protein domain functional descriptions  (InterPro Inc)

Journal: Heliyon

Article Title: Novel autosomal recessive SINO syndrome-associated KIDINS220 variants provide insight into the genotype-phenotype correlation

doi: 10.1016/j.heliyon.2024.e37355

Figure Lengend Snippet: KIDINS220 domain structure, identified variants distribution, and amino acid sequence alignment across different isoforms. (A) Domain organization of KIDINS220 protein (NP_065789.1): ANK, Ankyrin repeat-containing domain (4-396aa); KAP, KAP NTPase P-loop domain (440-953aa); TM, transmembrane domains (500-520aa, 525-545aa, 660-680aa, 686-706aa); Trks, Trks binding region (693-891aa); PR, proline-rich stretch (1057-1151aa); CRKL, CRKL-interacting motif (1089-1092aa); SAM, sterile alpha motif-like domain (1207-1283aa); KIM, kinase light chain (KLC)-interacting motif (1406-1445aa); p75 NTR , p75 NTR binding region (1591-1771aa); PDZ, PDZ binding region (1766-1771aa). (B) The KIDINS220 / Kidins220 transcripts described by Schmieg et al. . (C) Ten known isoforms lack exons 25 and 26 of the full-length transcript NM_020738.4 and lack an alternative terminal exon C2 sequence. (D) Distribution of pathogenic variants across the KIDINS220 protein isoforms. (E) Predicted tertiary structures of the KIDINS220 protein with functional domains highlighted in distinct colors. (F) Predicted recognition sites of calpain-2 within the KIDINS220 protein (1507–1529 aa) identified using the ProsperousPlus online server ( http://prosperousplus.unimelb-biotools.cloud.edu.au/index.php ). The distribution of AD-SINO pathogenic truncated variants (1280-1507aa, red-shaded area) and non-pathogenic truncated variants (1530-1740aa, gray-shaded area) suggests that the amino acid residues between the two regions may be crucial for determining variant pathogenicity (left). The predicted scores for amino acid residues K1508 and P1520 are 0.707 and 0.790, respectively (right).

Article Snippet: Protein domain functional descriptions were annotated by InterPro ( https://www.ebi.ac.uk/interpro/ ), UniProt ( https://www.uniprot.org/ ) and previous studies [ , , , ].

Techniques: Sequencing, Binding Assay, Sterility, Functional Assay, Variant Assay

Journal: Genetics

Article Title: OrthoList 2: A New Comparative Genomic Analysis of Human and Caenorhabditis elegans Genes

doi: 10.1534/genetics.118.301307

Figure Lengend Snippet: Workflow for genome analysis and generation of OL2. The workflow proceeded in four steps. Step 1: we addressed changes to gene models in the worm genome that have occurred since OL1 was published (File S1) to yield an updated OL1 (File S2). We also addressed changes to human gene predictions (File S3). Step 2: we queried updated versions of the orthology-prediction methods used in OL1 (see Table 1) to generate OL1.1 (File S4), and found that the number of worm genes added was within the parameters predicted by changes in individual programs (Table 2), whereas gene loss appeared to be buffered by combining results from the different methods (i.e., the meta-analysis approach). Step 3: we next added results from two additional orthology-prediction methods (see Table 1) and found that this had a low impact on the landscape of human–worm orthologs identified in OL1.1 (File S5). Finally, in step 4, we combined the genes identified by these two additional programs with OL1.1 to generate OL2 (File S5 and File S7). We note that genes that did not continue to be supported by orthology-prediction methods were retained as a legacy set present in the searchable database (File S6 and File S7). Both OL2 and the legacy set of genes were cross-referenced to the C. elegans feeding RNAi library, protein domain prediction databases (InterPro and SMART), and to a human disease association database (OMIM) to generate a final master list (File S7), which can be queried via the new Web-based tool found at http://ortholist.shaye-lab.org.

Article Snippet: Finally, we include links to SMART and InterPro protein domain descriptions, as well as to OMIM entries for human disease associations.

Techniques:

Journal: Genetics

Article Title: OrthoList 2: A New Comparative Genomic Analysis of Human and Caenorhabditis elegans Genes

doi: 10.1534/genetics.118.301307

Figure Lengend Snippet: OL2 query interface. (A) Input page at http://ortholist.shaye-lab.org. Users can select which fields to search (human and worm IDs, SMART or InterPro protein domains, and disease phenotypes described in OMIM); whether to set a threshold for orthology support (see main text); and whether partial matches should be allowed, which is useful when users want to find all members of a similarly named gene family (e.g., input “Notch” to find all human Notch family members). (B) Sample results page for the gene let-60, with a search conducted using the default settings, returning a set of Ras orthologs consistent with its sequence and genetic validation in a canonical Ras pathway (Han and Sternberg 1990; Sundaram 2013). The results page contains links for viewing additional information about results and for exporting results to a comma-separated value (CSV) spreadsheet.

Article Snippet: Finally, we include links to SMART and InterPro protein domain descriptions, as well as to OMIM entries for human disease associations.

Techniques: Sequencing, Biomarker Discovery