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Protein

Mitogen-activated protein kinase kinase kinase 1

Gene

Map3k1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1253ATPPROSITE-ProRule annotation1
Active sitei1350Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri333 – 361SWIM-typePROSITE-ProRule annotationAdd BLAST29
Zinc fingeri438 – 487RING-typePROSITE-ProRule annotationAdd BLAST50
Nucleotide bindingi1230 – 1238ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • activation of JUN kinase activity Source: BHF-UCL
  • apoptotic mitochondrial changes Source: MGI
  • camera-type eye development Source: MGI
  • epithelial cell morphogenesis Source: MGI
  • eyelid development in camera-type eye Source: MGI
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • JNK cascade Source: MGI
  • morphogenesis of an epithelial sheet Source: MGI
  • positive regulation of actin filament polymerization Source: MGI
  • regulation of cell migration Source: MGI
  • transforming growth factor beta receptor signaling pathway Source: MGI
  • 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.
ReactomeiR-MMU-2871796. FCERI mediated MAPK activation.
R-MMU-933542. 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
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1346872. Map3k1.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: MGI
  • cytoplasm Source: GO_Central
  • cytosol Source: Reactome
  • filamentous actin Source: MGI
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1381T → A: Fails to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. 2 Publications1
Mutagenesisi1381T → E: Loss of kinase activity and autophosphorylation. 2 Publications1
Mutagenesisi1381T → S: Reduced kinase activity and autophosphorylation. 2 Publications1
Mutagenesisi1393T → A: Loss of kinase activity and autophosphorylation. Fails to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. 2 Publications1
Mutagenesisi1393T → E: Loss of kinase activity and autophosphorylation. 2 Publications1
Mutagenesisi1393T → S: Reduced kinase activity and autophosphorylation. 2 Publications1
Mutagenesisi1394I → 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 Publication1
Mutagenesisi1396F → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Reduced ability to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. 1 Publication1
Mutagenesisi1397M → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Reduced ability to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. 1 Publication1
Mutagenesisi1401V → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Reduced ability to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. 1 Publication1
Mutagenesisi1402L → 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 Publication1
Mutagenesisi1403R → A: Loss of AP-1 transcription factor activity, no effect on NF-kappa-B activity. 1 Publication1
Mutagenesisi1404G → A: Loss of AP-1 and NF-kappa-B transcription factor activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000862412 – 1493Mitogen-activated protein kinase kinase kinase 1Add BLAST1492

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei21PhosphoserineBy similarity1
Modified residuei142PhosphoserineCombined sources1
Modified residuei270PhosphoserineBy similarity1
Modified residuei280PhosphothreonineBy similarity1
Modified residuei287PhosphoserineCombined sources1
Modified residuei292PhosphoserineBy similarity1
Modified residuei295PhosphoserineBy similarity1
Modified residuei502PhosphoserineBy similarity1
Modified residuei526PhosphoserineBy similarity1
Modified residuei915PhosphoserineBy similarity1
Modified residuei999PhosphoserineBy similarity1
Modified residuei1024PhosphoserineBy similarity1
Modified residuei1381Phosphothreonine; by autocatalysis1 Publication1
Modified residuei1393Phosphothreonine; by autocatalysis1 Publication1

Post-translational modificationi

Autophosphorylated.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP53349.
MaxQBiP53349.
PaxDbiP53349.
PeptideAtlasiP53349.
PRIDEiP53349.

PTM databases

iPTMnetiP53349.
PhosphoSitePlusiP53349.

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.

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
Tab1Q8CF894EBI-447913,EBI-1778503

GO - Molecular functioni

  • cytoskeletal protein binding Source: MGI
  • protein kinase binding Source: MGI

Protein-protein interaction databases

DIPiDIP-219N.
DIP-32487N.
IntActiP53349. 6 interactors.
MINTiMINT-1531520.
STRINGi10090.ENSMUSP00000104890.

Structurei

3D structure databases

ProteinModelPortaliP53349.
SMRiP53349.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1224 – 1489Protein kinasePROSITE-ProRule annotationAdd BLAST266

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi25 – 32Poly-Gly8
Compositional biasi74 – 149Pro-richAdd BLAST76
Compositional biasi233 – 291Pro-richAdd BLAST59
Compositional biasi417 – 426Poly-Ser10

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)DescriptionActionsGraphical viewLength
Zinc fingeri333 – 361SWIM-typePROSITE-ProRule annotationAdd BLAST29
Zinc fingeri438 – 487RING-typePROSITE-ProRule annotationAdd BLAST50

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4279. Eukaryota.
ENOG410XQGS. LUCA.
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.
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]
SMARTiSM00220. 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

« 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 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti30 – 39GGGALQGSGA → ALQGSG (PubMed:10523642).Curated10
Sequence conflicti103Missing in BAA85878 (PubMed:10523642).Curated1
Sequence conflicti257V → E in BAA85878 (PubMed:10523642).Curated1
Sequence conflicti307M → V in BAA85878 (PubMed:10523642).Curated1
Sequence conflicti413S → C in BAA85878 (PubMed:10523642).Curated1
Sequence conflicti559V → A in BAA85878 (PubMed:10523642).Curated1
Sequence conflicti883V → L in AAA85038 (PubMed:8385802).Curated1
Sequence conflicti1467V → L in AAA85038 (PubMed:8385802).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliP53349.
SMRiP53349.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-219N.
DIP-32487N.
IntActiP53349. 6 interactors.
MINTiMINT-1531520.
STRINGi10090.ENSMUSP00000104890.

PTM databases

iPTMnetiP53349.
PhosphoSitePlusiP53349.

Proteomic databases

EPDiP53349.
MaxQBiP53349.
PaxDbiP53349.
PeptideAtlasiP53349.
PRIDEiP53349.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:1346872. Map3k1.

Phylogenomic databases

eggNOGiKOG4279. Eukaryota.
ENOG410XQGS. LUCA.
HOGENOMiHOG000113437.
HOVERGENiHBG006302.
InParanoidiP53349.
PhylomeDBiP53349.

Enzyme and pathway databases

BRENDAi2.7.11.25. 3474.
ReactomeiR-MMU-2871796. FCERI mediated MAPK activation.
R-MMU-933542. TRAF6 mediated NF-kB activation.

Miscellaneous databases

ChiTaRSiMap3k1. mouse.
PROiP53349.
SOURCEiSearch...

Gene expression databases

CleanExiMM_MAP3K1.

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.
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]
SMARTiSM00220. 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]
ProtoNetiSearch...

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: November 2, 2016
This is version 159 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.