Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProtKB - P23443 (KS6B1_HUMAN)

(max 400 entries)x

Your basket is currently empty. i

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Ribosomal protein S6 kinase beta-1

Gene

RPS6KB1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:23429703). Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (PubMed:28178239).16 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.4 Publications

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 PDPK1.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei123ATPPROSITE-ProRule annotation1
Active sitei218Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi97 – 105ATPPROSITE-ProRule annotation9

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Cell cycle, Translation regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
ReactomeiR-HSA-166208 mTORC1-mediated signalling
SABIO-RKiP23443
SignaLinkiP23443
SIGNORiP23443

Names & Taxonomyi

Protein namesi
Recommended name:
Ribosomal protein S6 kinase beta-1 (EC:2.7.11.14 Publications)
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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000108443.13
HGNCiHGNC:10436 RPS6KB1
MIMi608938 gene
neXtProtiNX_P23443

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi167K → N: Greatly reduces activity. Greatly reduces phosphorylation at T-412 and moderately reduces phosphorylation at T-252. 1 Publication1
Mutagenesisi394S → A: Loss of activity. Loss of phosphorylation at T-412. 1 Publication1
Mutagenesisi412T → 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 Publications1
Mutagenesisi434S → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-441; E-444 and E-447. 1 Publication1
Mutagenesisi441S → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-444 and E-447. 1 Publication1
Mutagenesisi444T → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-441 and E-447. 1 Publication1
Mutagenesisi447S → E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-441 and E-444. 1 Publication1

Organism-specific databases

DisGeNETi6198
OpenTargetsiENSG00000108443
PharmGKBiPA34851

Chemistry databases

ChEMBLiCHEMBL4501
GuidetoPHARMACOLOGYi1525

Polymorphism and mutation databases

BioMutaiRPS6KB1
DMDMi54041234

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000243421 – 525Ribosomal protein S6 kinase beta-1Add BLAST525

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei252Phosphothreonine; by PDPK12 Publications1
Modified residuei394Phosphoserine1 Publication1
Modified residuei412Phosphothreonine; by MTOR, NEK6 and NEK7By similarity1
Modified residuei434PhosphoserineBy similarity1
Modified residuei441PhosphoserineCombined sources1
Modified residuei444PhosphothreonineCombined sources1 Publication1
Modified residuei447PhosphoserineCombined sources1 Publication1
Modified residuei452PhosphoserineCombined sources1
Modified residuei516N6-acetyllysineBy similarity1

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 similarity5 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP23443
MaxQBiP23443
PaxDbiP23443
PeptideAtlasiP23443
PRIDEiP23443
ProteomicsDBi54095
54096 [P23443-2]

PTM databases

iPTMnetiP23443
PhosphoSitePlusiP23443

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000108443
CleanExiHS_RPS6KB1
ExpressionAtlasiP23443 baseline and differential
GenevisibleiP23443 HS

Organism-specific databases

HPAiCAB003838
CAB018346
HPA039442

Interactioni

Subunit structurei

Interacts with PPP1R9A/neurabin-1 (By similarity). Interacts with RPTOR (PubMed:12150926). Interacts with IRS1 (PubMed:18952604). Interacts with EIF3B and EIF3C (PubMed:16286006). Interacts with TRAF4 (PubMed:12801526). Interacts with POLDIP3 (PubMed:15341740). Interacts (via N-terminus) with IER5 (PubMed:26496226).By similarity6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi112112, 70 interactors
DIPiDIP-29986N
ELMiP23443
IntActiP23443, 29 interactors
MINTiP23443
STRINGi9606.ENSP00000225577

Chemistry databases

BindingDBiP23443

Structurei

Secondary structure

1525
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi88 – 90Combined sources3
Beta strandi91 – 99Combined sources9
Beta strandi101 – 110Combined sources10
Turni114 – 117Combined sources4
Beta strandi119 – 126Combined sources8
Helixi127 – 132Combined sources6
Helixi137 – 149Combined sources13
Beta strandi158 – 164Combined sources7
Beta strandi167 – 173Combined sources7
Helixi180 – 187Combined sources8
Helixi192 – 212Combined sources21
Helixi221 – 223Combined sources3
Beta strandi224 – 226Combined sources3
Beta strandi232 – 234Combined sources3
Beta strandi246 – 249Combined sources4
Beta strandi252 – 255Combined sources4
Helixi262 – 265Combined sources4
Turni266 – 269Combined sources4
Helixi273 – 288Combined sources16
Helixi298 – 307Combined sources10
Beta strandi314 – 316Combined sources3
Helixi318 – 327Combined sources10
Helixi332 – 334Combined sources3
Turni340 – 342Combined sources3
Helixi343 – 347Combined sources5
Helixi350 – 352Combined sources3
Helixi357 – 361Combined sources5
Turni371 – 373Combined sources3
Beta strandi374 – 377Combined sources4
Turni380 – 382Combined sources3
Helixi409 – 411Combined sources3
Beta strandi413 – 415Combined sources3
Helixi418 – 421Combined sources4
Helixi423 – 426Combined sources4
Helixi429 – 431Combined sources3

