Mitogen-activated protein kinase kinase kinase 1

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P53349 (M3K1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified November 16, 2011. Version 113. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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 names

Name:	Map3k1
Synonyms:	Mekk, Mekk1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1493 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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
Domain	Zinc-finger
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of JUN kinase activity Inferred from direct assay Ref.2. Source: BHF-UCL
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction Ref.2. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed By similarity

Chain

2 – 1493

1492

Mitogen-activated protein kinase kinase kinase 1

PRO_0000086241

Regions

Domain

1224 – 1489

266

Protein kinase

Zinc finger

333 – 361

SWIM-type

Zinc finger

438 – 487

RING-type

Nucleotide binding

1230 – 1238

ATP By similarity

Compositional bias

25 – 32

Poly-Gly

Compositional bias

74 – 149

Pro-rich

Compositional bias

233 – 291

Pro-rich

Compositional bias

417 – 426

Poly-Ser

Sites

Active site

1350

Proton acceptor By similarity

Binding site

1253

ATP By similarity

Amino acid modifications

Modified residue

N-acetylalanine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

138

Phosphoserine By similarity

Modified residue

247

Phosphoserine By similarity

Modified residue

270

Phosphoserine By similarity

Modified residue

287

Phosphoserine By similarity

Modified residue

292

Phosphoserine By similarity

Modified residue

295

Phosphoserine By similarity

Modified residue

502

Phosphoserine By similarity

Modified residue

506

Phosphoserine By similarity

Modified residue

653

Phosphothreonine By similarity

Modified residue

661

Phosphothreonine By similarity

Modified residue

915

Phosphoserine By similarity

Modified residue

997

Phosphoserine By similarity

Modified residue

999

Phosphoserine By similarity

Modified residue

1024

Phosphoserine By similarity

Modified residue

1138

Phosphoserine By similarity

Modified residue

1381

Phosphothreonine; by autocatalysis Ref.5

Modified residue

1393

Phosphothreonine; by autocatalysis Ref.5

Experimental info

Mutagenesis

1381

T → A: Fails to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. Ref.5 Ref.6

Mutagenesis

1381

T → E: Loss of kinase activity and autophosphorylation. Ref.5 Ref.6

Mutagenesis

1381

T → S: Reduced kinase activity and autophosphorylation. Ref.5 Ref.6

Mutagenesis

1393

T → A: Loss of kinase activity and autophosphorylation. Fails to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. Ref.5 Ref.6

Mutagenesis

1393

T → E: Loss of kinase activity and autophosphorylation. Ref.5 Ref.6

Mutagenesis

1393

T → S: Reduced kinase activity and autophosphorylation. Ref.5 Ref.6

Mutagenesis

1394

I → 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

Mutagenesis

1396

F → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Reduced ability to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. Ref.6

Mutagenesis

1397

M → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Reduced ability to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. Ref.6

Mutagenesis

1401

V → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Reduced ability to activate MAP2K1, MAP2K4, MAP2K7, CHUK and IKBKB. Ref.6

Mutagenesis

1402

L → 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

Mutagenesis

1403

R → A: Loss of AP-1 transcription factor activity, no effect on NF-kappa-B activity. Ref.6

Mutagenesis

1404

G → A: Loss of AP-1 and NF-kappa-B transcription factor activity. Ref.6

Sequence conflict

30 – 39

GGGALQGSGA → ALQGSG Ref.2

Sequence conflict

103

Missing in BAA85878. Ref.2

Sequence conflict

257

V → E in BAA85878. Ref.2

Sequence conflict

307

M → V in BAA85878. Ref.2

Sequence conflict

413

S → C in BAA85878. Ref.2

Sequence conflict

559

V → A in BAA85878. Ref.2

Sequence conflict

883

V → L in AAA85038. Ref.3

Sequence conflict

1467

V → L in AAA85038. Ref.3

Sequences

Sequence

Length

Mass (Da)

Tools

P53349 [UniParc].

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

FASTA

1,493

161,289

        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

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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: 10523642] [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: 8385802] [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: 9078260] [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: 14500727] [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: 15262978] [Abstract] Cited for: INTERACTION WITH AXIN1.
+	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.
IPI	IPI00130375.
PIR	A46212.
UniGene	Mm.15918.
3D structure databases
ProteinModelPortal	P53349.
SMR	P53349. Positions 434-491, 1224-1490.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-219N. DIP-32487N.
IntAct	P53349. 3 interactions.
MINT	MINT-1531520.
STRING	P53349.
PTM databases
PhosphoSite	P53349.
Proteomic databases
PRIDE	P53349.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	uc007rwa.1. mouse.
Organism-specific databases
MGI	MGI:1346872. Map3k1.
Phylogenomic databases
eggNOG	roNOG06081.
GeneTree	ENSGT00600000084224.
HOGENOM	HBG282047.
HOVERGEN	HBG006302.
InParanoid	P53349.
OrthoDB	EOG4F1X27.
Enzyme and pathway databases
BRENDA	2.7.11.25. 3474.
Gene expression databases
ArrayExpress	P53349.
Bgee	P53349.
CleanEx	MM_MAP3K1.
Genevestigator	P53349.
GermOnline	ENSMUSG00000021754. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR007527. Znf_SWIM. [Graphical view]
Gene3D	G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.
Pfam	PF00069. Pkinase. 1 hit. PF04434. SWIM. 1 hit. [Graphical view]
SMART	SM00184. RING. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. PS50966. ZF_SWIM. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

M3K1_MOUSE

Accession

Primary (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:	November 16, 2011
This is version 113 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents