKLHYAFQTE
150
GKLYLILDFL
160
RGGDLFTRLS
170
KEVMFTEEDV
180
KFYLAELALA
190
LDHLHSLGII
200
YRDLKPENIL
210
LDEEGHIKLT
220
DFGLSKESID
230
HEKKAYSFCG
240
TVEYMAPEVV
250
NRRGHTQSAD
260
WWSFGVLMFE
270
MLTGTLPFQG
280
KDRKETMTMI
290
LKAKLGMPQF
300
LSPEAQSLLR
310
MLFKRNPANR
320
LGAGPDGVEE
330
IKRHSFFSTI
340
DWNKLYRREI
350
HPPFKPATGR
360
PEDTFYFDPE
370
FTAKTPKDSP
380
GIPPSANAHQ
390
LFRGFSFVAI
400
TSDDESQAMQ
410
TVGVHSIVQQ
420
LHRNSIQFTD
430
GYEVKEDIGV
440
GSYSVCKRCI
450
HKATNMEFAV
460
KIIDKSKRDP
470
TEEIEILLRY
480
GQHPNIITLK
490
DVYDDGKYVY
500
VVTELMKGGE
510
LLDKILRQKF
520
FSEREASAVL
530
FTITKTVEYL
540
HAQGVVHRDL
550
KPSNILYVDE
560
SGNPESIRIC
570
DFGFAKQLRA
580
ENGLLMTPCY
590
TANFVAPEVL
600
KRQGYDAACD
610
IWSLGVLLYT
620
MLTGYTPFAN
630
GPDDTPEEIL
640
ARIGSGKFSL
650
SGGYWNSVSD
660
TAKDLVSKML
670
HVDPHQRLTA
680
ALVLRHPWIV
690
HWDQLPQYQL
700
NRQDAPHLVK
710
GAMAATYSAL
720
NRNQSPVLEP
730
VGRSTLAQRR
740
GIKKITSTAL
Gene Ontology
| Classification |
GO ID |
Description |
| Biological Process |
GO:0043066 |
negative regulation of apoptotic process |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005730 |
nucleolus |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0045202 |
synapse |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0000287 |
magnesium ion binding |
| Molecular Function |
GO:0004672 |
protein kinase activity |
| Molecular Function |
GO:0019901 |
protein kinase binding |
| Molecular Function |
GO:0106310 |
protein serine kinase activity |
| Molecular Function |
GO:0004674 |
protein serine/threonine kinase activity |
| Molecular Function |
GO:0004711 |
ribosomal protein S6 kinase activity |
| Biological Process |
GO:0007417 |
central nervous system development |
| Biological Process |
GO:0007268 |
chemical synaptic transmission |
| Biological Process |
GO:0045597 |
positive regulation of cell differentiation |
| Biological Process |
GO:0030307 |
positive regulation of cell growth |
| Biological Process |
GO:0045944 |
positive regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0006355 |
regulation of DNA-templated transcription |
| Biological Process |
GO:0043555 |
regulation of translation in response to stress |
| Biological Process |
GO:0032496 |
response to lipopolysaccharide |
| Biological Process |
GO:0007165 |
signal transduction |
| Biological Process |
GO:0001501 |
skeletal system development |
| Biological Process |
GO:0002224 |
toll-like receptor signaling pathway |
| Biological Process |
GO:0038202 |
TORC1 signaling |
Reference
[1] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.