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Protein

Ribosomal protein S6 kinase alpha-6

Gene

RPS6KA6

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

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

ATP + a protein = ADP + a phosphoprotein.

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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei105ATPPROSITE-ProRule annotation1
Active sitei198Proton acceptorBy similarity1
Binding sitei455ATPPROSITE-ProRule annotation1
Active sitei543Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi79 – 87ATPPROSITE-ProRule annotation9
Nucleotide bindingi432 – 440ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • kinase activity Source: Reactome
  • magnesium ion binding Source: InterPro
  • protein kinase activity Source: ProtInc
  • ribosomal protein S6 kinase activity Source: GO_Central

GO - Biological processi

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-437239 Recycling pathway of L1
R-HSA-442742 CREB phosphorylation through the activation of Ras
R-HSA-444257 RSK activation
SignaLinkiQ9UK32

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000072133.10
HGNCiHGNC:10435 RPS6KA6
MIMi300303 gene
neXtProtiNX_Q9UK32

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi372S → A: No effect on activity. 1 Publication1
Mutagenesisi389S → A: Strongly decreases activity. 1 Publication1
Mutagenesisi581T → A: No effect on activity. 1 Publication1

Organism-specific databases

DisGeNETi27330
OpenTargetsiENSG00000072133
PharmGKBiPA34850

Chemistry databases

ChEMBLiCHEMBL4924
GuidetoPHARMACOLOGYi1530

Polymorphism and mutation databases

BioMutaiRPS6KA6
DMDMi11133131

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862091 – 745Ribosomal protein S6 kinase alpha-6Add BLAST745

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei232Phosphoserine1 Publication1
Modified residuei372Phosphoserine1 Publication1
Modified residuei389PhosphoserineCombined sources1 Publication1
Modified residuei581Phosphothreonine1 Publication1

Post-translational modificationi

Phosphorylated at Ser-232, Ser-372, and Ser-389 in serum-starved cells.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UK32
PaxDbiQ9UK32
PeptideAtlasiQ9UK32
PRIDEiQ9UK32
ProteomicsDBi84712

PTM databases

iPTMnetiQ9UK32
PhosphoSitePlusiQ9UK32

Expressioni

Gene expression databases

BgeeiENSG00000072133 Expressed in 161 organ(s), highest expression level in buccal mucosa cell
CleanExiHS_RPS6KA6
GenevisibleiQ9UK32 HS

Organism-specific databases

HPAiHPA002852
HPA003904

Interactioni

Subunit structurei

Forms a complex with MAPK3/ERK1 but not with MAPK9 or MAPK14 in serum-starved cells.

Protein-protein interaction databases

BioGridi118144, 36 interactors
IntActiQ9UK32, 29 interactors
MINTiQ9UK32
STRINGi9606.ENSP00000262752

Chemistry databases

BindingDBiQ9UK32

Structurei

3D structure databases

ProteinModelPortaliQ9UK32
SMRiQ9UK32
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini73 – 330Protein kinase 1PROSITE-ProRule annotationAdd BLAST258
Domaini331 – 400AGC-kinase C-terminalAdd BLAST70
Domaini426 – 683Protein kinase 2PROSITE-ProRule annotationAdd BLAST258

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0598 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00930000150811
HOGENOMiHOG000233033
HOVERGENiHBG108317
InParanoidiQ9UK32
KOiK04373
OMAiWIACRDQ
OrthoDBiEOG091G05Z7
PhylomeDBiQ9UK32
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q9UK32-1) [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
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
Length:745
Mass (Da):83,872
Last modified:May 1, 2000 - v1
Checksum:i5EC5AB2FA1C19DE8
GO
Isoform 2 (identifier: Q9UK32-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: MLPFAPQDEPWDREMEVFSGGGASSGE → MGLSTSAIWKNTRVEIVNPYEVKRKVK

Note: No experimental confirmation available.
Show »
Length:745
Mass (Da):84,093
Checksum:iD8EB15DB8C280DDD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti116D → G in CAG38803 (Ref. 2) Curated1
Sequence conflicti295F → L in CAG38803 (Ref. 2) Curated1
Sequence conflicti341R → G in CAG38803 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040637140Y → C in a lung large cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040638258S → T in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_030670692D → N1 PublicationCorresponds to variant dbSNP:rs6616890Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0561811 – 27MLPFA…ASSGE → MGLSTSAIWKNTRVEIVNPY EVKRKVK in isoform 2. 1 PublicationAdd BLAST27

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
CCDSiCCDS14451.1 [Q9UK32-1]
CCDS83480.1 [Q9UK32-2]
RefSeqiNP_001317441.1, NM_001330512.1 [Q9UK32-2]
NP_055311.1, NM_014496.4 [Q9UK32-1]
XP_011529219.1, XM_011530917.2 [Q9UK32-2]
UniGeneiHs.234478

Genome annotation databases

EnsembliENST00000262752; ENSP00000262752; ENSG00000072133 [Q9UK32-1]
ENST00000620340; ENSP00000483896; ENSG00000072133 [Q9UK32-2]
GeneIDi27330
KEGGihsa:27330
UCSCiuc004eej.3 human [Q9UK32-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar 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
CCDSiCCDS14451.1 [Q9UK32-1]
CCDS83480.1 [Q9UK32-2]
RefSeqiNP_001317441.1, NM_001330512.1 [Q9UK32-2]
NP_055311.1, NM_014496.4 [Q9UK32-1]
XP_011529219.1, XM_011530917.2 [Q9UK32-2]
UniGeneiHs.234478

3D structure databases

ProteinModelPortaliQ9UK32
SMRiQ9UK32
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118144, 36 interactors
IntActiQ9UK32, 29 interactors
MINTiQ9UK32
STRINGi9606.ENSP00000262752

Chemistry databases

BindingDBiQ9UK32
ChEMBLiCHEMBL4924
GuidetoPHARMACOLOGYi1530

PTM databases

iPTMnetiQ9UK32
PhosphoSitePlusiQ9UK32

Polymorphism and mutation databases

BioMutaiRPS6KA6
DMDMi11133131

Proteomic databases

EPDiQ9UK32
PaxDbiQ9UK32
PeptideAtlasiQ9UK32
PRIDEiQ9UK32
ProteomicsDBi84712

Protocols and materials databases

DNASUi27330
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262752; ENSP00000262752; ENSG00000072133 [Q9UK32-1]
ENST00000620340; ENSP00000483896; ENSG00000072133 [Q9UK32-2]
GeneIDi27330
KEGGihsa:27330
UCSCiuc004eej.3 human [Q9UK32-1]

Organism-specific databases

CTDi27330
DisGeNETi27330
EuPathDBiHostDB:ENSG00000072133.10
GeneCardsiRPS6KA6
HGNCiHGNC:10435 RPS6KA6
HPAiHPA002852
HPA003904
MIMi300303 gene
neXtProtiNX_Q9UK32
OpenTargetsiENSG00000072133
PharmGKBiPA34850
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0598 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00930000150811
HOGENOMiHOG000233033
HOVERGENiHBG108317
InParanoidiQ9UK32
KOiK04373
OMAiWIACRDQ
OrthoDBiEOG091G05Z7
PhylomeDBiQ9UK32
TreeFamiTF313438

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
ReactomeiR-HSA-437239 Recycling pathway of L1
R-HSA-442742 CREB phosphorylation through the activation of Ras
R-HSA-444257 RSK activation
SignaLinkiQ9UK32

Miscellaneous databases

ChiTaRSiRPS6KA6 human
GenomeRNAii27330
PROiPR:Q9UK32
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000072133 Expressed in 161 organ(s), highest expression level in buccal mucosa cell
CleanExiHS_RPS6KA6
GenevisibleiQ9UK32 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiKS6A6_HUMAN
AccessioniPrimary (citable) accession number: Q9UK32
Secondary accession number(s): B2R854
, B7ZL90, Q6FHX2, Q8WX28, Q9H4S6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: November 7, 2018
This is version 166 of the entry and version 1 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. SIMILARITY comments
    Index of protein domains and families
  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 chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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