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Protein

Ribosomal protein S6 kinase alpha-2

Gene

RPS6KA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-570 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-377, allowing binding of PDPK1, which in turn phosphorylates Ser-218 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei91ATPPROSITE-ProRule annotation1
Active sitei184Proton acceptorBy similarity1
Binding sitei444ATPPROSITE-ProRule annotation1
Active sitei532Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi65 – 73ATPPROSITE-ProRule annotation9
Nucleotide bindingi421 – 429ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01028-MONOMER.
BRENDAi2.7.11.1. 2681.
ReactomeiR-HSA-198753. ERK/MAPK targets.
R-HSA-199920. CREB phosphorylation.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-437239. Recycling pathway of L1.
R-HSA-442742. CREB phosphorylation through the activation of Ras.
R-HSA-444257. RSK activation.
R-HSA-881907. Gastrin-CREB signalling pathway via PKC and MAPK.
SignaLinkiQ15349.
SIGNORiQ15349.

Names & Taxonomyi

Protein namesi
Recommended name:
Ribosomal protein S6 kinase alpha-2 (EC:2.7.11.1)
Short name:
S6K-alpha-2
Alternative name(s):
90 kDa ribosomal protein S6 kinase 2
Short name:
p90-RSK 2
Short name:
p90RSK2
MAP kinase-activated protein kinase 1c
Short name:
MAPK-activated protein kinase 1c
Short name:
MAPKAP kinase 1c
Short name:
MAPKAPK-1c
Ribosomal S6 kinase 3
Short name:
RSK-3
pp90RSK3
Gene namesi
Name:RPS6KA2
Synonyms:MAPKAPK1C, RSK3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:10431. RPS6KA2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • nuclear membrane Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • spindle Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi6196.
OpenTargetsiENSG00000071242.
PharmGKBiPA34846.

Chemistry databases

ChEMBLiCHEMBL3906.
GuidetoPHARMACOLOGYi1529.

Polymorphism and mutation databases

BioMutaiRPS6KA2.
DMDMi90110031.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862011 – 733Ribosomal protein S6 kinase alpha-2Add BLAST733

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei218Phosphoserine; by PDPK11 Publication1
Modified residuei377PhosphoserineCombined sources1

Post-translational modificationi

Activated by phosphorylation at Ser-218 by PDPK1. Autophosphorylated on Ser-377, as part of the activation process. May be phosphorylated at Thr-356 and Ser-360 by MAPK1/ERK2 and MAPK3/ERK1 (By similarity).By similarity
N-terminal myristoylation results in an activated kinase in the absence of added growth factors.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ15349.
PaxDbiQ15349.
PeptideAtlasiQ15349.
PRIDEiQ15349.

2D gel databases

REPRODUCTION-2DPAGEQ15349.

PTM databases

iPTMnetiQ15349.
PhosphoSitePlusiQ15349.

Expressioni

Tissue specificityi

Widely expressed with higher expression in lung, skeletal muscle, brain, uterus, ovary, thyroid and prostate.2 Publications

Gene expression databases

BgeeiENSG00000071242.
CleanExiHS_RPS6KA2.
ExpressionAtlasiQ15349. baseline and differential.
GenevisibleiQ15349. HS.

Organism-specific databases

HPAiCAB026243.
CAB069428.
HPA045061.
HPA054237.

Interactioni

Subunit structurei

Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells. Transiently dissociates following mitogenic stimulation (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
BRAFP150562EBI-1384149,EBI-365980
MAPK3P273612EBI-1384149,EBI-73995
PRKCEQ021562EBI-1384149,EBI-706254

Protein-protein interaction databases

BioGridi112110. 26 interactors.
DIPiDIP-295N.
IntActiQ15349. 14 interactors.
MINTiMINT-1542928.
STRINGi9606.ENSP00000427015.

Chemistry databases

BindingDBiQ15349.

Structurei

3D structure databases

ProteinModelPortaliQ15349.
SMRiQ15349.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini59 – 318Protein kinase 1PROSITE-ProRule annotationAdd BLAST260
Domaini319 – 388AGC-kinase C-terminalAdd BLAST70
Domaini415 – 672Protein kinase 2PROSITE-ProRule annotationAdd BLAST258

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 2 protein kinase domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00860000133668.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ15349.
KOiK04373.
PhylomeDBiQ15349.
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.
IPR016239. Ribosomal_S6_kinase_II.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 2 hits.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000606. Ribsml_S6_kin_2. 1 hit.
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 2 hits.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 2 hits.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00108. PROTEIN_KINASE_ST. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15349-1) [UniParc]FASTAAdd to basket

