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O75582

- KS6A5_HUMAN

UniProt

O75582 - KS6A5_HUMAN

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Protein

Ribosomal protein S6 kinase alpha-5

Gene

RPS6KA5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Display
All None

  • Function
  • Names & Taxonomy
  • Subcellular locationSubcell. location
  • Pathology & BiotechPathol./Biotech
  • PTM / Processing
  • Expression
  • Interaction
  • Structure
  • Family & Domains
  • Sequences (2)
  • Cross-references
  • Publications
  • Entry information
  • Miscellaneous
  • Similar proteins
Top

Functioni

Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury.9 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.3 Publications

Cofactori

Mg2+3 Publications

Enzyme regulationi

Activated by phosphorylation at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-212, Ser-376 and Ser-381 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-750, Ser-752 and Ser-758 in its own C-terminal region.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei81 – 811ATPPROSITE-ProRule annotation
Active sitei177 – 1771Proton acceptorBy similarity
Binding sitei455 – 4551ATPPROSITE-ProRule annotation
Active sitei544 – 5441Proton acceptorBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi55 – 639ATPPROSITE-ProRule annotation
Nucleotide bindingi432 – 4409ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. magnesium ion binding Source: InterPro
  3. protein kinase activity Source: UniProtKB
  4. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. axon guidance Source: Reactome
  2. epidermal growth factor receptor signaling pathway Source: UniProtKB
  3. histone H2A-S1 phosphorylation Source: UniProtKB
  4. histone H3-S10 phosphorylation Source: UniProtKB
  5. histone H3-S28 phosphorylation Source: UniProtKB
  6. histone phosphorylation Source: UniProtKB
  7. inflammatory response Source: UniProtKB-KW
  8. innate immune response Source: Reactome
  9. interleukin-1-mediated signaling pathway Source: BHF-UCL
  10. intracellular signal transduction Source: UniProtKB
  11. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
  12. MyD88-independent toll-like receptor signaling pathway Source: Reactome
  13. negative regulation of cytokine production Source: UniProtKB
  14. negative regulation of transcription, DNA-templated Source: UniProtKB
  15. neurotrophin TRK receptor signaling pathway Source: Reactome
  16. positive regulation of CREB transcription factor activity Source: UniProtKB
  17. positive regulation of histone acetylation Source: BHF-UCL
  18. positive regulation of histone phosphorylation Source: BHF-UCL
  19. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  20. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  21. protein phosphorylation Source: UniProtKB
  22. regulation of transcription, DNA-templated Source: UniProtKB
  23. stress-activated MAPK cascade Source: Reactome
  24. toll-like receptor 10 signaling pathway Source: Reactome
  25. toll-like receptor 2 signaling pathway Source: Reactome
  26. toll-like receptor 3 signaling pathway Source: Reactome
  27. toll-like receptor 4 signaling pathway Source: Reactome
  28. toll-like receptor 5 signaling pathway Source: Reactome
  29. toll-like receptor 9 signaling pathway Source: Reactome
  30. toll-like receptor signaling pathway Source: Reactome
  31. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  32. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
  33. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Inflammatory response, Stress response

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_12524. CREB phosphorylation.
REACT_12599. ERK/MAPK targets.
REACT_18334. NCAM signaling for neurite out-growth.
REACT_22365. Recycling pathway of L1.
SignaLinkiO75582.

Names & Taxonomyi

Protein namesi
Recommended name:
Ribosomal protein S6 kinase alpha-5 (EC:2.7.11.1)
Short name:
S6K-alpha-5
Alternative name(s):
90 kDa ribosomal protein S6 kinase 5
Nuclear mitogen- and stress-activated protein kinase 1
RSK-like protein kinase
Short name:
RSKL
Gene namesi
Name:RPS6KA5
Synonyms:MSK1
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
ProteomesiUP000005640: Unplaced

Organism-specific databases

HGNCiHGNC:10434. RPS6KA5.

Subcellular locationi

Nucleus. Cytoplasm
Note: Predominantly nuclear. Exported into cytoplasm in response to glucocorticoid.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleoplasm Source: Reactome
  3. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi195 – 1951D → A: Loss of kinase activity. 1 Publication
Mutagenesisi212 – 2121S → A: Inactivates the N-terminal kinase domain. 1 Publication
Mutagenesisi360 – 3601S → A: Decreases kinase activity by 60% in response to PMA and UV-C. 1 Publication
Mutagenesisi376 – 3761S → A: Loss of kinase activity, and decreases the phosphorylation of S-360 and T-581. 1 Publication
Mutagenesisi565 – 5651D → A: Loss of kinase activity. 1 Publication
Mutagenesisi581 – 5811T → A: Loss of kinase activity, and blocks phosphorylation of S-212; S-376 and S-381 in response to PMA and UV-C. 1 Publication
Mutagenesisi700 – 7001T → A or D: Strongly reduces phosphorylation of T-581 in response to PMA and UV-C. 1 Publication

Organism-specific databases

PharmGKBiPA34849.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 802802Ribosomal protein S6 kinase alpha-5PRO_0000086207Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei212 – 2121Phosphoserine; by autocatalysis1 Publication
Modified residuei360 – 3601Phosphoserine; by MAPK1, MAPK3 and MAPK141 Publication
Modified residuei376 – 3761Phosphoserine; by autocatalysis3 Publications
Modified residuei381 – 3811Phosphoserine; by autocatalysis2 Publications
Modified residuei581 – 5811Phosphothreonine; by MAPK1, MAPK3 and MAPK141 Publication
Modified residuei647 – 6471Phosphoserine1 Publication
Modified residuei657 – 6571Phosphoserine1 Publication
Modified residuei695 – 6951Phosphoserine1 Publication
Modified residuei700 – 7001Phosphothreonine; by MAPK1, MAPK3 and MAPK141 Publication
Modified residuei750 – 7501Phosphoserine; by autocatalysis1 Publication
Modified residuei752 – 7521Phosphoserine; by autocatalysis1 Publication
Modified residuei758 – 7581Phosphoserine; by autocatalysis1 Publication

Post-translational modificationi

Ser-376 and Thr-581 phosphorylation is required for kinase activity. Ser-376 and Ser-212 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. Phosphorylated at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-750, Ser-752 and Ser-758 by the N-terminal kinase domain.4 Publications
Ubiquitinated.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO75582.
PaxDbiO75582.
PRIDEiO75582.

PTM databases

PhosphoSiteiO75582.

Expressioni

Tissue specificityi

Widely expressed with high levels in heart, brain and placenta. Less abundant in lung, kidney and liver.2 Publications

Gene expression databases

BgeeiO75582.
CleanExiHS_RPS6KA5.
ExpressionAtlasiO75582. baseline and differential.
GenevestigatoriO75582.

Organism-specific databases

HPAiCAB025458.
HPA001274.

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 RPS6KA5 associates with and phosphorylates the NF-kappa-B p65 subunit RELA. Interacts with CREBBP and EP300.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RELAQ042062EBI-73869,EBI-73886
ZAKQ9NYL24EBI-73869,EBI-602273

Protein-protein interaction databases

BioGridi114676. 49 interactions.
IntActiO75582. 35 interactions.
MINTiMINT-261060.
STRINGi9606.ENSP00000261991.

Structurei

Secondary structure

1
802
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi26 – 316Combined sources
Helixi46 – 483Combined sources
Beta strandi49 – 579Combined sources
Turni58 – 603Combined sources
Beta strandi61 – 688Combined sources
Turni72 – 754Combined sources
Beta strandi77 – 9418Combined sources
Helixi95 – 973Combined sources
Helixi101 – 1099Combined sources
Beta strandi117 – 1237Combined sources
Beta strandi126 – 1316Combined sources
Helixi139 – 1468Combined sources
Helixi151 – 17020Combined sources
Helixi180 – 1823Combined sources
Beta strandi183 – 1853Combined sources
Beta strandi191 – 1944Combined sources
Beta strandi196 – 2016Combined sources
Helixi204 – 2107Combined sources
Helixi222 – 2254Combined sources
Helixi235 – 25016Combined sources
Helixi264 – 27310Combined sources
Helixi284 – 29310Combined sources
Helixi298 – 3003Combined sources
Turni306 – 3083Combined sources
Helixi309 – 3135Combined sources
Helixi316 – 3183Combined sources
Helixi323 – 3275Combined sources
Helixi418 – 4225Combined sources
Beta strandi423 – 4253Combined sources
Beta strandi432 – 4354Combined sources
Beta strandi438 – 4458Combined sources
Turni446 – 4483Combined sources
Beta strandi451 – 4588Combined sources
Helixi459 – 4613Combined sources
Helixi462 – 47413Combined sources
Turni475 – 4773Combined sources
Beta strandi484 – 4896Combined sources
Beta strandi491 – 4988Combined sources
Helixi506 – 5127Combined sources
Helixi518 – 53720Combined sources
Helixi547 – 5493Combined sources
Beta strandi550 – 5534Combined sources
Beta strandi560 – 5634Combined sources
Helixi602 – 61716Combined sources
Helixi634 – 6418Combined sources
Turni642 – 6443Combined sources
Helixi651 – 6544Combined sources
Helixi658 – 66811Combined sources
Turni672 – 6743Combined sources
Turni678 – 6803Combined sources
Helixi685 – 6873Combined sources
Helixi700 – 72829Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1VZOX-ray1.80A2-348[»]
3KN5X-ray2.40A/B414-738[»]
3KN6X-ray2.00A/B414-738[»]
ProteinModelPortaliO75582.
SMRiO75582. Positions 24-729.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75582.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini49 – 318270Protein kinase 1PROSITE-ProRule annotationAdd
BLAST
Domaini319 – 38769AGC-kinase C-terminalAdd
BLAST
Domaini426 – 687262Protein kinase 2PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.Curated
Contains 1 AGC-kinase C-terminal domain.Curated
Contains 2 protein kinase domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00770000120454.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiO75582.
KOiK04445.
OMAiFQSHDKS.
OrthoDBiEOG76HQ0Z.
PhylomeDBiO75582.
TreeFamiTF313438.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016239. Ribosomal_S6_kinase_II.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 2 hits.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000606. Ribsml_S6_kin_2. 1 hit.
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 2 hits.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 2 hits.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00108. PROTEIN_KINASE_ST. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O75582-1) [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
MEEEGGSSGG AAGTSADGGD GGEQLLTVKH ELRTANLTGH AEKVGIENFE 
        60         70         80         90        100
LLKVLGTGAY GKVFLVRKIS GHDTGKLYAM KVLKKATIVQ KAKTTEHTRT 
       110        120        130        140        150
ERQVLEHIRQ SPFLVTLHYA FQTETKLHLI LDYINGGELF THLSQRERFT 
       160        170        180        190        200
EHEVQIYVGE IVLALEHLHK LGIIYRDIKL ENILLDSNGH VVLTDFGLSK 
       210        220        230        240        250
EFVADETERA YSFCGTIEYM APDIVRGGDS GHDKAVDWWS LGVLMYELLT 
       260        270        280        290        300
GASPFTVDGE KNSQAEISRR ILKSEPPYPQ EMSALAKDLI QRLLMKDPKK 
       310        320        330        340        350
RLGCGPRDAD EIKEHLFFQK INWDDLAAKK VPAPFKPVIR DELDVSNFAE 
       360        370        380        390        400
EFTEMDPTYS PAALPQSSEK LFQGYSFVAP SILFKRNAAV IDPLQFHMGV 
       410        420        430        440        450
ERPGVTNVAR SAMMKDSPFY QHYDLDLKDK PLGEGSFSIC RKCVHKKSNQ 
       460        470        480        490        500
AFAVKIISKR MEANTQKEIT ALKLCEGHPN IVKLHEVFHD QLHTFLVMEL 
       510        520        530        540        550
LNGGELFERI KKKKHFSETE ASYIMRKLVS AVSHMHDVGV VHRDLKPENL 
       560        570        580        590        600
LFTDENDNLE IKIIDFGFAR LKPPDNQPLK TPCFTLHYAA PELLNQNGYD 
       610        620        630        640        650
ESCDLWSLGV ILYTMLSGQV PFQSHDRSLT CTSAVEIMKK IKKGDFSFEG 
       660        670        680        690        700
EAWKNVSQEA KDLIQGLLTV DPNKRLKMSG LRYNEWLQDG SQLSSNPLMT 
       710        720        730        740        750
PDILGSSGAA VHTCVKATFH AFNKYKREGF CLQNVDKAPL AKRRKMKKTS 
       760        770        780        790        800
TSTETRSSSS ESSHSSSSHS HGKTTPTKTL QPSNPADSNN PETLFQFSDS 

VA
Length:802
Mass (Da):89,865
Last modified:November 1, 1998 - v1
Checksum:i76C27D0F6639BFA4
GO
Isoform 2 (identifier: O75582-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     549-549: N → V
     550-802: Missing.

Show »
Length:549
Mass (Da):61,769
Checksum:i3CED0A0C50E96C78
GO

Sequence cautioni

The sequence AAC69577.1 differs from that shown. Reason: Frameshift at several positions. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti452 – 4532FA → LQ in AAC69577. (PubMed:10702687)Curated
Sequence conflicti532 – 5321V → L in AAC69577. (PubMed:10702687)Curated
Sequence conflicti538 – 5381V → L in AAC69577. (PubMed:10702687)Curated
Sequence conflicti757 – 7582SS → RG in AAC69577. (PubMed:10702687)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti190 – 1901H → R.
Corresponds to variant rs34699345 [ dbSNP | Ensembl ].		VAR_051634
Natural varianti554 – 5541D → N.1 Publication
Corresponds to variant rs55911249 [ dbSNP | Ensembl ].		VAR_040634
Natural varianti574 – 5741P → L.1 Publication
Corresponds to variant rs34604933 [ dbSNP | Ensembl ].		VAR_040635
Natural varianti599 – 5991Y → C.1 Publication
Corresponds to variant rs55968863 [ dbSNP | Ensembl ].		VAR_040636

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei549 – 5491N → V in isoform 2. 1 PublicationVSP_041837
Alternative sequencei550 – 802253Missing in isoform 2. 1 PublicationVSP_041838Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF074393 mRNA. Translation: AAC31171.1.
AF080000 mRNA. Translation: AAD23915.1.
AF090421 mRNA. Translation: AAC69577.1. Frameshift.
AL121784 Genomic DNA. No translation available.
AL133454 Genomic DNA. No translation available.
AL159191 Genomic DNA. No translation available.
BC017187 mRNA. Translation: AAH17187.1.
CCDSiCCDS45149.1. [O75582-2]
CCDS9893.1. [O75582-1]
PIRiT13149.
RefSeqiNP_004746.2. NM_004755.2. [O75582-1]
NP_872198.1. NM_182398.1. [O75582-2]
UniGeneiHs.510225.

Genome annotation databases

GeneIDi9252.
KEGGihsa:9252.
UCSCiuc001xys.2. human. [O75582-1]
uc001xyt.3. human. [O75582-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
 AF074393 mRNA. Translation: AAC31171.1 .
AF080000 mRNA. Translation: AAD23915.1 .
AF090421 mRNA. Translation: AAC69577.1 . Frameshift.
AL121784 Genomic DNA. No translation available.
AL133454 Genomic DNA. No translation available.
AL159191 Genomic DNA. No translation available.
BC017187 mRNA. Translation: AAH17187.1 .
CCDSi CCDS45149.1. [O75582-2 ]
CCDS9893.1. [O75582-1 ]
PIRi T13149.
RefSeqi NP_004746.2. NM_004755.2. [O75582-1 ]
NP_872198.1. NM_182398.1. [O75582-2 ]
UniGenei Hs.510225.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1VZO X-ray 1.80 A 2-348 [» ]
3KN5 X-ray 2.40 A/B 414-738 [» ]
3KN6 X-ray 2.00 A/B 414-738 [» ]
ProteinModelPortali O75582.
SMRi O75582. Positions 24-729.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114676. 49 interactions.
IntActi O75582. 35 interactions.
MINTi MINT-261060.
STRINGi 9606.ENSP00000261991.

Chemistry

BindingDBi O75582.
ChEMBLi CHEMBL4237.
GuidetoPHARMACOLOGYi 1523.

PTM databases

PhosphoSitei O75582.

Proteomic databases

MaxQBi O75582.
PaxDbi O75582.
PRIDEi O75582.

Protocols and materials databases

DNASUi 9252.
Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 9252.
KEGGi hsa:9252.
UCSCi uc001xys.2. human. [O75582-1 ]
uc001xyt.3. human. [O75582-2 ]

Organism-specific databases

CTDi 9252.
GeneCardsi GC14M091337.
HGNCi HGNC:10434. RPS6KA5.
HPAi CAB025458.
HPA001274.
MIMi 603607. gene.
neXtProti NX_O75582.
PharmGKBi PA34849.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00770000120454.
HOGENOMi HOG000233033.
HOVERGENi HBG108317.
InParanoidi O75582.
KOi K04445.
OMAi FQSHDKS.
OrthoDBi EOG76HQ0Z.
PhylomeDBi O75582.
TreeFami TF313438.

Enzyme and pathway databases

Reactomei REACT_12524. CREB phosphorylation.
REACT_12599. ERK/MAPK targets.
REACT_18334. NCAM signaling for neurite out-growth.
REACT_22365. Recycling pathway of L1.
SignaLinki O75582.

Miscellaneous databases

ChiTaRSi RPS6KA5. human.
EvolutionaryTracei O75582.
GeneWikii RPS6KA5.
GenomeRNAii 9252.
NextBioi 34679.
PROi O75582.
SOURCEi Search...

Gene expression databases

Bgeei O75582.
CleanExi HS_RPS6KA5.
ExpressionAtlasi O75582. baseline and differential.
Genevestigatori O75582.

Family and domain databases

InterProi IPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016239. Ribosomal_S6_kinase_II.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 2 hits.
PF00433. Pkinase_C. 1 hit.
[Graphical view ]
PIRSFi PIRSF000606. Ribsml_S6_kin_2. 1 hit.
SMARTi SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 2 hits.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 2 hits.
PROSITEi PS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 2 hits.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00108. PROTEIN_KINASE_ST. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB."
    Deak M., Clifton A.D., Lucocq J.M., Alessi D.R.
    EMBO J. 17:4426-4441(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-195 AND ASP-565.
    Tissue: Pancreas1 Publication.
  2. "Cloning and characterization of RLPK, a novel RSK-related protein kinase."
    New L., Zhao M., Li Y., Bassett W.W., Feng Y., Ludwig S., Padova F.D., Gram H., Han J.
    J. Biol. Chem. 274:1026-1032(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
    Tissue: Placenta1 Publication.
  3. "Assignment of a member of the ribosomal protein S6 kinase family, RPS6KA5, to human chromosome 14q31-q32.1 by radiation hybrid mapping."
    Jiang C., Yu L., Tu Q., Zhao Y., Zhang H., Zhao S.
    Cytogenet. Cell Genet. 87:261-262(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHROMOSOMAL LOCATION.
  4. "The DNA sequence and analysis of human chromosome 14."
    Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
    , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
    Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: PlacentaImported.
  6. "MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts."
    Wiggin G.R., Soloaga A., Foster J.M., Murray-Tait V., Cohen P., Arthur J.S.
    Mol. Cell. Biol. 22:2871-2881(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1)."
    Vermeulen L., De Wilde G., Van Damme P., Vanden Berghe W., Haegeman G.
    EMBO J. 22:1313-1324(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH RELA.
  8. "MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14."
    Soloaga A., Thomson S., Wiggin G.R., Rampersaud N., Dyson M.H., Hazzalin C.A., Mahadevan L.C., Arthur J.S.
    EMBO J. 22:2788-2797(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF HISTONE H3 AND HMGN1/HMG14.
  9. "Erythropoietin-induced serine 727 phosphorylation of STAT3 in erythroid cells is mediated by a MEK-, ERK-, and MSK1-dependent pathway."
    Wierenga A.T., Vogelzang I., Eggen B.J., Vellenga E.
    Exp. Hematol. 31:398-405(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF STAT3.
  10. "Regulation of the ER81 transcription factor and its coactivators by mitogen- and stress-activated protein kinase 1 (MSK1)."
    Janknecht R.
    Oncogene 22:746-755(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF ETV1/ER81, INTERACTION WITH CREBBP AND EP300.
  11. "Phosphorylation of histone H2A inhibits transcription on chromatin templates."
    Zhang Y., Griffin K., Mondal N., Parvin J.D.
    J. Biol. Chem. 279:21866-21872(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF HISTONE H2A.
  12. "MSK1 activity is controlled by multiple phosphorylation sites."
    McCoy C.E., Campbell D.G., Deak M., Bloomberg G.B., Arthur J.S.C.
    Biochem. J. 387:507-517(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-212; SER-360; SER-376; SER-381; THR-581; SER-750; SER-752 AND SER-758, MUTAGENESIS OF SER-212; SER-360; SER-376 AND THR-581.
  13. "Identification of novel phosphorylation sites in MSK1 by precursor ion scanning MS."
    McCoy C.E., Macdonald A., Morrice N.A., Campbell D.G., Deak M., Toth R., McIlrath J., Arthur J.S.
    Biochem. J. 402:491-501(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-647; SER-657; SER-695 AND THR-700, MUTAGENESIS OF THR-700.
  14. "Altered subcellular distribution of MSK1 induced by glucocorticoids contributes to NF-kappaB inhibition."
    Beck I.M., Vanden Berghe W., Vermeulen L., Bougarne N., Vander Cruyssen B., Haegeman G., De Bosscher K.
    EMBO J. 27:1682-1693(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  15. "MSK activation and physiological roles."
    Arthur J.S.
    Front. Biosci. 13:5866-5879(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  16. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  17. Cited for: REVIEW ON FUNCTION.
  18. "Development and validation of a method for profiling post-translational modification activities using protein microarrays."
    Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B., Spruck C.
    PLoS ONE 5:E11332-E11332(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION.
  19. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376 AND SER-381, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  20. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  21. "The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein."
    Smith K.J., Carter P.S., Bridges A., Horrocks P., Lewis C., Pettman G., Clarke A., Brown M., Hughes J., Wilkinson M., Bax B., Reith A.
    Structure 12:1067-1077(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 2-348.
  22. "The crystal structure of the active form of the C-terminal kinase domain of mitogen- and stress-activated protein kinase 1."
    Malakhova M., D'Angelo I., Kim H.G., Kurinov I., Bode A.M., Dong Z.
    J. Mol. Biol. 399:41-52(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 414-738.
  23. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-554; LEU-574 AND CYS-599.
+Additional computationally mapped references.

Entry informationi

Entry nameiKS6A5_HUMAN
AccessioniPrimary (citable) accession number: O75582
Secondary accession number(s): O95316, Q96AF7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: November 1, 1998
Last modified: January 7, 2015
This is version 152 of the entry and version 1 of the sequence. [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

Miscellaneous

Enzyme activity requires the presence of both kinase domains.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.
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