Mitogen-activated protein kinase kinase kinase 4

Details

Name

Mitogen-activated protein kinase kinase kinase 4

Synonyms

• 2.7.11.25
• KIAA0213
• MAP three kinase 1
• MAPK/ERK kinase kinase 4
• MAPKKK4
• MEK kinase 4
• MEKK 4
• MEKK4
• MTK1

Gene Name

MAP3K4

Organism

Humans

Amino acid sequence

>lcl|BSEQ0051814|Mitogen-activated protein kinase kinase kinase 4
MREAAAALVPPPAFAVTPAAAMEEPPPPPPPPPPPPEPETESEPECCLAARQEGTLGDSA
CKSPESDLEDFSDETNTENLYGTSPPSTPRQMKRMSTKHQRNNVGRPASRSNLKEKMNAP
NQPPHKDTGKTVENVEEYSYKQEKKIRAALRTTERDRKKNVQCSFMLDSVGGSLPKKSIP
DVDLNKPYLSLGCSNAKLPVSVPMPIARPARQTSRTDCPADRLKFFETLRLLLKLTSVSK
KKDREQRGQENTSGFWLNRSNELIWLELQAWHAGRTINDQDFFLYTARQAIPDIINEILT
FKVDYGSFAFVRDRAGFNGTSVEGQCKATPGTKIVGYSTHHEHLQRQRVSFEQVKRIMEL
LEYIEALYPSLQALQKDYEKYAAKDFQDRVQALCLWLNITKDLNQKLRIMGTVLGIKNLS
DIGWPVFEIPSPRPSKGNEPEYEGDDTEGELKELESSTDESEEEQISDPRVPEIRQPIDN
SFDIQSRDCISKKLERLESEDDSLGWGAPDWSTEAGFSRHCLTSIYRPFVDKALKQMGLR
KLILRLHKLMDGSLQRARIALVKNDRPVEFSEFPDPMWGSDYVQLSRTPPSSEEKCSAVS
WEELKAMDLPSFEPAFLVLCRVLLNVIHECLKLRLEQRPAGEPSLLSIKQLVRECKEVLK
GGLLMKQYYQFMLQEVLEDLEKPDCNIDAFEEDLHKMLMVYFDYMRSWIQMLQQLPQASH
SLKNLLEEEWNFTKEITHYIRGGEAQAGKLFCDIAGMLLKSTGSFLEFGLQESCAEFWTS
ADDSSASDEIRRSVIEISRALKELFHEARERASKALGFAKMLRKDLEIAAEFRLSAPVRD
LLDVLKSKQYVKVQIPGLENLQMFVPDTLAEEKSIILQLLNAAAGKDCSKDSDDVLIDAY
LLLTKHGDRARDSEDSWGTWEAQPVKVVPQVETVDTLRSMQVDNLLLVVMQSAHLTIQRK
AFQQSIEGLMTLCQEQTSSQPVIAKALQQLKNDALELCNRISNAIDRVDHMFTSEFDAEV
DESESVTLQQYYREAMIQGYNFGFEYHKEVVRLMSGEFRQKIGDKYISFARKWMNYVLTK
CESGRGTRPRWATQGFDFLQAIEPAFISALPEDDFLSLQALMNECIGHVIGKPHSPVTGL
YLAIHRNSPRPMKVPRCHSDPPNPHLIIPTPEGFSTRSMPSDARSHGSPAAAAAAAAAAV
AASRPSPSGGDSVLPKSISSAHDTRGSSVPENDRLASIAAELQFRSLSRHSSPTEERDEP
AYPRGDSSGSTRRSWELRTLISQSKDTASKLGPIEAIQKSVRLFEEKRYREMRRKNIIGQ
VCDTPKSYDNVMHVGLRKVTFKWQRGNKIGEGQYGKVYTCISVDTGELMAMKEIRFQPND
HKTIKETADELKIFEGIKHPNLVRYFGVELHREEMYIFMEYCDEGTLEEVSRLGLQEHVI
RLYSKQITIAINVLHEHGIVHRDIKGANIFLTSSGLIKLGDFGCSVKLKNNAQTMPGEVN
STLGTAAYMAPEVITRAKGEGHGRAADIWSLGCVVIEMVTGKRPWHEYEHNFQIMYKVGM
GHKPPIPERLSPEGKDFLSHCLESDPKMRWTASQLLDHSFVKVCTDEE

Number of residues

1608

Molecular Weight

181683.025

Theoretical pI

Not Available

GO Classification

Functions

ATP binding / MAP kinase kinase kinase activity / metal ion binding

Processes

activation of MAPKK activity / chorionic trophoblast cell differentiation / intracellular signal transduction / male germ-line sex determination / placenta development / positive regulation of JUN kinase activity / positive regulation of p38MAPK cascade / positive regulation of telomerase activity / positive regulation of telomere capping / positive regulation of telomere maintenance via telomerase / regulation of apoptotic process / regulation of gene expression / regulation of mitotic cell cycle / response to UV-C

Components

cytoplasm / perinuclear region of cytoplasm

General Function

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.

Specific Function

Atp binding

Pfam Domain Function

• Pkinase (PF00069)

Transmembrane Regions

Not Available

Cellular Location

Cytoplasm

Gene sequence

>lcl|BSEQ0051815|Mitogen-activated protein kinase kinase kinase 4 (MAP3K4)
ATGAGAGAAGCCGCTGCCGCGCTGGTCCCTCCTCCCGCCTTTGCCGTCACGCCTGCCGCC
GCCATGGAGGAGCCGCCGCCACCGCCGCCGCCGCCACCACCGCCACCGGAACCCGAGACC
GAGTCAGAACCCGAGTGCTGCTTGGCGGCGAGGCAAGAGGGCACATTGGGAGATTCAGCT
TGCAAGAGTCCTGAATCTGATCTAGAAGACTTCTCCGATGAAACAAATACAGAGAATCTT
TATGGTACCTCTCCCCCCAGCACACCTCGACAGATGAAACGCATGTCAACCAAACATCAG
AGGAATAATGTGGGGAGGCCAGCCAGTCGGTCTAATTTGAAAGAAAAAATGAATGCACCA
AATCAGCCTCCACATAAAGACACTGGAAAAACAGTGGAGAATGTGGAAGAATACAGCTAT
AAGCAGGAGAAAAAGATCCGAGCAGCTCTTAGAACAACAGAGCGTGATCATAAAAAAAAT
GTACAGTGCTCATTCATGTTAGACTCAGTGGGTGGATCTTTGCCAAAAAAATCAATTCCA
GATGTGGATCTCAATAAGCCTTACCTCAGCCTTGGCTGTAGCAATGCTAAGCTTCCAGTA
TCTGTGCCCATGCCTATAGCCAGACCTGCACGCCAGACTTCTAGGACTGACTGTCCAGCA
GATCGTTTAAAGTTTTTTGAAACTTTACGACTTTTGCTAAAGCTTACCTCAGTCTCAAAG
AAAAAAGACAGGGAGCAAAGAGGACAAGAAAATACGTCTGGTTTCTGGCTTAACCGATCT
AACGAACTGATCTGGTTAGAGCTACAAGCCTGGCATGCAGGACGGACAATTAACGACCAG
GACTTCTTTTTATATACAGCCCGTCAAGCCATCCCAGATATTATTAATGAAATCCTTACT
TTCAAAGTCGACTATGGGAGCTTCGCCTTTGTTAGAGATAGAGCTGGTTTTAATGGTACT
TCAGTAGAAGGGCAGTGCAAAGCCACTCCTGGAACAAAGATTGTAGGTTACTCAACACAT
CATGAGCATCTCCAACGCCAGAGGGTCTCATTTGAGCAGGTAAAACGGATAATGGAGCTG
CTAGAGTACATAGAAGCACTTTATCCATCATTGCAGGCTCTTCAGAAGGACTATGAAAAA
TATGCTGCAAAAGACTTCCAGGACAGGGTGCAGGCACTCTGTTTGTGGTTAAACATCACA
AAAGACTTAAATCAGAAATTAAGGATTATGGGCACTGTTTTGGGCATCAAGAATTTATCA
GACATTGGCTGGCCAGTGTTTGAAATCCCTTCCCCTCGACCATCCAAAGGTAATGAGCCG
GAGTATGAGGGTGATGACACAGAAGGAGAATTAAAGGAGTTGGAAAGTAGTACGGATGAG
AGTGAAGAAGAACAAATCTCTGATCCTAGGGTACCGGAAATCAGACAGCCCATAGATAAC
AGCTTCGACATCCAGTCGCGGGACTGCATATCCAAGAAGCTTGAGAGGCTCGAATCTGAG
GATGATTCTCTTGGCTGGGGAGCACCAGACTGGAGCACAGAAGCAGGCTTTAGTAGACAT
TGTCTGACTTCTATTTATAGACCATTTGTAGACAAAGCACTGAAGCAGATGGGGTTAAGA
AAGTTAATTTTAAGACTTCACAAGCTAATGGATGGTTCCTTGCAAAGGGCACGTATAGCA
TTGGTAAAGAACGATCGTCCAGTGGAGTTTTCTGAATTTCCAGATCCCATGTGGGGTTCA
GATTATGTGCAGTTGTCAAGGACACCACCTTCATCTGAGGAGAAATGCAGTGCTGTGTCG
TGGGAGGAGCTGAAGGCCATGGATTTACCTTCATTCGAACCTGCCTTCCTAGTTCTCTGC
CGAGTCCTTCTGAATGTCATACATGAGTGTCTGAAGTTAAGATTGGAGCAGAGACCTGCT
GGAGAACCATCTCTCTTGAGTATTAAGCAGCTGGTGAGAGAGTGTAAGGAGGTCCTGAAG
GGCGGCCTGCTGATGAAGCAGTACTACCAGTTCATGCTGCAGGAGGTTCTGGAGGACTTG
GAGAAGCCCGACTGCAACATTGACGCTTTTGAAGAGGATCTACATAAAATGCTTATGGTG
TATTTTGATTACATGAGAAGCTGGATCCAAATGCTACAGCAATTACCTCAAGCATCGCAT
AGTTTAAAAAATCTGTTAGAAGAAGAATGGAATTTCACCAAAGAAATAACTCATTACATA
CGGGGAGGAGAAGCACAGGCCGGGAAGCTTTTCTGTGACATTGCAGGAATGCTGCTGAAA
TCTACAGGAAGTTTTTTAGAATTTGGCTTACAGGAGAGCTGTGCTGAATTTTGGACTAGT
GCGGATGACAGCAGTGCTTCCGACGAAATCAGGAGGTCTGTTATAGAGATCAGTCGAGCC
CTGAAGGAGCTCTTCCATGAAGCCAGAGAAAGGGCTTCCAAAGCACTTGGATTTGCTAAA
ATGTTGAGAAAGGACCTGGAAATAGCAGCAGAATTCAGGCTTTCAGCCCCAGTTAGAGAC
CTCCTGGATGTTCTGAAATCAAAACAGTATGTCAAGGTGCAAATTCCTGGGTTAGAAAAC
TTGCAAATGTTTGTTCCAGACACTCTTGCTGAGGAGAAGAGTATTATTTTGCAGTTACTC
AATGCAGCTGCAGGAAAGGACTGTTCAAAAGATTCAGATGACGTACTCATCGATGCCTAT
CTGCTTCTGACCAAGCACGGTGATCGAGCCCGTGATTCAGAGGACAGCTGGGGCACCTGG
GAGGCACAGCCTGTCAAAGTCGTGCCTCAGGTGGAGACTGTTGACACCCTGAGAAGCATG
CAGGTGGATAATCTTTTACTAGTTGTCATGCAGTCTGCGCATCTCACAATTCAGAGAAAA
GCTTTCCAGCAGTCCATTGAGGGACTTATGACTCTGTGCCAGGAGCAGACATCCAGTCAG
CCGGTCATCGCCAAAGCTTTGCAGCAGCTGAAGAATGATGCATTGGAGCTATGCAACAGG
ATAAGCAATGCCATTGACCGCGTGGACCACATGTTCACATCAGAATTTGATGCTGAGGTT
GATGAATCTGAATCTGTCACCTTGCAACAGTACTACCGAGAAGCAATGATTCAGGGGTAC
AATTTTGGATTTGAGTATCATAAAGAAGTTGTTCGTTTGATGTCTGGGGAGTTTAGACAG
AAGATAGGAGACAAATATATAAGCTTTGCCCGGAAGTGGATGAATTATGTCCTGACTAAA
TGTGAGAGTGGTAGAGGTACAAGACCCAGGTGGGCGACTCAAGGATTTGATTTTCTACAA
GCAATTGAACCTGCCTTTATTTCAGCTTTACCAGAAGATGACTTCTTGAGTTTACAAGCC
TTGATGAATGAATGCATTGGCCATGTCATAGGAAAACCACACAGTCCTGTTACAGGTTTG
TACCTTGCCATTCATCGGAACAGCCCCCGTCCTATGAAGGTACCTCGATGCCATAGTGAC
CCTCCTAACCCACACCTCATTATCCCCACTCCAGAGGGATTCAGCACTCGGAGCATGCCT
TCCGACGCGCGGAGCCATGGCAGCCCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGTT
GCTGCCAGTCGGCCCAGCCCCTCTGGTGGTGACTCTGTGCTGCCCAAATCCATCAGCAGT
GCCCATGATACCAGGGGTTCCAGCGTTCCTGAAAATGATCGATTGGCTTCCATAGCTGCT
GAATTGCAGTTTAGGTCCCTGAGTCGTCACTCAAGCCCCACGGAGGAGCGAGATGAACCA
GCATATCCAAGAGGAGATTCAAGTGGGTCCACAAGAAGAAGTTGGGAACTTCGGACACTA
ATCAGCCAGAGTAAAGATACTGCTTCTAAACTAGGACCCATAGAAGCTATCCAGAAGTCA
GTCCGATTGTTTGAAGAAAAGAGGTACCGAGAAATGAGGAGAAAGAATATCATTGGTCAA
GTTTGTGATACGCCTAAGTCCTATGATAATGTTATGCACGTTGGCTTGAGGAAGGTGACC
TTCAAATGGCAAAGAGGAAACAAAATTGGAGAAGGCCAGTATGGGAAGGTGTACACCTGC
ATCAGCGTCGACACCGGGGAGCTGATGGCCATGAAAGAGATTCGATTTCAACCTAATGAC
CATAAGACTATCAAGGAAACTGCAGACGAATTGAAAATATTCGAAGGCATCAAACACCCC
AATCTGGTTCGGTATTTTGGTGTGGAGCTCCATAGAGAAGAAATGTACATCTTCATGGAG
TACTGCGATGAGGGGACTTTAGAAGAGGTGTCAAGGCTGGGACTTCAGGAACATGTGATT
AGGCTGTATTCAAAGCAGATCACCATTGCGATCAACGTCCTCCATGAGCATGGCATAGTC
CACCGTGACATTAAAGGTGCCAATATCTTCCTTACCTCATCTGGATTAATCAAACTGGGA
GATTTTGGATGTTCAGTAAAGCTCAAAAACAATGCCCAGACCATGCCTGGTGAAGTGAAC
AGCACCCTGGGGACAGCAGCATACATGGCACCTGAAGTCATCACTCGTGCCAAAGGAGAG
GGCCATGGGCGTGCGGCCGACATCTGGAGTCTGGGGTGTGTTGTCATAGAGATGGTGACT
GGCAAGAGGCCTTGGCATGAGTATGAGCACAACTTTCAAATTATGTATAAAGTGGGGATG
GGACATAAGCCACCAATCCCTGAAAGATTAAGCCCTGAAGGAAAGGACTTCCTTTCTCAC
TGCCTTGAGAGTGACCCAAAGATGAGATGGACCGCCAGCCAGCTCCTCGACCATTCGTTT
GTCAAGGTTTGCACAGATGAAGAATGA

Chromosome Location

6

Locus

6q26

External Identifiers

Resource	Link
UniProtKB ID	Q9Y6R4
UniProtKB Entry Name	M3K4_HUMAN
HGNC ID	HGNC:6856

General References

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5. Mita H, Tsutsui J, Takekawa M, Witten EA, Saito H: Regulation of MTK1/MEKK4 kinase activity by its N-terminal autoinhibitory domain and GADD45 binding. Mol Cell Biol. 2002 Jul;22(13):4544-55. [Article]
6. Wong CK, Luo W, Deng Y, Zou H, Ye Z, Lin SC: The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms. J Biol Chem. 2004 Sep 17;279(38):39366-73. Epub 2004 Jul 15. [Article]
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8. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
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Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB12010	Fostamatinib	approved, investigational	unknown	inhibitor	Details