Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

O75582

- KS6A5_HUMAN

UniProt

O75582 - KS6A5_HUMAN

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 149 (01 Oct 2014)
      Sequence version 1 (01 Nov 1998)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

    Magnesium.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 binding Source: IntAct
    4. protein kinase activity Source: UniProtKB
    5. 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

    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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    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

    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

    ArrayExpressiO75582.
    BgeeiO75582.
    CleanExiHS_RPS6KA5.
    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. 50 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 – 316
    Helixi46 – 483
    Beta strandi49 – 579
    Turni58 – 603
    Beta strandi61 – 688
    Turni72 – 754
    Beta strandi77 – 9418
    Helixi95 – 973
    Helixi101 – 1099
    Beta strandi117 – 1237
    Beta strandi126 – 1316
    Helixi139 – 1468
    Helixi151 – 17020
    Helixi180 – 1823
    Beta strandi183 – 1853
    Beta strandi191 – 1944
    Beta strandi196 – 2016
    Helixi204 – 2107
    Helixi222 – 2254
    Helixi235 – 25016
    Helixi264 – 27310
    Helixi284 – 29310
    Helixi298 – 3003
    Turni306 – 3083
    Helixi309 – 3135
    Helixi316 – 3183
    Helixi323 – 3275
    Helixi418 – 4225
    Beta strandi423 – 4253
    Beta strandi432 – 4354
    Beta strandi438 – 4458
    Turni446 – 4483
    Beta strandi451 – 4588
    Helixi459 – 4613
    Helixi462 – 47413
    Turni475 – 4773
    Beta strandi484 – 4896
    Beta strandi491 – 4988
    Helixi506 – 5127
    Helixi518 – 53720
    Helixi547 – 5493
    Beta strandi550 – 5534
    Beta strandi560 – 5634
    Helixi602 – 61716
    Helixi634 – 6418
    Turni642 – 6443
    Helixi651 – 6544
    Helixi658 – 66811
    Turni672 – 6743
    Turni678 – 6803
    Helixi685 – 6873
    Helixi700 – 72829

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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

    Contains 1 AGC-kinase C-terminal domain.Curated
    Contains 2 protein kinase domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG0515.
    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_dom.
    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

    MEEEGGSSGG AAGTSADGGD GGEQLLTVKH ELRTANLTGH AEKVGIENFE    50
    LLKVLGTGAY GKVFLVRKIS GHDTGKLYAM KVLKKATIVQ KAKTTEHTRT 100
    ERQVLEHIRQ SPFLVTLHYA FQTETKLHLI LDYINGGELF THLSQRERFT 150
    EHEVQIYVGE IVLALEHLHK LGIIYRDIKL ENILLDSNGH VVLTDFGLSK 200
    EFVADETERA YSFCGTIEYM APDIVRGGDS GHDKAVDWWS LGVLMYELLT 250
    GASPFTVDGE KNSQAEISRR ILKSEPPYPQ EMSALAKDLI QRLLMKDPKK 300
    RLGCGPRDAD EIKEHLFFQK INWDDLAAKK VPAPFKPVIR DELDVSNFAE 350
    EFTEMDPTYS PAALPQSSEK LFQGYSFVAP SILFKRNAAV IDPLQFHMGV 400
    ERPGVTNVAR SAMMKDSPFY QHYDLDLKDK PLGEGSFSIC RKCVHKKSNQ 450
    AFAVKIISKR MEANTQKEIT ALKLCEGHPN IVKLHEVFHD QLHTFLVMEL 500
    LNGGELFERI KKKKHFSETE ASYIMRKLVS AVSHMHDVGV VHRDLKPENL 550
    LFTDENDNLE IKIIDFGFAR LKPPDNQPLK TPCFTLHYAA PELLNQNGYD 600
    ESCDLWSLGV ILYTMLSGQV PFQSHDRSLT CTSAVEIMKK IKKGDFSFEG 650
    EAWKNVSQEA KDLIQGLLTV DPNKRLKMSG LRYNEWLQDG SQLSSNPLMT 700
    PDILGSSGAA VHTCVKATFH AFNKYKREGF CLQNVDKAPL AKRRKMKKTS 750
    TSTETRSSSS ESSHSSSSHS HGKTTPTKTL QPSNPADSNN PETLFQFSDS 800
    VA 802
    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.

    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:
    EMBL
    GenBank
    DDBJ
    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

    EnsembliENST00000261991; ENSP00000261991; ENSG00000100784. [O75582-1]
    ENST00000418736; ENSP00000402787; ENSG00000100784. [O75582-2]
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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. 50 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

    Ensembli ENST00000261991 ; ENSP00000261991 ; ENSG00000100784 . [O75582-1 ]
    ENST00000418736 ; ENSP00000402787 ; ENSG00000100784 . [O75582-2 ]
    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.
    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

    ArrayExpressi O75582.
    Bgeei O75582.
    CleanExi HS_RPS6KA5.
    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_dom.
    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

    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.

    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: October 1, 2014
    This is version 149 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