We performed a multiple sequence alignment (MSA) to compare the FASTA sequence of all related proteins and LL5ß that we are studying. The MSA was performed with Clustal Omega [1][2] and rendered with BoxShade. 

 

The aim was to determine if there are any evolutionarily conserved sequences. We identified the Pleckstrin homology (PH) domain as the unique conserved modular domain in all isoforms (see Modular domains). The PH domain is highlighted in yellow in the sequence. 

 

Our MSA shows that there is an extremely high conservation between human isotypes.  There is less conservation between the different species we observed (naked mole rat and cattle), however the conservation rate is still relatively high. The PH domain is highly conserved, suggesting that it is crucial to protein function. PH domains are involved in a wide range of physiological activities and can bind to a variety of ligands. Among these ligands, PH-domain strongly binds to PI (3,4,5)P3 and (PI(4,5)P2). It also acts as an anchor of membrane phospholipids by interacting with βγ-subunits of G-protein and protein kinase C.