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Overview

Uniprot IDO75676
Protein NameRibosomal protein S6 kinase alpha-4
Gene NameRPS6KA4
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
729 VENAPLAKRRKQKLR
759 GRAPVASKGAPRRAN

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 factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. 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. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. 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

Protein Sequence

10 MGDEDDDESC 20 AVELRITEAN 30 LTGHEEKVSV 40 ENFELLKVLG 50 TGAYGKVFLV 60 RKAGGHDAGK 70 LYAMKVLRKA 80 ALVQRAKTQE 90 HTRTERSVLE 100 LVRQAPFLVT 110 LHYAFQTDAK 120 LHLILDYVSG 130 GEMFTHLYQR 140 QYFKEAEVRV 150 YGGEIVLALE 160 HLHKLGIIYR 170 DLKLENVLLD 180 SEGHIVLTDF 190 GLSKEFLTEE 200 KERTFSFCGT 210 IEYMAPEIIR 220 SKTGHGKAVD 230 WWSLGILLFE 240 LLTGASPFTL 250 EGERNTQAEV 260 SRRILKCSPP 270 FPPRIGPVAQ 280 DLLQRLLCKD 290 PKKRLGAGPQ 300 GAQEVRNHPF 310 FQGLDWVALA 320 ARKIPAPFRP 330 QIRSELDVGN 340 FAEEFTRLEP 350 VYSPPGSPPP 360 GDPRIFQGYS 370 FVAPSILFDH 380 NNAVMTDGLE 390 APGAGDRPGR 400 AAVARSAMMQ 410 DSPFFQQYEL 420 DLREPALGQG 430 SFSVCRRCRQ 440 RQSGQEFAVK 450 ILSRRLEANT 460 QREVAALRLC 470 QSHPNVVNLH 480 EVHHDQLHTY 490 LVLELLRGGE 500 LLEHIRKKRH 510 FSESEASQIL 520 RSLVSAVSFM 530 HEEAGVVHRD 540 LKPENILYAD 550 DTPGAPVKII 560 DFGFARLRPQ 570 SPGVPMQTPC 580 FTLQYAAPEL 590 LAQQGYDESC 600 DLWSLGVILY 610 MMLSGQVPFQ 620 GASGQGGQSQ 630 AAEIMCKIRE 640 GRFSLDGEAW 650 QGVSEEAKEL 660 VRGLLTVDPA 670 KRLKLEGLRG 680 SSWLQDGSAR 690 SSPPLRTPDV 700 LESSGPAVRS 710 GLNATFMAFN 720 RGKREGFFLK 730 SVENAPLAKR 740 RKQKLRSATA 750 SRRGSPAPAN 760 PGRAPVASKG 770 APRRANGPLP PS

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0045202 synapse
Molecular Function GO:0005524 ATP binding
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:0004711 ribosomal protein S6 kinase activity
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: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:0038202 TORC1 signaling

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.

[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[4] 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.