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Identification
HMDB Protein ID HMDBP08753
Secondary Accession Numbers
  • 14476
Name Mitogen-activated protein kinase kinase kinase 8
Synonyms
  1. Cancer Osaka thyroid oncogene
  2. Proto-oncogene c-Cot
  3. Serine/threonine-protein kinase cot
  4. TPL-2
  5. Tumor progression locus 2
Gene Name MAP3K8
Protein Type Unknown
Biological Properties
General Function Involved in magnesium ion binding
Specific Function Required for TLR4 activation of the MEK/ERK pathway. Able to activate NF-kappa-B 1 by stimulating proteasome-mediated proteolysis of NF-kappa-B 1/p105. Plays a role in the cell cycle. The longer form has some transforming activity, although it is much weaker than the activated cot oncoprotein
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
intracellular part
cytoplasm
Function
ion binding
cation binding
metal ion binding
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
magnesium ion binding
protein kinase activity
protein serine/threonine kinase activity
receptor signaling protein serine/threonine kinase activity
map kinase kinase kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular process
biological regulation
regulation of biological process
cellular metabolic process
cell cycle
regulation of cellular process
signal transduction
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location Chromosome:1
Locus 10p11.23
SNPs MAP3K8
Gene Sequence
>1404 bp
ATGGAGTACATGAGCACTGGAAGTGACAATAAAGAAGAGATTGATTTATTAATTAAACAT
TTAAATGTGTCTGATGTAATAGACATTATGGAAAATCTTTATGCAAGTGAAGAGCCAGCA
GTTTATGAACCCAGTCTAATGACCATGTGTCAAGACAGTAATCAAAACGATGAGCGTTCT
AAGTCTCTGCTGCTTAGTGGCCAAGAGGTACCATGGTTGTCATCAGTCAGATATGGAACT
GTGGAGGATTTGCTTGCTTTTGCAAACCATATATCCAACACTGCAAAGCATTTTTATGGA
CAACGACCACAGGAATCTGGAATTTTATTAAACATGGTCATCACTCCCCAAAATGGACGT
TACCAAATAGATTCCGATGTTCTCCTGATCCCCTGGAAGCTGACTTACAGGAATATTGGT
TCTGATTTTATTCCTCGGGGCGCCTTTGGAAAGGTATACTTGGCACAAGATATAAAGACG
AAGAAAAGAATGGCGTGTAAACTGATCCCAGTAGATCAATTTAAGCCATCTGATGTGGAA
ATCCAGGCTTGCTTCCGGCACGAGAACATCGCAGAGCTGTATGGCGCAGTCCTGTGGGGT
GAAACTGTCCATCTCTTTATGGAAGCAGGCGAGGGAGGGTCTGTTCTGGAGAAACTGGAG
AGCTGTGGACCAATGAGAGAATTTGAAATTATTTGGGTGACAAAGCATGTTCTCAAGGGA
CTTGATTTTCTACACTCAAAGAAAGTGATCCATCATGATATTAAACCTAGCAACATTGTT
TTCATGTCCACAAAAGCTGTTTTGGTGGATTTTGGCCTAAGTGTTCAAATGACCGAAGAT
GTCTATTTTCCTAAGGACCTCCGAGGAACAGAGATTTACATGAGCCCAGAGGTCATCCTG
TGCAGGGGCCATTCAACCAAAGCAGACATCTACAGCCTGGGGGCCACGCTCATCCACATG
CAGACGGGCACCCCACCCTGGGTGAAGCGCTACCCTCGCTCAGCCTATCCCTCCTACCTG
TACATAATCCACAAGCAAGCACCTCCACTGGAAGACATTGCAGATGACTGCAGTCCAGGG
ATGAGAGAGCTGATAGAAGCTTCCCTGGAGAGAAACCCCAATCACCGCCCAAGAGCCGCA
GACCTACTAAAACATGAGGCCCTGAACCCGCCCAGAGAGGATCAGCCACGCTGTCAGAGT
CTGGACTCTGCCCTCTTGGAGCGCAAGAGGCTGCTGAGTAGGAAGGAGCTGGAACTTCCT
GAGAACATTGCTGATTCTTCGTGCACAGGAAGCACCGAGGAATCTGAGATGCTCAAGAGG
CAACGCTCTCTCTACATCGACCTCGGCGCTCTGGCTGGCTACTTCAATCTTGTTCGGGGA
CCACCAACGCTTGAATATGGCTGA
Protein Properties
Number of Residues 467
Molecular Weight 52924.0
Theoretical pI 5.62
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Mitogen-activated protein kinase kinase kinase 8
MEYMSTGSDNKEEIDLLIKHLNVSDVIDIMENLYASEEPAVYEPSLMTMCQDSNQNDERS
KSLLLSGQEVPWLSSVRYGTVEDLLAFANHISNTAKHFYGQRPQESGILLNMVITPQNGR
YQIDSDVLLIPWKLTYRNIGSDFIPRGAFGKVYLAQDIKTKKRMACKLIPVDQFKPSDVE
IQACFRHENIAELYGAVLWGETVHLFMEAGEGGSVLEKLESCGPMREFEIIWVTKHVLKG
LDFLHSKKVIHHDIKPSNIVFMSTKAVLVDFGLSVQMTEDVYFPKDLRGTEIYMSPEVIL
CRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAYPSYLYIIHKQAPPLEDIADDCSPG
MRELIEASLERNPNHRPRAADLLKHEALNPPREDQPRCQSLDSALLERKRLLSRKELELP
ENIADSSCTGSTEESEMLKRQRSLYIDLGALAGYFNLVRGPPTLEYG
GenBank ID Protein 22035598
UniProtKB/Swiss-Prot ID P41279
UniProtKB/Swiss-Prot Entry Name M3K8_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_005204.2
GeneCard ID MAP3K8
GenAtlas ID MAP3K8
HGNC ID HGNC:6860
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  4. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. [PubMed:15164054 ]
  5. Lang V, Symons A, Watton SJ, Janzen J, Soneji Y, Beinke S, Howell S, Ley SC: ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential for TPL-2 protein stability. Mol Cell Biol. 2004 Jun;24(12):5235-48. [PubMed:15169888 ]
  6. Miyoshi J, Higashi T, Mukai H, Ohuchi T, Kakunaga T: Structure and transforming potential of the human cot oncogene encoding a putative protein kinase. Mol Cell Biol. 1991 Aug;11(8):4088-96. [PubMed:2072910 ]
  7. Aoki M, Hamada F, Sugimoto T, Sumida S, Akiyama T, Toyoshima K: The human cot proto-oncogene encodes two protein serine/threonine kinases with different transforming activities by alternative initiation of translation. J Biol Chem. 1993 Oct 25;268(30):22723-32. [PubMed:8226782 ]
  8. Chan AM, Chedid M, McGovern ES, Popescu NC, Miki T, Aaronson SA: Expression cDNA cloning of a serine kinase transforming gene. Oncogene. 1993 May;8(5):1329-33. [PubMed:8479752 ]
  9. Sanchez-Gongora E, Lisbona C, de Gregorio R, Ballester A, Calvo V, Perez-Jurado L, Alemany S: COT kinase proto-oncogene expression in T cells: implication of the JNK/SAPK signal transduction pathway in COT promoter activation. J Biol Chem. 2000 Oct 6;275(40):31379-86. [PubMed:10896655 ]
  10. Aoki M, Akiyama T, Miyoshi J, Toyoshima K: Identification and characterization of protein products of the cot oncogene with serine kinase activity. Oncogene. 1991 Sep;6(9):1515-9. [PubMed:1833717 ]