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P23443

- KS6B1_HUMAN

UniProt

P23443 - KS6B1_HUMAN

Protein

Ribosomal protein S6 kinase beta-1

Gene

RPS6KB1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 157 (01 Oct 2014)
      Sequence version 2 (11 Oct 2004)
      Previous versions | rss
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    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 – 1231ATPPROSITE-ProRule annotation
    Active sitei218 – 2181Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi97 – 1059ATPPROSITE-ProRule annotation

    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/tyrosine kinase activity Source: MGI
    6. ribosomal protein S6 kinase activity Source: Ensembl

    GO - Biological processi

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

    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.

    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. synapse Source: UniProtKB-KW

    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-1PRO_0000024342Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei252 – 2521Phosphothreonine; by PDPK13 Publications
    Modified residuei394 – 3941Phosphoserine2 Publications
    Modified residuei412 – 4121Phosphothreonine; by MTOR, NEK6 and NEK7By similarity
    Modified residuei434 – 4341PhosphoserineBy similarity
    Modified residuei441 – 4411Phosphoserine2 Publications
    Modified residuei444 – 4441Phosphothreonine3 Publications
    Modified residuei447 – 4471Phosphoserine4 Publications
    Modified residuei452 – 4521Phosphoserine2 Publications
    Modified residuei516 – 5161N6-acetyllysineBy 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.By similarity7 Publications

    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.By similarity5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    AKT1P317492EBI-1775921,EBI-296087
    GLI1P081514EBI-1775921,EBI-308084
    PPP2R2BQ000052EBI-1775921,EBI-1052159

    Protein-protein interaction databases

    BioGridi112112. 54 interactions.
    DIPiDIP-29986N.
    IntActiP23443. 21 interactions.
    MINTiMINT-203709.
    STRINGi9606.ENSP00000225577.

    Structurei

    Secondary structure

    1
    525
    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP23443.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini91 – 352262Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini353 – 42371AGC-kinase C-terminalAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni424 – 525102Autoinhibitory domainAdd
    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

    Contains 1 AGC-kinase C-terminal domain.Curated
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti222 – 2221E → V in BAG61973. (PubMed:14702039)Curated
    Sequence conflicti428 – 4281F → L in BAG35726. (PubMed:14702039)Curated

    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. 1 PublicationVSP_054613Add
    BLAST
    Alternative sequencei1 – 2323Missing in isoform Alpha II. 1 PublicationVSP_018839Add
    BLAST
    Alternative sequencei104 – 12623Missing in isoform 4. 1 PublicationVSP_055026Add
    BLAST
    Alternative sequencei448 – 52578PVKFS…LRMNL → TAMC in isoform 3. 1 PublicationVSP_054614Add
    BLAST

    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]
    CCDS62272.1. [P23443-5]
    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. [P23443-3]
    ENST00000406116; ENSP00000384335; ENSG00000108443. [P23443-4]
    ENST00000443572; ENSP00000441993; ENSG00000108443. [P23443-5]
    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 ]
    CCDS62272.1. [P23443-5 ]
    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. 21 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 . [P23443-3 ]
    ENST00000406116 ; ENSP00000384335 ; ENSG00000108443 . [P23443-4 ]
    ENST00000443572 ; ENSP00000441993 ; ENSG00000108443 . [P23443-5 ]
    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 ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 157 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