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P53349 (M3K1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Map3k1
Synonyms:Mekk, Mekk1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1493 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Activated by autophosphorylation on Thr-1381 and Thr-1393 following oligomerization. Ref.5 Ref.6

Subunit structure

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. Ref.6 Ref.7

Tissue specificity

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

Post-translational modification

Autophosphorylated. Ref.5

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.

Contains 1 protein kinase domain.

Contains 1 RING-type zinc finger.

Contains 1 SWIM-type zinc finger.

Sequence caution

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

Ontologies

Keywords
   DomainZinc-finger
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJNK cascade

Inferred from direct assay PubMed 14967141. Source: MGI

activation of JUN kinase activity

Inferred from direct assay Ref.2. Source: BHF-UCL

activation of MAPKK activity

Inferred from Biological aspect of Ancestor. Source: GOC

apoptotic mitochondrial changes

Inferred from mutant phenotype PubMed 15882989. Source: MGI

camera-type eye development

Inferred from mutant phenotype PubMed 12941696. Source: MGI

epithelial cell morphogenesis

Inferred from mutant phenotype PubMed 23201579. Source: MGI

eyelid development in camera-type eye

Inferred from mutant phenotype PubMed 23201579. Source: MGI

positive regulation of actin filament polymerization

Inferred from mutant phenotype PubMed 12941696. Source: MGI

regulation of cell migration

Inferred from mutant phenotype PubMed 12941696. Source: MGI

transforming growth factor beta receptor signaling pathway

Inferred from mutant phenotype PubMed 12941696. Source: MGI

wound healing

Inferred from mutant phenotype PubMed 12941696. Source: MGI

   Cellular_componentcytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytosol

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

JUN kinase kinase activity

Inferred from direct assay PubMed 14967141. Source: MGI

MAP kinase kinase kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein kinase activity

Inferred from sequence orthology PubMed 15001576. Source: MGI

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 14931492Mitogen-activated protein kinase kinase kinase 1
PRO_0000086241

Regions

Domain1224 – 1489266Protein kinase
Zinc finger333 – 36129SWIM-type
Zinc finger438 – 48750RING-type
Nucleotide binding1230 – 12389ATP By similarity
Compositional bias25 – 328Poly-Gly
Compositional bias74 – 14976Pro-rich
Compositional bias233 – 29159Pro-rich
Compositional bias417 – 42610Poly-Ser

Sites

Active site13501Proton acceptor By similarity
Binding site12531ATP By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue1421Phosphoserine Ref.8
Modified residue2701Phosphoserine By similarity
Modified residue2871Phosphoserine By similarity
Modified residue2921Phosphoserine By similarity
Modified residue2951Phosphoserine By similarity
Modified residue5021Phosphoserine By similarity
Modified residue9991Phosphoserine By similarity
Modified residue10241Phosphoserine By similarity
Modified residue13811Phosphothreonine; by autocatalysis Ref.5
Modified residue13931Phosphothreonine; by autocatalysis Ref.5

Experimental info

Mutagenesis13811T → A: Fails to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. Ref.5 Ref.6
Mutagenesis13811T → E: Loss of kinase activity and autophosphorylation. Ref.5 Ref.6
Mutagenesis13811T → S: Reduced kinase activity and autophosphorylation. Ref.5 Ref.6
Mutagenesis13931T → A: Loss of kinase activity and autophosphorylation. Fails to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. Ref.5 Ref.6
Mutagenesis13931T → E: Loss of kinase activity and autophosphorylation. Ref.5 Ref.6
Mutagenesis13931T → S: Reduced kinase activity and autophosphorylation. Ref.5 Ref.6
Mutagenesis13941I → 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. Ref.6
Mutagenesis13961F → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Reduced ability to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. Ref.6
Mutagenesis13971M → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Reduced ability to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. Ref.6
Mutagenesis14011V → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Reduced ability to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. Ref.6
Mutagenesis14021L → 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. Ref.6
Mutagenesis14031R → A: Loss of AP-1 transcription factor activity, no effect on NF-kappa-B activity. Ref.6
Mutagenesis14041G → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Ref.6
Sequence conflict30 – 3910GGGALQGSGA → ALQGSG Ref.2
Sequence conflict1031Missing in BAA85878. Ref.2
Sequence conflict2571V → E in BAA85878. Ref.2
Sequence conflict3071M → V in BAA85878. Ref.2
Sequence conflict4131S → C in BAA85878. Ref.2
Sequence conflict5591V → A in BAA85878. Ref.2
Sequence conflict8831V → L in AAA85038. Ref.3
Sequence conflict14671V → L in AAA85038. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P53349 [UniParc].

Last modified September 26, 2001. Version 3.
Checksum: CA65C9B7703C6BF9

FASTA1,493161,289
        10         20         30         40         50         60 
MAAAAGDRAS SSGFPGAAAA SPEAGGGGGG GGALQGSGAP AAGAAGLLRE PGSAGRERAD 

        70         80         90        100        110        120 
WRRRQLRKVR SVELDQLPEQ PLFLAAASPP CPSTSPSPEP ADAAAGASRF QPAAGPPPPG 

       130        140        150        160        170        180 
AASRCGSHSA ELAAARDSGA RSPAGAEPPS AAAPSGREME NKETLKGLHK MEDRPEERMI 

       190        200        210        220        230        240 
REKLKATCMP AWKHEWLERR NRRGPVVVKP IPIKGDGSEV NNLAAEPQGE GQAGSAAPAP 

       250        260        270        280        290        300 
KGRRSPSPGS SPSGRSVKPE SPGVRRKRVS PVPFQSGRIT PPRRAPSPDG FSPYSPEETS 

       310        320        330        340        350        360 
RRVNKVMRAR LYLLQQIGPN SFLIGGDSPD NKYRVFIGPQ NCSCGRGAFC IHLLFVMLRV 

       370        380        390        400        410        420 
FQLEPSDPML WRKTLKNFEV ESLFQKYHSR RSSRIKAPSR NTIQKFVSRM SNSHTLSSSS 

       430        440        450        460        470        480 
TSTSSSENSI KDEEEQMCPI CLLGMLDEES LTVCEDGCRN KLHHHCMSIW AEECRRNREP 

       490        500        510        520        530        540 
LICPLCRSKW RSHDFYSHEL SSPVESPASL RAVQQPSSPQ QPVAGSQRRN QESSFNLTHF 

       550        560        570        580        590        600 
GTQQIPSAYK DLAEPWIQVF GMELVGCLFS RNWNVREMAL RRLSHDVSGA LLLANGESTG 

       610        620        630        640        650        660 
NSGGGSGGSL SAGAASGSSQ PSISGDVVEA CCSVLSIVCA DPVYKVYVAA LKTLRAMLVY 

       670        680        690        700        710        720 
TPCHSLAERI KLQRLLRPVV DTILVKCADA NSRTSQLSIS TVLELCKGQA GELAVGREIL 

       730        740        750        760        770        780 
KAGSIGVGGV DYVLSCILGN QAESNNWQEL LGRLCLIDRL LLEFPAEFYP HIVSTDVSQA 

       790        800        810        820        830        840 
EPVEIRYKKL LSLLTFALQS IDNSHSMVGK LSRRIYLSSA RMVTAVPAVF SKLVTMLNAS 

       850        860        870        880        890        900 
GSTHFTRMRR RLMAIADEVE IAEVIQLGVE DTVDGHQDSL QAVAPTSCLE NSSLEHTVHR 

       910        920        930        940        950        960 
EKTGKGLSAT RLSASSEDIS DRLAGVSVGL PSSTTTEQPK PAVQTKGRPH SQCLNSSPLS 

       970        980        990       1000       1010       1020 
HAQLMFPAPS APCSSAPSVP DISKHRPQAF VPCKIPSASP QTQRKFSLQF QRNCSEHRDS 

      1030       1040       1050       1060       1070       1080 
DQLSPVFTQS RPPPSSNIHR PKPSRPVPGS TSKLGDATKS SMTLDLGSAS RCDDSFGGGG 

      1090       1100       1110       1120       1130       1140 
NSGNAVIPSD ETVFTPVEDK CRLDVNTELN SSIEDLLEAS MPSSDTTVTF KSEVAVLSPE 

      1150       1160       1170       1180       1190       1200 
KAENDDTYKD DVNHNQKCKE KMEAEEEEAL AIAMAMSASQ DALPIVPQLQ VENGEDIIII 

      1210       1220       1230       1240       1250       1260 
QQDTPETLPG HTKAKQPYRE DAEWLKGQQI GLGAFSSCYQ AQDVGTGTLM AVKQVTYVRN 

      1270       1280       1290       1300       1310       1320 
TSSEQEEVVE ALREEIRMMG HLNHPNIIRM LGATCEKSNY NLFIEWMAGG SVAHLLSKYG 

      1330       1340       1350       1360       1370       1380 
AFKESVVINY TEQLLRGLSY LHENQIIHRD VKGANLLIDS TGQRLRIADF GAAARLASKG 

      1390       1400       1410       1420       1430       1440 
TGAGEFQGQL LGTIAFMAPE VLRGQQYGRS CDVWSVGCAI IEMACAKPPW NAEKHSNHLA 

      1450       1460       1470       1480       1490 
LIFKIASATT APSIPSHLSP GLRDVAVRCL ELQPQDRPPS RELLKHPVFR TTW 

« Hide

References

« Hide 'large scale' references
[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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF117340 mRNA. Translation: AAD25049.1.
AB014614 mRNA. Translation: BAA85878.1.
L13103 mRNA. Translation: AAA97500.1. Different initiation.
U23470 mRNA. Translation: AAA85038.1.
PIRA46212.
UniGeneMm.15918.

3D structure databases

ProteinModelPortalP53349.
SMRP53349. Positions 1229-1487.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-219N.
DIP-32487N.
IntActP53349. 4 interactions.
MINTMINT-1531520.
STRING10090.ENSMUSP00000022274.

PTM databases

PhosphoSiteP53349.

Proteomic databases

PaxDbP53349.
PRIDEP53349.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:1346872. Map3k1.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000113437.
HOVERGENHBG006302.
InParanoidP53349.
PhylomeDBP53349.

Enzyme and pathway databases

BRENDA2.7.11.25. 3474.
ReactomeREACT_98458. Immune System.

Gene expression databases

CleanExMM_MAP3K1.
GenevestigatorP53349.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR016024. 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]
PfamPF00069. Pkinase. 1 hit.
PF04434. SWIM. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. 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]
ProtoNetSearch...

Other

ChiTaRSMAP3K1. mouse.
PROP53349.
SOURCESearch...

Entry information

Entry nameM3K1_MOUSE
AccessionPrimary (citable) accession number: P53349
Secondary accession number(s): Q60831, Q9R0U3, Q9R256
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: September 26, 2001
Last modified: April 16, 2014
This is version 133 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot