Descriptions

RSK1 plays an important role in many cellular processes. RSK1 is expressed ubiquitously in almost all human tissues, predominantly in kidney, lung and pancreas.The crystal structure of human RSK1 C-terminal kinase domain (CTKD) is reported at 2.7 횇 resolution. The structure indicates that the autoinhibition of the CTKD is caused by an α-helix occupying the substrate-binding groove.The structure shows autoinhibition of RSK1 CTKD by its αL helix, suggesting that ERK1/2 may activate RSK1 by phosphorylating RSK1 followed by the displacement of αL from its inhibitory position. A similar regulatory mechanism has been observed previously in MAP KAP kinase 2 and murine RSK2 CTKD. The atomic structure of human RSK1 CTKD is of great interest in order to understand the mechanism of RSK activation and for structure-based anticancer-drug development.

Autoinhibitory domains (AIDs)

Target domain

407-664 (Protein kinase domain)

Relief mechanism

PTM

Assay

Accessory elements

204-227 (Activation loop from InterPro)

Target domain

66-371 (N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase)

Relief mechanism

Assay

545-568 (Activation loop from InterPro)

Target domain

407-664 (Protein kinase domain)

Relief mechanism

Assay

Autoinhibited structure

Activated structure

1 structures for P18653

Entry ID Method Resolution Chain Position Source
AF-P18653-F1 Predicted AlphaFoldDB

3 variants for P18653

Variant ID(s) Position Change Description Diseaes Association Provenance
rs13459957 535 E>* No Ensembl
rs221060815 616 T>S No Ensembl
rs251507991 700 T>S No Ensembl

No associated diseases with P18653

9 regional properties for P18653

Type Name Position InterPro Accession
domain Protein kinase domain 62 - 310 IPR000719-1
domain Protein kinase domain 407 - 664 IPR000719-2
domain AGC-kinase, C-terminal 311 - 380 IPR000961
active_site Serine/threonine-protein kinase, active site 183 - 195 IPR008271-1
active_site Serine/threonine-protein kinase, active site 520 - 532 IPR008271-2
binding_site Protein kinase, ATP binding site 68 - 94 IPR017441-1
binding_site Protein kinase, ATP binding site 413 - 436 IPR017441-2
domain Protein kinase, C-terminal 333 - 370 IPR017892
domain Ribosomal S6 kinase, N-terminal catalytic domain 66 - 371 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

5 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.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
spindle The array of microtubules and associated molecules that forms between opposite poles of a eukaryotic cell during mitosis or meiosis and serves to move the duplicated chromosomes apart.

9 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.
DNA-binding transcription factor binding Binding to a DNA-binding transcription factor, a protein that interacts with a specific DNA sequence (sometimes referred to as a motif) within the regulatory region of a gene to modulate transcription.
kinase activity Catalysis of the transfer of a phosphate group, usually from ATP, to a substrate molecule.
magnesium ion binding Binding to a magnesium (Mg) ion.
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.

9 GO annotations of biological process

Name Definition
hepatocyte proliferation The multiplication or reproduction of hepatocytes, resulting in the expansion of a cell population. Hepatocytes form the main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.
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 apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
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 hepatic stellate cell activation Any process that activates or increases the frequency, rate or extent of hepatic stellate cell activation.
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.
positive regulation of transcription, DNA-templated Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
protein phosphorylation The process of introducing a phosphate group on to a protein.

19 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q5F3L1 RPS6KA5 Ribosomal protein S6 kinase alpha-5 Gallus gallus (Chicken) SS
P18652 RPS6KA Ribosomal protein S6 kinase 2 alpha 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
P51812 RPS6KA3 Ribosomal protein S6 kinase alpha-3 Homo sapiens (Human) EV
Q15349 RPS6KA2 Ribosomal protein S6 kinase alpha-2 Homo sapiens (Human) SS
O75582 RPS6KA5 Ribosomal protein S6 kinase alpha-5 Homo sapiens (Human) SS
Q15418 RPS6KA1 Ribosomal protein S6 kinase alpha-1 Homo sapiens (Human) EV
Q8BLK9 Rps6kc1 Ribosomal protein S6 kinase delta-1 Mus musculus (Mouse) PR
P18654 Rps6ka3 Ribosomal protein S6 kinase alpha-3 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
MPLAQLKEPW PLMELVPLDP ENGQTSGEEA GLQPSKDEAI LKEISITHHV KAGSEKADPS
70 80 90 100 110 120
QFELLKVLGQ GSFGKVFLVR KVTRPDSGHL YAMKVLKKAT LKVRDRVRTK MERDILADVN
130 140 150 160 170 180
HPFVVKLHYA FQTEGKLYLI LDFLRGGDLF TRLSKEVMFT EEDVKFYLAE LALGLDHLHS
190 200 210 220 230 240
LGIIYRDLKP ENILLDEEGH IKLTDFGLSK EAIDHEKKAY SFCGTVEYMA PEVVNRQGHT
250 260 270 280 290 300
HSADWWSYGV LMGKDRKETM TLILKAKLGM PQFLSTEAQS LLRALFKRNP ANRLGSGPDG
310 320 330 340 350 360
AEEIKRHIFY STIDWNKLYR REIKPPFKPA VAQPDDTFYF DTEFTSRTPR DSPGIPPSAG
370 380 390 400 410 420
AHQLFRGFSF VATGLMEDDG KPRTTQAPLH SVVQQLHGKN LVFSDGYVVK ETIGVGSYSV
430 440 450 460 470 480
CKRCVHKATN MEYAVKVIDK SKRDPSEEIE ILLRYGQHPN IITLKDVYDD GKHVYLVTEL
490 500 510 520 530 540
MRGGELLDKI LRQKFFSERE ASFVLHTISK TVEYLHSQGV VHRDLKPSNI LYVDESGNPE
550 560 570 580 590 600
CLRICDFGFA KQLRAENGLL MTPCYTANFV APEVLKRQGY DEGCDIWSLG ILLYTMLAGY
610 620 630 640 650 660
TPFANGPSDT PEEILTRIGS GKFTLSGGNW NTVSETAKDL VSKMLHVDPH QRLTAKQVLQ
670 680 690 700 710 720
HPWITQKDKL PQSQLSHQDL QLVKGAMAAT YSALNSSKPT PQLKPIESSI LAQRRVRKLP
STTL