P23443 (KS6B1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	525 AA.
Sequence status	Complete.
Protein existence	Evidence 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 RMP leading to dissociation of a RMP: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. Ref.4 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.14 Ref.16 Ref.18 Ref.20 Ref.22 Ref.25 Ref.26
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 Alpha I and isoform Alpha II are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1. Ref.3 Ref.15 Ref.21
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.5 Ref.6 Ref.7 Ref.10 Ref.18
Subcellular location	Cell junction › synapse › synaptosome By similarity. Mitochondrion outer membrane Ref.16 Ref.20. Isoform Alpha I: Nucleus. Cytoplasm Ref.16 Ref.20. Isoform Alpha II: Cytoplasm Ref.16 Ref.20.
Tissue specificity	Widely expressed. Ref.2
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.
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 process	Apoptosis Cell cycle Translation regulation
Cellular component	Cell junction Cytoplasm Membrane Mitochondrion Mitochondrion outer membrane Nucleus Synapse Synaptosome
Coding sequence diversity	Alternative initiation Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G1/S transition of mitotic cell cycle Inferred from mutant phenotype Ref.9. Source: UniProtKB TOR signaling cascade Inferred from direct assay Ref.5. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW insulin receptor signaling pathway Traceable author statement. Source: Reactome negative regulation of apoptotic process Inferred from mutant phenotype Ref.16. Source: UniProtKB phosphatidylinositol-mediated signaling Traceable author statement Ref.3. Source: UniProtKB positive regulation of mitotic cell cycle Inferred from mutant phenotype Ref.9. Source: UniProtKB positive regulation of translational initiation Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from direct assay Ref.20. Source: UniProtKB cytosol Traceable author statement. Source: Reactome mitochondrial outer membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell synapse Inferred from electronic annotation. Source: UniProtKB-KW synaptosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.5Ref.16Ref.18. Source: UniProtKB protein kinase activity Inferred from direct assay Ref.16Ref.18Ref.20. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PPP2R2B	Q00005	2	EBI-1775921,EBI-1052159

Alternative products

This entry describes 2 isoforms produced by 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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 525

525

Ribosomal protein S6 kinase beta-1

PRO_0000024342

Regions

Domain

91 – 352

262

Protein kinase

Domain

353 – 423

71

AGC-kinase C-terminal

Nucleotide binding

97 – 105

9

ATP By similarity

Region

424 – 525

102

Autoinhibitory domain

Motif

28 – 32

5

TOS motif

Sites

Active site

218

1

Proton acceptor By similarity

Binding site

123

1

ATP By similarity

Amino acid modifications

Modified residue

252

1

Phosphothreonine; by PDPK1 Ref.3 Ref.29

Modified residue

304

1

N6-acetyllysine Ref.24

Modified residue

394

1

Phosphoserine Ref.20

Modified residue

412

1

Phosphothreonine; by MTOR, NEK6 and NEK7 By similarity

Modified residue

441

1

Phosphoserine Ref.11 Ref.19 Ref.23

Modified residue

444

1

Phosphothreonine Ref.11 Ref.19 Ref.20 Ref.23

Modified residue

447

1

Phosphoserine Ref.11 Ref.13 Ref.19 Ref.20 Ref.23

Modified residue

516

1

N6-acetyllysine By similarity

Natural variations

Alternative sequence

1 – 23

23

Missing in isoform Alpha II.

VSP_018839

Natural variant

225

1

M → I. Ref.31

VAR_040639

Natural variant

272

1

R → C. Ref.31

VAR_040640

Natural variant

276

1

W → C. Ref.31

VAR_040641

Natural variant

289

1

G → E in a colorectal cancer sample; somatic mutation. Ref.30

VAR_035628

Natural variant

398

1

S → A. Ref.31

VAR_040642

Experimental info

Mutagenesis

167

1

K → N: Greatly reduces activity. Greatly reduces phosphorylation at T-412 and moderately reduces phosphorylation at T-252. Ref.15

Mutagenesis

394

1

S → A: Loss of activity. Loss of phosphorylation at T-412. Ref.15

Mutagenesis

412

1

T → 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.3 Ref.10 Ref.21

Mutagenesis

434

1

S → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-441; E-444 and E-447. Ref.3

Mutagenesis

441

1

S → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-444 and E-447. Ref.3

Mutagenesis

444

1

T → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-441 and E-447. Ref.3

Mutagenesis

447

1

S → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-441 and E-444. Ref.3

Secondary structure

1

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525

Helix Strand Turn

Details...

