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P23443 (KS6B1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ribosomal protein S6 kinase beta-1

Short name=S6K-beta-1
Short name=S6K1
EC=2.7.11.1
Alternative name(s):
70 kDa ribosomal protein S6 kinase 1
Short name=P70S6K1
Short name=p70-S6K 1
Ribosomal protein S6 kinase I
Serine/threonine-protein kinase 14A
p70 ribosomal S6 kinase alpha
Short name=p70 S6 kinase alpha
Short name=p70 S6K-alpha
Short name=p70 S6KA
Gene names
Name:RPS6KB1
Synonyms:STK14A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length525 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 pre-initiation 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. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR. Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.20 Ref.22 Ref.24 Ref.26 Ref.27 Ref.31

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

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 AlphaI and isoform AlphaII are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1. Ref.7 Ref.17 Ref.23

Subunit structure

Interacts with PPP1R9A/neurabin-1 By similarity. Interacts with RPTOR. Interacts with IRS1. Interacts with EIF3B and EIF3C. Interacts with POLDIP3 and TRAF4. Ref.9 Ref.10 Ref.11 Ref.14 Ref.20

Subcellular location

Cell junctionsynapsesynaptosome By similarity. Mitochondrion outer membrane. Mitochondrion. Note: Colocalizes with URI1 at mitochondrion. Ref.18 Ref.22

Isoform Alpha I: Nucleus. Cytoplasm Ref.18 Ref.22.

Isoform Alpha II: Cytoplasm Ref.18 Ref.22.

Tissue specificity

Widely expressed. Ref.6

Domain

The autoinhibitory domain is believed to block phosphorylation within the AGC-kinase C-terminal domain and the activation loop.

The TOS (TOR signaling) motif is essential for activation by mTORC1 By similarity.

Post-translational modification

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.

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
Translation regulation
   Cellular componentCell junction
Cytoplasm
Membrane
Mitochondrion
Mitochondrion outer membrane
Nucleus
Synapse
Synaptosome
   Coding sequence diversityAlternative initiation
Alternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from mutant phenotype Ref.13. Source: UniProtKB

TOR signaling

Inferred from direct assay Ref.9. Source: UniProtKB

aging

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell migration

Inferred from electronic annotation. Source: Ensembl

cellular response to growth factor stimulus

Inferred from direct assay Ref.18. Source: UniProtKB

germ cell development

Inferred from electronic annotation. Source: Ensembl

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

long-term memory

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.18. Source: UniProtKB

negative regulation of extrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of insulin receptor signaling pathway

Inferred from mutant phenotype Ref.20. Source: UniProtKB

phosphatidylinositol-mediated signaling

Traceable author statement Ref.7. Source: UniProtKB

positive regulation of mitotic cell cycle

Inferred from mutant phenotype Ref.13. Source: UniProtKB

positive regulation of skeletal muscle tissue growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of smooth muscle cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of translation

Inferred from mutant phenotype PubMed 18423201. Source: UniProtKB

positive regulation of translational initiation

Inferred from mutant phenotype PubMed 16763566. Source: UniProtKB

protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay Ref.22. Source: GOC

regulation of glucose import

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to electrical stimulus involved in regulation of muscle adaptation

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to glucagon

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

response to heat

Inferred from electronic annotation. Source: Ensembl

response to leucine

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

response to testosterone

Inferred from electronic annotation. Source: Ensembl

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

response to tumor necrosis factor

Inferred from electronic annotation. Source: Ensembl

response to wounding

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.1. Source: ProtInc

skeletal muscle atrophy

Inferred from electronic annotation. Source: Ensembl

skeletal muscle contraction

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cell surface

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay Ref.22. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

mitochondrial outer membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from direct assay Ref.18. Source: UniProtKB

neuron projection

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay. Source: HPA

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

synapse

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

peptide binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 22439934. Source: IntAct

protein kinase activity

Inferred from direct assay Ref.18Ref.20Ref.22. Source: UniProtKB

ribosomal protein S6 kinase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GLI1P081514EBI-1775921,EBI-308084
PPP2R2BQ000052EBI-1775921,EBI-1052159

Alternative products

This entry describes 5 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform Alpha I (identifier: P23443-1)

Also known as: p80-S6K 1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Alpha II (identifier: P23443-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: Missing.
Isoform 2 (identifier: P23443-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: P23443-5)

The sequence of this isoform differs from the canonical sequence as follows:
     104-126: Missing.
Isoform 3 (identifier: P23443-4)

The sequence of this isoform differs from the canonical sequence as follows:
     448-525: PVKFSPGDFW...KRPEHLRMNL → TAMC
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 525525Ribosomal protein S6 kinase beta-1
PRO_0000024342

Regions

Domain91 – 352262Protein kinase
Domain353 – 42371AGC-kinase C-terminal
Nucleotide binding97 – 1059ATP By similarity
Region424 – 525102Autoinhibitory domain
Motif28 – 325TOS motif

Sites

Active site2181Proton acceptor By similarity
Binding site1231ATP By similarity

Amino acid modifications

Modified residue2521Phosphothreonine; by PDPK1 Ref.7 Ref.32
Modified residue3941Phosphoserine Ref.22
Modified residue4121Phosphothreonine; by MTOR, NEK6 and NEK7 By similarity
Modified residue4341Phosphoserine By similarity
Modified residue4411Phosphoserine Ref.29
Modified residue4441Phosphothreonine Ref.22 Ref.29
Modified residue4471Phosphoserine Ref.22 Ref.25 Ref.29
Modified residue4521Phosphoserine Ref.29
Modified residue5161N6-acetyllysine By similarity

Natural variations

Alternative sequence1 – 5353Missing in isoform 2.
VSP_054613
Alternative sequence1 – 2323Missing in isoform Alpha II.
VSP_018839
Alternative sequence104 – 12623Missing in isoform 4.
VSP_055026
Alternative sequence448 – 52578PVKFS…LRMNL → TAMC in isoform 3.
VSP_054614
Natural variant2251M → I. Ref.34
VAR_040639
Natural variant2721R → C. Ref.34
VAR_040640
Natural variant2761W → C. Ref.34
VAR_040641
Natural variant2891G → E in a colorectal cancer sample; somatic mutation. Ref.33
VAR_035628
Natural variant3981S → A. Ref.34
VAR_040642

Experimental info

Mutagenesis1671K → N: Greatly reduces activity. Greatly reduces phosphorylation at T-412 and moderately reduces phosphorylation at T-252. Ref.17
Mutagenesis3941S → A: Loss of activity. Loss of phosphorylation at T-412. Ref.17
Mutagenesis4121T → E: Mimics phosphorylation. Facilitates phosphorylation of T-252 by PDPK1; when associated with E-434; E-441; E-444 and E-447. Mimics phosphorylation. No effect on interaction with PDPK1 and phosphorylation of T-252. Impairs association with the eIF3 complex. Ref.7 Ref.14 Ref.23
Mutagenesis4341S → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-441; E-444 and E-447. Ref.7
Mutagenesis4411S → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-444 and E-447. Ref.7
Mutagenesis4441T → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-441 and E-447. Ref.7
Mutagenesis4471S → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-441 and E-444. Ref.7
Sequence conflict2221E → V in BAG61973. Ref.2
Sequence conflict4281F → L in BAG35726. Ref.2

Secondary structure

........................................................ 525
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha I (p80-S6K 1) [UniParc].

Last modified October 11, 2004. Version 2.
Checksum: 2C3BA13CCDAF4AB3

FASTA52559,140
        10         20         30         40         50         60 
MRRRRRRDGF YPAPDFRDRE AEDMAGVFDI DLDQPEDAGS EDELEEGGQL NESMDHGGVG 

        70         80         90        100        110        120 
PYELGMEHCE KFEISETSVN RGPEKIRPEC FELLRVLGKG GYGKVFQVRK VTGANTGKIF 

       130        140        150        160        170        180 
AMKVLKKAMI VRNAKDTAHT KAERNILEEV KHPFIVDLIY AFQTGGKLYL ILEYLSGGEL 

       190        200        210        220        230        240 
FMQLEREGIF MEDTACFYLA EISMALGHLH QKGIIYRDLK PENIMLNHQG HVKLTDFGLC 

       250        260        270        280        290        300 
KESIHDGTVT HTFCGTIEYM APEILMRSGH NRAVDWWSLG ALMYDMLTGA PPFTGENRKK 

       310        320        330        340        350        360 
TIDKILKCKL NLPPYLTQEA RDLLKKLLKR NAASRLGAGP GDAGEVQAHP FFRHINWEEL 

       370        380        390        400        410        420 
LARKVEPPFK PLLQSEEDVS QFDSKFTRQT PVDSPDDSTL SESANQVFLG FTYVAPSVLE 

       430        440        450        460        470        480 
SVKEKFSFEP KIRSPRRFIG SPRTPVSPVK FSPGDFWGRG ASASTANPQT PVEYPMETSG 

       490        500        510        520 
IEQMDVTMSG EASAPLPIRQ PNSGPYKKQA FPMISKRPEH LRMNL 

« Hide

Isoform Alpha II [UniParc].

Checksum: 2DE6CF3FCABB9FD2
Show »

FASTA50256,189
Isoform 2 [UniParc].

Checksum: C7296AB8D6151840
Show »

FASTA47252,997
Isoform 4 [UniParc].

Checksum: A4021FE84D488609
Show »

FASTA50256,593
Isoform 3 [UniParc].

Checksum: DE4CDC28ADBA8927
Show »

FASTA45151,016

References

« Hide 'large scale' references
[1]"Cloning and expression of two human p70 S6 kinase polypeptides differing only at their amino termini."
Grove J., Bonerjee P., Balasubramanyam A., Coffer P., Price D.J., Avruch J., Woodgett J.R.
Mol. Cell. Biol. 11:5541-5550(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA I AND ALPHA II), ALTERNATIVE INITIATION.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA I; 2 AND 4).
Tissue: Placenta and Trachea.
[3]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Eye.
[6]"Molecular cloning and characterization of a novel p70 S6 kinase, p70 S6 kinase beta containing a proline-rich region."
Gout I., Minami T., Hara K., Tsujishita Y., Filonenko V., Waterfield M.D., Yonezawa K.
J. Biol. Chem. 273:30061-30064(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[7]"Phosphorylation and activation of p70s6k by PDK1."
Pullen N., Dennis P.B., Andjelkovic M., Dufner A., Kozma S.C., Hemmings B.A., Thomas G.
Science 279:707-710(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, PHOSPHORYLATION AT THR-252, MUTAGENESIS OF THR-412; SER-434; SER-441; THR-444 AND SER-447.
[8]"Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase."
Wang X., Li W., Williams M., Terada N., Alessi D.R., Proud C.G.
EMBO J. 20:4370-4379(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF EEF2K, FUNCTION IN TRANSLATION REGULATION.
[9]"Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action."
Hara K., Maruki Y., Long X., Yoshino K., Oshiro N., Hidayat S., Tokunaga C., Avruch J., Yonezawa K.
Cell 110:177-189(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RPTOR.
[10]"Tumor necrosis factor receptor-associated factor (TRAF) 4 is a new binding partner for the p70S6 serine/threonine kinase."
Fleckenstein D.S., Dirks W.G., Drexler H.G., Quentmeier H.
Leuk. Res. 27:687-694(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TRAF4.
[11]"SKAR is a specific target of S6 kinase 1 in cell growth control."
Richardson C.J., Broenstrup M., Fingar D.C., Julich K., Ballif B.A., Gygi S., Blenis J.
Curr. Biol. 14:1540-1549(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH POLDIP3.
[12]"Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases."
Raught B., Peiretti F., Gingras A.C., Livingstone M., Shahbazian D., Mayeur G.L., Polakiewicz R.D., Sonenberg N., Hershey J.W.
EMBO J. 23:1761-1769(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF EIF4B.
[13]"mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E."
Fingar D.C., Richardson C.J., Tee A.R., Cheatham L., Tsou C., Blenis J.
Mol. Cell. Biol. 24:200-216(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL CYCLE PROGRESSION.
[14]"mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events."
Holz M.K., Ballif B.A., Gygi S.P., Blenis J.
Cell 123:569-580(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TRANSLATION INITIATION, INTERACTION WITH EIF3B AND EIF3C, MUTAGENESIS OF THR-412.
[15]"S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt."
Zhang H.H., Lipovsky A.I., Dibble C.C., Sahin M., Manning B.D.
Mol. Cell 24:185-197(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF GSK3B.
[16]"S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth."
Dorrello N.V., Peschiaroli A., Guardavaccaro D., Colburn N.H., Sherman N.E., Pagano M.
Science 314:467-471(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[17]"Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation."
Hauge C., Antal T.L., Hirschberg D., Doehn U., Thorup K., Idrissova L., Hansen K., Jensen O.N., Jorgensen T.J., Biondi R.M., Frodin M.
EMBO J. 26:2251-2261(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, MUTAGENESIS OF LYS-167 AND SER-394.
[18]"S6K1-mediated disassembly of mitochondrial URI/PP1gamma complexes activates a negative feedback program that counters S6K1 survival signaling."
Djouder N., Metzler S.C., Schmidt A., Wirbelauer C., Gstaiger M., Aebersold R., Hess D., Krek W.
Mol. Cell 28:28-40(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF URI1, DEPHOSPHORYLATION AT THR-412 BY PPP1CC, SUBCELLULAR LOCATION.
[19]"mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)."
Garcia-Martinez J.M., Alessi D.R.
Biochem. J. 416:375-385(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-412.
[20]"S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2."
Zhang J., Gao Z., Yin J., Quon M.J., Ye J.
J. Biol. Chem. 283:35375-35382(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF IRS1, FUNCTION IN GLUCOSE HOMEOSTASIS, INTERACTION WITH IRS1.
[21]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"Regulation and localization of ribosomal protein S6 kinase 1 isoforms."
Kim D., Akcakanat A., Singh G., Sharma C., Meric-Bernstam F.
Growth Factors 27:12-21(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ALTERNATIVE SPLICING, PHOSPHORYLATION AT SER-394; THR-412; THR-444 AND SER-447, SUBCELLULAR LOCATION.
[23]"Mechanism of PDK1-catalyzed Thr-229 phosphorylation of the S6K1 protein kinase."
Keshwani M.M., Gao X., Harris T.K.
J. Biol. Chem. 284:22611-22624(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, MUTAGENESIS OF THR-412.
[24]"Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1."
Dibble C.C., Asara J.M., Manning B.D.
Mol. Cell. Biol. 29:5657-5670(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RICTOR.
[25]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[26]"mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling."
Julien L.A., Carriere A., Moreau J., Roux P.P.
Mol. Cell. Biol. 30:908-921(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RICTOR.
[27]"Rictor is a novel target of p70 S6 kinase-1."
Treins C., Warne P.H., Magnuson M.A., Pende M., Downward J.
Oncogene 29:1003-1016(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RICTOR.
[28]"Coordinate regulation of ribosome biogenesis and function by the ribosomal protein S6 kinase, a key mediator of mTOR function."
Jastrzebski K., Hannan K.M., Tchoubrieva E.B., Hannan R.D., Pearson R.B.
Growth Factors 25:209-226(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION, REVIEW ON ENZYME REGULATION.
[29]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-441; THR-444; SER-447 AND SER-452, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[30]"Functions and regulation of the 70kDa ribosomal S6 kinases."
Fenton T.R., Gout I.T.
Int. J. Biochem. Cell Biol. 43:47-59(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION, REVIEW ON ENZYME REGULATION.
[31]"Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1."
Ben-Sahra I., Howell J.J., Asara J.M., Manning B.D.
Science 339:1323-1328(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION OF CAD, PHOSPHORYLATION BY MTOR.
[32]"Structural basis of human p70 ribosomal S6 kinase-1 regulation by activation loop phosphorylation."
Sunami T., Byrne N., Diehl R.E., Funabashi K., Hall D.L., Ikuta M., Patel S.B., Shipman J.M., Smith R.F., Takahashi I., Zugay-Murphy J., Iwasawa Y., Lumb K.J., Munshi S.K., Sharma S.
J. Biol. Chem. 285:4587-4594(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 75-399, PHOSPHORYLATION AT THR-252.
[33]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-289.
[34]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ILE-225; CYS-272; CYS-276 AND ALA-398.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M60724 mRNA. Translation: AAA36410.1.
M60725 mRNA. Translation: AAA36411.1.
AK297147 mRNA. Translation: BAG59646.1.
AK300202 mRNA. Translation: BAG61973.1.
AK312875 mRNA. Translation: BAG35726.1.
AC004686 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94384.1.
BC053365 mRNA. Translation: AAH53365.1.
CCDSCCDS11621.1. [P23443-1]
PIRA41687.
RefSeqNP_001258971.1. NM_001272042.1.
NP_001258972.1. NM_001272043.1. [P23443-4]
NP_001258973.1. NM_001272044.1. [P23443-3]
NP_001258989.1. NM_001272060.1. [P23443-2]
NP_003152.1. NM_003161.3. [P23443-1]
UniGeneHs.463642.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3A60X-ray2.80A/B75-399[»]
3A61X-ray3.43A75-399[»]
3A62X-ray2.35A75-399[»]
4L3JX-ray2.10A75-375[»]
4L3LX-ray2.10A75-375[»]
4L42X-ray2.80A75-417[»]
4L43X-ray3.00A75-417[»]
4L44X-ray2.90A75-417[»]
4L45X-ray2.90A75-417[»]
4L46X-ray3.01A75-417[»]
ProteinModelPortalP23443.
SMRP23443. Positions 81-417.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112112. 54 interactions.
DIPDIP-29986N.
IntActP23443. 19 interactions.
MINTMINT-203709.
STRING9606.ENSP00000225577.

