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Protein

Ribosomal protein S6 kinase alpha-2

Gene

RPS6KA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • intracellular signal transduction Source: GO_Central
  • negative regulation of cell cycle Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • signal transduction Source: ProtInc

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000071242.11
HGNCiHGNC:10431 RPS6KA2
MIMi601685 gene
neXtProtiNX_Q15349

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

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-2DPAGEiQ15349

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

Show more details

Protein-protein interaction databases

BioGridi112110, 30 interactors
DIPiDIP-295N
IntActiQ15349, 15 interactors
MINTiQ15349
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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0598 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00890000139324
HOGENOMiHOG000233033
HOVERGENiHBG108317
InParanoidiQ15349
KOiK04373
PhylomeDBiQ15349
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
IPR016239 Ribosomal_S6_kinase_II
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 2 hits
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000606 Ribsml_S6_kin_2, 1 hit
SMARTiView protein in SMART
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 2 hits
SUPFAMiSSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS00107 PROTEIN_KINASE_ATP, 2 hits
PS50011 PROTEIN_KINASE_DOM, 2 hits
PS00108 PROTEIN_KINASE_ST, 2 hits

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 dbSNP:rs267600891Ensembl.1
Natural variantiVAR_040628732R → Q in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs376029388Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiKS6A2_HUMAN
AccessioniPrimary (citable) accession number: Q15349
Secondary accession number(s): B3KTK9
, Q15419, Q59GJ3, Q5TI68, Q96J38, Q9UJN5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: March 21, 2006
Last modified: April 25, 2018
This is version 185 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

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

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