Conserved iRhom homology domain (IRHD). Genes encoding iRhoms were found in all animal genomes accessible by the Ensembl genome browser. ClustalW-based multiple sequence alignment of the extremely conserved luminal domain between TMD1 and TMD2 (for accession numbers, see below). Two paralogs were found in vertebrates, excluding fish (D. rerio and T. rubripes), and in C. elegans. Variable inserted sequences from C. intestalis (three residues), D. melanogaster (10 and six residues), A. gambiae (Ag) (two and six residues), C. elegans iRhom1 (eight residues), and C. elegans iRhom2 (27 residues) are hidden as indicated by an asterisk; position of the conserved cysteine (C) is indicated by red dots. The region showing the highest degree in variation between the vertebrate orthologs iRhom1 and iRhom2 is marked; degree of conservation is colored as in Figure 1. Note that A. gambiae iRhom appears to lack one of the 16 cysteine residues.
Accession Numbers: For human and mouse iRhoms, see Table S1. Due to the current coverage of the D. pseudoobscura genome project, no iRhom is currently annotated, but a clear ortholog was found in all insect genomes accessible by the Ensembl genome browser (e.g., Anopheles gambiae (Ag); Ensembl:ENSANGP00000021207). Note that the gene for Drosophila melanogaster (Dm) (Swiss-Prot:Q76NQ1) (Rhomboid-5) is ambiguously predicted. Comparison with predicted exon-intron structure of Ag iRhom suggests that the related Dm iRhom mRNA starts with the sequence (GenBank: AA699010) (M.K. Lemberg and M. Freeman, unpubl.). The Swiss-Prot entry (Swiss-Prot:Q8IH64) that is falsely annotated as Rhomboid-5 consists of a fragment of Ribophorin I (Swiss-Prot:Q76NQ0). The accession number for zebrafish (Danio rerio, Dr) iRhom is Swiss-Prot:Q6GMF8, Takifugu rubripes (Fr) iRhom is Ensembl: SINFRUP00000147713, and Ciona intestalis (Ci) iRhom is Ensembl:ENSCINT00000006045. For the other species, the accession numbers of iRhom1 and iRhom2, respectively, are: Pan troglodytes (Pt), Ensembl:ENSPTRP00000012854 and Ensembl:ENSPTRP00000016460; Canis familiaris (Cf), GenBank:XP_547222.1 and Ensembl:ENSCAFP00000007595; Bos taurus (Bt), Ensembl:ENSBTAP00000026388 and Ensembl:ENSBTAP00000004463; Rattus norvegicus (Rn), GenBank:NP_001025205.1 and GenBank:XP_221133.3; Gallus gallus (Gg), Ensembl:ENSGALP00000012018 and Ensembl: ENSGALP00000003004; and Caenorhabditis elegans (Ce), GenBank:NP_503013 [ROM3 by automated annotation] and GenBank:NP_001041013 [ROM4 by automated annotation].
