MARK2
Microtubule associated regulating kinase 2
Domain analysis
All five proteins have a protein kinase domain. Additionally, the ATP binding site as well as Serine/threonine-protein kinase active site were specified and found to be at similar sites across the five proteins. The five proteins also have Kinase associated domain 1 and Ubiquitin-associated/translation elongation factor EF1B.
Analysis was done using Interproscan and confirmed with PFAM. However PFAM did not detect Ubiquitin-associated/translation elongation factor EF1B so Interproscan is preferable in this case.
Rattus norvegicus
Interproscan
PFAM
Homo sapiens
Interproscan
PFAM
Mus musculus
Interproscan
PFAM
Xenopus laevis
Interproscan
PFAM
Bos taurus
Interproscan
PFAM
The KA1 Domain
Interestingly, the KA1 domain did not appear in the crystal structure of MARK2. The presence of Kinase Associated-1 domains which are located at the C terminus is one of the characteristics of the MARK family. The KA1 domains of all MARK family kinases end in a highly conserved sequence ELKL.
While there has been no study examining the structure of KA1 domain in MARK 2, the KA1 domain of another MARK, mouse MARK3 had been looked at. It showed the KA1 domain adopts an α + β sandwich fold, which consists of two side-by-side α-helices (α1, Pro672–Ala685; α2, Ser737–Glu750) and a five-stranded antiparallel β-sheet (β1, Thr667–Ser668; β2, Asp689–Glu694; β3, Leu697–His702; β4, Val711–Lys719; β5, Asn726–Arg732)[1].
The function of the KA1 domain in MARK 2 has not been well studied. However, a recent study which examine a number of proteins with KA1 domains including MARK1 that it might have a role in membrane localisation and association as the domain binds acidic phospholipids[2].
Figure 1: Ribbon diagram showing KA1 domain. Red represents alpha helices and green represent beta strands[1].
REFERENCES
[1] Tochio N., Koshiba S., Kobayashi N., Inoue M., Yabuki T., Aoki M., Seki E., Matsuda T., Tomo Y., Motoda Y., Kobayashi A., Tanaka A., Hayashizaki Y., Terada T., Shirouzu M., Kigawa T. and Yokoyama S. (2006). Solution structure of the kinase-associated domain 1 of mouse microtubule-associated protein/microtubule affinity-regulating kinase 3. Protein Sci. 15(11): 2534–2543.
[2] Moravcevic K., Mendrola J.M., Schmitz K.R., Wang Y., Slochower D., Janmey P.A. and Lemmon M.A.(2010). Kinase Associated-1 (KA1) Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids Cell. 143(6): 966–977.