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P53349

- M3K1_MOUSE

UniProt

P53349 - M3K1_MOUSE

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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

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 kinase activity Source: MGI
  5. 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
Complete GO annotation...

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
Complete GO annotation...

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

MaxQBiP53349.
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 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.
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 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAAAAGDRAS SSGFPGAAAA SPEAGGGGGG GGALQGSGAP AAGAAGLLRE
60 70 80 90 100
PGSAGRERAD WRRRQLRKVR SVELDQLPEQ PLFLAAASPP CPSTSPSPEP
110 120 130 140 150
ADAAAGASRF QPAAGPPPPG AASRCGSHSA ELAAARDSGA RSPAGAEPPS
160 170 180 190 200
AAAPSGREME NKETLKGLHK MEDRPEERMI REKLKATCMP AWKHEWLERR
210 220 230 240 250
NRRGPVVVKP IPIKGDGSEV NNLAAEPQGE GQAGSAAPAP KGRRSPSPGS
260 270 280 290 300
SPSGRSVKPE SPGVRRKRVS PVPFQSGRIT PPRRAPSPDG FSPYSPEETS
310 320 330 340 350
RRVNKVMRAR LYLLQQIGPN SFLIGGDSPD NKYRVFIGPQ NCSCGRGAFC
360 370 380 390 400
IHLLFVMLRV FQLEPSDPML WRKTLKNFEV ESLFQKYHSR RSSRIKAPSR
410 420 430 440 450
NTIQKFVSRM SNSHTLSSSS TSTSSSENSI KDEEEQMCPI CLLGMLDEES
460 470 480 490 500
LTVCEDGCRN KLHHHCMSIW AEECRRNREP LICPLCRSKW RSHDFYSHEL
510 520 530 540 550
SSPVESPASL RAVQQPSSPQ QPVAGSQRRN QESSFNLTHF GTQQIPSAYK
560 570 580 590 600
DLAEPWIQVF GMELVGCLFS RNWNVREMAL RRLSHDVSGA LLLANGESTG
610 620 630 640 650
NSGGGSGGSL SAGAASGSSQ PSISGDVVEA CCSVLSIVCA DPVYKVYVAA
660 670 680 690 700
LKTLRAMLVY TPCHSLAERI KLQRLLRPVV DTILVKCADA NSRTSQLSIS
710 720 730 740 750
TVLELCKGQA GELAVGREIL KAGSIGVGGV DYVLSCILGN QAESNNWQEL
760 770 780 790 800
LGRLCLIDRL LLEFPAEFYP HIVSTDVSQA EPVEIRYKKL LSLLTFALQS
810 820 830 840 850
IDNSHSMVGK LSRRIYLSSA RMVTAVPAVF SKLVTMLNAS GSTHFTRMRR
860 870 880 890 900
RLMAIADEVE IAEVIQLGVE DTVDGHQDSL QAVAPTSCLE NSSLEHTVHR
910 920 930 940 950
EKTGKGLSAT RLSASSEDIS DRLAGVSVGL PSSTTTEQPK PAVQTKGRPH
960 970 980 990 1000
SQCLNSSPLS HAQLMFPAPS APCSSAPSVP DISKHRPQAF VPCKIPSASP
1010 1020 1030 1040 1050
QTQRKFSLQF QRNCSEHRDS DQLSPVFTQS RPPPSSNIHR PKPSRPVPGS
1060 1070 1080 1090 1100
TSKLGDATKS SMTLDLGSAS RCDDSFGGGG NSGNAVIPSD ETVFTPVEDK
1110 1120 1130 1140 1150
CRLDVNTELN SSIEDLLEAS MPSSDTTVTF KSEVAVLSPE KAENDDTYKD
1160 1170 1180 1190 1200
DVNHNQKCKE KMEAEEEEAL AIAMAMSASQ DALPIVPQLQ VENGEDIIII
1210 1220 1230 1240 1250
QQDTPETLPG HTKAKQPYRE DAEWLKGQQI GLGAFSSCYQ AQDVGTGTLM
1260 1270 1280 1290 1300
AVKQVTYVRN TSSEQEEVVE ALREEIRMMG HLNHPNIIRM LGATCEKSNY
1310 1320 1330 1340 1350
NLFIEWMAGG SVAHLLSKYG AFKESVVINY TEQLLRGLSY LHENQIIHRD
1360 1370 1380 1390 1400
VKGANLLIDS TGQRLRIADF GAAARLASKG TGAGEFQGQL LGTIAFMAPE
1410 1420 1430 1440 1450
VLRGQQYGRS CDVWSVGCAI IEMACAKPPW NAEKHSNHLA LIFKIASATT
1460 1470 1480 1490
APSIPSHLSP GLRDVAVRCL ELQPQDRPPS RELLKHPVFR TTW
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 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

MaxQBi P53349.
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.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 139 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