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Details on Person UniProt:O75582 RPS6KA5

Class:Id	ReferenceGeneProduct:93593
_chainChangeLog	chain:1-802 added on Fri February 6 2015
_displayName	UniProt:O75582 RPS6KA5
_timestamp	2025-02-21 20:00:28
chain	chain:1-802
checksum	76C27D0F6639BFA4
comment	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).CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)COFACTOR Activated by phosphorylation at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-212, Ser-376 and Ser-381 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-750, Ser-752 and Ser-758 in its own C-terminal region.SUBUNIT Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells which transiently dissociates following mitogenic stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA5 associates with and phosphorylates the NF-kappa-B p65 subunit RELA. Interacts with CREBBP and EP300.INTERACTION Predominantly nuclear. Exported into cytoplasm in response to glucocorticoid.ALTERNATIVE PRODUCTS Widely expressed with high levels in heart, brain and placenta. Less abundant in lung, kidney and liver.PTM Ser-376 and Thr-581 phosphorylation is required for kinase activity. Ser-376 and Ser-212 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. Phosphorylated at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-750, Ser-752 and Ser-758 by the N-terminal kinase domain.PTM Ubiquitinated.MISCELLANEOUS Enzyme activity requires the presence of both kinase domains.SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.
description	recommendedName: Ribosomal protein S6 kinase alpha-5 shortName: S6K-alpha-5 ecNumber: 2.7.11.1 alternativeName: 90 kDa ribosomal protein S6 kinase 5 alternativeName: Nuclear mitogen- and stress-activated protein kinase 1 alternativeName: RSK-like protein kinase shortName: RSKL
geneName	RPS6KA5 MSK1
identifier	O75582
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing ATP-binding Cytoplasm Inflammatory response Kinase Magnesium Metal-binding Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Serine/threonine-protein kinase Stress response Transferase Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21
name	RPS6KA5
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8962272] ENSEMBL:ENSG00000100784 RPS6KA5 [Homo sapiens]
secondaryIdentifier	KS6A5_HUMAN B7Z2Y5 O95316 Q96AF7
sequenceLength	802
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8975182] UniProt:O75582-1 RPS6KA5 [Homo sapiens] [ReferenceIsoform:8975183] UniProt:O75582-2 RPS6KA5 [Homo sapiens] [ReferenceIsoform:8975184] UniProt:O75582-3 RPS6KA5 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:198657] RPS6KA5 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:198683] p-S212,S360,S376,T581-RPS6KA5 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:772525] RPS6KA5 [cytosol] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:198661] O-phospho-L-serine at 212 [ModifiedResidue:198676] O-phospho-L-serine at 376 [ModifiedResidue:198677] O-phospho-L-serine at 360 [ModifiedResidue:198680] O-phospho-L-threonine at 581
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No pathways have been reviewed or authored by UniProt:O75582 RPS6KA5 (93593)