Domains & Motifs Identified

 

Tubulin binding repeats

Using PFAM, tubulin-binding repeats were identified in the C-terminus. Some isoforms contain three repeats, others contain four. This is due to alternative splicing of exon 10. Exon 10 is spliced out in several isoforms, and as it codes for one of the repeats, these isoforms without exon 10 only contain three repeats instead of four. The region containing these repeats is highly conserved. Not only do all human isoforms share the same sequence for these repeats, but mouse and monkey isoforms also show nearly identical tubulin binding repeat sequences. Between the different repeats, there are some differences in sequence, but each repeat contains a highly conserved Pro-Gly-Gly-Gly near the end of the sequence. 

 

Tubulin binding repeat 1

 

 

 

 

 

Tubulin binding repeat 2

 

 

 

 

 

Tubulin binding repeat 3

 

 

 

 

 

Tubulin binding repeat 4

 

 

 

 

 

As this region is highly conserved between species, this suggests it is an important functional region. Mutations in the tubulin binding repeat are associated with diseases like Alzheimer’s.

 

SH3-binding domain

In 1998, an SH3-domain binding sequence was identified in human Tau [1]. The sequence identified is Arg-Thr-Pro-Pro-Lys-Ser-Pro-Ser-Ser, in which the Pro-Lys-Ser-Pro region is where the SH3 domain will bind. This sequence is present in the proline-rich region.

 

Motifs

6 motifs were identified by a PRINTS search:

 

Tau protein motif I-1

KIATPRGAAPPG

 

Tau protein motif II-1

QKGQANATRI

 

Tau protein motif III-1

GEPPKSGD

 

Tau protein motif IV-1

PSLPTPPTR

 

Tau protein motif V-1

EPKKVAVV

 

Tau protein motif VI-1

QTAPVPMPDL

 

 

 

 

 

REFERENCES

1. http://www.ncbi.nlm.nih.gov/pubmed/9763511