Chemistry

BindingDBP23443.
ChEMBLCHEMBL4501.
GuidetoPHARMACOLOGY1525.

PTM databases

PhosphoSiteP23443.

Polymorphism databases

DMDM54041234.

Proteomic databases

MaxQBP23443.
PaxDbP23443.
PRIDEP23443.

Protocols and materials databases

DNASU6198.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000225577; ENSP00000225577; ENSG00000108443. [P23443-1]
ENST00000393021; ENSP00000376744; ENSG00000108443.
ENST00000406116; ENSP00000384335; ENSG00000108443.
ENST00000443572; ENSP00000441993; ENSG00000108443.
GeneID6198.
KEGGhsa:6198.
UCSCuc002ixy.4. human. [P23443-1]

Organism-specific databases

CTD6198.
GeneCardsGC17P057970.
HGNCHGNC:10436. RPS6KB1.
HPACAB003838.
CAB018346.
HPA039442.
MIM608938. gene.
neXtProtNX_P23443.
PharmGKBPA34851.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidP23443.
KOK04688.
OMAANRMPAR.
PhylomeDBP23443.
TreeFamTF313438.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_111102. Signal Transduction.
SignaLinkB2R779.
B4DTG1.
F6UYM1.
P23443.

Gene expression databases

ArrayExpressP23443.
BgeeP23443.
CleanExHS_RPS6KB1.
GenevestigatorP23443.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016238. Ribosomal_S6_kinase.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000605. Ribsml_S6_kin_1. 1 hit.
SMARTSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRPS6KB1. human.
EvolutionaryTraceP23443.
GeneWikiP70-S6_Kinase_1.
GenomeRNAi6198.
NextBio24073.
PROP23443.
SOURCESearch...

Entry information

Entry nameKS6B1_HUMAN
AccessionPrimary (citable) accession number: P23443
Secondary accession number(s): B2R779 expand/collapse secondary AC list , B4DLT4, B4DTG1, E7ESB8, F6UYM1, Q7Z721
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: October 11, 2004
Last modified: July 9, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM