SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

O08648

- M3K4_MOUSE

UniProt

O08648 - M3K4_MOUSE

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Mitogen-activated protein kinase kinase kinase 4

Gene
Map3k4, Mekk4
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 CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.

Enzyme regulationi

N-terminal autoinhibitory domain interacts with the C-terminal kinase domain, inhibiting kinase activity, and preventing interaction with its substrate, MAP2K6. The GADD45 proteins activate the kinase by binding to the N-terminal domain. Activated by phosphorylation on Thr-1494 By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei1361 – 13611ATP
Active sitei1452 – 14521Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1338 – 13469ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase kinase kinase activity Source: UniProtKB-EC
  3. metal ion binding Source: UniProtKB-KW
  4. protein binding Source: UniProtKB
  5. protein kinase activity Source: UniProtKB

GO - Biological processi

  1. chorionic trophoblast cell differentiation Source: MGI
  2. determination of dorsal identity Source: MGI
  3. intracellular signal transduction Source: UniProtKB
  4. male germ-line sex determination Source: MGI
  5. placenta development Source: MGI
  6. positive regulation of JUN kinase activity Source: UniProtKB
  7. positive regulation of p38MAPK cascade Source: Ensembl
  8. regulation of gene expression Source: MGI
  9. response to UV-C Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

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

Enzyme and pathway databases

BRENDAi2.7.11.25. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase 4 (EC:2.7.11.25)
Alternative name(s):
MAPK/ERK kinase kinase 4
Short name:
MEK kinase 4
Short name:
MEKK 4
Gene namesi
Name:Map3k4
Synonyms:Mekk4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 17

Organism-specific databases

MGIiMGI:1346875. Map3k4.

Subcellular locationi

Cytoplasmperinuclear region
Note: Localized in perinuclear vesicular-like structures, probably Golgi-associated vesicles.1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. perinuclear region of cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1361 – 13611K → A or R: Loss of kinase activity. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 15971597Mitogen-activated protein kinase kinase kinase 4PRO_0000086248Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei449 – 4491Phosphoserine By similarity
Modified residuei451 – 4511Phosphothreonine By similarity
Modified residuei454 – 4541Phosphoserine By similarity
Modified residuei492 – 4921Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO08648.
PaxDbiO08648.
PRIDEiO08648.

PTM databases

PhosphoSiteiO08648.

Expressioni

Tissue specificityi

Widely expressed. High expression was found in skeletal muscle, kidney, testis followed by heart brain and lung. Low expression was found in spleen.

Gene expression databases

ArrayExpressiO08648.
BgeeiO08648.
CleanExiMM_MAP3K4.
GenevestigatoriO08648.

Interactioni

Subunit structurei

Monomer and homodimer. Homodimerization enhances kinase activity. Interacts with TRAF4; this promotes homodimerization. Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with AXIN1 and DIXDC1; interaction with DIXDC1 prevents interaction with AXIN1.3 Publications

Protein-protein interaction databases

BioGridi204960. 2 interactions.
STRINGi10090.ENSMUSP00000086459.

Structurei

3D structure databases

ProteinModelPortaliO08648.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1332 – 1590259Protein kinaseAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1178 – 11825Poly-Ala

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00590000083157.
HOGENOMiHOG000139909.
HOVERGENiHBG006304.
InParanoidiQ6PDG6.
KOiK04428.
OMAiFVKVCTD.
OrthoDBiEOG7P5T02.
TreeFamiTF105114.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform A (identifier: O08648-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

MRDAIAEPVP PPALADTPAA AMEELRPAPP PQPEPDPECC PAARQECMLG     50
ESARKSMESD PEDFSDETNT ETLYGTSPPS TPRQMKRLSA KHQRNSAGRP 100
ASRSNLKEKM NTPSQSPHKD LGKGVETVEE YSYKQEKKIR ATLRTTERDH 150
KKNAQCSFML DSVAGSLPKK SIPDVDLNKP YLSLGCSNAK LPVSMPMPIA 200
RTARQTSRTD CPADRLKFFE TLRLLLKLTS VSKKKDREQR GQENTAAFWF 250
NRSNELIWLE LQAWHAGRTI NDQDLFLYTA RQAIPDIINE ILTFKVNYGS 300
IAFSSNGAGF NGPLVEGQCR TPQETNRVGC SSYHEHLQRQ RVSFEQVKRI 350
MELLEYMEAL YPSLQALQKD YERYAAKDFE DRVQALCLWL NITKDLNQKL 400
RIMGTVLGIK NLSDIGWPVF EIPSPRPSKG YEPEDEVEDT EVELRELESG 450
TEESDEEPTP SPRVPELRLS TDAILDSRSQ GCVSRKLERL ESEEDSIGWG 500
TADCGPEASR HCLTSIYRPF VDKALKQMGL RKLILRLHKL MNGSLQRARV 550
ALVKDDRPVE FSDFPGPMWG SDYVQLSGTP PSSEQKCSAV SWEELRAMDL 600
PSFEPAFLVL CRVLLNVIHE CLKLRLEQRP AGEPSLLSIK QLVRECKEVL 650
KGGLLMKQYY QFMLQEVLGG LEKTDCNMDA FEEDLQKMLM VYFDYMRSWI 700
QMLQQLPQAS HSLKNLLEEE WNFTKEITHY IRGGEAQAGK LFCDIAGMLL 750
KSTGSFLESG LQESCAELWT SADDNGAADE LRRSVIEISR ALKELFHEAR 800
ERASKALGFA KMLRKDLEIA AEFVLSASAR ELLDALKAKQ YVKVQIPGLE 850
NLHVFVPDSL AEEKKIILQL LNAATGKDCS KDPDDVFMDA FLLLTKHGDR 900
ARDSEDGWGT WEARAVKIVP QVETVDTLRS MQVDNLLLVV MESAHLVLQR 950
KAFQQSIEGL MTVRHEQTSS QPIIAKGLQQ LKNDALELCN RISDAIDRVD 1000
HMFTLEFDAE VEESESATLQ QYYREAMIQG YNFGFEYHKE VVRLMSGEFR 1050
QKIGDKYISF AQKWMNYVLT KCESGRGTRP RWATQGFDFL QAIEPAFISA 1100
LPEDDFLSLQ ALMNECIGHV IGKPHSPVTA IHRNSPRPVK VPRCHSDPPN 1150
PHLIIPTPEG FSTRSVPSDA RTHGNSVAAA AAVAAAATTA AGRPGPGGGD 1200
SVPAKPVNTA PDTRGSSVPE NDRLASIAAE LQFRSLSRHS SPTEERDEPA 1250
YPRSDSSGST RRSWELRTLI SQTKDSASKQ GPIEAIQKSV RLFEERRYRE 1300
MRRKNIIGQV CDTPKSYDNV MHVGLRKVTF KWQRGNKIGE GQYGKVYTCI 1350
SVDTGELMAM KEIRFQPNDH KTIKETADEL KIFEGIKHPN LVRYFGVELH 1400
REEMYIFMEY CDEGTLEEVS RLGLQEHVIR LYTKQITVAI NVLHEHGIVH 1450
RDIKGANIFL TSSGLIKLGD FGCSVKLKNN AQTMPGEVNS TLGTAAYMAP 1500
EVITRAKGEG HGRAADIWSL GCVVIEMVTG KRPWHEYEHN FQIMYKVGMG 1550
HKPPIPERLS PEGKAFLSHC LESDPKIRWT ASQLLDHAFV KVCTDEE 1597
Length:1,597
Mass (Da):179,834
Last modified:July 27, 2011 - v2
Checksum:iE9C43EB9A4F056BC
GO
Isoform B (identifier: O08648-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1162-1213: Missing.

Show »
Length:1,545
Mass (Da):175,069
Checksum:i9D5EA5911CC54998
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1162 – 121352Missing in isoform B. VSP_004885Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti363 – 3642SL → NS in AAC08286. 1 Publication
Sequence conflicti473 – 4731A → T in AAC53126. 1 Publication
Sequence conflicti473 – 4731A → T in AAC53127. 1 Publication
Sequence conflicti1184 – 11841A → R in AAC53126. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U85607 mRNA. Translation: AAC53126.1.
U85608 mRNA. Translation: AAC53127.1.
BC058719 mRNA. Translation: AAH58719.1.
U66240 mRNA. Translation: AAC08286.1.
CCDSiCCDS37435.1. [O08648-1]
RefSeqiNP_036078.2. NM_011948.2. [O08648-1]
XP_006523392.1. XM_006523329.1. [O08648-2]
UniGeneiMm.28587.

Genome annotation databases

EnsembliENSMUST00000089058; ENSMUSP00000086459; ENSMUSG00000014426. [O08648-1]
GeneIDi26407.
KEGGimmu:26407.
UCSCiuc008akn.1. mouse. [O08648-1]
uc008ako.1. mouse. [O08648-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U85607 mRNA. Translation: AAC53126.1 .
U85608 mRNA. Translation: AAC53127.1 .
BC058719 mRNA. Translation: AAH58719.1 .
U66240 mRNA. Translation: AAC08286.1 .
CCDSi CCDS37435.1. [O08648-1 ]
RefSeqi NP_036078.2. NM_011948.2. [O08648-1 ]
XP_006523392.1. XM_006523329.1. [O08648-2 ]
UniGenei Mm.28587.

3D structure databases

ProteinModelPortali O08648.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 204960. 2 interactions.
STRINGi 10090.ENSMUSP00000086459.

PTM databases

PhosphoSitei O08648.

Proteomic databases

MaxQBi O08648.
PaxDbi O08648.
PRIDEi O08648.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000089058 ; ENSMUSP00000086459 ; ENSMUSG00000014426 . [O08648-1 ]
GeneIDi 26407.
KEGGi mmu:26407.
UCSCi uc008akn.1. mouse. [O08648-1 ]
uc008ako.1. mouse. [O08648-2 ]

Organism-specific databases

CTDi 4216.
MGIi MGI:1346875. Map3k4.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00590000083157.
HOGENOMi HOG000139909.
HOVERGENi HBG006304.
InParanoidi Q6PDG6.
KOi K04428.
OMAi FVKVCTD.
OrthoDBi EOG7P5T02.
TreeFami TF105114.

Enzyme and pathway databases

BRENDAi 2.7.11.25. 3474.

Miscellaneous databases

ChiTaRSi MAP3K4. mouse.
NextBioi 304385.
PROi O08648.
SOURCEi Search...

Gene expression databases

ArrayExpressi O08648.
Bgeei O08648.
CleanExi MM_MAP3K4.
Genevestigatori O08648.

Family and domain databases

InterProi 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.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the c-Jun amino terminal kinase pathway."
    Gerwins P., Blank J.L., Johnson G.L.
    J. Biol. Chem. 272:8288-8295(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), FUNCTION, INTERACTION WITH CDC42, MUTAGENESIS OF LYS-1361.
    Tissue: Brain.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
    Strain: C57BL/6.
    Tissue: Brain.
  3. "Characterization of the C3 YAC contig from proximal mouse chromosome 17 and analysis of allelic expression of genes flanking the imprinted Igf2r gene."
    Schweifer N., Valk P.J., Delwel R., Cox R., Francis F., Meier-Ewert S., Lehrach H., Barlow D.P.
    Genomics 43:285-297(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 363-1049.
    Strain: C57BL/6.
    Tissue: Ectoplacental cone.
  4. "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 AND DIXDC1.
  5. "MEKK4 is an effector of the embryonic TRAF4 for JNK activation."
    Abell A.N., Johnson G.L.
    J. Biol. Chem. 280:35793-35796(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-1361, INTERACTION WITH TRAF4.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-492, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiM3K4_MOUSE
AccessioniPrimary (citable) accession number: O08648
Secondary accession number(s): O08649, O70124, Q6PDG6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 126 of the entry and version 2 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

Similar proteinsi