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. 2011 Aug 23;32(6):755–797. doi: 10.1210/er.2010-0027

Fig. 4.

Fig. 4.

Evolutionary conservation of vertebrate and invertebrate granins. Protein sequences for SgIII (SCG3), 7B2, VGF, and proSAAS were aligned using the program ClustalW2 (422), edited with Jalview version 2.5.1 (423), and displayed using the ClustalX color scheme. Amino acid numbers shown in the alignments correspond to the entire protein coding sequences for rat SCG3 (A), the mature human 7B2 protein (B), rat VGF (C), and human proSAAS (D). Three functional domains of SCG3, which bind to cholesterol, CgA, and carboxypeptidase E (CPE), each contain regions that have been highly conserved throughout vertebrate evolution (A). For 7B2, the most highly conserved regions include the cysteine-stabilized PC2 interaction domain that is conserved even in invertebrates, and the C-terminal peptide catalytic inhibitor of PC2, which is highly conserved in vertebrates (B). Three highly conserved regions of VGF, one that includes the NERP-2 peptide and another that includes the C-terminal TLQP and AQEE peptides, are each conserved in higher and lower vertebrates (C). For proSAAS, the C-terminal PC1/3 inhibitory peptide with its LLRVKRL motif is conserved in vertebrates (D). No bird orthologs of VGF or proSAAS were identified using looser BLAST search parameters (51), querying with these short conserved domains. SgIII (SCG3) sequences are human isoform 1 (NP_037375), dog (XP_535482), cow (NP_001095567), mouse (NP_0331561), rat (NP_446308), chicken (XP_413807), Xenopus (NP_001079046), and zebrafish (NP_957051). 7B2 sequences aligned are human isoform I (accession number NP_001138229), mouse (NP_033188), rat (NP_037307), cow (NP_001039463), chimpanzee (NP_001092019), zebrafish (NP_957020), Aplysia (ABF21075), C. elegans (NP_508020), and Drosophila isoform B (NP_001014608). VGF sequences aligned are human (NP_003369), rat (NP_112259), mouse (NP_001034474), cow (XP_875466), horse (XP_001916046), macaca (NC_007860), chimpanzee (XP_519275), opossum (XP_001371271), and zebrafish (XP_001343121). ProSAAS sequences included are human (NP_037403), mouse (NP_038920), rat (NP_062152), cow (NP_001077149), orangutan (XP_002831656), and zebrafish (NP_001159601).