Hmdb loader
Identification
HMDB Protein ID HMDBP01445
Secondary Accession Numbers
  • 6741
Name Mitogen-activated protein kinase kinase kinase 4
Synonyms
  1. MAP three kinase 1
  2. MAPK/ERK kinase kinase 4
  3. MEK kinase 4
  4. MEKK 4
Gene Name MAP3K4
Protein Type Unknown
Biological Properties
General Function Involved in protein serine/threonine kinase activity
Specific 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
Pathways
  • Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
  • Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Cytoplasm
  2. perinuclear region
Gene Properties
Chromosome Location Chromosome:6
Locus 6q26
SNPs MAP3K4
Gene Sequence
>4827 bp
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
Protein Properties
Number of Residues 1608
Molecular Weight 181683.0
Theoretical pI 6.26
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>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
GenBank ID Protein 55956904
UniProtKB/Swiss-Prot ID Q9Y6R4
UniProtKB/Swiss-Prot Entry Name M3K4_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_005922.2
GeneCard ID MAP3K4
GenAtlas ID MAP3K4
HGNC ID HGNC:6856
References
General References
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  2. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  3. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  4. 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. [PubMed:19413330 ]
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  6. Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N: Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. DNA Res. 1996 Oct 31;3(5):321-9, 341-54. [PubMed:9039502 ]
  7. 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. [PubMed:15262978 ]
  8. Takekawa M, Posas F, Saito H: A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress-induced activation of the p38 and JNK pathways. EMBO J. 1997 Aug 15;16(16):4973-82. [PubMed:9305639 ]
  9. 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. [PubMed:12052864 ]
  10. Abell AN, Johnson GL: MEKK4 is an effector of the embryonic TRAF4 for JNK activation. J Biol Chem. 2005 Oct 28;280(43):35793-6. Epub 2005 Sep 12. [PubMed:16157600 ]