Descriptions

The 90-kDa ribosomal S6 kinase 2 (RSK2) is broadly expressed in response to growth factors, peptide hormones, neurotransmitters, chemokines and other stimuli. The scaffold of the RSK2 CTD is stabilized by the αL-helix, which occupies the 쁟radle, rather than by the T-loop. On the basis of this structure of the CTD of RSK2, ERKs are likely to be involved in abolishing the autoinhibitory function of the CTD. The ERKs binding site (residues 726735) is located at the RSK2 C terminus close to the αL-helix (residues 696710). Efficient activation of RSK2 requires interaction with extracellular signal뱑egulated protein kinases (ERKs) at a docking site in the RSK2 C terminus (residues 726735) and subsequent phosphorylation of Thr577 in the CTD T-activation loop.

Autoinhibitory domains (AIDs)

Target domain

422-679 (Protein kinase domain)

Relief mechanism

PTM, Partner binding

Assay

Accessory elements

210-233 (Activation loop from InterPro)

Target domain

72-388 (N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase)

Relief mechanism

Assay

560-583 (Activation loop from InterPro)

Target domain

402-740 (C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2, also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)

Relief mechanism

Assay

Autoinhibited structure

Activated structure

10 structures for P18654

Entry ID Method Resolution Chain Position Source
2QR7 X-ray 200 A A 399-740 PDB
2QR8 X-ray 200 A A 399-740 PDB
3G51 X-ray 180 A A 44-367 PDB
3UBD X-ray 153 A A 45-346 PDB
4EL9 X-ray 155 A A 45-346 PDB
4GUE X-ray 180 A A 45-346 PDB
4M8T X-ray 300 A A 399-740 PDB
4MAO X-ray 260 A A 399-740 PDB
5O1S X-ray 190 A A 400-740 PDB
AF-P18654-F1 Predicted AlphaFoldDB

No variants for P18654

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P18654

No associated diseases with P18654

10 regional properties for P18654

Type Name Position InterPro Accession
domain Protein kinase domain 68 - 327 IPR000719-1
domain Protein kinase domain 422 - 679 IPR000719-2
domain AGC-kinase, C-terminal 328 - 397 IPR000961
active_site Serine/threonine-protein kinase, active site 189 - 201 IPR008271-1
active_site Serine/threonine-protein kinase, active site 535 - 547 IPR008271-2
binding_site Protein kinase, ATP binding site 74 - 100 IPR017441-1
binding_site Protein kinase, ATP binding site 428 - 451 IPR017441-2
domain Protein kinase, C-terminal 351 - 387 IPR017892
domain Ribosomal protein S6 kinase alpha-3, C-terminal catalytic domain 402 - 740 IPR041905
domain Ribosomal S6 kinase, N-terminal catalytic domain 72 - 388 IPR041906

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • Nucleus
  • Cytoplasm
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

4 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nucleolus A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.

8 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
cysteine-type endopeptidase inhibitor activity involved in apoptotic process Binds to and stops, prevents or reduces the activity of a cysteine-type endopeptidase involved in the apoptotic process.
magnesium ion binding Binding to a magnesium (Mg) ion.
protein kinase binding Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein serine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
ribosomal protein S6 kinase activity Catalysis of the reaction: ribosomal protein S6 + ATP = ribosomal protein S6 phosphate + ATP.

7 GO annotations of biological process

Name Definition
cell cycle The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division.
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of a cysteine-type endopeptidase activity involved in the apoptotic process.
peptidyl-serine phosphorylation The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
positive regulation of transcription by RNA polymerase II Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
response to lipopolysaccharide Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
toll-like receptor signaling pathway The series of molecular signals initiated by a ligand binding to a toll-like receptor on the surface of a target cell. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate an innate immune response.

19 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P18652 RPS6KA Ribosomal protein S6 kinase 2 alpha Gallus gallus (Chicken) SS
Q5F3L1 RPS6KA5 Ribosomal protein S6 kinase alpha-5 Gallus gallus (Chicken) SS
Q9UK32 RPS6KA6 Ribosomal protein S6 kinase alpha-6 Homo sapiens (Human) SS
O75676 RPS6KA4 Ribosomal protein S6 kinase alpha-4 Homo sapiens (Human) SS
Q96S38 RPS6KC1 Ribosomal protein S6 kinase delta-1 Homo sapiens (Human) PR
Q15349 RPS6KA2 Ribosomal protein S6 kinase alpha-2 Homo sapiens (Human) SS
Q15418 RPS6KA1 Ribosomal protein S6 kinase alpha-1 Homo sapiens (Human) EV
O75582 RPS6KA5 Ribosomal protein S6 kinase alpha-5 Homo sapiens (Human) SS
P51812 RPS6KA3 Ribosomal protein S6 kinase alpha-3 Homo sapiens (Human) EV
Q8BLK9 Rps6kc1 Ribosomal protein S6 kinase delta-1 Mus musculus (Mouse) PR
P18653 Rps6ka1 Ribosomal protein S6 kinase alpha-1 Mus musculus (Mouse) SS
Q9WUT3 Rps6ka2 Ribosomal protein S6 kinase alpha-2 Mus musculus (Mouse) SS
Q9Z2B9 Rps6ka4 Ribosomal protein S6 kinase alpha-4 Mus musculus (Mouse) SS
Q8C050 Rps6ka5 Ribosomal protein S6 kinase alpha-5 Mus musculus (Mouse) PR
Q9Z1M4 Rps6kb2 Ribosomal protein S6 kinase beta-2 Mus musculus (Mouse) SS
Q8BSK8 Rps6kb1 Ribosomal protein S6 kinase beta-1 Mus musculus (Mouse) SS
Q63531 Rps6ka1 Ribosomal protein S6 kinase alpha-1 Rattus norvegicus (Rat) SS
Q18846 rskn-2 Putative ribosomal protein S6 kinase alpha-2 Caenorhabditis elegans PR
Q21734 rskn-1 Putative ribosomal protein S6 kinase alpha-1 Caenorhabditis elegans SS
10 20 30 40 50 60
MPLAQLADPW QKMAVESPSD SAENGQQIMD EPMGEEEINP QTEEGSIKEI AITHHVKEGH
70 80 90 100 110 120
EKADPSQFEL LKVLGQGSFG KVFLVKKISG SDARQLYAMK VLKKATLKVR DRVRTKMERD
130 140 150 160 170 180
ILVEVNHPFI VKLHYAFQTE GKLYLILDFL RGGDLFTRLS KEVMFTEEDV KFYLAELALA
190 200 210 220 230 240
LDHLHSLGII YRDLKPENIL LDEEGHIKLT DFGLSKESID HEKKAYSFCG TVEYMAPEVV
250 260 270 280 290 300
NRRGHTQSAD WWSFGVLMFE MLTGTLPFQG KDRKETMTMI LKAKLGMPQF LSPEAQSLLR
310 320 330 340 350 360
MLFKRNPANR LGAGPDGVEE IKRHSFFSTI DWNKLYRREI HPPFKPATGR PEDTFYFDPE
370 380 390 400 410 420
FTAKTPKDSP GIPPSANAHQ LFRGFSFVAI TSDDESQAMQ TVGVHSIVQQ LHRNSIQFTD
430 440 450 460 470 480
GYEVKEDIGV GSYSVCKRCI HKATNMEFAV KIIDKSKRDP TEEIEILLRY GQHPNIITLK
490 500 510 520 530 540
DVYDDGKYVY VVTELMKGGE LLDKILRQKF FSEREASAVL FTITKTVEYL HAQGVVHRDL
550 560 570 580 590 600
KPSNILYVDE SGNPESIRIC DFGFAKQLRA ENGLLMTPCY TANFVAPEVL KRQGYDAACD
610 620 630 640 650 660
IWSLGVLLYT MLTGYTPFAN GPDDTPEEIL ARIGSGKFSL SGGYWNSVSD TAKDLVSKML
670 680 690 700 710 720
HVDPHQRLTA ALVLRHPWIV HWDQLPQYQL NRQDAPHLVK GAMAATYSAL NRNQSPVLEP
730
VGRSTLAQRR GIKKITSTAL