KS6A6_MOUSE
ID KS6A6_MOUSE Reviewed; 764 AA.
AC Q7TPS0; Q8BWZ2; Q9CUR6;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Ribosomal protein S6 kinase alpha-6;
DE Short=S6K-alpha-6;
DE EC=2.7.11.1;
GN Name=Rps6ka6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION IN EMBRYOGENESIS.
RX PubMed=15121846; DOI=10.1128/mcb.24.10.4255-4266.2004;
RA Myers A.P., Corson L.B., Rossant J., Baker J.C.;
RT "Characterization of mouse Rsk4 as an inhibitor of fibroblast growth
RT factor-RAS-extracellular signal-regulated kinase signaling.";
RL Mol. Cell. Biol. 24:4255-4266(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Constitutively active serine/threonine-protein kinase that
CC exhibits growth-factor-independent kinase activity and that may
CC participate in p53/TP53-dependent cell growth arrest signaling and play
CC an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15121846}.
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: Constitutively activated by phosphorylation at
CC Ser-252, Ser-392, and Ser-409 in serum-starved cells. Does not require
CC growth factor stimulation for significant kinase activity (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Forms a complex with MAPK3/ERK1 but not with MAPK9 or MAPK14
CC in serum-starved cells. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Nucleus. Note=Predominantly
CC cytosolic. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q7TPS0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7TPS0-2; Sequence=VSP_023129;
CC Name=3;
CC IsoId=Q7TPS0-3; Sequence=VSP_023128;
CC -!- PTM: Phosphorylated at Ser-252, Ser-392, and Ser-409 in serum-starved
CC cells. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. S6 kinase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC33698.1; Type=Frameshift; Evidence={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; AK012150; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK014822; BAB29568.2; -; mRNA.
DR EMBL; AK049349; BAC33698.1; ALT_SEQ; mRNA.
DR EMBL; BC054113; AAH54113.1; -; mRNA.
DR RefSeq; NP_080225.2; NM_025949.3.
DR AlphaFoldDB; Q7TPS0; -.
DR SMR; Q7TPS0; -.
DR STRING; 10090.ENSMUSP00000080694; -.
DR iPTMnet; Q7TPS0; -.
DR PhosphoSitePlus; Q7TPS0; -.
DR jPOST; Q7TPS0; -.
DR MaxQB; Q7TPS0; -.
DR PaxDb; Q7TPS0; -.
DR PRIDE; Q7TPS0; -.
DR ProteomicsDB; 263467; -. [Q7TPS0-1]
DR ProteomicsDB; 263468; -. [Q7TPS0-2]
DR ProteomicsDB; 263469; -. [Q7TPS0-3]
DR DNASU; 67071; -.
DR GeneID; 67071; -.
DR KEGG; mmu:67071; -.
DR CTD; 27330; -.
DR MGI; MGI:1914321; Rps6ka6.
DR eggNOG; KOG0603; Eukaryota.
DR InParanoid; Q7TPS0; -.
DR OrthoDB; 1132245at2759; -.
DR BioGRID-ORCS; 67071; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Rps6ka6; mouse.
DR PRO; PR:Q7TPS0; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q7TPS0; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004711; F:ribosomal protein S6 kinase activity; IBA:GO_Central.
DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; ISS:UniProtKB.
DR GO; GO:0045992; P:negative regulation of embryonic development; IDA:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:2000381; P:negative regulation of mesoderm development; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR CDD; cd05582; STKc_RSK_N; 1.
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; IPR041906; RSK_N.
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 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..764
FT /note="Ribosomal protein S6 kinase alpha-6"
FT /id="PRO_0000278162"
FT DOMAIN 93..350
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 351..420
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 446..706
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 218
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 563
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 99..107
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 125
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 452..460
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 475
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UK32"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UK32"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 601
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UK32"
FT VAR_SEQ 613..617
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023128"
FT VAR_SEQ 678..721
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023129"
FT CONFLICT 75
FT /note="V -> I (in Ref. 1; BAC33698)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="T -> S (in Ref. 1; BAC33698)"
FT /evidence="ECO:0000305"
FT CONFLICT 269
FT /note="A -> G (in Ref. 1; BAC33698)"
FT /evidence="ECO:0000305"
FT CONFLICT 450..451
FT /note="ED -> KR (in Ref. 1; AK012150)"
FT /evidence="ECO:0000305"
FT CONFLICT 632
FT /note="L -> M (in Ref. 1; BAB29568)"
FT /evidence="ECO:0000305"
FT CONFLICT 657
FT /note="I -> V (in Ref. 1; BAC33698)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 764 AA; 86571 MW; 181053F9E6A70764 CRC64;
MLPFAPVEDP WDQEDMEVFG STSSSEPQVV FTMKNAATVM REHERKEVND LKMVDEPMEE
GEPVSCRREE LVKEVPITQH VKEGYEKADP AQFDLLKVLG QGSFGKVFLV RKKTGPDAGQ
LYAMKVLRKA SLKVRDRVRT KMERDILVEV NHPFIVKLHY AFQTEGKLYL ILDFLRGGDV
FTRLSKEVLF TEEDVKFYLA ELALALDHLH RLGIVYRDLK PENILLDEIG HIKLTDFGLS
KESVDQEKKA YSFCGTVEYM APEVVNRRAH SQSADWWSYG VLMFEMLTGT LPFQGKDRNE
TMNMILKAKL GMPQFLSAEA QSLLRMLFKR NPANRLGSEG VEEVKRHAFF ASIDWNKLYK
REVQPPFRPA SGKPDDTFCF DPEFTAKTPK DSPGLPASAN AHQLFKGFSF VATSIAEEYK
ITPVTSSNVL PIVQINGNAA QFSEAYELKE DIGIGSYSVC KRCIHSASNV EFAVKIIDKN
KRDPSEEIEI LMRYGQHPNI ISLKEVFDDG KYVYLVTDLM KGGELLDRIL KKKCFSEQEA
SNVLYVITKT VECLHSQGVV HRDLKPSNIL YMDESAHPDS IKICDFGFAK QLRGENGLLL
TPCYTANFVA PEVLTQQGYD AACDIWSLGV LLYTMLAGYT PFSNGPNDTP EEILLRIGNG
RFSLSGGIWD NISRGAKDLL SHMLHMDPHQ RYTAEQVLKH PWITQREQLP RHQPNSDEPP
QEAVAAPYSV LARNPNRHHP ILEPVTASRL AQRRNMKKRT STGL
