STK10_MOUSE
ID STK10_MOUSE Reviewed; 966 AA.
AC O55098; B1ATW8;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Serine/threonine-protein kinase 10;
DE EC=2.7.11.1;
DE AltName: Full=Lymphocyte-oriented kinase;
GN Name=Stk10; Synonyms=Lok;
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 [MRNA].
RC TISSUE=Thymus;
RX PubMed=9278426; DOI=10.1074/jbc.272.36.22679;
RA Kuramochi S., Moriguchi T., Kuida K., Endo J., Semba K., Nishida E.,
RA Karasuyama H.;
RT "LOK is a novel mouse STE20-like protein kinase that is expressed
RT predominantly in lymphocytes.";
RL J. Biol. Chem. 272:22679-22684(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=10692593; DOI=10.1016/s0014-5793(00)01219-9;
RA Endo J., Toyama-Sorimachi N., Taya C., Kuramochi-Miyagawa S., Nagata K.,
RA Kuida K., Takashi T., Yonekawa H., Yoshizawa Y., Miyasaka N.,
RA Karasuyama H.;
RT "Deficiency of a STE20/PAK family kinase LOK leads to the acceleration of
RT LFA-1 clustering and cell adhesion of activated lymphocytes.";
RL FEBS Lett. 468:234-238(2000).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-950, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19255442; DOI=10.1073/pnas.0805963106;
RA Belkina N.V., Liu Y., Hao J.J., Karasuyama H., Shaw S.;
RT "LOK is a major ERM kinase in resting lymphocytes and regulates
RT cytoskeletal rearrangement through ERM phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:4707-4712(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-191; SER-449; SER-453 AND
RP THR-950, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Lung, Pancreas, Spleen, and Testis;
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: Serine/threonine-protein kinase involved in regulation of
CC lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved
CC in regulation of lymphocyte migration by mediating phosphorylation of
CC ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1.
CC May also act as a cell cycle regulator by acting as a polo kinase
CC kinase: mediates phosphorylation of PLK1 in vitro; however such data
CC require additional evidences in vivo. {ECO:0000269|PubMed:19255442}.
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 -!- ACTIVITY REGULATION: Inhibited by the pyrrole-indolinone inhibitor
CC SU11274 (K00593): intercalates between the ATP-binding Lys-65 and
CC alpha-C glutamate (Glu-81), resulting in a partial disordering of the
CC lysine side chain. Also specifically inhibited by erlotinib. Slightly
CC inhibited by gefitinib (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; homodimerization is required for activation segment
CC autophosphorylation. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in lymphoid organs such as
CC spleen, thymus, and bone marrow.
CC -!- PTM: Autophosphorylates following homodimerization, leading to
CC activation of the protein. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice do not show any obvious abnormalities.
CC Lymphocytes develop normally but activated lymphocytes show enhanced
CC cell adhesion. Decreased phosphorylation of ERM proteins.
CC {ECO:0000269|PubMed:10692593, ECO:0000269|PubMed:19255442}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; D89728; BAA24073.1; -; mRNA.
DR EMBL; AL669844; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS24529.1; -.
DR RefSeq; NP_033314.2; NM_009288.2.
DR AlphaFoldDB; O55098; -.
DR SMR; O55098; -.
DR BioGRID; 203540; 3.
DR IntAct; O55098; 2.
DR STRING; 10090.ENSMUSP00000099885; -.
DR iPTMnet; O55098; -.
DR PhosphoSitePlus; O55098; -.
DR EPD; O55098; -.
DR jPOST; O55098; -.
DR MaxQB; O55098; -.
DR PaxDb; O55098; -.
DR PRIDE; O55098; -.
DR ProteomicsDB; 257493; -.
DR Antibodypedia; 28880; 287 antibodies from 32 providers.
DR DNASU; 20868; -.
DR Ensembl; ENSMUST00000102821; ENSMUSP00000099885; ENSMUSG00000020272.
DR GeneID; 20868; -.
DR KEGG; mmu:20868; -.
DR UCSC; uc007ijt.1; mouse.
DR CTD; 6793; -.
DR MGI; MGI:1099439; Stk10.
DR VEuPathDB; HostDB:ENSMUSG00000020272; -.
DR eggNOG; KOG0579; Eukaryota.
DR GeneTree; ENSGT00940000156818; -.
DR HOGENOM; CLU_001965_3_1_1; -.
DR InParanoid; O55098; -.
DR OMA; QCDSNMS; -.
