Human Gene RPS6KB1 (ENST00000393021.7) Description and Page Index
  Description: Homo sapiens ribosomal protein S6 kinase B1 (RPS6KB1), transcript variant 8, mRNA. (from RefSeq NM_001369672)
RefSeq Summary (NM_001272044): This gene encodes a member of the ribosomal S6 kinase family of serine/threonine kinases. The encoded protein responds to mTOR (mammalian target of rapamycin) signaling to promote protein synthesis, cell growth, and cell proliferation. Activity of this gene has been associated with human cancer. Alternatively spliced transcript variants have been observed. The use of alternative translation start sites results in isoforms with longer or shorter N-termini which may differ in their subcellular localizations. There are two pseudogenes for this gene on chromosome 17. [provided by RefSeq, Jan 2013].
Gencode Transcript: ENST00000393021.7
Gencode Gene: ENSG00000108443.14
Transcript (Including UTRs)
   Position: hg38 chr17:59,893,046-59,950,421 Size: 57,376 Total Exon Count: 16 Strand: +
Coding Region
   Position: hg38 chr17:59,910,580-59,946,788 Size: 36,209 Coding Exon Count: 14 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:59,893,046-59,950,421)mRNA (may differ from genome)Protein (472 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: KS6B1_HUMAN
DESCRIPTION: RecName: Full=Ribosomal protein S6 kinase beta-1; Short=S6K-beta-1; Short=S6K1; EC=2.7.11.1; AltName: Full=70 kDa ribosomal protein S6 kinase 1; Short=P70S6K1; Short=p70-S6K 1; AltName: Full=Ribosomal protein S6 kinase I; AltName: Full=Serine/threonine-protein kinase 14A; AltName: Full=p70 ribosomal S6 kinase alpha; Short=p70 S6 kinase alpha; Short=p70 S6K-alpha; Short=p70 S6KA;
FUNCTION: Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the preinitiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at 'Thr-412', which is proposed to be a negative feedback mechanism for the RPS6KB1 anti- apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1- 2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
ENZYME REGULATION: Inactivated by binding to URI1. Activation requires multiple phosphorylation events on serine/threonine residues. Activation appears to be first mediated by phosphorylation of multiple sites in the autoinhibitory domain, which facilitates phosphorylation at Thr-412, disrupting the autoinhibitory mechanism and allowing phosphorylation of Thr-252 by PDPK1. The active conformation of the kinase is believed to be stabilized by a mechanism involving three conserved phosphorylation sites located in the kinase domain activation loop (Thr-252) and in the AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker region and Thr-412 within a hydrophobic motif at its end). Activated by mTORC1; isoform Alpha I and isoform Alpha II are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1.
SUBUNIT: Interacts with PPP1R9A/neurabin-1 (By similarity). Interacts with RPTOR. Interacts with IRS1. Interacts with EIF3B and EIF3C. Interacts with POLDIP3 and TRAF4.
INTERACTION: P08151:GLI1; NbExp=4; IntAct=EBI-1775921, EBI-308084; Q00005:PPP2R2B; NbExp=2; IntAct=EBI-1775921, EBI-1052159;
SUBCELLULAR LOCATION: Cell junction, synapse, synaptosome (By similarity). Mitochondrion outer membrane. Mitochondrion. Note=Colocalizes with URI1 at mitochondrion.
SUBCELLULAR LOCATION: Isoform Alpha I: Nucleus. Cytoplasm.
SUBCELLULAR LOCATION: Isoform Alpha II: Cytoplasm.
TISSUE SPECIFICITY: Widely expressed.
DOMAIN: The autoinhibitory domain is believed to block phosphorylation within the AGC-kinase C-terminal domain and the activation loop.
DOMAIN: The TOS (TOR signaling) motif is essential for activation by mTORC1 (By similarity).
PTM: Phosphorylation at Thr-412 is regulated by mTORC1. The phosphorylation at this site is maintained by an agonist-dependent autophosphorylation mechanism (By similarity). Activated by phosphorylation at Thr-252 by PDPK1. Dephosphorylation by PPP1CC at Thr-412 in mitochondrion.
SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.
SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
SIMILARITY: Contains 1 protein kinase domain.

-  MalaCards Disease Associations
  MalaCards Gene Search: RPS6KB1
Diseases sorted by gene-association score: tuberous sclerosis (5), glioblastoma multiforme (4), lymphangioleiomyomatosis (3), pancreatic cancer (3), breast cancer (2), colorectal cancer (2), lung cancer (2), corticobasal degeneration (2), triple-receptor negative breast cancer (1), mental retardation, x-linked syndromic, lubs type (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 8.01 RPKM in Ovary
Total median expression: 283.48 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -167.90427-0.393 Picture PostScript Text
3' UTR -834.103633-0.230 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000961 - AGC-kinase_C
IPR011009 - Kinase-like_dom
IPR017892 - Pkinase_C
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR016238 - Ribosomal_S6_kinase
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF00069 - Protein kinase domain
PF00433 - Protein kinase C terminal domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

3A60
- X-ray MuPIT

3A61
- X-ray MuPIT

3A62
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P23443
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologGenome BrowserGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
MGIRGD EnsemblWormBase 
Protein SequenceProtein Sequence Protein SequenceProtein Sequence 
AlignmentAlignment AlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004711 ribosomal protein S6 kinase activity
GO:0004712 protein serine/threonine/tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0030165 PDZ domain binding
GO:0042277 peptide binding
GO:0042802 identical protein binding
GO:0051721 protein phosphatase 2A binding

Biological Process:
GO:0000082 G1/S transition of mitotic cell cycle
GO:0001662 behavioral fear response
GO:0003009 skeletal muscle contraction
GO:0006417 regulation of translation
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0007049 cell cycle
GO:0007165 signal transduction
GO:0007281 germ cell development
GO:0007568 aging
GO:0007584 response to nutrient
GO:0007616 long-term memory
GO:0009408 response to heat
GO:0009611 response to wounding
GO:0009612 response to mechanical stimulus
GO:0009636 response to toxic substance
GO:0009749 response to glucose
GO:0010033 response to organic substance
GO:0010243 response to organonitrogen compound
GO:0014070 response to organic cyclic compound
GO:0014732 skeletal muscle atrophy
GO:0014878 response to electrical stimulus involved in regulation of muscle adaptation
GO:0014911 positive regulation of smooth muscle cell migration
GO:0016310 phosphorylation
GO:0016477 cell migration
GO:0018105 peptidyl-serine phosphorylation
GO:0031929 TOR signaling
GO:0032496 response to lipopolysaccharide
GO:0032868 response to insulin
GO:0032869 cellular response to insulin stimulus
GO:0032870 cellular response to hormone stimulus
GO:0033574 response to testosterone
GO:0033762 response to glucagon
GO:0034612 response to tumor necrosis factor
GO:0042493 response to drug
GO:0043066 negative regulation of apoptotic process
GO:0043200 response to amino acid
GO:0043201 response to leucine
GO:0043434 response to peptide hormone
GO:0043491 protein kinase B signaling
GO:0044539 long-chain fatty acid import
GO:0045471 response to ethanol
GO:0045727 positive regulation of translation
GO:0045931 positive regulation of mitotic cell cycle
GO:0045948 positive regulation of translational initiation
GO:0046324 regulation of glucose import
GO:0046627 negative regulation of insulin receptor signaling pathway
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048633 positive regulation of skeletal muscle tissue growth
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0051384 response to glucocorticoid
GO:0071346 cellular response to interferon-gamma
GO:0071363 cellular response to growth factor stimulus
GO:0071407 cellular response to organic cyclic compound
GO:0071549 cellular response to dexamethasone stimulus
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005741 mitochondrial outer membrane
GO:0005829 cytosol
GO:0009986 cell surface
GO:0016020 membrane
GO:0030054 cell junction
GO:0043005 neuron projection
GO:0045202 synapse
GO:0048471 perinuclear region of cytoplasm


-  Descriptions from all associated GenBank mRNAs
  BC036033 - Homo sapiens ribosomal protein S6 kinase, 70kDa, polypeptide 1, mRNA (cDNA clone IMAGE:5271809), complete cds.
AK293247 - Homo sapiens cDNA FLJ54786 complete cds, highly similar to Ribosomal protein S6 kinase beta-1 (EC 2.7.11.1).
AK300202 - Homo sapiens cDNA FLJ53918 complete cds, highly similar to Ribosomal protein S6 kinase beta-1 (EC 2.7.11.1).
AK312875 - Homo sapiens cDNA, FLJ93319, highly similar to Homo sapiens ribosomal protein S6 kinase, 70kDa, polypeptide 1(RPS6KB1), mRNA.
BC053365 - Homo sapiens ribosomal protein S6 kinase, 70kDa, polypeptide 1, mRNA (cDNA clone MGC:61512 IMAGE:6142009), complete cds.
M60724 - Human p70 ribosomal S6 kinase alpha-I mRNA, complete cds.
AB384946 - Synthetic construct DNA, clone: pF1KB4421, Homo sapiens RPS6KB1 gene for ribosomal protein S6 kinase beta-1, complete cds, without stop codon, in Flexi system.
CU690966 - Synthetic construct Homo sapiens gateway clone IMAGE:100021802 5' read RPS6KB1 mRNA.
KJ901715 - Synthetic construct Homo sapiens clone ccsbBroadEn_11109 RPS6KB1 gene, encodes complete protein.
KJ905310 - Synthetic construct Homo sapiens clone ccsbBroadEn_14833 RPS6KB1 gene, encodes complete protein.
M60725 - Human p70 ribosomal S6 kinase alpha-II mRNA, complete cds.
AK297147 - Homo sapiens cDNA FLJ53847 complete cds, highly similar to Ribosomal protein S6 kinase beta-1 (EC 2.7.11.1).
JD022970 - Sequence 3994 from Patent EP1572962.
JD333974 - Sequence 314998 from Patent EP1572962.
JD286247 - Sequence 267271 from Patent EP1572962.
JD490646 - Sequence 471670 from Patent EP1572962.
JD440706 - Sequence 421730 from Patent EP1572962.
LF209246 - JP 2014500723-A/16749: Polycomb-Associated Non-Coding RNAs.
MA444823 - JP 2018138019-A/16749: Polycomb-Associated Non-Coding RNAs.
JD534099 - Sequence 515123 from Patent EP1572962.
LF327163 - JP 2014500723-A/134666: Polycomb-Associated Non-Coding RNAs.
MA562740 - JP 2018138019-A/134666: Polycomb-Associated Non-Coding RNAs.
LF209245 - JP 2014500723-A/16748: Polycomb-Associated Non-Coding RNAs.
MA444822 - JP 2018138019-A/16748: Polycomb-Associated Non-Coding RNAs.
LF327158 - JP 2014500723-A/134661: Polycomb-Associated Non-Coding RNAs.
MA562735 - JP 2018138019-A/134661: Polycomb-Associated Non-Coding RNAs.
LF327157 - JP 2014500723-A/134660: Polycomb-Associated Non-Coding RNAs.
MA562734 - JP 2018138019-A/134660: Polycomb-Associated Non-Coding RNAs.
JD496594 - Sequence 477618 from Patent EP1572962.
JD048543 - Sequence 29567 from Patent EP1572962.
LF327156 - JP 2014500723-A/134659: Polycomb-Associated Non-Coding RNAs.
MA562733 - JP 2018138019-A/134659: Polycomb-Associated Non-Coding RNAs.
JD059202 - Sequence 40226 from Patent EP1572962.
JD346033 - Sequence 327057 from Patent EP1572962.
JD361657 - Sequence 342681 from Patent EP1572962.
JD337894 - Sequence 318918 from Patent EP1572962.
JD357252 - Sequence 338276 from Patent EP1572962.
JD042404 - Sequence 23428 from Patent EP1572962.
JD103024 - Sequence 84048 from Patent EP1572962.
JD428671 - Sequence 409695 from Patent EP1572962.
JD530793 - Sequence 511817 from Patent EP1572962.
JD549359 - Sequence 530383 from Patent EP1572962.
JD039574 - Sequence 20598 from Patent EP1572962.
JD465061 - Sequence 446085 from Patent EP1572962.
AK091503 - Homo sapiens cDNA FLJ34184 fis, clone FCBBF3017024.
AK026730 - Homo sapiens cDNA: FLJ23077 fis, clone LNG05840.
LF327155 - JP 2014500723-A/134658: Polycomb-Associated Non-Coding RNAs.
MA562732 - JP 2018138019-A/134658: Polycomb-Associated Non-Coding RNAs.
BC030763 - Homo sapiens ribosomal protein S6 kinase, 70kDa, polypeptide 1, mRNA (cDNA clone IMAGE:4799942).

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04012 - ErbB signaling pathway
hsa04150 - mTOR signaling pathway
hsa04350 - TGF-beta signaling pathway
hsa04666 - Fc gamma R-mediated phagocytosis
hsa04910 - Insulin signaling pathway
hsa05221 - Acute myeloid leukemia

BioCarta from NCI Cancer Genome Anatomy Project
h_ctcfPathway - CTCF: First Multivalent Nuclear Factor
h_ptdinsPathway - Phosphoinositides and their downstream targets.
h_rac1Pathway - Rac 1 cell motility signaling pathway
h_eif4Pathway - Regulation of eIF4e and p70 S6 Kinase
h_igf1mtorpathway - Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway
h_il4Pathway - IL 4 signaling pathway
h_mapkPathway - MAPKinase Signaling Pathway
h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart)
h_mTORPathway - mTOR Signaling Pathway
h_il2rbPathway - IL-2 Receptor Beta Chain in T cell Activation

Reactome (by CSHL, EBI, and GO)

Protein P23443 (Reactome details) participates in the following event(s):

R-HSA-165718 mTORC1 phosphorylation of RPS6KB1 (S6K)
R-HSA-165726 Phosphorylation of Ribosomal protein S6 by activated S6K1
R-HSA-165758 Phosphorylation and inactivation of eEF2K by activated S6K1
R-HSA-165766 Phosphorylation and activation of eIF4G by activated S6K1
R-HSA-165777 Phosphorylation and activation of eIF4B by activated S6K1
R-HSA-166208 mTORC1-mediated signalling
R-HSA-165159 mTOR signalling
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: KS6B1_HUMAN, NM_001369672, P23443, STK14A, uc010wom.1, uc010wom.2, uc010wom.3, uc010wom.4
UCSC ID: uc010wom.4
RefSeq Accession: NM_001272044
Protein: P23443 (aka KS6B1_HUMAN)
CCDS: CCDS62273.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.