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MGP002700

UniProt Annotations

Entry Information

Gene Name	ribosomal protein S6 kinase, 90kDa, polypeptide 1
Protein Entry	KS6A1_HUMAN
UniProt ID	Q15418
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q15418-1; Sequence=Displayed; Name=2; IsoId=Q15418-2; Sequence=VSP_041380; Name=3; IsoId=Q15418-3; Sequence=VSP_041580; Note=No experimental confirmation available.;
Catalytic Activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme Regulation	Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-573 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-380, allowing binding of PDPK1, which in turn phosphorylates Ser-221 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD. {ECO:0000269\|PubMed:15117958, ECO:0000269\|PubMed:9430688}.
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. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin- derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. 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. Mediates cell survival by phosphorylating the pro- apoptotic proteins BAD and DAPK1 and suppressing their pro- apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). 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. {ECO:0000269\|PubMed:10679322, ECO:0000269\|PubMed:11684016, ECO:0000269\|PubMed:12213813, ECO:0000269\|PubMed:15117958, ECO:0000269\|PubMed:15342917, ECO:0000269\|PubMed:16213824, ECO:0000269\|PubMed:16223362, ECO:0000269\|PubMed:16763566, ECO:0000269\|PubMed:17360704, ECO:0000269\|PubMed:18722121, ECO:0000269\|PubMed:9430688}.
Interaction	P08238:HSP90AB1; NbExp=2; IntAct=EBI-963034, EBI-352572; P50552:VASP; NbExp=4; IntAct=EBI-963034, EBI-748201;
Ptm	Activated by phosphorylation at Ser-221 by PDPK1. Autophosphorylated on Ser-380, as part of the activation process. May be phosphorylated at Thr-359 and Ser-363 by MAPK1/ERK2 and MAPK3/ERK1. {ECO:0000269\|PubMed:18669648, ECO:0000269\|PubMed:18691976, ECO:0000269\|PubMed:19369195, ECO:0000269\|PubMed:20068231, ECO:0000269\|PubMed:21406692, ECO:0000269\|PubMed:9430688}.
Ptm	N-terminal myristoylation results in an activated kinase in the absence of added growth factors.
Similarity	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. {ECO:0000305}.
Similarity	Contains 1 AGC-kinase C-terminal domain. {ECO:0000305}.
Similarity	Contains 2 protein kinase domains. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Subcellular Location	Nucleus. Cytoplasm.
Subunit	Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells. Transiently dissociates following mitogenic stimulation. Interacts with ETV1/ER81 and FGFR1. {ECO:0000269\|PubMed:12213813, ECO:0000269\|PubMed:12832467, ECO:0000269\|PubMed:15117958, ECO:0000269\|PubMed:15342917, ECO:0000269\|PubMed:17965187}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/RPS6KA1ID43477ch1p36.html";