DR OrthoDB; 851098at2759; -.
DR PhylomeDB; O55098; -.
DR TreeFam; TF351445; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013026; RHOB GTPase cycle.
DR Reactome; R-MMU-9013106; RHOC GTPase cycle.
DR BioGRID-ORCS; 20868; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Stk10; mouse.
DR PRO; PR:O55098; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O55098; protein.
DR Bgee; ENSMUSG00000020272; Expressed in peripheral lymph node and 231 other tissues.
DR Genevisible; O55098; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0071593; P:lymphocyte aggregation; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:2000401; P:regulation of lymphocyte migration; IMP:UniProtKB.
DR CDD; cd06644; STKc_STK10; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR022165; PKK.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR042743; STK10_STKc.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF12474; PKK; 2.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Cell membrane; Coiled coil; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..966
FT /note="Serine/threonine-protein kinase 10"
FT /id="PRO_0000086698"
FT DOMAIN 36..294
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 175..224
FT /note="Activation segment"
FT /evidence="ECO:0000250"
FT REGION 341..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 660..692
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 826..865
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 901..966
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 588..936
FT /evidence="ECO:0000255"
FT COMPBIAS 341..365
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 372..397
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 417..432
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 434..460
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 469..497
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 839..861
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 901..942
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 948..966
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 157
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 42..50
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 65
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94804"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PTG8"
FT MOD_RES 185
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 191
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 437
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94804"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94804"
FT MOD_RES 513
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94804"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94804"
FT MOD_RES 950
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:21183079"
FT CONFLICT 375..377
FT /note="SGS -> NGP (in Ref. 1; BAA24073)"
FT /evidence="ECO:0000305"
FT CONFLICT 814
FT /note="K -> E (in Ref. 1; BAA24073)"
FT /evidence="ECO:0000305"
FT CONFLICT 863
FT /note="N -> H (in Ref. 1; BAA24073)"
FT /evidence="ECO:0000305"
FT CONFLICT 888
FT /note="H -> Y (in Ref. 1; BAA24073)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 966 AA; 111906 MW; 7A95ABF9D58C8699 CRC64;
MAFANFRRIL RLSTFEKRKS REYEHVRRDL DPNDVWEIVG ELGDGAFGKV YKAKNKETGA
LAAAKVIETK SEEELEDYIV EIEILATCDH PYIVKLLGAY YYDGKLWIMI EFCPGGAVDA
IMLELDRGLT EPQIQVVCRQ MLEALNFLHG KRIIHRDLKA GNVLMTLEGD IRLADFGVSA
KNLKTLQKRD SFIGTPYWMA PEVVLCETMK DAPYDYKADI WSLGITLIEM AQIEPPHHEL
NPMRVLLKIA KSDPPTLLTP SKWSVEFRDF LKIALDKNPE TRPSAAQLLQ HPFVSRVTSN
KALRELVAEA KAEVMEEIED GREDGEEEDA VDAVPPLVNH TQDSANVTQP SLDSNKLLQD
SSTPLPPSQP QEPVSGSCSQ PSGDGPLQTT SPADGLSKND NDLKVPVPLR KSRPLSMDAR
IQMDEEKQIP DQDENPSPAA SKSQKANQSR PNSSALETLG GEALTNGGLE LPSSVTPSHS
KRASDCSNLS TSESMDYGTS LSADLSLNKE TGSLSLKGSK LHNKTLKRTR RFVVDGVEVS
ITTSKIISED EKKDEEMRFL RRQELRELRL LQKEEHRNQT QLSSKHELQL EQMHKRFEQE
INAKKKFYDV ELENLERQQK QQVEKMEQDH SVRRKEEAKR IRLEQDRDYA KFQEQLKQMK
KEVKSEVEKL PRQQRKESMK QKMEEHSQKK QRLDRDFVAK QKEDLELAMR KLTTENRREI
CDKERDCLSK KQELLRDREA ALWEMEEHQL QERHQLVKQQ LKDQYFLQRH DLLRKHEKER
EQMQRYNQRM MEQLKVRQQQ EKARLPKIQR SDGKTRMAMY KKSLHINGAG SASEQREKIK
QFSQQEEKRQ KAERLQQQQK HENQMRDMVA QCESNMSELQ QLQNEKCHLL VEHETQKLKA
LDESHNQSLK EWRDKLRPRK KALEEDLNQK KREQEMFFKL SEEAEPRPTT PSKASNFFPY
SSGDAS