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
MDLSMKKFAV RRFFSVYLRR KSRSKSSSLS RLEEEGVVKE IDISHHVKEG
60 70 80 90 100
FEKADPSQFE LLKVLGQGSY GKVFLVRKVK GSDAGQLYAM KVLKKATLKV
110 120 130 140 150
RDRVRSKMER DILAEVNHPF IVKLHYAFQT EGKLYLILDF LRGGDLFTRL
160 170 180 190 200
SKEVMFTEED VKFYLAELAL ALDHLHSLGI IYRDLKPENI LLDEEGHIKI
210 220 230 240 250
TDFGLSKEAI DHDKRAYSFC GTIEYMAPEV VNRRGHTQSA DWWSFGVLMF
260 270 280 290 300
EMLTGSLPFQ GKDRKETMAL ILKAKLGMPQ FLSGEAQSLL RALFKRNPCN
310 320 330 340 350
RLGAGIDGVE EIKRHPFFVT IDWNTLYRKE IKPPFKPAVG RPEDTFHFDP
360 370 380 390 400
EFTARTPTDS PGVPPSANAH HLFRGFSFVA SSLIQEPSQQ DLHKVPVHPI
410 420 430 440 450
VQQLHGNNIH FTDGYEIKED IGVGSYSVCK RCVHKATDTE YAVKIIDKSK
460 470 480 490 500
RDPSEEIEIL LRYGQHPNII TLKDVYDDGK FVYLVMELMR GGELLDRILR
510 520 530 540 550
QRYFSEREAS DVLCTITKTM DYLHSQGVVH RDLKPSNILY RDESGSPESI
560 570 580 590 600
RVCDFGFAKQ LRAGNGLLMT PCYTANFVAP EVLKRQGYDA ACDIWSLGIL
610 620 630 640 650
LYTMLAGFTP FANGPDDTPE EILARIGSGK YALSGGNWDS ISDAAKDVVS
660 670 680 690 700
KMLHVDPHQR LTAMQVLKHP WVVNREYLSP NQLSRQDVHL VKGAMAATYF
710 720 730
ALNRTPQAPR LEPVLSSNLA QRRGMKRLTS TRL
Length:733
Mass (Da):83,239
Last modified:March 21, 2006 - v2
Checksum:i087CFB819A313760
GO
Isoform 2 (identifier: Q15349-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-32: MDLSMKKFAVRRFFSVYLRRKSRSKSSSLSRL → MPIAQLLELW...ACKTKVAGSV

Note: No experimental confirmation available.
Show »
Length:758
Mass (Da):85,532
Checksum:i1C30759D0B188D4A
GO
Isoform 3 (identifier: Q15349-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-32: MDLSMKKFAVRRFFSVYLRRKSRSKSSSLSRL → MPIAQLLELWKKIEVEPMEIETTEEDLNLDVEPTTEDTAE

Show »
Length:741
Mass (Da):84,014
Checksum:i146D3569D1C9A193
GO

Sequence cautioni

The sequence AAC82496 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAD92353 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAG53121 differs from that shown. Reason: Frameshift at position 527.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti256S → A in AAC82496 (PubMed:8141249).Curated1
Sequence conflicti269A → S in AAC82496 (PubMed:8141249).Curated1
Sequence conflicti339V → L in CAA59427 (PubMed:7623830).Curated1
Sequence conflicti339V → L in AAC82496 (PubMed:8141249).Curated1
Sequence conflicti447D → G in AAC82496 (PubMed:8141249).Curated1
Isoform 3 (identifier: Q15349-3)
Sequence conflicti32E → G in BAG53121 (PubMed:14702039).Curated1
Sequence conflicti34T → A in BAG53121 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040627311E → K in a metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant rs267600891dbSNPEnsembl.1
Natural variantiVAR_040628732R → Q in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant rs376029388dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0177321 – 32MDLSM…SLSRL → MPIAQLLELWKKIEVEPMEI ETTEEDLNLDVGPATEDTAE EGKSDSAACKTKVAGSV in isoform 2. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_0418361 – 32MDLSM…SLSRL → MPIAQLLELWKKIEVEPMEI ETTEEDLNLDVEPTTEDTAE in isoform 3. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X85106 mRNA. Translation: CAA59427.1.
AB209116 mRNA. Translation: BAD92353.1. Different initiation.
AK095751 mRNA. Translation: BAG53121.1. Frameshift.
AL022069, Z98049 Genomic DNA. Translation: CAI19651.1.
AL023775 Genomic DNA. No translation available.
AL159163 Genomic DNA. No translation available.
Z98049, AL022069 Genomic DNA. Translation: CAI20579.1.
BC002363 mRNA. Translation: AAH02363.1.
L07598 mRNA. Translation: AAC82496.1. Different initiation.
CCDSiCCDS34570.1. [Q15349-3]
CCDS5294.1. [Q15349-1]
CCDS83148.1. [Q15349-2]
PIRiA57459.
RefSeqiNP_001006933.2. NM_001006932.2.
NP_001305865.1. NM_001318936.1.
NP_001305866.1. NM_001318937.1.
NP_001305867.1. NM_001318938.1.
NP_066958.2. NM_021135.5. [Q15349-1]
UniGeneiHs.655277.

Genome annotation databases

EnsembliENST00000265678; ENSP00000265678; ENSG00000071242. [Q15349-1]
ENST00000503859; ENSP00000427015; ENSG00000071242. [Q15349-3]
GeneIDi6196.
KEGGihsa:6196.
UCSCiuc003qvb.2. human. [Q15349-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X85106 mRNA. Translation: CAA59427.1.
AB209116 mRNA. Translation: BAD92353.1. Different initiation.
AK095751 mRNA. Translation: BAG53121.1. Frameshift.
AL022069, Z98049 Genomic DNA. Translation: CAI19651.1.
AL023775 Genomic DNA. No translation available.
AL159163 Genomic DNA. No translation available.
Z98049, AL022069 Genomic DNA. Translation: CAI20579.1.
BC002363 mRNA. Translation: AAH02363.1.
L07598 mRNA. Translation: AAC82496.1. Different initiation.
CCDSiCCDS34570.1. [Q15349-3]
CCDS5294.1. [Q15349-1]
CCDS83148.1. [Q15349-2]
PIRiA57459.
RefSeqiNP_001006933.2. NM_001006932.2.
NP_001305865.1. NM_001318936.1.
NP_001305866.1. NM_001318937.1.
NP_001305867.1. NM_001318938.1.
NP_066958.2. NM_021135.5. [Q15349-1]
UniGeneiHs.655277.

3D structure databases

ProteinModelPortaliQ15349.
SMRiQ15349.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112110. 26 interactors.
DIPiDIP-295N.
IntActiQ15349. 14 interactors.
MINTiMINT-1542928.
STRINGi9606.ENSP00000427015.

Chemistry databases

BindingDBiQ15349.
ChEMBLiCHEMBL3906.
GuidetoPHARMACOLOGYi1529.

PTM databases

iPTMnetiQ15349.
PhosphoSitePlusiQ15349.

Polymorphism and mutation databases

BioMutaiRPS6KA2.
DMDMi90110031.

2D gel databases

REPRODUCTION-2DPAGEQ15349.

Proteomic databases

MaxQBiQ15349.
PaxDbiQ15349.
PeptideAtlasiQ15349.
PRIDEiQ15349.

Protocols and materials databases

DNASUi6196.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265678; ENSP00000265678; ENSG00000071242. [Q15349-1]
ENST00000503859; ENSP00000427015; ENSG00000071242. [Q15349-3]
GeneIDi6196.
KEGGihsa:6196.
UCSCiuc003qvb.2. human. [Q15349-1]

Organism-specific databases

CTDi6196.
DisGeNETi6196.
GeneCardsiRPS6KA2.
HGNCiHGNC:10431. RPS6KA2.
HPAiCAB026243.
CAB069428.
HPA045061.
HPA054237.
MIMi601685. gene.
neXtProtiNX_Q15349.
OpenTargetsiENSG00000071242.
PharmGKBiPA34846.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00860000133668.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ15349.
KOiK04373.
PhylomeDBiQ15349.
TreeFamiTF313438.

Enzyme and pathway databases

BioCyciZFISH:HS01028-MONOMER.
BRENDAi2.7.11.1. 2681.
ReactomeiR-HSA-198753. ERK/MAPK targets.
R-HSA-199920. CREB phosphorylation.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-437239. Recycling pathway of L1.
R-HSA-442742. CREB phosphorylation through the activation of Ras.
R-HSA-444257. RSK activation.
R-HSA-881907. Gastrin-CREB signalling pathway via PKC and MAPK.
SignaLinkiQ15349.
SIGNORiQ15349.

Miscellaneous databases

ChiTaRSiRPS6KA2. human.
GeneWikiiRPS6KA2.
GenomeRNAii6196.
PROiQ15349.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000071242.
CleanExiHS_RPS6KA2.
ExpressionAtlasiQ15349. baseline and differential.
GenevisibleiQ15349. HS.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016239. Ribosomal_S6_kinase_II.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 2 hits.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000606. Ribsml_S6_kin_2. 1 hit.
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 2 hits.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 2 hits.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00108. PROTEIN_KINASE_ST. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKS6A2_HUMAN
AccessioniPrimary (citable) accession number: Q15349
Secondary accession number(s): B3KTK9
, Q15419, Q59GJ3, Q5TI68, Q96J38, Q9UJN5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: March 21, 2006
Last modified: November 30, 2016
This is version 175 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.