M4K5_MOUSE
ID M4K5_MOUSE Reviewed; 847 AA.
AC Q8BPM2; Q6PEQ2; Q8C3U5; Q8CGF3; Q99LM7; Q9CX73;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 30-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase kinase 5;
DE EC=2.7.11.1;
DE AltName: Full=MAPK/ERK kinase kinase kinase 5;
DE Short=MEK kinase kinase 5;
DE Short=MEKKK 5;
GN Name=Map4k5 {ECO:0000312|MGI:MGI:1925503};
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 2).
RC STRAIN=C57BL/6J; TISSUE=Fetal eye, Fetal liver, and Fetal lung;
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] {ECO:0000305, ECO:0000312|EMBL:AAH02309.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Czech II; 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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-335, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP IDENTIFICATION BY 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC 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: 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:Q9Y4K4};
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:Q9Y4K4};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4K4};
CC -!- SUBUNIT: Interacts with both SH3 domains of the adapter proteins CRK
CC and CRKL. {ECO:0000250|UniProtKB:Q9Y4K4}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000305};
CC IsoId=Q8BPM2-1; Sequence=Displayed;
CC Name=2 {ECO:0000305};
CC IsoId=Q8BPM2-2; Sequence=VSP_050478;
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; AK019468; BAB31739.1; -; mRNA.
DR EMBL; AK053775; BAC35517.1; -; mRNA.
DR EMBL; AK084891; BAC39305.1; -; mRNA.
DR EMBL; BC002309; AAH02309.1; -; mRNA.
DR EMBL; BC040381; AAH40381.2; -; mRNA.
DR EMBL; BC057930; AAH57930.1; -; mRNA.
DR RefSeq; NP_958927.2; NM_201519.2. [Q8BPM2-1]
DR AlphaFoldDB; Q8BPM2; -.
DR SMR; Q8BPM2; -.
DR STRING; 10090.ENSMUSP00000106199; -.
DR iPTMnet; Q8BPM2; -.
DR PhosphoSitePlus; Q8BPM2; -.
DR jPOST; Q8BPM2; -.
DR MaxQB; Q8BPM2; -.
DR PaxDb; Q8BPM2; -.
DR PeptideAtlas; Q8BPM2; -.
DR PRIDE; Q8BPM2; -.
DR ProteomicsDB; 252703; -. [Q8BPM2-1]
DR ProteomicsDB; 252704; -. [Q8BPM2-2]
DR Antibodypedia; 23648; 181 antibodies from 25 providers.
DR DNASU; 399510; -.
DR Ensembl; ENSMUST00000110567; ENSMUSP00000106196; ENSMUSG00000034761. [Q8BPM2-2]
DR Ensembl; ENSMUST00000110570; ENSMUSP00000106199; ENSMUSG00000034761. [Q8BPM2-1]
DR GeneID; 399510; -.
DR KEGG; mmu:399510; -.
DR UCSC; uc007nsu.1; mouse. [Q8BPM2-1]
DR UCSC; uc011yne.1; mouse. [Q8BPM2-2]
DR CTD; 11183; -.
DR MGI; MGI:1925503; Map4k5.
DR VEuPathDB; HostDB:ENSMUSG00000034761; -.
DR eggNOG; KOG0576; Eukaryota.
DR GeneTree; ENSGT00940000158072; -.
DR HOGENOM; CLU_006347_1_0_1; -.
DR InParanoid; Q8BPM2; -.
DR PhylomeDB; Q8BPM2; -.
DR TreeFam; TF105121; -.
DR BioGRID-ORCS; 399510; 2 hits in 37 CRISPR screens.
DR ChiTaRS; Map4k5; mouse.
DR PRO; PR:Q8BPM2; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8BPM2; protein.
DR Bgee; ENSMUSG00000034761; Expressed in secondary oocyte and 249 other tissues.
DR ExpressionAtlas; Q8BPM2; baseline and differential.
DR Genevisible; Q8BPM2; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
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 Alternative splicing; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..847
FT /note="Mitogen-activated protein kinase kinase kinase
FT kinase 5"
FT /id="PRO_0000086283"
FT DOMAIN 20..277
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000305"
FT DOMAIN 507..820
FT /note="CNH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT REGION 378..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 402..418
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..467
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 140
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O00506,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 26..34
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O00506,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4K4,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 433
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 294..312
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_050478"
FT CONFLICT 79
FT /note="A -> P (in Ref. 1; BAC35517)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="Q -> H (in Ref. 1; BAC35517)"
FT /evidence="ECO:0000305"
FT CONFLICT 118
FT /note="A -> P (in Ref. 1; BAC35517)"
FT /evidence="ECO:0000305"
FT CONFLICT 441
FT /note="A -> V (in Ref. 2; AAH40381)"
FT /evidence="ECO:0000305"
FT CONFLICT 727
FT /note="L -> Q (in Ref. 1; BAB31739)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 847 AA; 95045 MW; 377F0EFFC6EECFA3 CRC64;
MEAPLRPAAD ILRRNPQHDY ELVQRVGSGT YGDVYKARNV HTGELAAVKI IKLEPGDDFS
LIQQEIFMVK ECKHCNIVAY FGSYLSREKL WICMEYCGGG SLQDIYHVTG PLSEMQIAYV
CRETLQGLAY LHTKGKMHRD IKGANILLTD HGDVKLADFG VAAKITATIA KRKSFIGTPY
WMAPEVAAVE KNGGYNQLCD IWAVGITAIE LGELQPPMFD LHPMRALFLM SKSNFQPPKL
KDKTKWSSTF HNFVKIALTK NPKKRPTAER LLTHTFVGQP GLSRALAVEL LDKVSNPDNH
APYSEGDEDD LEPHAIIRHT IRSTNRNSRA ERTASEINFD KLQFEPPLRK ETEARDEMGL
SSEPNFILHW NPFVDGANTG RSTSKRAIPP PLPPKPRVNT YPEDSLPDEE KSSTIKRCPD
LEARAPQVLR RQSSPSCVPV AETSSSIGNG DGISKLISEN TEGSAQAPQL PRKKDKRDFP
KPTINGLPPT PKVLMGACFS KVFDGCPLKI NCATSWIHPD TKDQYIIFGT EDGIYTLNLN
ELHEATMEQL FPRKCTWLYV INNTLMSLSE GKTFQLYSHN LIALFEQAKK PGLAAHIQTH
RFPDRILPRK FALTTKIPDT KGCHKCCIVR NPYTGHKYLC GALQSGIVLL QWYEPMQKFM
LIKHFDFPLP SPLNVFEMLV IPEQEYPMVC VAISKGSDSS QVVQFETINL NSASSWFTEI
GAGSQQLDSI HVTQLERDTV LVCLDKFVKI VNLQGKLKSS KKLASELSFD FRIESVVCLQ
DSVLAFWKHG MQGKSFKSDE VTQEISDETR VFRLLGSDRV VVLESRPTEN PAAHSNLYIL
AGHENSY
