Jump to content

Kozak consensus sequence

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by Fallon Turner (talk | contribs) at 09:21, 9 April 2011. The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

The Kozak consensus sequence, Kozak consensus or Kozak sequence, is a sequence which occurs on eukaryotic mRNA and has the consensus (gcc)gccRccAUGG, where R is a purine (adenine or guanine) three bases upstream of the start codon (AUG), which is followed by another 'G'.[1] The Kozak consensus sequence plays a major role in the initiation of the translation process.[2] The sequence was named after its discoverer, Marilyn Kozak.

Introduction

This sequence on an mRNA molecule is recognized by the ribosome as the translational start site, from which a protein is coded by that mRNA molecule. The ribosome requires this sequence, or a possible variation (see below) to initiate translation. The Kozak sequence is not to be confused with the ribosomal binding site (RBS), that being either the 5' cap of a messenger RNA or an Internal Ribosome Entry Site (IRES).

In vivo, this site is often not matched exactly on different mRNAs and the amount of protein synthesized from a given mRNA is dependent on the strength of the Kozak sequence.[3] Some nucleotides in this sequence are more important than others: the AUG is most important because it is the actual initiation codon encoding a methionine amino acid at the N-terminus of the protein. (Rarely, CTG is used as an initiation codon, encoding a leucine instead of its typical methionine.) The A nucleotide of the "AUG" is referred to as number 1. For a 'strong' consensus, the nucleotides at positions +4 (i.e. G in the consensus) and -3 (i.e. either A or G in the consensus) relative to the number 1 nucleotide must both match the consensus (there is no number 0 position). An 'adequate' consensus has only 1 of these sites, while a 'weak' consensus has neither. The cc at -1 and -2 are not as conserved, but contribute to the overall strength.[4] There is also evidence that a G in the -6 position is important in the initiation of translation.[2]

There are examples in vivo of each of these types of Kozak consensus, and they probably evolved as yet another mechanism of gene regulation. Lmx1b is an example of a gene with a weak Kozak consensus sequence.[5] For initiation of translation from such a site, other features are required in the mRNA sequence in order for the ribosome to recognize the initiation codon.

A sequence logo showing the most conserved bases around the initiation codon from all human mRNAs.

Mutations

Research has shown that a mutation of G—>C in the -6 position of the β-globin gene (β+45; human) disrupted the haematological and biosynthetic phenotype function. This was the first mutation found in the Kozak sequence. It was found in a family from the Southeast Italy and they suffered from thalassaemia intermedia.[2]

Variations in the consensus sequence

(gcc)gccRccAUGG
       AGNNAUGN
        ANNAUGG
        ACCAUGG
     GACACCAUGG
Kozak-like sequences in various eukaryotes
Biota Phylum Consensus sequences
Vertebrate
gccRccATGG[1]
Fruit fly (Drosophila spp.) Arthropoda   cAAaATG[6]
Budding yeast (Saccharomyces cerevisiae) Ascomycota aAaAaAATGTCt[7]
Slime mold (Dictyostelium discoideum) Amoebozoa aaaAAAATGRna[8]
Ciliate Ciliophora nTaAAAATGRct[8]
Malarial protozoa (Plasmodium spp.) Apicomplexa taaAAAATGAan[8]
Toxoplasma (Toxoplasma gondii) Apicomplexa gncAaaATGg[9]
Trypanosomatidae Euglenozoa nnnAnnATGnC[8]
Terrestrial plants
  AACAATGGC[10]

See also

References

  1. ^ a b Kozak M (1987). "An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs". Nucleic Acids Res. 15 (20): 8125–8148. doi:10.1093/nar/15.20.8125. PMC 306349. PMID 3313277. {{cite journal}}: Unknown parameter |month= ignored (help)
  2. ^ a b c De Angioletti M, Lacerra G, Sabato V, Carestia C (2004). "Beta+45 G --> C: a novel silent beta-thalassaemia mutation, the first in the Kozak sequence". Br J Haematol. 124 (2): 224–31. doi:10.1046/j.1365-2141.2003.04754.x. PMID 14687034.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ Kozak M (1984). "Point mutations close to the AUG initiator codon affect the efficiency of translation of rat preproinsulin in vivo". Nature. 308 (5956): 241–246. doi:10.1038/308241a0. PMID 6700727.
  4. ^ Kozak M (1986). "Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes". Cell. 44 (2): 283–92. doi:10.1016/0092-8674(86)90762-2. PMID 3943125.
  5. ^ Dunston JA, Hamlington JD, Zaveri J; et al. (2004). "The human LMX1B gene: transcription unit, promoter, and pathogenic mutations". Genomics. 84 (3): 565–76. doi:10.1016/j.ygeno.2004.06.002. PMID 15498463. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Cavener DR (1987). "Comparison of the consensus sequence flanking translational start sites in Drosophila and vertebrates". Nucleic Acids Res. 15 (4): 1353–61. doi:10.1093/nar/15.4.1353. PMC 340553. PMID 3822832. {{cite journal}}: Unknown parameter |month= ignored (help)
  7. ^ Hamilton R, Watanabe CK, de Boer HA (1987). "Compilation and comparison of the sequence context around the AUG startcodons in Saccharomyces cerevisiae mRNAs". Nucleic Acids Res. 15 (8): 3581–93. doi:10.1093/nar/15.8.3581. PMC 340751. PMID 3554144. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ a b c d Yamauchi K (1991). "The sequence flanking translational initiation site in protozoa". Nucleic Acids Res. 19 (10): 2715–20. doi:10.1093/nar/19.10.2715. PMC 328191. PMID 2041747. {{cite journal}}: Unknown parameter |month= ignored (help)
  9. ^ Seeber, F. (1997). "Consensus sequence of translational initiation sites from Toxoplasma gondii genes". Parasitology Research. 83 (3): 309–311. doi:10.1007/s004360050254. PMID 9089733.
  10. ^ Lütcke HA, Chow KC, Mickel FS, Moss KA, Kern HF, Scheele GA (1987). "Selection of AUG initiation codons differs in plants and animals". EMBO J. 6 (1): 43–8. PMC 553354. PMID 3556162. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

Further reading

Retrieved from "https://en.wikipedia.org/w/index.php?title=Kozak_consensus_sequence&oldid=423149623"