This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Notch1 protein homology and alignment
The Notch1 protein is highly conserved in many species, ranging from insects and fish to newts and various mammals [1]. Homologs of Notch1 are identified using Homologene and BLAST. Searches using Homologene failed to return results for conserved Notch1 sequences in Eukaryota but did provide results for Coelomata, which is a subgroup under Eukaryota (NCBI). Guided by the results from Homologene, additional searches were done via reciprocal BLAST. Many homologs with E values of 0 or very close to 0 were identified, but only the first 8 organisms (in blue) were used to generate alignment and phylogenetic trees.
Pan troglodytes (chimpanzee)
Protein name: neurogenic locus notch homolog protein 1 isoform 2 Accession number: XP_520371 GI: 114627589 Macaca mulatta (rhesus monkey) Protein name: hypothetical protein EGK_07186, partial Accession number: EHH23670 GI: 355567329 Mus musculus (mouse) Protein name: neurogenic locus notch homolog protein 1 precursor Accession number: NP_032740.3 GI: 224967065 Rattus norvegicus (rat) Protein name: Neurogenic locus notch homolog protein 1Accession number: Q07008 GI: 6093542 Canis lupus (dog) Protein name: neurogenic locus notch homolog protein 1Accession number: XP_537795.3 GI: 345806174 Bos taurus (cattle) Protein name: neurogenic locus notch homolog protein 1 Accession number: XP_002691666.1 GI: 297480858 |
Cavia porcellus (Guinea pig)
Protein name: neurogenic locus notch homolog protein 1-like Accession number: XP_003473037 GI:348574518 Cynops pyrrhogaster (Japanese firebelly newt) Protein name: receptor protein Notch1 Accession number: BAC41349 GI: 26005794 Danio rerio (zebrafish) Protein name: neurogenic locus notch homolog protein 1 precursor Accession number: NP_571516 GI: 18859115 Oreochromis niloticus (nile tilapia) Protein name: neurogenic locus notch homolog protein 1-like Accession number: XP_003451508 GI: 348528003 Gallus gallus (chicken) Protein name: neurogenic locus notch homolog protein 1 Accession number: XP_415420 GI: 363740489 Drosophila melanogaster (fruit fly) Protein name: notch Accession number: NP_476859 GI: 24639454 |
Apart from the orthologs listed above, there are also Notch paralogs in humans, although their sequence similarities with Notch1 are not very high:
Alignments:
Sequences were aligned using ClustalW2 and T-Coffee. For T-Coffee alignment, ends of proteins sequences were eliminated to fit the 2000 amino acids limit. This deletion of amino acids should not greatly affect the alignment results because the ends of Notch1 proteins are less functionally significant (UniProtKB). In fact, T-Coffee alignment results revealed that the ends of Notch1 proteins are relatively poorly conserved in all organisms analyzed.
Sequences were aligned using ClustalW2 and T-Coffee. For T-Coffee alignment, ends of proteins sequences were eliminated to fit the 2000 amino acids limit. This deletion of amino acids should not greatly affect the alignment results because the ends of Notch1 proteins are less functionally significant (UniProtKB). In fact, T-Coffee alignment results revealed that the ends of Notch1 proteins are relatively poorly conserved in all organisms analyzed.
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Analysis:
The Notch1 protein is well-conserved in many species, as shown above. In particular, the homology is highest with the Notch protein in monkeys and chimpanzees. On the other hand, although Notch was first discovered in Drosophila [2], its homology with the human Notch1 protein is significantly less (~49%). Caenorhabditis elegans (worm) also possesses homologs of Notch protein: glp-1(NP_499014) and lin-12 (NP_499007), but the percent similarity is low (39% and 31% respectively). In comparison with the analysis using DNA sequences, it is noticed that protein analysis is a better reflection of Notch1 homology since the NOTCH1 gene is large and poses difficulties in its alignment (see DNA homology and alignment).
The Notch1 protein is well-conserved in many species, as shown above. In particular, the homology is highest with the Notch protein in monkeys and chimpanzees. On the other hand, although Notch was first discovered in Drosophila [2], its homology with the human Notch1 protein is significantly less (~49%). Caenorhabditis elegans (worm) also possesses homologs of Notch protein: glp-1(NP_499014) and lin-12 (NP_499007), but the percent similarity is low (39% and 31% respectively). In comparison with the analysis using DNA sequences, it is noticed that protein analysis is a better reflection of Notch1 homology since the NOTCH1 gene is large and poses difficulties in its alignment (see DNA homology and alignment).
References:
1. Kawamata, S., Du, C., Li, K., & Lavau, C. (2002). Notch1 Perturbation of Hemopoiesis Involves Non-Cell-Autonomous Modifications. The Journal of Immunology, 168: 1738-1745. [PubMed]
2. Fiuza, U-M, & Arias, A.M. (2007). Cell and molecular biology of Notch. Journal of Endocrinology. 194: 459-474. doi: 10.1677/JOE-07-0242
1. Kawamata, S., Du, C., Li, K., & Lavau, C. (2002). Notch1 Perturbation of Hemopoiesis Involves Non-Cell-Autonomous Modifications. The Journal of Immunology, 168: 1738-1745. [PubMed]
2. Fiuza, U-M, & Arias, A.M. (2007). Cell and molecular biology of Notch. Journal of Endocrinology. 194: 459-474. doi: 10.1677/JOE-07-0242