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P23443

- KS6B1_HUMAN

UniProt

P23443 - KS6B1_HUMAN

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Protein
Ribosomal protein S6 kinase beta-1
Gene
RPS6KB1, STK14A
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.15 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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 PDPK1.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei123 – 1231ATP By similarity
Active sitei218 – 2181Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi97 – 1059ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. peptide binding Source: Ensembl
  3. protein binding Source: IntAct
  4. protein kinase activity Source: UniProtKB
  5. protein serine/threonine kinase activity Source: UniProtKB-KW
  6. protein serine/threonine/tyrosine kinase activity Source: MGI
  7. ribosomal protein S6 kinase activity Source: Ensembl

GO - Biological processi

  1. G1/S transition of mitotic cell cycle Source: UniProtKB
  2. TOR signaling Source: UniProtKB
  3. aging Source: Ensembl
  4. apoptotic process Source: UniProtKB-KW
  5. cell migration Source: Ensembl
  6. cellular response to growth factor stimulus Source: UniProtKB
  7. germ cell development Source: Ensembl
  8. insulin receptor signaling pathway Source: Reactome
  9. long-term memory Source: Ensembl
  10. negative regulation of apoptotic process Source: UniProtKB
  11. negative regulation of extrinsic apoptotic signaling pathway Source: Ensembl
  12. negative regulation of insulin receptor signaling pathway Source: UniProtKB
  13. phosphatidylinositol-mediated signaling Source: UniProtKB
  14. positive regulation of mitotic cell cycle Source: UniProtKB
  15. positive regulation of skeletal muscle tissue growth Source: Ensembl
  16. positive regulation of smooth muscle cell migration Source: Ensembl
  17. positive regulation of smooth muscle cell proliferation Source: Ensembl
  18. positive regulation of translation Source: UniProtKB
  19. positive regulation of translational initiation Source: UniProtKB
  20. protein kinase B signaling Source: Ensembl
  21. protein phosphorylation Source: GOC
  22. regulation of glucose import Source: Ensembl
  23. response to drug Source: Ensembl
  24. response to electrical stimulus involved in regulation of muscle adaptation Source: Ensembl
  25. response to ethanol Source: Ensembl
  26. response to glucagon Source: Ensembl
  27. response to glucocorticoid Source: Ensembl
  28. response to glucose Source: Ensembl
  29. response to heat Source: Ensembl
  30. response to leucine Source: Ensembl
  31. response to lipopolysaccharide Source: Ensembl
  32. response to mechanical stimulus Source: Ensembl
  33. response to nutrient Source: Ensembl
  34. response to testosterone Source: Ensembl
  35. response to toxic substance Source: Ensembl
  36. response to tumor necrosis factor Source: Ensembl
  37. response to wounding Source: Ensembl
  38. signal transduction Source: InterPro
  39. skeletal muscle atrophy Source: Ensembl
  40. skeletal muscle contraction Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle, Translation regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiREACT_6754. S6K1-mediated signalling.
REACT_6772. S6K1 signalling.
SignaLinkiB2R779.
B4DTG1.
F6UYM1.
P23443.

Names & Taxonomyi

Protein namesi
Recommended name:
Ribosomal protein S6 kinase beta-1 (EC:2.7.11.1)
Short name:
S6K-beta-1
Short name:
S6K1
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 namesi
Name:RPS6KB1
Synonyms:STK14A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:10436. RPS6KB1.

Subcellular locationi

Cell junctionsynapsesynaptosome By similarity. Mitochondrion outer membrane. Mitochondrion
Note: Colocalizes with URI1 at mitochondrion.2 Publications
Isoform Alpha I : Nucleus. Cytoplasm 2 Publications
Isoform Alpha II : Cytoplasm 2 Publications

GO - Cellular componenti

  1. cell junction Source: UniProtKB-KW
  2. cell surface Source: Ensembl
  3. cytoplasm Source: UniProtKB
  4. cytosol Source: Reactome
  5. mitochondrial outer membrane Source: UniProtKB-SubCell
  6. mitochondrion Source: UniProtKB
  7. neuron projection Source: UniProtKB-SubCell
  8. nucleus Source: HPA
  9. perinuclear region of cytoplasm Source: Ensembl
  10. ribosome Source: UniProtKB-KW
  11. synapse Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Membrane, Mitochondrion, Mitochondrion outer membrane, Nucleus, Synapse, Synaptosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi167 – 1671K → N: Greatly reduces activity. Greatly reduces phosphorylation at T-412 and moderately reduces phosphorylation at T-252. 1 Publication
Mutagenesisi394 – 3941S → A: Loss of activity. Loss of phosphorylation at T-412. 1 Publication
Mutagenesisi412 – 4121T → 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. 3 Publications
Mutagenesisi434 – 4341S → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-441; E-444 and E-447. 1 Publication
Mutagenesisi441 – 4411S → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-444 and E-447. 1 Publication
Mutagenesisi444 – 4441T → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-441 and E-447. 1 Publication
Mutagenesisi447 – 4471S → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-441 and E-444. 1 Publication

Organism-specific databases

PharmGKBiPA34851.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 525525Ribosomal protein S6 kinase beta-1
PRO_0000024342Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei252 – 2521Phosphothreonine; by PDPK12 Publications
Modified residuei394 – 3941Phosphoserine1 Publication
Modified residuei412 – 4121Phosphothreonine; by MTOR, NEK6 and NEK7 By similarity
Modified residuei434 – 4341Phosphoserine By similarity
Modified residuei441 – 4411Phosphoserine1 Publication
Modified residuei444 – 4441Phosphothreonine2 Publications
Modified residuei447 – 4471Phosphoserine3 Publications
Modified residuei452 – 4521Phosphoserine1 Publication
Modified residuei516 – 5161N6-acetyllysine By similarity

Post-translational modificationi

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.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP23443.
PaxDbiP23443.
PRIDEiP23443.

PTM databases

PhosphoSiteiP23443.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

ArrayExpressiP23443.
BgeeiP23443.
CleanExiHS_RPS6KB1.
GenevestigatoriP23443.

Organism-specific databases

HPAiCAB003838.
CAB018346.
HPA039442.

Interactioni

Subunit structurei

Interacts with PPP1R9A/neurabin-1 By similarity. Interacts with RPTOR. Interacts with IRS1. Interacts with EIF3B and EIF3C. Interacts with POLDIP3 and TRAF4.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GLI1P081514EBI-1775921,EBI-308084
PPP2R2BQ000052EBI-1775921,EBI-1052159

Protein-protein interaction databases

BioGridi112112. 54 interactions.
DIPiDIP-29986N.
IntActiP23443. 19 interactions.
MINTiMINT-203709.
STRINGi9606.ENSP00000225577.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi88 – 903
Beta strandi91 – 999
Beta strandi101 – 11010
Turni114 – 1174
Beta strandi119 – 1279
Turni128 – 1325
Helixi134 – 14916
Beta strandi158 – 1636
Beta strandi165 – 1739
Helixi180 – 1878
Helixi192 – 21120
Helixi221 – 2233
Beta strandi224 – 2263
Beta strandi232 – 2343
Beta strandi246 – 2494
Helixi262 – 2665
Helixi273 – 28816
Helixi298 – 30710
Beta strandi314 – 3163
Helixi318 – 32710
Helixi332 – 3343
Turni340 – 3423
Helixi343 – 3475
Helixi350 – 3523
Helixi357 – 3615
Helixi371 – 3733
Beta strandi374 – 3774
Turni380 – 3823
Helixi409 – 4113
Beta strandi413 – 4153

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliP23443.
SMRiP23443. Positions 81-417.

Miscellaneous databases

EvolutionaryTraceiP23443.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini91 – 352262Protein kinase
Add
BLAST
Domaini353 – 42371AGC-kinase C-terminal
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni424 – 525102Autoinhibitory domain
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi28 – 325TOS motif

Domaini

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.

