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P53349

- M3K1_MOUSE

UniProt

P53349 - M3K1_MOUSE

Protein

Mitogen-activated protein kinase kinase kinase 1

Gene

Map3k1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 3 (26 Sep 2001)
      Previous versions | rss
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    Functioni

    Component of a protein kinase signal transduction cascade. Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4. Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway.1 Publication

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.

    Enzyme regulationi

    Activated by autophosphorylation on Thr-1381 and Thr-1393 following oligomerization.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei1253 – 12531ATPPROSITE-ProRule annotation
    Active sitei1350 – 13501Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri333 – 36129SWIM-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri438 – 48750RING-typePROSITE-ProRule annotationAdd
    BLAST
    Nucleotide bindingi1230 – 12389ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. JUN kinase kinase activity Source: MGI
    3. MAP kinase kinase kinase activity Source: UniProtKB-EC
    4. protein binding Source: BHF-UCL
    5. protein kinase activity Source: MGI
    6. zinc ion binding Source: InterPro

    GO - Biological processi

    1. activation of JUN kinase activity Source: BHF-UCL
    2. apoptotic mitochondrial changes Source: MGI
    3. camera-type eye development Source: MGI
    4. epithelial cell morphogenesis Source: MGI
    5. eyelid development in camera-type eye Source: MGI
    6. JNK cascade Source: MGI
    7. positive regulation of actin filament polymerization Source: MGI
    8. regulation of cell migration Source: MGI
    9. transforming growth factor beta receptor signaling pathway Source: MGI
    10. wound healing Source: MGI

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    BRENDAi2.7.11.25. 3474.
    ReactomeiREACT_188530. FCERI mediated MAPK activation.
    REACT_202898. TRAF6 mediated NF-kB activation.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 1 (EC:2.7.11.25)
    Alternative name(s):
    MAPK/ERK kinase kinase 1
    Short name:
    MEK kinase 1
    Short name:
    MEKK 1
    Gene namesi
    Name:Map3k1
    Synonyms:Mekk, Mekk1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:1346872. Map3k1.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi1381 – 13811T → A: Fails to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. 2 Publications
    Mutagenesisi1381 – 13811T → E: Loss of kinase activity and autophosphorylation. 2 Publications
    Mutagenesisi1381 – 13811T → S: Reduced kinase activity and autophosphorylation. 2 Publications
    Mutagenesisi1393 – 13931T → A: Loss of kinase activity and autophosphorylation. Fails to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. 2 Publications
    Mutagenesisi1393 – 13931T → E: Loss of kinase activity and autophosphorylation. 2 Publications
    Mutagenesisi1393 – 13931T → S: Reduced kinase activity and autophosphorylation. 2 Publications
    Mutagenesisi1394 – 13941I → A: Loss of NF-kappa-B transcription factor activity and reduced ability to activate MAP2K1, MAP2K4, MAP2K7. No effect on AP-1 activity or activation of CHUK and IKBKB. Loss of binding to IKBKB. 1 Publication
    Mutagenesisi1396 – 13961F → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Reduced ability to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. 1 Publication
    Mutagenesisi1397 – 13971M → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Reduced ability to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. 1 Publication
    Mutagenesisi1401 – 14011V → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Reduced ability to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. 1 Publication
    Mutagenesisi1402 – 14021L → A: Loss of AP-1 transcription factor activity and reduced ability to activate CHUK and IKBKB. No effect on NF-kappa-B activity or activation of MAP2K1, MAP2K4, MAP2K7. Loss of binding to MAP2K4. 1 Publication
    Mutagenesisi1403 – 14031R → A: Loss of AP-1 transcription factor activity, no effect on NF-kappa-B activity. 1 Publication
    Mutagenesisi1404 – 14041G → A: Loss of AP-1 and NF-kappa-B transcription factor activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 14931492Mitogen-activated protein kinase kinase kinase 1PRO_0000086241Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei142 – 1421Phosphoserine1 Publication
    Modified residuei270 – 2701PhosphoserineBy similarity
    Modified residuei287 – 2871PhosphoserineBy similarity
    Modified residuei292 – 2921PhosphoserineBy similarity
    Modified residuei295 – 2951PhosphoserineBy similarity
    Modified residuei502 – 5021PhosphoserineBy similarity
    Modified residuei999 – 9991PhosphoserineBy similarity
    Modified residuei1024 – 10241PhosphoserineBy similarity
    Modified residuei1381 – 13811Phosphothreonine; by autocatalysis1 Publication
    Modified residuei1393 – 13931Phosphothreonine; by autocatalysis1 Publication

    Post-translational modificationi

    Autophosphorylated.2 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PaxDbiP53349.
    PRIDEiP53349.

    PTM databases

    PhosphoSiteiP53349.

    Expressioni

    Tissue specificityi

    Highly expressed in the heart and spleen while a lower level expression is seen in the liver.

    Gene expression databases

    CleanExiMM_MAP3K1.
    GenevestigatoriP53349.

    Interactioni

    Subunit structurei

    Binds both upstream activators and downstream substrates in multimolecular complexes through its N-terminus. Oligomerizes after binding MAP4K2 or TRAF2. Interacts with AXIN1. Interacts (via the kinase catalytic domain) with STK38 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Map2k4P478092EBI-447913,EBI-447934
    Mapk8ip3Q9ESN9-23EBI-447913,EBI-9549291

    Protein-protein interaction databases

    DIPiDIP-219N.
    DIP-32487N.
    IntActiP53349. 5 interactions.
    MINTiMINT-1531520.
    STRINGi10090.ENSMUSP00000022274.

    Structurei

    3D structure databases

    ProteinModelPortaliP53349.
    SMRiP53349. Positions 438-490, 1229-1487.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1224 – 1489266Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi25 – 328Poly-Gly
    Compositional biasi74 – 14976Pro-richAdd
    BLAST
    Compositional biasi233 – 29159Pro-richAdd
    BLAST
    Compositional biasi417 – 42610Poly-Ser

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
    Contains 1 SWIM-type zinc finger.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri333 – 36129SWIM-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri438 – 48750RING-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000113437.
    HOVERGENiHBG006302.
    InParanoidiP53349.
    PhylomeDBiP53349.

    Family and domain databases

    Gene3Di3.30.40.10. 1 hit.
    InterProiIPR016024. ARM-type_fold.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    IPR001841. Znf_RING.
    IPR013083. Znf_RING/FYVE/PHD.
    IPR007527. Znf_SWIM.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    PF04434. SWIM. 1 hit.
    [Graphical view]
    SMARTiSM00184. RING. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF48371. SSF48371. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    PS50966. ZF_SWIM. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P53349-1 [UniParc]FASTAAdd to Basket

