Ribosomal protein S6 kinase alpha-3

Details

Name
Ribosomal protein S6 kinase alpha-3
Synonyms
  • 2.7.11.1
  • 90 kDa ribosomal protein S6 kinase 3
  • Insulin-stimulated protein kinase 1
  • ISPK-1
  • ISPK1
  • MAP kinase-activated protein kinase 1b
  • MAPK-activated protein kinase 1b
  • MAPKAP kinase 1b
  • MAPKAPK-1b
  • MAPKAPK1B
  • p90-RSK 3
  • p90RSK3
  • pp90RSK2
  • Ribosomal S6 kinase 2
  • RSK-2
  • RSK2
  • S6K-alpha-3
Gene Name
RPS6KA3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008668|Ribosomal protein S6 kinase alpha-3
MPLAQLADPWQKMAVESPSDSAENGQQIMDEPMGEEEINPQTEEVSIKEIAITHHVKEGH
EKADPSQFELLKVLGQGSFGKVFLVKKISGSDARQLYAMKVLKKATLKVRDRVRTKMERD
ILVEVNHPFIVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELALA
LDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKESIDHEKKAYSFCGTVEYMAPEVV
NRRGHTQSADWWSFGVLMFEMLTGTLPFQGKDRKETMTMILKAKLGMPQFLSPEAQSLLR
MLFKRNPANRLGAGPDGVEEIKRHSFFSTIDWNKLYRREIHPPFKPATGRPEDTFYFDPE
FTAKTPKDSPGIPPSANAHQLFRGFSFVAITSDDESQAMQTVGVHSIVQQLHRNSIQFTD
GYEVKEDIGVGSYSVCKRCIHKATNMEFAVKIIDKSKRDPTEEIEILLRYGQHPNIITLK
DVYDDGKYVYVVTELMKGGELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDL
KPSNILYVDESGNPESIRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDAACD
IWSLGVLLYTMLTGYTPFANGPDDTPEEILARIGSGKFSLSGGYWNSVSDTAKDLVSKML
HVDPHQRLTAALVLRHPWIVHWDQLPQYQLNRQDAPHLVKGAMAATYSALNRNQSPVLEP
VGRSTLAQRRGIKKITSTAL
Number of residues
740
Molecular Weight
83735.325
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / magnesium ion binding / protein kinase activity / protein serine/threonine kinase activity / ribosomal protein S6 kinase activity
Processes
axon guidance / cell cycle / central nervous system development / innate immune response / intracellular signal transduction / MyD88-dependent toll-like receptor signaling pathway / MyD88-independent toll-like receptor signaling pathway / negative regulation of apoptotic process / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / neurotrophin TRK receptor signaling pathway / positive regulation of cell differentiation / positive regulation of cell growth / positive regulation of transcription from RNA polymerase II promoter / protein phosphorylation / regulation of DNA-templated transcription in response to stress / regulation of translation in response to stress / response to lipopolysaccharide / signal transduction / skeletal system development / stress-activated MAPK cascade / synaptic transmission / toll-like receptor 10 signaling pathway / toll-like receptor 2 signaling pathway / toll-like receptor 3 signaling pathway / toll-like receptor 4 signaling pathway / toll-like receptor 5 signaling pathway / toll-like receptor 9 signaling pathway / toll-like receptor signaling pathway / toll-like receptor TLR1 / toll-like receptor TLR6 / TRIF-dependent toll-like receptor signaling pathway
Components
cytoplasm / cytosol / nucleoplasm
General Function
Ribosomal protein s6 kinase activity
Specific 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 and histone H3 at 'Ser-10', 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. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0013342|Ribosomal protein S6 kinase alpha-3 (RPS6KA3)
ATGCCGCTGGCGCAGCTGGCGGACCCGTGGCAGAAGATGGCTGTGGAGAGCCCGTCCGAC
AGCGCTGAGAATGGACAGCAAATTATGGATGAACCTATGGGAGAGGAGGAGATTAACCCA
CAAACTGAAGAAGTCAGTATCAAAGAAATTGCAATCACACATCATGTAAAGGAAGGACAT
GAAAAGGCAGATCCTTCCCAGTTTGAACTTTTAAAAGTATTAGGGCAGGGATCATTTGGA
AAGGTTTTCTTAGTTAAAAAAATCTCAGGCTCTGATGCTAGGCAGCTTTATGCCATGAAG
GTATTGAAGAAGGCCACACTGAAAGTTCGAGACCGAGTTCGGACAAAAATGGAACGTGAT
ATCTTGGTAGAGGTTAATCATCCTTTTATTGTCAAGTTGCATTATGCTTTTCAAACTGAA
GGGAAGTTGTATCTTATTTTGGATTTTCTCAGGGGAGGAGATTTGTTTACACGCTTATCC
AAAGAGGTGATGTTCACAGAAGAAGATGTCAAATTCTACTTGGCTGAACTTGCACTTGCT
TTAGACCATCTACATAGCCTGGGAATAATTTATAGAGACTTAAAACCAGAAAATATACTT
CTTGATGAAGAAGGTCACATCAAGTTAACAGATTTCGGCCTAAGTAAAGAGTCTATTGAC
CATGAAAAGAAGGCATATTCTTTTTGTGGAACTGTGGAGTATATGGCTCCAGAAGTAGTT
AATCGTCGAGGTCATACTCAGAGTGCTGACTGGTGGTCTTTTGGTGTGTTAATGTTTGAA
ATGCTTACTGGTACACTCCCTTTCCAAGGAAAAGATCGAAAAGAAACAATGACTATGATT
CTTAAAGCCAAACTTGGAATGCCACAGTTTTTGAGTCCTGAAGCGCAGAGTCTTTTACGA
ATGCTTTTCAAGCGAAATCCTGCAAACAGATTAGGTGCAGGACCAGATGGAGTTGAAGAA
ATTAAAAGACATTCATTTTTCTCAACGATAGACTGGAATAAACTGTATAGAAGAGAAATT
CATCCGCCATTTAAACCTGCAACGGGCAGGCCTGAAGATACATTCTATTTTGATCCTGAG
TTTACTGCAAAAACTCCCAAAGATTCACCTGGCATTCCACCTAGTGCTAATGCACATCAG
CTTTTTCGGGGGTTTAGTTTTGTTGCTATTACCTCAGATGATGAAAGCCAAGCTATGCAG
ACAGTTGGTGTACATTCAATTGTTCAGCAGTTACACAGGAACAGTATTCAGTTTACTGAT
GGATATGAAGTAAAAGAAGATATTGGAGTTGGCTCCTACTCTGTTTGCAAGAGATGTATA
CATAAAGCTACAAACATGGAGTTTGCAGTGAAGATTATTGATAAAAGCAAGAGAGACCCA
ACAGAAGAAATTGAAATTCTTCTTCGTTATGGACAGCATCCAAACATTATCACTCTAAAG
GATGTATATGATGATGGAAAGTATGTGTATGTAGTAACAGAACTTATGAAAGGAGGTGAA
TTGCTGGATAAAATTCTTAGACAAAAATTTTTCTCTGAACGAGAGGCCAGTGCTGTCCTG
TTCACTATAACTAAAACCGTTGAATATCTTCACGCACAAGGGGTGGTTCATAGAGACTTG
AAACCTAGCAACATTCTTTATGTGGATGAATCTGGTAATCCGGAATCTATTCGAATTTGT
GATTTTGGCTTTGCAAAACAGCTGAGAGCGGAAAATGGTCTTCTCATGACTCCTTGTTAC
ACTGCAAATTTTGTTGCACCAGAGGTTTTAAAAAGACAAGGCTATGATGCTGCTTGTGAT
ATATGGAGTCTTGGTGTCCTACTCTATACAATGCTTACCGGTTACACTCCATTTGCAAAT
GGTCCTGATGATACACCAGAGGAAATATTGGCACGAATAGGTAGCGGAAAATTCTCACTC
AGTGGTGGTTACTGGAATTCTGTTTCAGACACAGCAAAGGACCTGGTGTCAAAGATGCTT
CATGTAGACCCTCATCAGAGACTGACTGCTGCTCTTGTGCTCAGACATCCTTGGATCGTC
CACTGGGACCAACTGCCACAATACCAACTAAACAGACAGGATGCACCACATCTAGTAAAG
GGTGCCATGGCAGCTACATATTCTGCTTTGAACCGTAATCAGTCACCAGTTTTGGAACCA
GTAGGCCGCTCTACTCTTGCTCAGCGGAGAGGTATTAAAAAAATCACCTCAACAGCCCTG
TGA
Chromosome Location
X
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP51812
UniProtKB Entry NameKS6A3_HUMAN
HGNC IDHGNC:10432
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00945Acetylsalicylic acidapproved, vet_approvedunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails