KS6A5_PONAB
ID KS6A5_PONAB Reviewed; 802 AA.
AC Q5R4K3;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Ribosomal protein S6 kinase alpha-5;
DE Short=S6K-alpha-5;
DE EC=2.7.11.1;
GN Name=RPS6KA5;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Serine/threonine-protein kinase that is required for the
CC mitogen or stress-induced phosphorylation of the transcription factors
CC CREB1 and ATF1 and for the regulation of the transcription factors
CC RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by
CC histone phosphorylation and functions in the regulation of inflammatory
CC genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress
CC stimuli such as UV-C irradiation, epidermal growth factor (EGF) and
CC anisomycin. Plays an essential role in the control of RELA
CC transcriptional activity in response to TNF and upon glucocorticoid,
CC associates in the cytoplasm with the glucocorticoid receptor NR3C1 and
CC contributes to RELA inhibition and repression of inflammatory gene
CC expression. In skeletal myoblasts is required for phosphorylation of
CC RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated
CC cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and
CC regulation of its transcriptional potential. Phosphorylates ETV1/ER81
CC at 'Ser-191' and 'Ser-216', and thereby regulates its ability to
CC stimulate transcription, which may be important during development and
CC breast tumor formation. Directly represses transcription via
CC phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of
CC histone H3 in response to mitogenics, stress stimuli and EGF, which
CC results in the transcriptional activation of several immediate early
CC genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also
CC phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-
CC induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14).
CC In lipopolysaccharide-stimulated primary macrophages, acts downstream
CC of the Toll-like receptor TLR4 to limit the production of pro-
CC inflammatory cytokines. Functions probably by inducing transcription of
CC the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine
CC interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays
CC a role in neuronal cell death by mediating the downstream effects of
CC excitotoxic injury (By similarity). Phosphorylates TRIM7 at 'Ser-107'
CC in response to growth factor signaling via the MEK/ERK pathway, thereby
CC stimulating its ubiquitin ligase activity (By similarity).
CC {ECO:0000250|UniProtKB:O75582}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation at Ser-360, Thr-581
CC and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by
CC further autophosphorylation of Ser-212, Ser-376 and Ser-381 by the
CC activated C-terminal kinase domain. The active N-terminal kinase domain
CC finally phosphorylates downstream substrates, as well as Ser-750, Ser-
CC 752 and Ser-758 in its own C-terminal region (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in
CC quiescent cells which transiently dissociates following mitogenic
CC stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA5
CC associates with and phosphorylates the NF-kappa-B p65 subunit RELA.
CC Interacts with CREBBP and EP300 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- DOMAIN: Enzyme activity requires the presence of both kinase domains.
CC {ECO:0000250}.
CC -!- PTM: Ser-376 and Thr-581 phosphorylation is required for kinase
CC activity. Ser-376 and Ser-212 are autophosphorylated by the C-terminal
CC kinase domain, and their phosphorylation is essential for the catalytic
CC activity of the N-terminal kinase domain. Phosphorylated at Ser-360,
CC Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha.
CC Autophosphorylated at Ser-750, Ser-752 and Ser-758 by the N-terminal
CC kinase domain (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated. {ECO:0000250}.
CC -!- MISCELLANEOUS: Enzyme activity requires the presence of both kinase
CC domains. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. S6 kinase subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CR861243; CAH93313.1; -; mRNA.
DR RefSeq; NP_001126949.1; NM_001133477.1.
DR AlphaFoldDB; Q5R4K3; -.
DR SMR; Q5R4K3; -.
DR STRING; 9601.ENSPPYP00000006894; -.
DR GeneID; 100173967; -.
DR KEGG; pon:100173967; -.
DR CTD; 9252; -.
DR eggNOG; KOG0603; Eukaryota.
DR InParanoid; Q5R4K3; -.
DR OrthoDB; 1132245at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0044024; F:histone kinase activity (H2A-S1 specific); ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016239; Ribosomal_S6_kinase_II.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 2.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000606; Ribsml_S6_kin_2; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 2.
DR SUPFAM; SSF56112; SSF56112; 2.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 2.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 2.
PE 2: Evidence at transcript level;
KW ATP-binding; Inflammatory response; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Stress response; Transferase;
KW Ubl conjugation.
FT CHAIN 1..802
FT /note="Ribosomal protein S6 kinase alpha-5"
FT /id="PRO_0000232733"
FT DOMAIN 49..318
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 319..387
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 426..687
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 741..802
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 752..802
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 177
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 544
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 55..63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 81
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 432..440
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 455
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 212
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O75582"
FT MOD_RES 360
FT /note="Phosphoserine; by MAPK1, MAPK3 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:O75582"
FT MOD_RES 376
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O75582"
FT MOD_RES 381
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O75582"
FT MOD_RES 581
FT /note="Phosphothreonine; by MAPK1, MAPK3 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:O75582"
FT MOD_RES 647
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75582"
FT MOD_RES 657
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75582"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C050"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75582"
FT MOD_RES 700
FT /note="Phosphothreonine; by MAPK1, MAPK3 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:O75582"
FT MOD_RES 750
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O75582"
FT MOD_RES 752
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O75582"
FT MOD_RES 758
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O75582"
FT MOD_RES 798
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C050"
SQ SEQUENCE 802 AA; 89950 MW; BAC1A1901A13C63F CRC64;
MEEEGGSSGG AAGTSADGGD GGEQLLTVKH ELRTANLTGH AERVGIENFE LLKVLGTGAY
GKVFLVRKIS GHDTGKLYAM KVLKKATIVQ KAKTTEHTRT ERQVLEHTRQ SPFLVTLHYA
FQTETKLHLI LDYINGGELF THLSQRERFT EHEVQIYVGE IVLALEHLHK LGIIYRDIKL
ENILLDSNGH VMLTDFGLSK EFVADETERA YSFCGTIEYM APDIVRGGDS GHDKAVDWWS
LGVLMYELLT GASPFTVDGE KNSQAEISRR ILKSEPPYPQ EMSALAKDLI QHLLMKDPKK
RLGCGPRDAD EIKEHLFFQK INWDDLAAKK VPAPFKPVIR DELDVSNFAE EFTEMDPTYS
PAALPQSSEK LFQGYSFVAP SILFKRNAAV IDPLQFHMEV ERPGVTNVAR SAMMKDSPFY
QHYDLDLKDK PLGEGSFSIC RKCVHKKSNQ AFAVKIISKR MEANTQKEIT ALKLCEGHPN
IVKLHEVFHD QLHTFLVMEL LNGGELFERI KKKKHFSETE ASYIMRKLVS AVSHMHDVGV
VHRDLKPENL LFTDENDNLE IKIIDFGFAR PKPPDNQPLK TPCFTLHYAA PELLNQNGYD
ESCDLWSLGV ILYTMLSGQV PFQSHDRSLT CTSAVEIMKK IKKGDFSFEG EAWKNVSQEA
KDLIQGLLTV DPNKRLKMSG LRYNEWLQDG SQLSSNPLMT PDILGSSGAA VHTCVKATFH
AFNKYKREGF CLQNVDKAPL AKRRKMKKTS TSTETRSSSS ESSHSSSSHS HGKTTPTKTL
QPSNPADSNN PETLFQFSDS VA
