Kinase Subfamily HH498

Kinase Classification: Group TKL: Family MLK: : Subfamily HH498

Evolution

HH498 is found throughout unikonts. Like the ZAK subfamily of MLK, it is absent from most arthropods, and it is also lost from most fungi and several other invertebrate lineages. It has a single gene in vertebrates, HH398/CARK/CCDD/TNNI3K.

Domain Structure

Animal members have several Ankyrin repeats followed by a kinase domain, and this is also seen in Dictyostelium. The large 28-gene expansion in sponge has several other domain organizations, including members with DUSP phosphatase domains, repeated Kelch domains, an SH2 domain, or a Macro/A1pp domain.

Functions

Human TNNI3K interacts with cardiac troponin-I and is implicated in cardiac disease [1, 2]. TNNI3K expression is elevated in failing hearts [3] and engineered overexpression promotes cardiac cell hypertrophy [4, 5].

TNNI3K is reported to be a dual-specific kinase [6] and may form dimers. It is expressed almost exclusively in heart and cerebellum in human gTEX.

References

1. Feng Y, Cao HQ, Liu Z, Ding JF, and Meng XM. Identification of the dual specificity and the functional domains of the cardiac-specific protein kinase TNNI3K. Gen Physiol Biophys. 2007 Jun;26(2):104-9.
2. Theis JL, Zimmermann MT, Larsen BT, Rybakova IN, Long PA, Evans JM, Middha S, de Andrade M, Moss RL, Wieben ED, Michels VV, and Olson TM. TNNI3K mutation in familial syndrome of conduction system disease, atrial tachyarrhythmia and dilated cardiomyopathy. Hum Mol Genet. 2014 Nov 1;23(21):5793-804. DOI:10.1093/hmg/ddu297 |
3. Wei YJ, Cui CJ, Huang YX, Zhang XL, Zhang H, and Hu SS. Upregulated expression of cardiac ankyrin repeat protein in human failing hearts due to arrhythmogenic right ventricular cardiomyopathy. Eur J Heart Fail. 2009 Jun;11(6):559-66. DOI:10.1093/eurjhf/hfp049 |
4. Wang L, Wang H, Ye J, Xu RX, Song L, Shi N, Zhang YW, Chen X, and Meng XM. Adenovirus-mediated overexpression of cardiac troponin I-interacting kinase promotes cardiomyocyte hypertrophy. Clin Exp Pharmacol Physiol. 2011 Apr;38(4):278-84. DOI:10.1111/j.1440-1681.2011.05499.x |
5. Lai ZF, Chen YZ, Feng LP, Meng XM, Ding JF, Wang LY, Ye J, Li P, Cheng XS, Kitamoto Y, Monzen K, Komuro I, Sakaguchi N, and Kim-Mitsuyama S. Overexpression of TNNI3K, a cardiac-specific MAP kinase, promotes P19CL6-derived cardiac myogenesis and prevents myocardial infarction-induced injury. Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H708-16. DOI:10.1152/ajpheart.00252.2008 |
6. Feng Y, Cao HQ, Liu Z, Ding JF, and Meng XM. Identification of the dual specificity and the functional domains of the cardiac-specific protein kinase TNNI3K. Gen Physiol Biophys. 2007 Jun;26(2):104-9.