UniProtKB - Q9UK32 (KS6A6_HUMAN)
Protein
Ribosomal protein S6 kinase alpha-6
Gene
RPS6KA6
Organism
Homo sapiens (Human)
Status
Functioni
Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis.2 Publications
Catalytic activityi
Cofactori
Mg2+By similarity
Activity regulationi
Constitutively activated by phosphorylation at Ser-232, Ser-372, and Ser-389 in serum-starved cells. Does not require growth factor stimulation for significant kinase activity.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 105 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 198 | Proton acceptorBy similarity | 1 | |
Binding sitei | 455 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 543 | Proton acceptorBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 79 – 87 | ATPPROSITE-ProRule annotation | 9 | |
Nucleotide bindingi | 432 – 440 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- magnesium ion binding Source: InterPro
- protein kinase activity Source: ProtInc
- protein serine kinase activity Source: UniProtKB-EC
- protein threonine kinase activity Source: UniProtKB-EC
- ribosomal protein S6 kinase activity Source: GO_Central
GO - Biological processi
- central nervous system development Source: ProtInc
- DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: UniProtKB
- negative regulation of embryonic development Source: UniProtKB
- negative regulation of ERK1 and ERK2 cascade Source: UniProtKB
- negative regulation of mesoderm development 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 |
PathwayCommonsi | Q9UK32 |
Reactomei | R-HSA-437239, Recycling pathway of L1 R-HSA-442742, CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling R-HSA-444257, RSK activation |
SignaLinki | Q9UK32 |
Names & Taxonomyi
Protein namesi | Recommended name: Ribosomal protein S6 kinase alpha-6 (EC:2.7.11.1)Short name: S6K-alpha-6 Alternative name(s): 90 kDa ribosomal protein S6 kinase 6 Short name: p90-RSK 6 Short name: p90RSK6 Ribosomal S6 kinase 4 Short name: RSK-4 pp90RSK4 |
Gene namesi | Name:RPS6KA6 Synonyms:RSK4 |
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
HGNCi | HGNC:10435, RPS6KA6 |
MIMi | 300303, gene |
neXtProti | NX_Q9UK32 |
VEuPathDBi | HostDB:ENSG00000072133.10 |
Subcellular locationi
Cytosol
- cytosol Source: UniProtKB-SubCell
Mitochondrion
- mitochondrion Source: HPA
Nucleus
- fibrillar center Source: HPA
- nucleolus Source: HPA
- nucleoplasm Source: HPA
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 372 | S → A: No effect on activity. 1 Publication | 1 | |
Mutagenesisi | 389 | S → A: Strongly decreases activity. 1 Publication | 1 | |
Mutagenesisi | 581 | T → A: No effect on activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 27330 |
OpenTargetsi | ENSG00000072133 |
PharmGKBi | PA34850 |
Miscellaneous databases
Pharosi | Q9UK32, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4924 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q9UK32 |
GuidetoPHARMACOLOGYi | 1530 |
Genetic variation databases
BioMutai | RPS6KA6 |
DMDMi | 11133131 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086209 | 1 – 745 | Ribosomal protein S6 kinase alpha-6Add BLAST | 745 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 232 | Phosphoserine1 Publication | 1 | |
Modified residuei | 372 | Phosphoserine1 Publication | 1 | |
Modified residuei | 389 | PhosphoserineCombined sources1 Publication | 1 | |
Modified residuei | 581 | Phosphothreonine1 Publication | 1 |
Post-translational modificationi
Phosphorylated at Ser-232, Ser-372, and Ser-389 in serum-starved cells.1 Publication
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9UK32 |
jPOSTi | Q9UK32 |
MassIVEi | Q9UK32 |
PaxDbi | Q9UK32 |
PeptideAtlasi | Q9UK32 |
PRIDEi | Q9UK32 |
ProteomicsDBi | 7217 84712 [Q9UK32-1] |
PTM databases
iPTMneti | Q9UK32 |
PhosphoSitePlusi | Q9UK32 |
Expressioni
Gene expression databases
Bgeei | ENSG00000072133, Expressed in buccal mucosa cell and 179 other tissues |
Genevisiblei | Q9UK32, HS |
Organism-specific databases
HPAi | ENSG00000072133, Tissue enhanced (ductus) |
Interactioni
Subunit structurei
Forms a complex with MAPK3/ERK1 but not with MAPK9 or MAPK14 in serum-starved cells.
Binary interactionsi
Q9UK32
With | #Exp. | IntAct |
---|---|---|
SPRED2 [Q7Z698] | 3 | EBI-722467,EBI-7082156 |
Protein-protein interaction databases
BioGRIDi | 118144, 46 interactors |
IntActi | Q9UK32, 30 interactors |
MINTi | Q9UK32 |
STRINGi | 9606.ENSP00000262752 |
Chemistry databases
BindingDBi | Q9UK32 |
Miscellaneous databases
RNActi | Q9UK32, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9UK32 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 73 – 330 | Protein kinase 1PROSITE-ProRule annotationAdd BLAST | 258 | |
Domaini | 331 – 400 | AGC-kinase C-terminalPROSITE-ProRule annotationAdd BLAST | 70 | |
Domaini | 426 – 683 | 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 | KOG0603, Eukaryota |
GeneTreei | ENSGT00940000159242 |
HOGENOMi | CLU_000288_58_3_1 |
InParanoidi | Q9UK32 |
OMAi | SFSHCDE |
OrthoDBi | 1132245at2759 |
PhylomeDBi | Q9UK32 |
TreeFami | TF313438 |
Family and domain databases
CDDi | cd05582, STKc_RSK_N, 1 hit |
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 IPR041906, RSK_N 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 (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q9UK32-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MLPFAPQDEP WDREMEVFSG GGASSGEVNG LKMVDEPMEE GEADSCHDEG
60 70 80 90 100
VVKEIPITHH VKEGYEKADP AQFELLKVLG QGSFGKVFLV RKKTGPDAGQ
110 120 130 140 150
LYAMKVLKKA SLKVRDRVRT KMERDILVEV NHPFIVKLHY AFQTEGKLYL
160 170 180 190 200
ILDFLRGGDV FTRLSKEVLF TEEDVKFYLA ELALALDHLH QLGIVYRDLK
210 220 230 240 250
PENILLDEIG HIKLTDFGLS KESVDQEKKA YSFCGTVEYM APEVVNRRGH
260 270 280 290 300
SQSADWWSYG VLMFEMLTGT LPFQGKDRNE TMNMILKAKL GMPQFLSAEA
310 320 330 340 350
QSLLRMLFKR NPANRLGSEG VEEIKRHLFF ANIDWDKLYK REVQPPFKPA
360 370 380 390 400
SGKPDDTFCF DPEFTAKTPK DSPGLPASAN AHQLFKGFSF VATSIAEEYK
410 420 430 440 450
ITPITSANVL PIVQINGNAA QFGEVYELKE DIGVGSYSVC KRCIHATTNM
460 470 480 490 500
EFAVKIIDKS KRDPSEEIEI LMRYGQHPNI ITLKDVFDDG RYVYLVTDLM
510 520 530 540 550
KGGELLDRIL KQKCFSEREA SDILYVISKT VDYLHCQGVV HRDLKPSNIL
560 570 580 590 600
YMDESASADS IRICDFGFAK QLRGENGLLL TPCYTANFVA PEVLMQQGYD
610 620 630 640 650
AACDIWSLGV LFYTMLAGYT PFANGPNDTP EEILLRIGNG KFSLSGGNWD
660 670 680 690 700
NISDGAKDLL SHMLHMDPHQ RYTAEQILKH SWITHRDQLP NDQPKRNDVS
710 720 730 740
HVVKGAMVAT YSALTHKTFQ PVLEPVAASS LAQRRSMKKR TSTGL
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 116 | D → G in CAG38803 (Ref. 2) Curated | 1 | |
Sequence conflicti | 295 | F → L in CAG38803 (Ref. 2) Curated | 1 | |
Sequence conflicti | 341 | R → G in CAG38803 (Ref. 2) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040637 | 140 | Y → C in a lung large cell carcinoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_040638 | 258 | S → T in a lung adenocarcinoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_030670 | 692 | D → N1 PublicationCorresponds to variant dbSNP:rs6616890Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056181 | 1 – 27 | MLPFA…ASSGE → MGLSTSAIWKNTRVEIVNPY EVKRKVK in isoform 2. 1 PublicationAdd BLAST | 27 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF184965 mRNA Translation: AAF13190.1 CR536566 mRNA Translation: CAG38803.1 AK313240 mRNA Translation: BAG36051.1 AL389887 Genomic DNA No translation available. AL354653 Genomic DNA No translation available. CH471104 Genomic DNA Translation: EAW98575.1 BC143648 mRNA Translation: AAI43649.1 |
CCDSi | CCDS14451.1 [Q9UK32-1] CCDS83480.1 [Q9UK32-2] |
RefSeqi | NP_001317441.1, NM_001330512.1 [Q9UK32-2] NP_055311.1, NM_014496.4 [Q9UK32-1] XP_011529219.1, XM_011530917.2 [Q9UK32-2] |
Genome annotation databases
Ensembli | ENST00000262752; ENSP00000262752; ENSG00000072133 [Q9UK32-1] ENST00000620340; ENSP00000483896; ENSG00000072133 [Q9UK32-2] |
GeneIDi | 27330 |
KEGGi | hsa:27330 |
UCSCi | uc004eej.3, human [Q9UK32-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF184965 mRNA Translation: AAF13190.1 CR536566 mRNA Translation: CAG38803.1 AK313240 mRNA Translation: BAG36051.1 AL389887 Genomic DNA No translation available. AL354653 Genomic DNA No translation available. CH471104 Genomic DNA Translation: EAW98575.1 BC143648 mRNA Translation: AAI43649.1 |
CCDSi | CCDS14451.1 [Q9UK32-1] CCDS83480.1 [Q9UK32-2] |
RefSeqi | NP_001317441.1, NM_001330512.1 [Q9UK32-2] NP_055311.1, NM_014496.4 [Q9UK32-1] XP_011529219.1, XM_011530917.2 [Q9UK32-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6G76 | X-ray | 3.00 | A/B | 48-349 | [»] | |
6G77 | X-ray | 2.50 | A/B | 48-349 | [»] | |
6G78 | X-ray | 2.50 | A/B | 48-349 | [»] | |
SMRi | Q9UK32 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 118144, 46 interactors |
IntActi | Q9UK32, 30 interactors |
MINTi | Q9UK32 |
STRINGi | 9606.ENSP00000262752 |
Chemistry databases
BindingDBi | Q9UK32 |
ChEMBLi | CHEMBL4924 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q9UK32 |
GuidetoPHARMACOLOGYi | 1530 |
PTM databases
iPTMneti | Q9UK32 |
PhosphoSitePlusi | Q9UK32 |
Genetic variation databases
BioMutai | RPS6KA6 |
DMDMi | 11133131 |
Proteomic databases
EPDi | Q9UK32 |
jPOSTi | Q9UK32 |
MassIVEi | Q9UK32 |
PaxDbi | Q9UK32 |
PeptideAtlasi | Q9UK32 |
PRIDEi | Q9UK32 |
ProteomicsDBi | 7217 84712 [Q9UK32-1] |
Protocols and materials databases
Antibodypediai | 489, 226 antibodies |
DNASUi | 27330 |
Genome annotation databases
Ensembli | ENST00000262752; ENSP00000262752; ENSG00000072133 [Q9UK32-1] ENST00000620340; ENSP00000483896; ENSG00000072133 [Q9UK32-2] |
GeneIDi | 27330 |
KEGGi | hsa:27330 |
UCSCi | uc004eej.3, human [Q9UK32-1] |
Organism-specific databases
CTDi | 27330 |
DisGeNETi | 27330 |
GeneCardsi | RPS6KA6 |
HGNCi | HGNC:10435, RPS6KA6 |
HPAi | ENSG00000072133, Tissue enhanced (ductus) |
MIMi | 300303, gene |
neXtProti | NX_Q9UK32 |
OpenTargetsi | ENSG00000072133 |
PharmGKBi | PA34850 |
VEuPathDBi | HostDB:ENSG00000072133.10 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0603, Eukaryota |
GeneTreei | ENSGT00940000159242 |
HOGENOMi | CLU_000288_58_3_1 |
InParanoidi | Q9UK32 |
OMAi | SFSHCDE |
OrthoDBi | 1132245at2759 |
PhylomeDBi | Q9UK32 |
TreeFami | TF313438 |
Enzyme and pathway databases
BRENDAi | 2.7.11.1, 2681 |
PathwayCommonsi | Q9UK32 |
Reactomei | R-HSA-437239, Recycling pathway of L1 R-HSA-442742, CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling R-HSA-444257, RSK activation |
SignaLinki | Q9UK32 |
Miscellaneous databases
BioGRID-ORCSi | 27330, 6 hits in 529 CRISPR screens |
ChiTaRSi | RPS6KA6, human |
GenomeRNAii | 27330 |
Pharosi | Q9UK32, Tchem |
PROi | PR:Q9UK32 |
RNActi | Q9UK32, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000072133, Expressed in buccal mucosa cell and 179 other tissues |
Genevisiblei | Q9UK32, HS |
Family and domain databases
CDDi | cd05582, STKc_RSK_N, 1 hit |
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 IPR041906, RSK_N 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KS6A6_HUMAN | |
Accessioni | Q9UK32Primary (citable) accession number: Q9UK32 Secondary accession number(s): B2R854 Q9H4S6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | May 1, 2000 | |
Last modified: | February 10, 2021 | |
This is version 184 of the entry and version 1 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome X
Human chromosome X: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human and mouse protein kinases
Human and mouse protein kinases: classification and index