M3K10_MOUSE
ID M3K10_MOUSE Reviewed; 940 AA.
AC Q66L42; Q80UW4;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 10;
DE EC=2.7.11.25;
GN Name=Map3k10;
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 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 136-940.
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Mammary tumor;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498; SER-502; SER-506 AND
RP THR-552, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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).
RN [4]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-843, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Activates the JUN N-terminal pathway. {ECO:0000250}.
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=2.7.11.25;
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=2.7.11.25;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Homodimerization via the leucine zipper domains is
CC required for autophosphorylation and subsequent activation.
CC {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with SH3RF2. {ECO:0000250,
CC ECO:0000250|UniProtKB:D3ZG83}.
CC -!- PTM: Autophosphorylation on serine and threonine residues within the
CC activation loop plays a role in enzyme activation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase kinase subfamily.
CC {ECO:0000305}.
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DR EMBL; AC074312; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC046514; AAH46514.1; -; mRNA.
DR EMBL; BC078445; AAH78445.1; -; mRNA.
DR CCDS; CCDS39850.2; -.
DR RefSeq; NP_001277457.1; NM_001290528.1.
DR AlphaFoldDB; Q66L42; -.
DR SMR; Q66L42; -.
DR BioGRID; 234726; 6.
DR IntAct; Q66L42; 1.
DR MINT; Q66L42; -.
DR STRING; 10090.ENSMUSP00000103978; -.
DR iPTMnet; Q66L42; -.
DR PhosphoSitePlus; Q66L42; -.
DR MaxQB; Q66L42; -.
DR PaxDb; Q66L42; -.
DR PRIDE; Q66L42; -.
DR ProteomicsDB; 287281; -.
DR Antibodypedia; 2053; 266 antibodies from 33 providers.
DR DNASU; 269881; -.
DR Ensembl; ENSMUST00000036453; ENSMUSP00000037725; ENSMUSG00000040390.
DR GeneID; 269881; -.
DR KEGG; mmu:269881; -.
DR UCSC; uc009fwv.2; mouse.
DR CTD; 4294; -.
DR MGI; MGI:1346879; Map3k10.
DR VEuPathDB; HostDB:ENSMUSG00000040390; -.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00940000160518; -.
DR HOGENOM; CLU_000288_7_14_1; -.
DR InParanoid; Q66L42; -.
DR OMA; CNQRKKS; -.
DR OrthoDB; 115270at2759; -.
DR BioGRID-ORCS; 269881; 3 hits in 60 CRISPR screens.
DR ChiTaRS; Map3k10; mouse.
DR PRO; PR:Q66L42; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q66L42; protein.
DR Bgee; ENSMUSG00000040390; Expressed in superior frontal gyrus and 195 other tissues.
DR ExpressionAtlas; Q66L42; baseline and differential.
DR Genevisible; Q66L42; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:MGI.
DR GO; GO:0004706; F:JUN kinase kinase kinase activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:MGI.
DR GO; GO:0008219; P:cell death; ISO:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IPI:MGI.
DR GO; GO:0007224; P:smoothened signaling pathway; ISO:MGI.
DR CDD; cd12059; SH3_MLK1-3; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR015785; MAP3K10.
DR InterPro; IPR035779; MLK1-3_SH3.
DR InterPro; IPR016231; MLK1-4.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR44329:SF39; PTHR44329:SF39; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF14604; SH3_9; 1.
DR PIRSF; PIRSF000556; MAPKKK9_11; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 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.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Kinase; Methylation; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; SH3 domain;
KW Transferase.
FT CHAIN 1..940
FT /note="Mitogen-activated protein kinase kinase kinase 10"
FT /id="PRO_0000277826"
FT DOMAIN 16..81
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 98..360
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 384..405
FT /note="Leucine-zipper 1"
FT REGION 419..440
FT /note="Leucine-zipper 2"
FT REGION 490..599
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 687..734
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 749..917
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 763..777
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 222
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 104..112
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 MOD_RES 258
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 262
FT /note="Phosphoserine; by autocatalysis and MAP4K1"
FT /evidence="ECO:0000250"
FT MOD_RES 498
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 502
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 506
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 552
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 843
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CONFLICT 350..353
FT /note="FGSI -> PTRP (in Ref. 2; AAH46514)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 940 AA; 103187 MW; BE27F39679DC63D0 CRC64;
MEEEEGAAAR EWGATPAGPV WTAVFDYEAV GDEELTLRRG DRVQVLSQDC AVSGDEGWWT
GQLPSGRVGV FPSNYVAPAA PAAPSDLQLP QEIPFHELQL EEIIGVGGFG KVYRAVWRGE
EVAVKAARLD PERDPAVTAE QVRQEARLFG ALQHPNIIAL RGACLSPPNL CLVMEYARGG
ALSRVLAGRR VPPHVLVNWA VQVARGMNYL HNDAPVPIIH RDLKSINILI LEAIENHNLA
DTVLKITDFG LAREWHKTTK MSAAGTYAWM APEVIRLSLF SKSSDVWSFG VLLWELLTGE
VPYREIDALA VAYGVAMNKL TLPIPSTCPE PFARLLEECW DPDPHGRPDF GSILKQLEVI
EQSALFQMPL ESFHSLQEDW KLEIQHMFDD LRTKEKELRS REEELLRAAQ EQRFQEEQLR
RREQELAERE MDIVERELHL LMSQLSQEKP RVRKRKGNFK RSRLLKLREG SSHISLPSGF
EHKITVQASP TLDKRKGSDG ASPPASPSII PRLRAIRLTP MDCGGSSGSG TWSRSGPPKK
EELVGGKKKG RTWGPSSTLQ KERAGGEERL KALGEGSKQW SSSAPNLGKS PKHTPMAPGF
ASLNEMEEFA EADEGNNVPP SPYSTPSYLK VPLPAEPSPC VQAPWEPPAV TPSRPGHGAR
RRCDLALLSC ATLLSAVGLG ADVAEARAGD GEEQRRWLDS LFFPRPGRFP RGLSPTGRPG
GRREDTAPGL GLAPSATLVS LSSVSDCNST RSLLRSDSDE AAPAAPSPPP SPLAPSPSTN
PLVDVELESF KKDPRQSLTP THVTAAHAVS RGHRRTPSDG ALRQREPLEL TNHGPRDPLD
FPRLPDPQAL FPTRRRPLEF PGRPTTLTFA PRPRPAASRP RLDPWKLVSF GRTLSISPPS
RPDTPESPGP PSVQPTLLDM DMEGQSQDNT VPLCGVYGSH