Helix

88 – 90

3

Beta strand

91 – 96

6

Beta strand

105 – 110

6

Beta strand

119 – 125

7

Helix

143 – 149

7

Beta strand

158 – 163

6

Beta strand

168 – 173

6

Helix

180 – 186

7

Helix

192 – 205

14

Turn

209 – 211

3

Turn

221 – 223

3

Beta strand

224 – 226

3

Beta strand

232 – 234

3

Helix

262 – 265

4

Helix

273 – 278

6

Helix

282 – 287

6

Helix

298 – 307

10

Helix

318 – 327

10

Helix

332 – 335

4

Turn

346 – 348

3

Helix

350 – 352

3

Helix

357 – 361

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha I (p80-S6K 1) [UniParc]. Last modified October 11, 2004. Version 2. Checksum: 2C3BA13CCDAF4AB3	FASTA	525	59,140
	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
	Isoform Alpha II [UniParc]. Checksum: 2DE6CF3FCABB9FD2	FASTA	502	56,189
	10 20 30 40 50 60 MAGVFDIDLD QPEDAGSEDE LEEGGQLNES MDHGGVGPYE LGMEHCEKFE ISETSVNRGP 70 80 90 100 110 120 EKIRPECFEL LRVLGKGGYG KVFQVRKVTG ANTGKIFAMK VLKKAMIVRN AKDTAHTKAE 130 140 150 160 170 180 RNILEEVKHP FIVDLIYAFQ TGGKLYLILE YLSGGELFMQ LEREGIFMED TACFYLAEIS 190 200 210 220 230 240 MALGHLHQKG IIYRDLKPEN IMLNHQGHVK LTDFGLCKES IHDGTVTHTF CGTIEYMAPE 250 260 270 280 290 300 ILMRSGHNRA VDWWSLGALM YDMLTGAPPF TGENRKKTID KILKCKLNLP PYLTQEARDL 310 320 330 340 350 360 LKKLLKRNAA SRLGAGPGDA GEVQAHPFFR HINWEELLAR KVEPPFKPLL QSEEDVSQFD 370 380 390 400 410 420 SKFTRQTPVD SPDDSTLSES ANQVFLGFTY VAPSVLESVK EKFSFEPKIR SPRRFIGSPR 430 440 450 460 470 480 TPVSPVKFSP GDFWGRGASA STANPQTPVE YPMETSGIEQ MDVTMSGEAS APLPIRQPNS 490 500 GPYKKQAFPM ISKRPEHLRM NL

References

	« Hide 'large scale' referencesShow '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: 1922062] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE INITIATION.
[2]	"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: 9804755] [Abstract] Cited for: TISSUE SPECIFICITY.
[3]	"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: 9445476] [Abstract] Cited for: ENZYME REGULATION, PHOSPHORYLATION AT THR-252, MUTAGENESIS OF THR-412; SER-434; SER-441; THR-444 AND SER-447.
[4]	"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: 11500364] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF EEF2K, FUNCTION IN TRANSLATION REGULATION.
[5]	"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: 12150926] [Abstract] Cited for: INTERACTION WITH RPTOR.
[6]	"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: 12801526] [Abstract] Cited for: FUNCTION, INTERACTION WITH TRAF4.
[7]	"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: 15341740] [Abstract] Cited for: FUNCTION, INTERACTION WITH POLDIP3.
[8]	"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: 15071500] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF EIF4B.
[9]	"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: 14673156] [Abstract] Cited for: FUNCTION IN CELL CYCLE PROGRESSION.
[10]	"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: 16286006] [Abstract] Cited for: FUNCTION IN TRANSLATION INITIATION, INTERACTION WITH EIF3B AND EIF3C, MUTAGENESIS OF THR-412.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-441; THR-444 AND SER-447, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"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: 17052453] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF GSK3B.
[13]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"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: 17053147] [Abstract] Cited for: FUNCTION.
[15]	"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: 17446865] [Abstract] Cited for: ENZYME REGULATION, MUTAGENESIS OF LYS-167 AND SER-394.
[16]	"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: 17936702] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF RMP, SUBCELLULAR LOCATION.
[17]	"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: 18925875] [Abstract] Cited for: PHOSPHORYLATION AT THR-412.
[18]	"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: 18952604] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF IRS1, FUNCTION IN GLUCOSE HOMEOSTASIS, INTERACTION WITH IRS1.
[19]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-441; THR-444 AND SER-447, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"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: 19085255] [Abstract] Cited for: FUNCTION, ALTERNATIVE SPLICING, PHOSPHORYLATION AT SER-394; THR-412; THR-444 AND SER-447, SUBCELLULAR LOCATION.
[21]	"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: 19570988] [Abstract] Cited for: ENZYME REGULATION, MUTAGENESIS OF THR-412.
[22]	"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: 19720745] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF RICTOR.
[23]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-441; THR-444 AND SER-447, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[24]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-304, MASS SPECTROMETRY.
[25]	"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: 19995915] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF RICTOR.
[26]	"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: 19935711] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF RICTOR.
[27]	"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: 18092230] [Abstract] Cited for: REVIEW ON FUNCTION, REVIEW ON ENZYME REGULATION.
[28]	"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: 20932932] [Abstract] Cited for: REVIEW ON FUNCTION, REVIEW ON ENZYME REGULATION.
[29]	"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: 19864428] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 75-399, PHOSPHORYLATION AT THR-252.
[30]	"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. , 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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-289.
[31]	"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. , 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: 17344846] [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.

IPI

IPI00216132.
IPI00759649.

PIR

A41687.

RefSeq

NP_003152.1. NM_003161.2.

UniGene

Hs.463642.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3A60	X-ray	2.80	A/B	75-399	[»]
3A61	X-ray	3.43	A	75-399	[»]
3A62	X-ray	2.35	A	75-399	[»]

ProteinModelPortal

P23443.

SMR

P23443. Positions 85-414.

ModBase

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Protein-protein interaction databases

DIP

DIP-29986N.

IntAct

P23443. 6 interactions.

MINT

MINT-203709.

STRING

P23443.

PTM databases

PhosphoSite

P23443.

Polymorphism databases

DMDM

54041234.

Proteomic databases

PRIDE

P23443.

Protocols and materials databases

StructuralBiologyKnowledgebase

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Genome annotation databases

Ensembl

ENST00000225577; ENSP00000225577; ENSG00000108443.

GeneID

6198.

KEGG

hsa:6198.

UCSC

uc002ixy.1. human.

Organism-specific databases

CTD

6198.

GeneCards

GC17P057970.

H-InvDB

HIX0014049.

HGNC

HGNC:10436. RPS6KB1.

HPA

CAB003838.
CAB018346.

MIM

608938. gene.

neXtProt

NX_P23443.

PharmGKB

PA34851.

GenAtlas

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Phylogenomic databases

eggNOG

prNOG13558.

GeneTree

ENSGT00600000084335.

HOGENOM

HBG755340.

HOVERGEN

HBG108317.

InParanoid

P23443.

OMA

DELEEGX.

OrthoDB

EOG4Q2DFF.

PhylomeDB

P23443.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
igf1_pathway. IGF1 pathway.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il4_2pathway. IL4-mediated signaling events.
insulin_pathway. Insulin Pathway.
avb3_integrin_pathway. Integrins in angiogenesis.
mtor_4pathway. mTOR signaling pathway.
telomerasepathway. Regulation of Telomerase.
rxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
tgfbrpathway. TGF-beta receptor signaling.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P23443.

Bgee

P23443.

CleanEx

HS_RPS6KB1.

Genevestigator

P23443.

GermOnline

ENSG00000108443. Homo sapiens.

Family and domain databases

InterPro

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.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR002290. Ser/Thr_kinase_dom.
[Graphical view]

KO

K04688.

Pfam

PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]

PIRSF

PIRSF000605. Ribsml_S6_kin_1. 1 hit.

SMART

SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS51285. 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]

ProtoNet

Search...

Other

NextBio

24073.

SOURCE

Search...

Entry information

Entry name

KS6B1_HUMAN

Accession

Primary (citable) accession number: P23443

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	October 11, 2004
Last modified:	January 25, 2012
This is version 127 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.