UniProtKB - Q15349 (KS6A2_HUMAN)
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Protein
Ribosomal protein S6 kinase alpha-2
Gene
RPS6KA2
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 91 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 184 | Proton acceptorBy similarity | 1 | |
Binding sitei | 444 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 532 | Proton acceptorBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 65 – 73 | ATPPROSITE-ProRule annotation | 9 | |
Nucleotide bindingi | 421 – 429 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- kinase activity Source: Reactome
- magnesium ion binding Source: InterPro
- protein serine/threonine/tyrosine kinase activity Source: MGI
- protein serine/threonine kinase activity Source: GO_Central
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 function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.1. 2681. |
Reactomei | R-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. |
SignaLinki | Q15349. |
SIGNORi | Q15349. |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000071242.11. |
HGNCi | HGNC:10431. RPS6KA2. |
MIMi | 601685. gene. |
neXtProti | NX_Q15349. |
Pathology & Biotechi
Keywords - Diseasei
Tumor suppressorOrganism-specific databases
DisGeNETi | 6196. |
OpenTargetsi | ENSG00000071242. |
PharmGKBi | PA34846. |
Chemistry databases
ChEMBLi | CHEMBL3906. |
GuidetoPHARMACOLOGYi | 1529. |
Polymorphism and mutation databases
BioMutai | RPS6KA2. |
DMDMi | 90110031. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086201 | 1 – 733 | Ribosomal protein S6 kinase alpha-2Add BLAST | 733 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 218 | Phosphoserine; by PDPK11 Publication | 1 | |
Modified residuei | 377 | PhosphoserineCombined sources | 1 |
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
PhosphoproteinProteomic databases
MaxQBi | Q15349. |
PaxDbi | Q15349. |
PeptideAtlasi | Q15349. |
PRIDEi | Q15349. |
2D gel databases
REPRODUCTION-2DPAGEi | Q15349. |
PTM databases
iPTMneti | Q15349. |
PhosphoSitePlusi | Q15349. |
Expressioni
Tissue specificityi
Widely expressed with higher expression in lung, skeletal muscle, brain, uterus, ovary, thyroid and prostate.2 Publications
Gene expression databases
Bgeei | ENSG00000071242. |
CleanExi | HS_RPS6KA2. |
ExpressionAtlasi | Q15349. baseline and differential. |
Genevisiblei | Q15349. HS. |
Organism-specific databases
HPAi | CAB026243. 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
Protein-protein interaction databases
BioGridi | 112110. 29 interactors. |
DIPi | DIP-295N. |
IntActi | Q15349. 15 interactors. |
MINTi | Q15349. |
STRINGi | 9606.ENSP00000427015. |
Chemistry databases
BindingDBi | Q15349. |
Structurei
3D structure databases
ProteinModelPortali | Q15349. |
SMRi | Q15349. |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 59 – 318 | Protein kinase 1PROSITE-ProRule annotationAdd BLAST | 260 | |
Domaini | 319 – 388 | AGC-kinase C-terminalAdd BLAST | 70 | |
Domaini | 415 – 672 | Protein kinase 2PROSITE-ProRule annotationAdd BLAST | 258 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.Curated
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG0598. Eukaryota. ENOG410XNPH. LUCA. |
GeneTreei | ENSGT00890000139324. |
HOGENOMi | HOG000233033. |
HOVERGENi | HBG108317. |
InParanoidi | Q15349. |
KOi | K04373. |
PhylomeDBi | Q15349. |
TreeFami | TF313438. |
Family and domain databases
InterProi | View 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. |
Pfami | View protein in Pfam PF00069. Pkinase. 2 hits. PF00433. Pkinase_C. 1 hit. |
PIRSFi | PIRSF000606. Ribsml_S6_kin_2. 1 hit. |
SMARTi | View protein in SMART SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 2 hits. |
SUPFAMi | SSF56112. SSF56112. 2 hits. |
PROSITEi | View 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. |
s (3)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative 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.
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
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Sequence conflicti | 256 | S → A in AAC82496 (PubMed:8141249).Curated | 1 | ||
Sequence conflicti | 269 | A → S in AAC82496 (PubMed:8141249).Curated | 1 | ||
Sequence conflicti | 339 | V → L in CAA59427 (PubMed:7623830).Curated | 1 | ||
Sequence conflicti | 339 | V → L in AAC82496 (PubMed:8141249).Curated | 1 | ||
Sequence conflicti | 447 | D → G in AAC82496 (PubMed:8141249).Curated | 1 | ||
Isoform 3 (identifier: Q15349-3) | |||||
Sequence conflicti | 32 | E → G in BAG53121 (PubMed:14702039).Curated | 1 | ||
Sequence conflicti | 34 | T → A in BAG53121 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040627 | 311 | E → K in a metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs267600891Ensembl. | 1 | |
Natural variantiVAR_040628 | 732 | R → Q in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs376029388Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_017732 | 1 – 32 | MDLSM…SLSRL → MPIAQLLELWKKIEVEPMEI ETTEEDLNLDVGPATEDTAE EGKSDSAACKTKVAGSV in isoform 2. 1 PublicationAdd BLAST | 32 | |
Alternative sequenceiVSP_041836 | 1 – 32 | MDLSM…SLSRL → MPIAQLLELWKKIEVEPMEI ETTEEDLNLDVEPTTEDTAE in isoform 3. 1 PublicationAdd BLAST | 32 |
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. |
CCDSi | CCDS34570.1. [Q15349-3] CCDS5294.1. [Q15349-1] CCDS83148.1. [Q15349-2] |
PIRi | A57459. |
RefSeqi | NP_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] |
UniGenei | Hs.655277. |
Genome annotation databases
Ensembli | ENST00000265678; ENSP00000265678; ENSG00000071242. [Q15349-1] ENST00000503859; ENSP00000427015; ENSG00000071242. [Q15349-3] |
GeneIDi | 6196. |
KEGGi | hsa:6196. |
UCSCi | uc003qvb.2. human. [Q15349-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | KS6A2_HUMAN | |
Accessioni | Q15349Primary (citable) accession number: Q15349 Secondary accession number(s): B3KTK9 Q9UJN5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
Last sequence update: | March 21, 2006 | |
Last modified: | March 28, 2018 | |
This is version 184 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |