M4K3_MOUSE
ID M4K3_MOUSE Reviewed; 894 AA.
AC Q99JP0; E9PWI4; Q9CUS8;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 4.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase kinase 3;
DE EC=2.7.11.1;
DE AltName: Full=Germinal center kinase-related protein kinase;
DE Short=GLK;
DE AltName: Full=MAPK/ERK kinase kinase kinase 3;
DE Short=MEK kinase kinase 3;
DE Short=MEKKK 3;
GN Name=Map4k3;
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 {ECO:0000312|EMBL:AAH05781.1};
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 1-255.
RC STRAIN=C57BL/6J; TISSUE=Head;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 469-894.
RC TISSUE=Mammary gland;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-329, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Lung, and Spleen;
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: May play a role in the response to environmental stress.
CC Appears to act upstream of the JUN N-terminal pathway (By similarity).
CC {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=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q8IVH8};
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; Evidence={ECO:0000250|UniProtKB:Q8IVH8};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8IVH8};
CC -!- SUBUNIT: Interacts with SH3GL2. Interaction appears to regulate MAP4K3-
CC mediated JNK activation (By similarity).
CC {ECO:0000250|UniProtKB:Q924I2}.
CC -!- INTERACTION:
CC Q99JP0; Q02111: Prkcq; NbExp=2; IntAct=EBI-5324222, EBI-2639157;
CC Q99JP0; Q13094: LCP2; Xeno; NbExp=2; IntAct=EBI-5324222, EBI-346946;
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; AC131712; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC169501; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK014711; BAB29516.1; -; mRNA.
DR EMBL; BC005781; AAH05781.1; -; mRNA.
DR CCDS; CCDS70847.1; -.
DR RefSeq; NP_001277274.1; NM_001290345.1.
DR AlphaFoldDB; Q99JP0; -.
DR SMR; Q99JP0; -.
DR BioGRID; 230353; 1.
DR IntAct; Q99JP0; 3.
DR STRING; 10090.ENSMUSP00000108008; -.
DR iPTMnet; Q99JP0; -.
DR PhosphoSitePlus; Q99JP0; -.
DR MaxQB; Q99JP0; -.
DR PaxDb; Q99JP0; -.
DR PeptideAtlas; Q99JP0; -.
DR PRIDE; Q99JP0; -.
DR ProteomicsDB; 252702; -.
DR Antibodypedia; 29616; 362 antibodies from 33 providers.
DR DNASU; 225028; -.
DR Ensembl; ENSMUST00000025089; ENSMUSP00000025089; ENSMUSG00000024242.
DR GeneID; 225028; -.
DR KEGG; mmu:225028; -.
DR UCSC; uc008drj.2; mouse.
DR CTD; 8491; -.
DR MGI; MGI:2154405; Map4k3.
DR VEuPathDB; HostDB:ENSMUSG00000024242; -.
DR eggNOG; KOG0576; Eukaryota.
DR GeneTree; ENSGT00940000155483; -.
DR HOGENOM; CLU_006347_1_0_1; -.
DR InParanoid; Q99JP0; -.
DR OMA; VIKLEPX; -.
DR OrthoDB; 996262at2759; -.
DR BioGRID-ORCS; 225028; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Map4k3; mouse.
DR PRO; PR:Q99JP0; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q99JP0; protein.
DR Bgee; ENSMUSG00000024242; Expressed in vestibular membrane of cochlear duct and 265 other tissues.
DR ExpressionAtlas; Q99JP0; baseline and differential.
DR Genevisible; Q99JP0; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0008349; F:MAP kinase 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; ISS:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0034612; P:response to tumor necrosis factor; ISO:MGI.
DR GO; GO:0009411; P:response to UV; ISS:UniProtKB.
DR InterPro; IPR001180; CNH_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR021160; MAPKKKK.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF00780; CNH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF038172; MAPKKKK; 1.
DR SMART; SM00036; CNH; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50219; CNH; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..894
FT /note="Mitogen-activated protein kinase kinase kinase
FT kinase 3"
FT /id="PRO_0000086278"
FT DOMAIN 16..273
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 556..867
FT /note="CNH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT REGION 339..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 408..537
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 340..357
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 408..427
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 448..465
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 469..487
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 492..517
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 136
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 22..30
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 45
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q8IVH8"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 398
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IVH8"
FT CONFLICT 874
FT /note="P -> R (in Ref. 3; AAH05781)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 894 AA; 101119 MW; A9D9086ADC9DDA4F CRC64;
MNPGFDLSRR NPQEDFELIQ RIGSGTYGDV YKARNVNTGE LAAIKVIKLE PGEDFAVVQQ
EIIMMKDCKH PNIVAYFGSY LRRDKLWICM EFCGGGSLQD IYHVTGPLSE LQIAYVSRET
LQGLYYLHSK GKMHRDIKGA NILLTDNGHV KLADFGVSAQ ITATIAKRKS FIGTPYWMAP
EVAAVERKGG YNQLCDLWAV GITAIELAEL QPPMFDLHPM RALFLMTKSN FQPPKLKDKL
KWSNSFHHFV KMALTKNPKK RPNAEKLLQH PFVTQPLTRS LAIELLDKVN NPDHSTYHDF
DDDDPEPLVA VPHRIPSTSR NVREEKTRSE INFGQVKFDP PLRKETEPHH ELPDSDGFFD
SSEEIYYTAR SNLDLQLEYG QGHQSHCFLG GNKSLLKSVE EELHQRGHVA HLEDDEGDDD
DSKHSTMKAK VPPPLPPKPK SIFIPQDTHS AEDGNQGTIK RCPSSGSPAK PSHVPPRPPP
PRLPPQKPAV LGNGVNSFQL NGERDGSLYQ QQSEQRGTNL SRKEKKDVPK PISNGLPPTP
KVHMGACFSK VFNGCPLKIH CATSWINPDT RDQYLIFGAE EGIYTLNLNE LHETSMEQLF
PRRCTWLYVM NNCLLSVSGK ASQLYSHNLP GLFDYARQMQ KLPVAIPAHK LPDRILPRKF
AVSAKIPETK WCQKCCVVRN PYTGHKYLCG ALQTSIVLLE WVEPMQKFML IKHIEFPMPC
PLRMFEMLVV PEQEYPLVCV GVSRGRDFNQ VVRFETVNPN STSSWFTESD APQTSVTHVT
QLERDTILVC LDCCIKIVNL QGRLKSSRKL SSELTFDFQI ESIVCLQDSV LAFWKHGMQG
RSFRSNEVTQ EISDNTRIFR LLGSDRVVVL ESRPTDNPTA NSNLYILAGH ENSY
