Overview
| Uniprot ID | Q15418 |
|---|
| Protein Name | Ribosomal protein S6 kinase alpha-1 |
|---|
| Gene Name | RPS6KA1 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 505 |
LDKILRQKFFSEREA |
| 729 |
LAQRRVRKLPSTTL* |
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:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, 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:18508509, PubMed:18813292). 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 (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). 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:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (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 (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404)
Protein Sequence
10
MPLAQLKEPW
20
PLMELVPLDP
30
ENGQTSGEEA
40
GLQPSKDEGV
50
LKEISITHHV
60
KAGSEKADPS
70
HFELLKVLGQ
80
GSFGKVFLVR
90
KVTRPDSGHL
100
YAMKVLKKAT
110
LKVRDRVRTK
120
MERDILADVN
130
HPFVVKLHYA
140
FQTEGKLYLI
150
LDFLRGGDLF
160
TRLSKEVMFT
170
EEDVKFYLAE
180
LALGLDHLHS
190
LGIIYRDLKP
200
ENILLDEEGH
210
IKLTDFGLSK
220
EAIDHEKKAY
230
SFCGTVEYMA
240
PEVVNRQGHS
250
HSADWWSYGV
260
LMFEMLTGSL
270
PFQGKDRKET
280
MTLILKAKLG
290
MPQFLSTEAQ
300
SLLRALFKRN
310
PANRLGSGPD
320
GAEEIKRHVF
330
YSTIDWNKLY
340
RREIKPPFKP
350
AVAQPDDTFY
360
FDTEFTSRTP
370
KDSPGIPPSA
380
GAHQLFRGFS
390
FVATGLMEDD
400
GKPRAPQAPL
410
HSVVQQLHGK
420
NLVFSDGYVV
430
KETIGVGSYS
440
ECKRCVHKAT
450
NMEYAVKVID
460
KSKRDPSEEI
470
EILLRYGQHP
480
NIITLKDVYD
490
DGKHVYLVTE
500
LMRGGELLDK
510
ILRQKFFSER
520
EASFVLHTIG
530
KTVEYLHSQG
540
VVHRDLKPSN
550
ILYVDESGNP
560
ECLRICDFGF
570
AKQLRAENGL
580
LMTPCYTANF
590
VAPEVLKRQG
600
YDEGCDIWSL
610
GILLYTMLAG
620
YTPFANGPSD
630
TPEEILTRIG
640
SGKFTLSGGN
650
WNTVSETAKD
660
LVSKMLHVDP
670
HQRLTAKQVL
680
QHPWVTQKDK
690
LPQSQLSHQD
700
LQLVKGAMAA
710
TYSALNSSKP
720
TPQLKPIESS
730
ILAQRRVRKL
PSTTL
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| 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:0106310 |
protein serine kinase activity |
| Molecular Function |
GO:0004674 |
protein serine/threonine kinase activity |
| Molecular Function |
GO:0004712 |
protein serine/threonine/tyrosine kinase activity |
| Molecular Function |
GO:0004711 |
ribosomal protein S6 kinase activity |
| Biological Process |
GO:0007268 |
chemical synaptic transmission |
| Biological Process |
GO:0072574 |
hepatocyte proliferation |
| Biological Process |
GO:0043066 |
negative regulation of apoptotic process |
| Biological Process |
GO:0032007 |
negative regulation of TOR signaling |
| Biological Process |
GO:0045597 |
positive regulation of cell differentiation |
| Biological Process |
GO:0030307 |
positive regulation of cell growth |
| Biological Process |
GO:0045893 |
positive regulation of DNA-templated transcription |
| Biological Process |
GO:2000491 |
positive regulation of hepatic stellate cell activation |
| Biological Process |
GO:0045944 |
positive regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0006468 |
protein phosphorylation |
| Biological Process |
GO:0006355 |
regulation of DNA-templated transcription |
| Biological Process |
GO:0043555 |
regulation of translation in response to stress |
| Biological Process |
GO:0007165 |
signal transduction |
| 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.