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    MAAAAGDRAS SSGFPGAAAA SPEAGGGGGG GGALQGSGAP AAGAAGLLRE     50
    PGSAGRERAD WRRRQLRKVR SVELDQLPEQ PLFLAAASPP CPSTSPSPEP 100
    ADAAAGASRF QPAAGPPPPG AASRCGSHSA ELAAARDSGA RSPAGAEPPS 150
    AAAPSGREME NKETLKGLHK MEDRPEERMI REKLKATCMP AWKHEWLERR 200
    NRRGPVVVKP IPIKGDGSEV NNLAAEPQGE GQAGSAAPAP KGRRSPSPGS 250
    SPSGRSVKPE SPGVRRKRVS PVPFQSGRIT PPRRAPSPDG FSPYSPEETS 300
    RRVNKVMRAR LYLLQQIGPN SFLIGGDSPD NKYRVFIGPQ NCSCGRGAFC 350
    IHLLFVMLRV FQLEPSDPML WRKTLKNFEV ESLFQKYHSR RSSRIKAPSR 400
    NTIQKFVSRM SNSHTLSSSS TSTSSSENSI KDEEEQMCPI CLLGMLDEES 450
    LTVCEDGCRN KLHHHCMSIW AEECRRNREP LICPLCRSKW RSHDFYSHEL 500
    SSPVESPASL RAVQQPSSPQ QPVAGSQRRN QESSFNLTHF GTQQIPSAYK 550
    DLAEPWIQVF GMELVGCLFS RNWNVREMAL RRLSHDVSGA LLLANGESTG 600
    NSGGGSGGSL SAGAASGSSQ PSISGDVVEA CCSVLSIVCA DPVYKVYVAA 650
    LKTLRAMLVY TPCHSLAERI KLQRLLRPVV DTILVKCADA NSRTSQLSIS 700
    TVLELCKGQA GELAVGREIL KAGSIGVGGV DYVLSCILGN QAESNNWQEL 750
    LGRLCLIDRL LLEFPAEFYP HIVSTDVSQA EPVEIRYKKL LSLLTFALQS 800
    IDNSHSMVGK LSRRIYLSSA RMVTAVPAVF SKLVTMLNAS GSTHFTRMRR 850
    RLMAIADEVE IAEVIQLGVE DTVDGHQDSL QAVAPTSCLE NSSLEHTVHR 900
    EKTGKGLSAT RLSASSEDIS DRLAGVSVGL PSSTTTEQPK PAVQTKGRPH 950
    SQCLNSSPLS HAQLMFPAPS APCSSAPSVP DISKHRPQAF VPCKIPSASP 1000
    QTQRKFSLQF QRNCSEHRDS DQLSPVFTQS RPPPSSNIHR PKPSRPVPGS 1050
    TSKLGDATKS SMTLDLGSAS RCDDSFGGGG NSGNAVIPSD ETVFTPVEDK 1100
    CRLDVNTELN SSIEDLLEAS MPSSDTTVTF KSEVAVLSPE KAENDDTYKD 1150
    DVNHNQKCKE KMEAEEEEAL AIAMAMSASQ DALPIVPQLQ VENGEDIIII 1200
    QQDTPETLPG HTKAKQPYRE DAEWLKGQQI GLGAFSSCYQ AQDVGTGTLM 1250
    AVKQVTYVRN TSSEQEEVVE ALREEIRMMG HLNHPNIIRM LGATCEKSNY 1300
    NLFIEWMAGG SVAHLLSKYG AFKESVVINY TEQLLRGLSY LHENQIIHRD 1350
    VKGANLLIDS TGQRLRIADF GAAARLASKG TGAGEFQGQL LGTIAFMAPE 1400
    VLRGQQYGRS CDVWSVGCAI IEMACAKPPW NAEKHSNHLA LIFKIASATT 1450
    APSIPSHLSP GLRDVAVRCL ELQPQDRPPS RELLKHPVFR TTW 1493
    Length:1,493
    Mass (Da):161,289
    Last modified:September 26, 2001 - v3
    Checksum:iCA65C9B7703C6BF9
    GO

    Sequence cautioni

    The sequence AAA97500.1 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti30 – 3910GGGALQGSGA → ALQGSG(PubMed:10523642)Curated
    Sequence conflicti103 – 1031Missing in BAA85878. (PubMed:10523642)Curated
    Sequence conflicti257 – 2571V → E in BAA85878. (PubMed:10523642)Curated
    Sequence conflicti307 – 3071M → V in BAA85878. (PubMed:10523642)Curated
    Sequence conflicti413 – 4131S → C in BAA85878. (PubMed:10523642)Curated
    Sequence conflicti559 – 5591V → A in BAA85878. (PubMed:10523642)Curated
    Sequence conflicti883 – 8831V → L in AAA85038. (PubMed:8385802)Curated
    Sequence conflicti1467 – 14671V → L in AAA85038. (PubMed:8385802)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF117340 mRNA. Translation: AAD25049.1.
    AB014614 mRNA. Translation: BAA85878.1.
    L13103 mRNA. Translation: AAA97500.1. Different initiation.
    U23470 mRNA. Translation: AAA85038.1.
    CCDSiCCDS26771.1.
    PIRiA46212.
    UniGeneiMm.15918.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF117340 mRNA. Translation: AAD25049.1 .
    AB014614 mRNA. Translation: BAA85878.1 .
    L13103 mRNA. Translation: AAA97500.1 . Different initiation.
    U23470 mRNA. Translation: AAA85038.1 .
    CCDSi CCDS26771.1.
    PIRi A46212.
    UniGenei Mm.15918.

    3D structure databases

    ProteinModelPortali P53349.
    SMRi P53349. Positions 438-490, 1229-1487.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-219N.
    DIP-32487N.
    IntActi P53349. 5 interactions.
    MINTi MINT-1531520.
    STRINGi 10090.ENSMUSP00000022274.

    PTM databases

    PhosphoSitei P53349.

    Proteomic databases

    PaxDbi P53349.
    PRIDEi P53349.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    MGIi MGI:1346872. Map3k1.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000113437.
    HOVERGENi HBG006302.
    InParanoidi P53349.
    PhylomeDBi P53349.

    Enzyme and pathway databases

    BRENDAi 2.7.11.25. 3474.
    Reactomei REACT_188530. FCERI mediated MAPK activation.
    REACT_202898. TRAF6 mediated NF-kB activation.

    Miscellaneous databases

    ChiTaRSi MAP3K1. mouse.
    PROi P53349.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_MAP3K1.
    Genevestigatori P53349.

    Family and domain databases

    Gene3Di 3.30.40.10. 1 hit.
    InterProi IPR016024. ARM-type_fold.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    IPR001841. Znf_RING.
    IPR013083. Znf_RING/FYVE/PHD.
    IPR007527. Znf_SWIM.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    PF04434. SWIM. 1 hit.
    [Graphical view ]
    SMARTi SM00184. RING. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48371. SSF48371. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    PS50966. ZF_SWIM. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Lange C.A., Blumer K.J., Sather S.L., Johnson G.L.
      Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a scaffold factor in the JNK signaling pathway."
      Ito M., Yoshioka K., Akechi M., Yamashita S., Takamatsu N., Sugiyama K., Hibi M., Nakabeppu Y., Shiba T., Yamamoto K.
      Mol. Cell. Biol. 19:7539-7548(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-659.
      Tissue: Spleen.
    3. "A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf."
      Lange-Carter C.A., Pleiman C.M., Gardner A.M., Blumer K.J., Johnson G.L.
      Science 260:315-319(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 660-1493.
      Strain: BALB/c.
      Tissue: Brain.
    4. Whitmarsh A.J., Shore P., Sharrocks A.D., Davis R.J.
      Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 796-1493.
      Strain: BALB/c.
      Tissue: Heart.
    5. "Regulation of the activity of MEK kinase 1 (MEKK1) by autophosphorylation within the kinase activation domain."
      Deak J.C., Templeton D.J.
      Biochem. J. 322:185-192(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION, MUTAGENESIS OF THR-1381 AND THR-1393, PHOSPHORYLATION AT THR-1381 AND THR-1393.
    6. "Subdomain VIII is a specificity-determining region in MEKK1."
      Tu Z., Lee F.S.
      J. Biol. Chem. 278:48498-48505(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH IKBKB AND MAP2K4, ENZYME REGULATION, MUTAGENESIS OF THR-1381; THR-1393; ISO-1394; PHE-1396; MET-1397; VAL-1401; LEU-1402; ARG-1403 AND GLY-1404.
    7. "The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms."
      Wong C.K., Luo W., Deng Y., Zou H., Ye Z., Lin S.-C.
      J. Biol. Chem. 279:39366-39373(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AXIN1.
    8. "The phagosomal proteome in interferon-gamma-activated macrophages."
      Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
      Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-142, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiM3K1_MOUSE
    AccessioniPrimary (citable) accession number: P53349
    Secondary accession number(s): Q60831, Q9R0U3, Q9R256
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: September 26, 2001
    Last modified: October 1, 2014
    This is version 138 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3