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiP23443.
KOiK04688.
OMAiANRMPAR.
PhylomeDBiP23443.
TreeFamiTF313438.

Family and domain databases

InterProiIPR000961. 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]
PfamiPF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000605. Ribsml_S6_kin_1. 1 hit.
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing and alternative initiation. Align

Note: Additional isoforms seem to exist.

Isoform Alpha I (identifier: P23443-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MRRRRRRDGF YPAPDFRDRE AEDMAGVFDI DLDQPEDAGS EDELEEGGQL    50
NESMDHGGVG PYELGMEHCE KFEISETSVN RGPEKIRPEC FELLRVLGKG 100
GYGKVFQVRK VTGANTGKIF AMKVLKKAMI VRNAKDTAHT KAERNILEEV 150
KHPFIVDLIY AFQTGGKLYL ILEYLSGGEL FMQLEREGIF MEDTACFYLA 200
EISMALGHLH QKGIIYRDLK PENIMLNHQG HVKLTDFGLC KESIHDGTVT 250
HTFCGTIEYM APEILMRSGH NRAVDWWSLG ALMYDMLTGA PPFTGENRKK 300
TIDKILKCKL NLPPYLTQEA RDLLKKLLKR NAASRLGAGP GDAGEVQAHP 350
FFRHINWEEL LARKVEPPFK PLLQSEEDVS QFDSKFTRQT PVDSPDDSTL 400
SESANQVFLG FTYVAPSVLE SVKEKFSFEP KIRSPRRFIG SPRTPVSPVK 450
FSPGDFWGRG ASASTANPQT PVEYPMETSG IEQMDVTMSG EASAPLPIRQ 500
PNSGPYKKQA FPMISKRPEH LRMNL 525
Length:525
Mass (Da):59,140
Last modified:October 11, 2004 - v2
Checksum:i2C3BA13CCDAF4AB3
GO
Isoform Alpha II (identifier: P23443-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: Missing.

Show »
Length:502
Mass (Da):56,189
Checksum:i2DE6CF3FCABB9FD2
GO
Isoform 2 (identifier: P23443-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: Missing.

Note: No experimental confirmation available.

Show »
Length:472
Mass (Da):52,997
Checksum:iC7296AB8D6151840
GO
Isoform 4 (identifier: P23443-5) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     104-126: Missing.

Show »
Length:502
Mass (Da):56,593
Checksum:iA4021FE84D488609
GO
Isoform 3 (identifier: P23443-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     448-525: PVKFSPGDFW...KRPEHLRMNL → TAMC

Note: No experimental confirmation available.

Show »
Length:451
Mass (Da):51,016
Checksum:iDE4CDC28ADBA8927
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti225 – 2251M → I.1 Publication
VAR_040639
Natural varianti272 – 2721R → C.1 Publication
VAR_040640
Natural varianti276 – 2761W → C.1 Publication
VAR_040641
Natural varianti289 – 2891G → E in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_035628
Natural varianti398 – 3981S → A.1 Publication
VAR_040642

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5353Missing in isoform 2.
VSP_054613Add
BLAST
Alternative sequencei1 – 2323Missing in isoform Alpha II.
VSP_018839Add
BLAST
Alternative sequencei104 – 12623Missing in isoform 4.
VSP_055026Add
BLAST
Alternative sequencei448 – 52578PVKFS…LRMNL → TAMC in isoform 3.
VSP_054614Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti222 – 2221E → V in BAG61973. 1 Publication
Sequence conflicti428 – 4281F → L in BAG35726. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS11621.1. [P23443-1]
CCDS62271.1. [P23443-4]
CCDS62273.1. [P23443-3]
PIRiA41687.
RefSeqiNP_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]
UniGeneiHs.463642.

Genome annotation databases

EnsembliENST00000225577; ENSP00000225577; ENSG00000108443. [P23443-1]
ENST00000393021; ENSP00000376744; ENSG00000108443.
ENST00000406116; ENSP00000384335; ENSG00000108443.
ENST00000443572; ENSP00000441993; ENSG00000108443.
GeneIDi6198.
KEGGihsa:6198.
UCSCiuc002ixy.4. human. [P23443-1]
uc010ddj.3. human.

Polymorphism databases

DMDMi54041234.

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS11621.1. [P23443-1 ]
CCDS62271.1. [P23443-4 ]
CCDS62273.1. [P23443-3 ]
PIRi A41687.
RefSeqi NP_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 ]
UniGenei Hs.463642.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
4L3J X-ray 2.10 A 75-375 [» ]
4L3L X-ray 2.10 A 75-375 [» ]
4L42 X-ray 2.80 A 75-417 [» ]
4L43 X-ray 3.00 A 75-417 [» ]
4L44 X-ray 2.90 A 75-417 [» ]
4L45 X-ray 2.90 A 75-417 [» ]
4L46 X-ray 3.01 A 75-417 [» ]
ProteinModelPortali P23443.
SMRi P23443. Positions 81-417.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112112. 54 interactions.
DIPi DIP-29986N.
IntActi P23443. 19 interactions.
MINTi MINT-203709.
STRINGi 9606.ENSP00000225577.

Chemistry

BindingDBi P23443.
ChEMBLi CHEMBL4501.
GuidetoPHARMACOLOGYi 1525.

PTM databases

PhosphoSitei P23443.

Polymorphism databases

DMDMi 54041234.

Proteomic databases

MaxQBi P23443.
PaxDbi P23443.
PRIDEi P23443.

Protocols and materials databases

DNASUi 6198.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000225577 ; ENSP00000225577 ; ENSG00000108443 . [P23443-1 ]
ENST00000393021 ; ENSP00000376744 ; ENSG00000108443 .
ENST00000406116 ; ENSP00000384335 ; ENSG00000108443 .
ENST00000443572 ; ENSP00000441993 ; ENSG00000108443 .
GeneIDi 6198.
KEGGi hsa:6198.
UCSCi uc002ixy.4. human. [P23443-1 ]
uc010ddj.3. human.

Organism-specific databases

CTDi 6198.
GeneCardsi GC17P057970.
HGNCi HGNC:10436. RPS6KB1.
HPAi CAB003838.
CAB018346.
HPA039442.
MIMi 608938. gene.
neXtProti NX_P23443.
PharmGKBi PA34851.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233033.
HOVERGENi HBG108317.
InParanoidi P23443.
KOi K04688.
OMAi ANRMPAR.
PhylomeDBi P23443.
TreeFami TF313438.

Enzyme and pathway databases

BRENDAi 2.7.11.1. 2681.
Reactomei REACT_6754. S6K1-mediated signalling.
REACT_6772. S6K1 signalling.
SignaLinki B2R779.
B4DTG1.
F6UYM1.
P23443.

Miscellaneous databases

ChiTaRSi RPS6KB1. human.
EvolutionaryTracei P23443.
GeneWikii P70-S6_Kinase_1.
GenomeRNAii 6198.
NextBioi 24073.
PROi P23443.
SOURCEi Search...

Gene expression databases

ArrayExpressi P23443.
Bgeei P23443.
CleanExi HS_RPS6KB1.
Genevestigatori P23443.

Family and domain databases

InterProi IPR000961. 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 ]
Pfami PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view ]
PIRSFi PIRSF000605. Ribsml_S6_kin_1. 1 hit.
SMARTi SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi 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 ]
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Publicationsi

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  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.
    , 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.
    , 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. 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. 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. 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. 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. Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 75-399, PHOSPHORYLATION AT THR-252.
  33. 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.
    , 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.

Entry informationi

Entry nameiKS6B1_HUMAN
AccessioniPrimary (citable) accession number: P23443
Secondary accession number(s): B2R779
, B4DLT4, B4DTG1, E7ESB8, F6UYM1, Q7Z721
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: October 11, 2004
Last modified: September 3, 2014
This is version 156 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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