M3K9_MOUSE
ID M3K9_MOUSE Reviewed; 1077 AA.
AC Q3U1V8; E9QLZ4; Q8BIG8;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 9;
DE EC=2.7.11.25;
GN Name=Map3k9;
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].
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 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 TISSUE SPECIFICITY.
RX PubMed=20971179; DOI=10.1016/j.heares.2010.10.008;
RA Polesskaya O., Cunningham L.L., Francis S.P., Luebke A.E., Zhu X.,
RA Collins D., Vasilyeva O.N., Sahler J., Desmet E.A., Gelbard H.A.,
RA Maggirwar S.B., Walton J.P., Frisina R.D. Jr., Dewhurst S.;
RT "Ablation of mixed lineage kinase 3 (Mlk3) does not inhibit ototoxicity
RT induced by acoustic trauma or aminoglycoside exposure.";
RL Hear. Res. 270:21-27(2010).
CC -!- FUNCTION: Serine/threonine kinase which acts as an essential component
CC of the MAP kinase signal transduction pathway. Plays an important role
CC in the cascades of cellular responses evoked by changes in the
CC environment. Once activated, acts as an upstream activator of the
CC MKK/JNK signal transduction cascade through the phosphorylation of
CC MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The
CC MKK/JNK signaling pathway regulates stress response via activator
CC protein-1 (JUN) and GATA4 transcription factors. Also plays a role in
CC mitochondrial death signaling pathway, including the release cytochrome
CC c, leading to apoptosis (By similarity). {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 of multiple sites in the activation
CC loop and subsequent activation. Autophosphorylation at Thr-305 is the
CC key step in activation of MAP3K9/MLK1 and is required for full
CC phosphorylation. Autophosphorylation at Thr-297 and Ser-301 have been
CC shown to be of secondary importance in the activation of MAP3K9/MLK1.
CC {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in cochlea and utricle.
CC {ECO:0000269|PubMed:20971179}.
CC -!- PTM: Autophosphorylation on serine and threonine residues within the
CC activation loop plays a role in enzyme activation. Thr-305 is likely to
CC be the main autophosphorylation site (By similarity).
CC Autophosphorylation also occurs on Thr-297 and Ser-301 (By similarity).
CC {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; AK053843; BAC35552.1; -; mRNA.
DR EMBL; AK155677; BAE33385.1; -; mRNA.
DR EMBL; AC124595; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC125351; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS49104.1; -.
DR RefSeq; NP_001167578.1; NM_001174107.1.
DR RefSeq; NP_796369.2; NM_177395.5.
DR AlphaFoldDB; Q3U1V8; -.
DR SMR; Q3U1V8; -.
DR BioGRID; 237224; 1.
DR IntAct; Q3U1V8; 2.
DR STRING; 10090.ENSMUSP00000041819; -.
DR iPTMnet; Q3U1V8; -.
DR PhosphoSitePlus; Q3U1V8; -.
DR MaxQB; Q3U1V8; -.
DR PaxDb; Q3U1V8; -.
DR PeptideAtlas; Q3U1V8; -.
DR PRIDE; Q3U1V8; -.
DR ProteomicsDB; 252701; -.
DR Antibodypedia; 75; 369 antibodies from 33 providers.
DR DNASU; 338372; -.
DR Ensembl; ENSMUST00000035987; ENSMUSP00000041819; ENSMUSG00000042724.
DR GeneID; 338372; -.
DR KEGG; mmu:338372; -.
DR UCSC; uc007oco.2; mouse.
DR CTD; 4293; -.
DR MGI; MGI:2449952; Map3k9.
DR VEuPathDB; HostDB:ENSMUSG00000042724; -.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00940000158243; -.
DR HOGENOM; CLU_000288_7_14_1; -.
DR InParanoid; Q3U1V8; -.
DR OrthoDB; 115270at2759; -.
DR PhylomeDB; Q3U1V8; -.
DR TreeFam; TF105118; -.
DR BioGRID-ORCS; 338372; 1 hit in 75 CRISPR screens.
DR PRO; PR:Q3U1V8; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q3U1V8; protein.
DR Bgee; ENSMUSG00000042724; Expressed in embryonic brain and 50 other tissues.
DR ExpressionAtlas; Q3U1V8; baseline and differential.
DR Genevisible; Q3U1V8; MM.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004706; F:JUN kinase kinase kinase activity; IBA:GO_Central.
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:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0008219; P:cell death; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR CDD; cd12059; SH3_MLK1-3; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
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 Pfam; PF00069; Pkinase; 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 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; SH3 domain;
KW Stress response; Transcription; Transcription regulation; Transferase.
FT CHAIN 1..1077
FT /note="Mitogen-activated protein kinase kinase kinase 9"
FT /id="PRO_0000277825"
FT DOMAIN 45..109
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 137..405
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 423..444
FT /note="Leucine-zipper 1"
FT REGION 458..479
FT /note="Leucine-zipper 2"
FT REGION 491..511
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 526..606
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 646..713
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 748..790
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 860..971
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 986..1011
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 526..545
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 571..588
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 689..710
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 753..771
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 864..884
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 900..920
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 928..942
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 988..1011
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 261
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 143..151
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 164
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 297
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P80192"
FT MOD_RES 298
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P80192"
FT MOD_RES 301
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P80192"
FT MOD_RES 305
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P80192"
FT MOD_RES 526
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P80192"
FT CONFLICT 176
FT /note="Q -> K (in Ref. 1; BAC35552)"
FT /evidence="ECO:0000305"
FT CONFLICT 284
FT /note="K -> E (in Ref. 1; BAE33385)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1077 AA; 118805 MW; 6D2060CEB04B97F8 CRC64;
MESSRSLLGC LASATAAPPG DDATGAGAEE EEDEEEAAAE LGSHAALPYW TAVFEYEAAG
EDELTLRLGD VVEVLSKDSQ VSGDEGWWTG QLNQRVGIFP SNYVTPRSAF SSRCQPGAED
PSCYPPIQLL EIDFAELTLE EIIGIGGFGK VYRAFWAGDE VAVKAARHDP DEDISQTIEN
VRQEAKLFAM LKHPNIIALR GVCLKEPNLC LVMEFARGGP LNRVLSGKRI PPDILVNWAV
QIARGMNYLH DEAIVPIIHR DLKSSNILIL QKVENGDLSN KILKITDFGL AREWHRTTKM
SAAGTYAWMA PEVIRASMFS KGSDVWSYGV LLWELLTGEV PFRGIDGLAV AYGVAMNKLA
LPIPSTCPEP FAKLMEDCWN PDPHSRPSFT SILDQLTTIE ESGFFEMPKD SFHCLQDDWK
HEIQEMFDQL RAKEKELRTW EEELTRAALQ QKNQEELLRR REQELAEREI DILERELNII
IHQLCQEKPR VKKRKGKFRK SRLKLKDGNR ISLPSDFQHK FTVQASPTMD KRKSLISNRS
SPPASPTIIP RLRAIQLTPG ESSKTWGRSS VVPKEEGEEE EKRAPKKKGR TWGPGTLGQK
ELTSGDEGLK SLVDGYKQWS SSAPNLGKGP RSSPALPGFT SLMEIEDEDS EGPGSGENHQ
QHSPNQSYLC IPFPRGEDGD GPSSDGVHEE PTPVNSATST PQLTPTNSLK RGGTHHRRCE
VALLGCGAVL AATGLGFDLL EAGKCQLLPP EEPEPPAREE KKRREGLFQR ASRPRRSTSP
PSRKLFKKEE PMTLLGDPSA SLTLLSLSSI SECNSTRSLL RSDSDEIVVY EMPVSPVEAP
PLTQCTHNPL VNVRVERFKR DPNQSLTPTH VTLTAPTQPS GHRRTPSDGA LKPTAAPAVL
GSRSPSSNGM SPSPGTGMLK TPSPSRDPGE FPRLPDPNVV FPPTPRRWNT QRDSTLERPK
TLEFLPRPRP SANRQRLDPW WFVSPSHARS ASPANSSSTE TPSNLDSCFA SSSSTVEERP
GLPALLPLQA GPLLPAERTL LDLDAEGQSQ DSTVPLCRAE LNAHGPSPYE IQQEFWS
