Adaptor protein SH2B3/LNK functions as a negative regulator of the JAK-STAT pathway. Its mutations are involved in myeloproliferative neoplasms (MPNs) that are usually associated with elevated levels of red blood cells (RBC). It is known that animals living under hypoxic conditions have high RBC. We hypothesize that genetic alterations in SH2B3 may be an intrinsic factor. In this study, we analyzed the amino acid sequences of SH2B3 of mammals living in normoxic and hypoxic habitats in comparison with known mutations or single nucleotide polymorphisms (SNPs) in the human genome. This comparative analysis is also intended to identify potential gene alterations responsible for RBC disorders. SH2B3 protein sequences of 30 distinct animals were downloaded from the NCBI (National Center for Biotechnology Information) GenBank database and aligned by using the Multalin program. Mutations and SNPs in human SH2B3 were obtained from the dSNP database and published literature. The Protein Variation Effect Analyzer (PROVEAN) program was used to predict the effects of the identified amino acid alterations. Several highly conserved regions in SH2B3 were observed to have amino acid alterations among hypoxic animals. Amino acid residues at positions 109, 180, 308, 311, 313, 315, 396, 483, 537 show good correlation between deleterious amino acid alterations, animal's habitations and RBC levels. Potentially deleterious amino acid alterations in SH2B3 may help some animals to adapt to their hypoxic environments but may, however, lead to the development of MPNs in humans. Our data should help develop therapeutic strategies to treat RBC-related diseases.

Comparative analysis of the SH2B3/LNK gene in mammals: A key to understanding myeloproliferative neoplasms

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.