UniProtKB - O75676 (KS6A4_HUMAN)
Ribosomal protein S6 kinase alpha-4
RPS6KA4
Functioni
Miscellaneous
Catalytic activityi
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 65 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 161 | Proton acceptorBy similarity | 1 | |
Binding sitei | 440 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 530 | Proton acceptorBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 39 – 47 | ATPPROSITE-ProRule annotation | 9 | |
Nucleotide bindingi | 417 – 425 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- magnesium ion binding Source: InterPro
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: UniProtKB-EC
- protein threonine kinase activity Source: UniProtKB-EC
- ribosomal protein S6 kinase activity Source: UniProtKB
GO - Biological processi
- histone H3-S10 phosphorylation Source: UniProtKB
- histone H3-S28 phosphorylation Source: UniProtKB
- histone phosphorylation Source: BHF-UCL
- inflammatory response Source: UniProtKB-KW
- interleukin-1-mediated signaling pathway Source: BHF-UCL
- intracellular signal transduction Source: UniProtKB
- negative regulation of cytokine production Source: UniProtKB
- positive regulation of CREB transcription factor activity Source: UniProtKB
- positive regulation of histone acetylation Source: BHF-UCL
- positive regulation of histone phosphorylation Source: BHF-UCL
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- protein phosphorylation Source: UniProtKB
- regulation of transcription, DNA-templated Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Inflammatory response, Stress response |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | O75676 |
Reactomei | R-HSA-437239, Recycling pathway of L1 |
SignaLinki | O75676 |
SIGNORi | O75676 |
Names & Taxonomyi
Protein namesi | Recommended name: Ribosomal protein S6 kinase alpha-4 (EC:2.7.11.1)Short name: S6K-alpha-4 Alternative name(s): 90 kDa ribosomal protein S6 kinase 4 Nuclear mitogen- and stress-activated protein kinase 2 Ribosomal protein kinase B Short name: RSKB |
Gene namesi | Name:RPS6KA4 Synonyms:MSK2 |
Organismi | Homo sapiens (Human)Imported |
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:10433, RPS6KA4 |
MIMi | 603606, gene |
neXtProti | NX_O75676 |
VEuPathDBi | HostDB:ENSG00000162302.12 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
Cytosol
- cytosol Source: HPA
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 709 | F → A: Strongly elevates basal activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 8986 |
OpenTargetsi | ENSG00000162302 |
PharmGKBi | PA34848 |
Miscellaneous databases
Pharosi | O75676, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3125 |
DrugBanki | DB03247, Flavin mononucleotide |
DrugCentrali | O75676 |
GuidetoPHARMACOLOGYi | 1524 |
Genetic variation databases
BioMutai | RPS6KA4 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086205 | 1 – 772 | Ribosomal protein S6 kinase alpha-4Add BLAST | 772 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 196 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 343 | Phosphoserine; by MAPK1, MAPK3 and MAPK14Curated | 1 | |
Modified residuei | 347 | PhosphoserineCombined sources | 1 | |
Modified residuei | 360 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 365 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 542 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 568 | Phosphothreonine; by MAPK1, MAPK3 and MAPK14By similarity | 1 | |
Modified residuei | 634 | PhosphoserineCombined sources | 1 | |
Modified residuei | 678 | PhosphoserineCombined sources | 1 | |
Modified residuei | 687 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 737 | Phosphoserine; by autocatalysisCurated | 1 | |
Modified residuei | 745 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | O75676 |
jPOSTi | O75676 |
MassIVEi | O75676 |
MaxQBi | O75676 |
PaxDbi | O75676 |
PeptideAtlasi | O75676 |
PRIDEi | O75676 |
ProteomicsDBi | 50149 [O75676-1] 50150 [O75676-2] |
PTM databases
iPTMneti | O75676 |
PhosphoSitePlusi | O75676 |
Expressioni
Gene expression databases
Bgeei | ENSG00000162302, Expressed in cerebellar hemisphere and 190 other tissues |
ExpressionAtlasi | O75676, baseline and differential |
Genevisiblei | O75676, HS |
Organism-specific databases
HPAi | ENSG00000162302, Low tissue specificity |
Interactioni
Subunit structurei
Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells which transiently dissociates following mitogenic stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA4 associates with and phosphorylates the NF-kappa-B p65 subunit RELA.
Binary interactionsi
Hide detailsO75676
With | #Exp. | IntAct |
---|---|---|
MAPK14 [Q16539] | 6 | EBI-73933,EBI-73946 |
Isoform 2 [O75676-2]
With | #Exp. | IntAct |
---|---|---|
KLF11 [O14901] | 3 | EBI-21622593,EBI-948266 |
Protein-protein interaction databases
BioGRIDi | 114468, 36 interactors |
ELMi | O75676 |
IntActi | O75676, 13 interactors |
MINTi | O75676 |
STRINGi | 9606.ENSP00000333896 |
Chemistry databases
BindingDBi | O75676 |
Miscellaneous databases
RNActi | O75676, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 33 – 301 | Protein kinase 1PROSITE-ProRule annotationAdd BLAST | 269 | |
Domaini | 302 – 371 | AGC-kinase C-terminalPROSITE-ProRule annotationAdd BLAST | 70 | |
Domaini | 411 – 674 | Protein kinase 2PROSITE-ProRule annotationAdd BLAST | 264 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 725 – 772 | Required for nuclear targeting and association with MAPK14Add BLAST | 48 |
Sequence similaritiesi
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG0603, Eukaryota |
GeneTreei | ENSGT00940000161083 |
InParanoidi | O75676 |
OMAi | HDVHHDQ |
PhylomeDBi | O75676 |
TreeFami | TF313438 |
Family and domain databases
CDDi | cd05614, STKc_MSK2_N, 1 hit |
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR011009, Kinase-like_dom_sf IPR037714, MSK2_N_dom 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 (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
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
MGDEDDDESC AVELRITEAN LTGHEEKVSV ENFELLKVLG TGAYGKVFLV
60 70 80 90 100
RKAGGHDAGK LYAMKVLRKA ALVQRAKTQE HTRTERSVLE LVRQAPFLVT
110 120 130 140 150
LHYAFQTDAK LHLILDYVSG GEMFTHLYQR QYFKEAEVRV YGGEIVLALE
160 170 180 190 200
HLHKLGIIYR DLKLENVLLD SEGHIVLTDF GLSKEFLTEE KERTFSFCGT
210 220 230 240 250
IEYMAPEIIR SKTGHGKAVD WWSLGILLFE LLTGASPFTL EGERNTQAEV
260 270 280 290 300
SRRILKCSPP FPPRIGPVAQ DLLQRLLCKD PKKRLGAGPQ GAQEVRNHPF
310 320 330 340 350
FQGLDWVALA ARKIPAPFRP QIRSELDVGN FAEEFTRLEP VYSPPGSPPP
360 370 380 390 400
GDPRIFQGYS FVAPSILFDH NNAVMTDGLE APGAGDRPGR AAVARSAMMQ
410 420 430 440 450
DSPFFQQYEL DLREPALGQG SFSVCRRCRQ RQSGQEFAVK ILSRRLEANT
460 470 480 490 500
QREVAALRLC QSHPNVVNLH EVHHDQLHTY LVLELLRGGE LLEHIRKKRH
510 520 530 540 550
FSESEASQIL RSLVSAVSFM HEEAGVVHRD LKPENILYAD DTPGAPVKII
560 570 580 590 600
DFGFARLRPQ SPGVPMQTPC FTLQYAAPEL LAQQGYDESC DLWSLGVILY
610 620 630 640 650
MMLSGQVPFQ GASGQGGQSQ AAEIMCKIRE GRFSLDGEAW QGVSEEAKEL
660 670 680 690 700
VRGLLTVDPA KRLKLEGLRG SSWLQDGSAR SSPPLRTPDV LESSGPAVRS
710 720 730 740 750
GLNATFMAFN RGKREGFFLK SVENAPLAKR RKQKLRSATA SRRGSPAPAN
760 770
PGRAPVASKG APRRANGPLP PS
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PJN1 | E9PJN1_HUMAN | Ribosomal protein S6 kinase | RPS6KA4 | 765 | Annotation score: | ||
A0A0A6YYC0 | A0A0A6YYC0_HUMAN | Non-specific serine/threonine prote... | RPS6KA4 | 704 | Annotation score: | ||
E9PKU3 | E9PKU3_HUMAN | Ribosomal protein S6 kinase alpha-4 | RPS6KA4 | 48 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Sequence conflicti | 477 | L → P in BAD97281 (Ref. 3) Curated | 1 | ||
Isoform 2 (identifier: O75676-2) | |||||
Sequence conflicti | 400 – 401 | QQ → Q in BAD97281 (Ref. 3) Curated | 2 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040632 | 236 | S → L in a breast infiltrating ductal carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs746466314Ensembl. | 1 | |
Natural variantiVAR_040633 | 758 | S → A2 PublicationsCorresponds to variant dbSNP:rs17857342Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_017733 | 401 – 406 | Missing in isoform 2. 2 Publications | 6 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ010119 mRNA Translation: CAA09009.1 AK223561 mRNA Translation: BAD97281.1 AK292163 mRNA Translation: BAF84852.1 CH471076 Genomic DNA Translation: EAW74260.1 AF074715 mRNA Translation: AAC67395.1 |
CCDSi | CCDS8073.1 [O75676-1] |
RefSeqi | NP_001006945.1, NM_001006944.1 [O75676-2] NP_001287731.1, NM_001300802.1 NP_001305290.1, NM_001318361.1 NP_003933.1, NM_003942.2 [O75676-1] |
Genome annotation databases
Ensembli | ENST00000334205; ENSP00000333896; ENSG00000162302 [O75676-1] |
GeneIDi | 8986 |
KEGGi | hsa:8986 |
UCSCi | uc001oae.4, human [O75676-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ010119 mRNA Translation: CAA09009.1 AK223561 mRNA Translation: BAD97281.1 AK292163 mRNA Translation: BAF84852.1 CH471076 Genomic DNA Translation: EAW74260.1 AF074715 mRNA Translation: AAC67395.1 |
CCDSi | CCDS8073.1 [O75676-1] |
RefSeqi | NP_001006945.1, NM_001006944.1 [O75676-2] NP_001287731.1, NM_001300802.1 NP_001305290.1, NM_001318361.1 NP_003933.1, NM_003942.2 [O75676-1] |
3D structure databases
SMRi | O75676 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 114468, 36 interactors |
ELMi | O75676 |
IntActi | O75676, 13 interactors |
MINTi | O75676 |
STRINGi | 9606.ENSP00000333896 |
Chemistry databases
BindingDBi | O75676 |
ChEMBLi | CHEMBL3125 |
DrugBanki | DB03247, Flavin mononucleotide |
DrugCentrali | O75676 |
GuidetoPHARMACOLOGYi | 1524 |
PTM databases
iPTMneti | O75676 |
PhosphoSitePlusi | O75676 |
Genetic variation databases
BioMutai | RPS6KA4 |
Proteomic databases
EPDi | O75676 |
jPOSTi | O75676 |
MassIVEi | O75676 |
MaxQBi | O75676 |
PaxDbi | O75676 |
PeptideAtlasi | O75676 |
PRIDEi | O75676 |
ProteomicsDBi | 50149 [O75676-1] 50150 [O75676-2] |
Protocols and materials databases
Antibodypediai | 3272, 254 antibodies |
Genome annotation databases
Ensembli | ENST00000334205; ENSP00000333896; ENSG00000162302 [O75676-1] |
GeneIDi | 8986 |
KEGGi | hsa:8986 |
UCSCi | uc001oae.4, human [O75676-1] |
Organism-specific databases
CTDi | 8986 |
DisGeNETi | 8986 |
GeneCardsi | RPS6KA4 |
HGNCi | HGNC:10433, RPS6KA4 |
HPAi | ENSG00000162302, Low tissue specificity |
MIMi | 603606, gene |
neXtProti | NX_O75676 |
OpenTargetsi | ENSG00000162302 |
PharmGKBi | PA34848 |
VEuPathDBi | HostDB:ENSG00000162302.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0603, Eukaryota |
GeneTreei | ENSGT00940000161083 |
InParanoidi | O75676 |
OMAi | HDVHHDQ |
PhylomeDBi | O75676 |
TreeFami | TF313438 |
Enzyme and pathway databases
PathwayCommonsi | O75676 |
Reactomei | R-HSA-437239, Recycling pathway of L1 |
SignaLinki | O75676 |
SIGNORi | O75676 |
Miscellaneous databases
BioGRID-ORCSi | 8986, 14 hits in 905 CRISPR screens |
ChiTaRSi | RPS6KA4, human |
GeneWikii | RPS6KA4 |
GenomeRNAii | 8986 |
Pharosi | O75676, Tchem |
PROi | PR:O75676 |
RNActi | O75676, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000162302, Expressed in cerebellar hemisphere and 190 other tissues |
ExpressionAtlasi | O75676, baseline and differential |
Genevisiblei | O75676, HS |
Family and domain databases
CDDi | cd05614, STKc_MSK2_N, 1 hit |
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR011009, Kinase-like_dom_sf IPR037714, MSK2_N_dom 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KS6A4_HUMAN | |
Accessioni | O75676Primary (citable) accession number: O75676 Secondary accession number(s): A8K7Z8, O75585, Q53ES8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 24, 2003 |
Last sequence update: | November 1, 1998 | |
Last modified: | February 10, 2021 | |
This is version 196 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
Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - 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 - SIMILARITY comments
Index of protein domains and families