RPS6KA4

Protein identityUniProt · HPA

UniProt accession

O75676

Gene

RPS6KA4

Ensembl

ENSG00000162302

Chromosome

11

Canonical length

772 aa

Protein class

Enzymes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates various substrates, including CREB1 and ATF1. The encoded protein can also phosphorylate histone H3 to regulate certain inflammatory genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

Canonical amino-acid sequenceUniProt

772 residues, UniProt reviewed canonical sequence.

>O75676|RPS6KA4
     1  MGDEDDDESC AVELRITEAN LTGHEEKVSV ENFELLKVLG TGAYGKVFLV RKAGGHDAGK
    61  LYAMKVLRKA ALVQRAKTQE HTRTERSVLE LVRQAPFLVT LHYAFQTDAK LHLILDYVSG
   121  GEMFTHLYQR QYFKEAEVRV YGGEIVLALE HLHKLGIIYR DLKLENVLLD SEGHIVLTDF
   181  GLSKEFLTEE KERTFSFCGT IEYMAPEIIR SKTGHGKAVD WWSLGILLFE LLTGASPFTL
   241  EGERNTQAEV SRRILKCSPP FPPRIGPVAQ DLLQRLLCKD PKKRLGAGPQ GAQEVRNHPF
   301  FQGLDWVALA ARKIPAPFRP QIRSELDVGN FAEEFTRLEP VYSPPGSPPP GDPRIFQGYS
   361  FVAPSILFDH NNAVMTDGLE APGAGDRPGR AAVARSAMMQ DSPFFQQYEL DLREPALGQG
   421  SFSVCRRCRQ RQSGQEFAVK ILSRRLEANT QREVAALRLC QSHPNVVNLH EVHHDQLHTY
   481  LVLELLRGGE LLEHIRKKRH FSESEASQIL RSLVSAVSFM HEEAGVVHRD LKPENILYAD
   541  DTPGAPVKII DFGFARLRPQ SPGVPMQTPC FTLQYAAPEL LAQQGYDESC DLWSLGVILY
   601  MMLSGQVPFQ GASGQGGQSQ AAEIMCKIRE GRFSLDGEAW QGVSEEAKEL VRGLLTVDPA
   661  KRLKLEGLRG SSWLQDGSAR SSPPLRTPDV LESSGPAVRS GLNATFMAFN RGKREGFFLK
   721  SVENAPLAKR RKQKLRSATA SRRGSPAPAN PGRAPVASKG APRRANGPLP PS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RPS6KA4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

54 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.27

gnomAD pLI

1

gnomAD missense Z

3.7

DepMap mean gene effect

-0.2

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• inflammatory response
• interleukin-1-mediated signaling pathway
• intracellular signal transduction
• negative regulation of cytokine production
• positive regulation of CREB transcription factor activity
• positive regulation of NF-kappaB transcription factor activity
• positive regulation of transcription by RNA polymerase II
• post-translational protein modification
• protein phosphorylation
• regulation of DNA-templated transcription
• TORC1 signaling

Molecular functions

• ATP binding
• histone H3S10 kinase activity
• histone H3S28 kinase activity
• magnesium ion binding
• protein serine kinase activity
• protein serine/threonine kinase activity
• ribosomal protein S6 kinase activity

Cellular components

• cytoplasm
• cytosol
• nucleoplasm
• nucleus
• synapse

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• AGC-kinase, C-terminal
• Serine/threonine-protein kinase, active site
• Protein kinase-like domain superfamily
• Ribosomal protein S6 kinase II
• Protein kinase, ATP binding site
• Protein kinase, C-terminal
• Protein kinase domain
• Protein kinase C terminal domain
• MSK2, N-terminal catalytic domain

KeywordsUniProt

• ATP-binding
• Inflammatory response
• Kinase
• Magnesium
• Metal-binding
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Repeat
• Serine/threonine-protein kinase
• Stress response
• Transferase

InteractionsUniProt · HPA

Protein binding partners of RPS6KA4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CDC37
• CSNK2B
• HSP90AB1
• MAPK14
• MYLK2