PMC:4408447 / 10313-12675 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4408447","sourcedb":"PMC","sourceid":"4408447","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4408447","text":"10.7554/eLife.06315.003Figure 1. Kindreds with hypertension and primary aldosteronism (PA) with CACNA1HM1549V mutation at conserved position of S6 domain.\n(A) Pedigrees of kindreds with CACNA1HM1549V mutation are shown. Studied subjects with early-onset hypertension are shown as black filled symbols, and subjects with early-onset hypertension by family history (K333) or low renin with normal blood pressure (K1393) are shown as grey filled symbols. Genotypes are indicated below each symbol (+/+ denotes wild type sequence; +/M denotes heterozygosity for CACNA1HM1549V variant). Corresponding Sanger sequencing results for selected subjects are depicted to the right. (B) Transmembrane structure of CaV3.2 (encoded by CACNA1H), the pore-forming subunit of a voltage-gated Ca2+ channel, is shown. These channels have four internal homologous repeats (I–IV), each with six transmembrane segments (S1–S6) and a membrane-associated loop between the pore-forming S5 and S6 segments. The p.Met1549Val mutation is located in S6 of repeat III. (C) Conservation of CACNA1HM1549 in CACNA1H orthologs and paralogs. The amino acid sequences of the S6 segment of domain III of CACNA1H, orthologs and paralogs are shown. The S6 segment, including Met1549, is virtually completely conserved (highlighted in yellow) among orthologs and all paralogs that are activated by small changes in membrane potential (l, low voltage-activated) but not those activated by large changes (h, high voltage-activated). M1549 is part of the Met-Phe-Val sequence that is implicated in rapid channel inactivation (Marksteiner et al., 2001).\nDOI: http://dx.doi.org/10.7554/eLife.06315.003\n10.7554/eLife.06315.004Figure 1—source data 1. Source data corresponding to Figure 1.\nDOI: http://dx.doi.org/10.7554/eLife.06315.00410.7554/eLife.06315.005Figure 1—figure supplement 1. Cohort population structure by principal component analysis (PCA).\nPCA of subjects referred for PA. Individuals in the cohort (orange crosses) mostly cluster with HapMap subjects of European and African American subjects. The five individuals with CACNA1H mutation (filled red circles) are of African American (1390-1), Hispanic (1393-1) and European (1368-1, 1347-1 and 333-2) origin, respectively, by history and PCA. Source files are available in Figure 1—source data 1.\nDOI: http://dx.doi.org/10.7554/eLife.06315.005","divisions":[{"label":"Title","span":{"begin":33,"end":154}},{"label":"Title","span":{"begin":1704,"end":1742}},{"label":"Title","span":{"begin":1842,"end":1908}}],"tracks":[{"project":"2_test","denotations":[{"id":"25907736-11711558-27146352","span":{"begin":1603,"end":1607},"obj":"11711558"}],"attributes":[{"subj":"25907736-11711558-27146352","pred":"source","obj":"2_test"}]},{"project":"MyTest","denotations":[{"id":"25907736-11711558-27146352","span":{"begin":1603,"end":1607},"obj":"11711558"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"attributes":[{"subj":"25907736-11711558-27146352","pred":"source","obj":"MyTest"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec93d5","default":true},{"id":"MyTest","color":"#93ece9"}]}]}}