From Wikipedia, the free encyclopedia
Jump to: navigation, search
Mitogen-activated protein kinase kinase kinase 3
Protein MAP3K3 PDB 2c60.png
PDB rendering based on 2c60.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols MAP3K3 ; MAPKKK3; MEKK3
External IDs OMIM602539 MGI1346874 HomoloGene69110 ChEMBL: 5970 GeneCards: MAP3K3 Gene
EC number
RNA expression pattern
PBB GE MAP3K3 203514 at tn.png
More reference expression data
Species Human Mouse
Entrez 4215 26406
Ensembl ENSG00000198909 ENSMUSG00000020700
UniProt Q99759 Q61084
RefSeq (mRNA) NM_002401 NM_011947
RefSeq (protein) NP_002392 NP_036077
Location (UCSC) Chr 17:
63.62 – 63.7 Mb
Chr 11:
106.08 – 106.16 Mb
PubMed search [1] [2]

Mitogen-activated protein kinase kinase kinase 3 is an enzyme that in humans is encoded by the MAP3K3 gene.[1]

This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed.[2]


MAP3K3 has been shown to interact with [SQSTM1/p62], MAP2K5,[3][4] YWHAE,[5] GAB1[6] and BRCA1.[7]


  1. ^ Ellinger-Ziegelbauer H, Brown K, Kelly K, Siebenlist U (March 1997). "Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative". J Biol Chem 272 (5): 2668–74. doi:10.1074/jbc.272.5.2668. PMID 9006902. 
  2. ^ "Entrez Gene: MAP3K3 mitogen-activated protein kinase kinase kinase 3". 
  3. ^ Sun, W; Kesavan K; Schaefer B C; Garrington T P; Ware M; Johnson N L; Gelfand E W; Johnson G L (February 2001). "MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway". J. Biol. Chem. (United States) 276 (7): 5093–100. doi:10.1074/jbc.M003719200. ISSN 0021-9258. PMID 11073940. 
  4. ^ Bouwmeester, Tewis; Bauch Angela, Ruffner Heinz, Angrand Pierre-Olivier, Bergamini Giovanna, Croughton Karen, Cruciat Cristina, Eberhard Dirk, Gagneur Julien, Ghidelli Sonja, Hopf Carsten, Huhse Bettina, Mangano Raffaella, Michon Anne-Marie, Schirle Markus, Schlegl Judith, Schwab Markus, Stein Martin A, Bauer Andreas, Casari Georg, Drewes Gerard, Gavin Anne-Claude, Jackson David B, Joberty Gerard, Neubauer Gitte, Rick Jens, Kuster Bernhard, Superti-Furga Giulio (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. (England) 6 (2): 97–105. doi:10.1038/ncb1086. ISSN 1465-7392. PMID 14743216. 
  5. ^ Fanger, G R; Widmann C; Porter A C; Sather S; Johnson G L; Vaillancourt R R (February 1998). "14-3-3 proteins interact with specific MEK kinases". J. Biol. Chem. (UNITED STATES) 273 (6): 3476–83. doi:10.1074/jbc.273.6.3476. ISSN 0021-9258. PMID 9452471. 
  6. ^ Che, Wenyi; Lerner-Marmarosh Nicole, Huang Qunhua, Osawa Masaki, Ohta Shinsuke, Yoshizumi Masanori, Glassman Michael, Lee Jiing-Dwan, Yan Chen, Berk Bradford C, Abe Jun-Ichi (June 2002). "Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-alpha-induced c-Jun and NF-kappaB activation and adhesion molecule expression". Circ. Res. (United States) 90 (11): 1222–30. doi:10.1161/01.RES.0000021127.83364.7D. PMID 12065326. 
  7. ^ Gilmore, Paula M; McCabe Nuala, Quinn Jennifer E, Kennedy Richard D, Gorski Julia J, Andrews Heather N, McWilliams Stewart, Carty Michael, Mullan Paul B, Duprex W Paul, Liu Edison T, Johnston Patrick G, Harkin D Paul (June 2004). "BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". Cancer Res. (United States) 64 (12): 4148–54. doi:10.1158/0008-5472.CAN-03-4080. ISSN 0008-5472. PMID 15205325. 

Further reading[edit]