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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3216504","sourcedb":"PMC","sourceid":"3216504","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3216504","text":"Zic orthologues are widely distributed among the eumetazoans and show evolutionary conserved domains in their protein-coding regions28. Multi-species alignment of the three Zic2 mutations revealed that R409P was located within the highly conserved regions of the published Zic sequences, including those of the protostomians and cnidarians (Figure 6A and data not shown). We also showed that R409 position has conserved in a zinc-finger-type transcription factor, GLI1, in which the side chain of the encoded amino acid residue is responsible for side-chain-base interactions (Figure S2)29. Both A95T and S444R were conserved in most of the vertebrate Zic2 sequences examined, but these sequences did not align with those in invertebrates (Figure 6A and data not shown). We used the computer algorithm PolyPhen Polyphen30 to predict the effect of the mutations on protein structure and function. PolyPhen analysis predicted that the amino acid change in R409P most likely caused abnormal protein structure and function, whereas it was only a possibility for S444R and even less likely for A95T (Table 2).","tracks":[{"project":"2_test","denotations":[{"id":"22355535-16574373-138031316","span":{"begin":132,"end":134},"obj":"16574373"},{"id":"22355535-8378770-138031317","span":{"begin":587,"end":589},"obj":"8378770"},{"id":"22355535-12202775-138031318","span":{"begin":819,"end":821},"obj":"12202775"}],"attributes":[{"subj":"22355535-16574373-138031316","pred":"source","obj":"2_test"},{"subj":"22355535-8378770-138031317","pred":"source","obj":"2_test"},{"subj":"22355535-12202775-138031318","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#c9ec93","default":true}]}]}}