Overview
| Uniprot ID | O75582 |
|---|
| Protein Name | Ribosomal protein S6 kinase alpha-5 |
|---|
| Gene Name | RPS6KA5 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 726 |
FHAFNKYKREGFCLQ |
| 737 |
FCLQNVDKAPLAKRR |
| 742 |
VDKAPLAKRRKMKKT |
Function
Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes (PubMed:11909979, PubMed:12569367, PubMed:12763138, PubMed:18511904, PubMed:9687510, PubMed:9873047). Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin (PubMed:11909979, PubMed:9873047). Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression (PubMed:12628924, PubMed:18511904). In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress (PubMed:12628924). In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential (PubMed:12763138). Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation (PubMed:12569367). Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A (PubMed:15010469). Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN (PubMed:12773393). May also phosphorylate 'Ser-28' of histone H3 (PubMed:12773393). Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14) (PubMed:12773393). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines (By similarity). Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors (By similarity). Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury (By similarity). Phosphorylates TRIM7 at 'Ser-107' in response to growth factor signaling via the MEK/ERK pathway, thereby stimulating its ubiquitin ligase activity (PubMed:25851810)
Protein Sequence
10
MEEEGGSSGG
20
AAGTSADGGD
30
GGEQLLTVKH
40
ELRTANLTGH
50
AEKVGIENFE
60
LLKVLGTGAY
70
GKVFLVRKIS
80
GHDTGKLYAM
90
KVLKKATIVQ
100
KAKTTEHTRT
110
ERQVLEHIRQ
120
SPFLVTLHYA
130
FQTETKLHLI
140
LDYINGGELF
150
THLSQRERFT
160
EHEVQIYVGE
170
IVLALEHLHK
180
LGIIYRDIKL
190
ENILLDSNGH
200
VVLTDFGLSK
210
EFVADETERA
220
YSFCGTIEYM
230
APDIVRGGDS
240
GHDKAVDWWS
250
LGVLMYELLT
260
GASPFTVDGE
270
KNSQAEISRR
280
ILKSEPPYPQ
290
EMSALAKDLI
300
QRLLMKDPKK
310
RLGCGPRDAD
320
EIKEHLFFQK
330
INWDDLAAKK
340
VPAPFKPVIR
350
DELDVSNFAE
360
EFTEMDPTYS
370
PAALPQSSEK
380
LFQGYSFVAP
390
SILFKRNAAV
400
IDPLQFHMGV
410
ERPGVTNVAR
420
SAMMKDSPFY
430
QHYDLDLKDK
440
PLGEGSFSIC
450
RKCVHKKSNQ
460
AFAVKIISKR
470
MEANTQKEIT
480
ALKLCEGHPN
490
IVKLHEVFHD
500
QLHTFLVMEL
510
LNGGELFERI
520
KKKKHFSETE
530
ASYIMRKLVS
540
AVSHMHDVGV
550
VHRDLKPENL
560
LFTDENDNLE
570
IKIIDFGFAR
580
LKPPDNQPLK
590
TPCFTLHYAA
600
PELLNQNGYD
610
ESCDLWSLGV
620
ILYTMLSGQV
630
PFQSHDRSLT
640
CTSAVEIMKK
650
IKKGDFSFEG
660
EAWKNVSQEA
670
KDLIQGLLTV
680
DPNKRLKMSG
690
LRYNEWLQDG
700
SQLSSNPLMT
710
PDILGSSGAA
720
VHTCVKATFH
730
AFNKYKREGF
740
CLQNVDKAPL
750
AKRRKMKKTS
760
TSTETRSSSS
770
ESSHSSSSHS
780
HGKTTPTKTL
790
QPSNPADSNN
800
PETLFQFSDS
VA
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0044024 |
histone H2AS1 kinase activity |
| Molecular Function |
GO:0035175 |
histone H3S10 kinase activity |
| Molecular Function |
GO:0044022 |
histone H3S28 kinase activity |
| 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:0004713 |
protein tyrosine kinase activity |
| Biological Process |
GO:0007411 |
axon guidance |
| Biological Process |
GO:0006954 |
inflammatory response |
| Biological Process |
GO:0070498 |
interleukin-1-mediated signaling pathway |
| Biological Process |
GO:0035556 |
intracellular signal transduction |
| Biological Process |
GO:0001818 |
negative regulation of cytokine production |
| Biological Process |
GO:0045892 |
negative regulation of DNA-templated transcription |
| Biological Process |
GO:0045944 |
positive regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0043687 |
post-translational protein modification |
| Biological Process |
GO:0006468 |
protein phosphorylation |
| Biological Process |
GO:0006355 |
regulation of DNA-templated transcription |
| Biological Process |
GO:0099175 |
regulation of postsynapse organization |
| 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.