Kozak consensus sequence

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The Kozak consensus sequence is gccgcc(A/G)ccAUGG, the (A/G) being a purine 3 bases upstream of the start codon, AUG followed by another 'G' on eukaryotic mRNA. This sequence on an mRNA molecule is recognized by the ribosome as the translational start site, from which point 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 RNAor an Internal Ribosome Entry Site, or 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. Some nucleotides in this sequence are more important than others: the AUG is essential since it is the actual initiation codon encoding a methionine amino acid at the N-terminus of the protein. The A nucleotide 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) of the number 1 nucleotide must match the consensus (no 0). An 'adequate' consensus has only 1 of these sites, while a 'weak' consensus has neither. The cc dinucleotides at -5 and -2 are not necessary, but contribute to the overall strength.

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. 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.

[edit] References

Kozak, M. (1991) An analysis of vertebrate mRNA sequences: Intimations of translational control, J. Cell. Biol. 115, 887–903.
Kozak, M. (1990) Downstream secondary structure facilitates recognition of initiator codons by eukaryotic ribosomes.
Kozak, M. (1984) Nature, 308:241-246.
Dunston, JA et al. (2004) The human LMX1B gene: transcription unit, promoter, and pathogenic mutations. Genomics. 2004 Sep;84(3):565-76.