3D structure databases

ProteinModelPortaliP23443
SMRiP23443
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23443

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini91 – 352Protein kinasePROSITE-ProRule annotationAdd BLAST262
Domaini353 – 423AGC-kinase C-terminalAdd BLAST71

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni424 – 525Autoinhibitory domainAdd BLAST102

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi28 – 32TOS motif5

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

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

Phylogenomic databases

eggNOGiKOG0598 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00920000148962
HOGENOMiHOG000233033
HOVERGENiHBG108317
InParanoidiP23443
KOiK04688
OMAiENCMLNS
OrthoDBiEOG091G05Z7
PhylomeDBiP23443
TreeFamiTF313438

Family and domain databases

InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR011009 Kinase-like_dom_sf
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR016238 Ribosomal_S6_kinase
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000605 Ribsml_S6_kin_1, 1 hit
SMARTiView protein in SMART
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

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

        10         20         30         40         50
MRRRRRRDGF YPAPDFRDRE AEDMAGVFDI DLDQPEDAGS EDELEEGGQL 
        60         70         80         90        100
NESMDHGGVG PYELGMEHCE KFEISETSVN RGPEKIRPEC FELLRVLGKG 
       110        120        130        140        150
GYGKVFQVRK VTGANTGKIF AMKVLKKAMI VRNAKDTAHT KAERNILEEV 
       160        170        180        190        200
KHPFIVDLIY AFQTGGKLYL ILEYLSGGEL FMQLEREGIF MEDTACFYLA 
       210        220        230        240        250
EISMALGHLH QKGIIYRDLK PENIMLNHQG HVKLTDFGLC KESIHDGTVT 
       260        270        280        290        300
HTFCGTIEYM APEILMRSGH NRAVDWWSLG ALMYDMLTGA PPFTGENRKK 
       310        320        330        340        350
TIDKILKCKL NLPPYLTQEA RDLLKKLLKR NAASRLGAGP GDAGEVQAHP 
       360        370        380        390        400
FFRHINWEEL LARKVEPPFK PLLQSEEDVS QFDSKFTRQT PVDSPDDSTL 
       410        420        430        440        450
SESANQVFLG FTYVAPSVLE SVKEKFSFEP KIRSPRRFIG SPRTPVSPVK 
       460        470        480        490        500
FSPGDFWGRG ASASTANPQT PVEYPMETSG IEQMDVTMSG EASAPLPIRQ 
       510        520 
PNSGPYKKQA FPMISKRPEH LRMNL
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)DescriptionActionsGraphical viewLength
Sequence conflicti222E → V in BAG61973 (PubMed:14702039).Curated1
Sequence conflicti428F → L in BAG35726 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040639225M → I1 Publication1
Natural variantiVAR_040640272R → C1 PublicationCorresponds to variant dbSNP:rs766645749Ensembl.1
Natural variantiVAR_040641276W → C1 Publication1
Natural variantiVAR_035628289G → E in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_040642398S → A1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0546131 – 53Missing in isoform 2. 1 PublicationAdd BLAST53
Alternative sequenceiVSP_0188391 – 23Missing in isoform Alpha II. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_055026104 – 126Missing in isoform 4. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_054614448 – 525PVKFS…LRMNL → TAMC in isoform 3. 1 PublicationAdd BLAST78

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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 [P23443-5]
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.5 human [P23443-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKS6B1_HUMAN
AccessioniPrimary (citable) accession number: P23443
Secondary accession number(s): B2R779
, B4DLT4, B4DTG1, E7ESB8, F6UYM1, Q7Z721
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: October 11, 2004
Last modified: July 18, 2018
This is version 194 of the entry and version 2 of the sequence. See 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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health