TNNI3K

TNNI3K
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4YFI, 4YFF
Identifiers
Aliases	TNNI3K , CARK, CCDD, TNNI3 interacting kinase
External IDs	OMIM: 613932 MGI: 2443276 HomoloGene: 41084 GeneCards: TNNI3K
Gene location (Human)
Chr.	Chromosome 1 (human)
End	74,544,428 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	154,761,044 bp
RNA expression pattern
	Top expressed in
	left ventricle; ; cerebellar hemisphere; ; Brodmann area 9; ; superior frontal gyrus; ; sural nerve; ; prefrontal cortex; ; cingulate gyrus; ; corpus callosum; ; Achilles tendon; ; nucleus accumbens;
	Top expressed in
	myocardium of ventricle; ; atrium; ; atrioventricular valve; ; endocardial cushion; ; left ventricle; ; olfactory epithelium; ; semi-lunar valve; ; aortic valve; ; esophagus; ; aorta;
	More reference expression data
	n/a
Gene ontology
Molecular function	transferase activity ; protein kinase activity ; protein serine/threonine kinase activity ; nucleotide binding ; protein C-terminus binding ; protein binding ; troponin I binding ; ATP binding ; metal ion binding ; kinase activity ; signal transducer activity ;
Cellular component	cytoplasm ; nucleus ;
Biological process	protein phosphorylation ; regulation of cardiac muscle contraction ; regulation of cardiac conduction ; bundle of His cell to Purkinje myocyte communication ; phosphorylation ; regulation of heart rate ; intracellular signal transduction ;
	Sources:Amigo / QuickGO
Orthologs
	51086
	435766
	ENSG00000116783
	ENSMUSG00000040086
	Q59H18
	Q5GIG6
	NM_015978
	NM_001012364 ; NM_177066
	NP_001106279 ; NP_001186256 ; NP_057062
	NP_796040
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated October 12, 2022

TNNI3 interacting kinase is a protein that in humans is encoded by the TNNI3K gene.^[5]

Function

This gene encodes a protein that belongs to the MAP kinase kinase kinase (MAPKKK) family of protein kinases. The protein contains ankyrin repeat, protein kinase and serine-rich domains and is thought to play a role in cardiac physiology.^[5]

Clinical significance

Mutations in TNNI3K are associated to cardiomyopathies.^[6]

Related Research Articles

Titin is a protein that in humans is encoded by the TTN gene. Titin is a giant protein, greater than 1 µm in length, that functions as a molecular spring that is responsible for the passive elasticity of muscle. It comprises 244 individually folded protein domains connected by unstructured peptide sequences. These domains unfold when the protein is stretched and refold when the tension is removed.

Caveolin-3 is a protein that in humans is encoded by the CAV3 gene. Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites.

Integrin-linked kinase is an enzyme that in humans is encoded by the ILK gene involved with integrin-mediated signal transduction. Mutations in ILK are associated with cardiomyopathies. It is a 59kDa protein originally identified in a yeast-two hybrid screen with integrin β1 as the bait protein. Since its discovery, ILK has been associated with multiple cellular functions including cell migration, proliferation, and adhesion.

Protein kinase C epsilon type (PKCε) is an enzyme that in humans is encoded by the PRKCE gene. PKCε is an isoform of the large PKC family of protein kinases that play many roles in different tissues. In cardiac muscle cells, PKCε regulates muscle contraction through its actions at sarcomeric proteins, and PKCε modulates cardiac cell metabolism through its actions at mitochondria. PKCε is clinically significant in that it is a central player in cardioprotection against ischemic injury and in the development of cardiac hypertrophy.

Troponin I, cardiac muscle is a protein that in humans is encoded by the TNNI3 gene. It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex.

Cardiac muscle troponin T (cTnT) is a protein that in humans is encoded by the TNNT2 gene. Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration.

Gamma-aminobutyric acid receptor subunit gamma-2 is a protein that in humans is encoded by the GABRG2 gene.

Alpha II-spectrin, also known as Spectrin alpha chain, brain is a protein that in humans is encoded by the SPTAN1 gene. Alpha II-spectrin is expressed in a variety of tissues, and is highly expressed in cardiac muscle at Z-disc structures, costameres and at the sarcolemma membrane. Mutations in alpha II-spectrin have been associated with early infantile epileptic encephalopathy-5, and alpha II-spectrin may be a valuable biomarker for Guillain–Barré syndrome and infantile congenital heart disease.

The myosin-binding protein C, cardiac-type is a protein that in humans is encoded by the MYBPC3 gene. This isoform is expressed exclusively in heart muscle during human and mouse development, and is distinct from those expressed in slow skeletal muscle (MYBPC1) and fast skeletal muscle (MYBPC2).

Telethonin, also known as Tcap, is a protein that in humans is encoded by the TCAP gene. Telethonin is expressed in cardiac and skeletal muscle at Z-discs and functions to regulate sarcomere assembly, T-tubule function and apoptosis. Telethonin has been implicated in several diseases, including limb-girdle muscular dystrophy, hypertrophic cardiomyopathy, dilated cardiomyopathy and idiopathic cardiomyopathy.

Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC-2) also known as the regulatory light chain of myosin (RLC) is a protein that in humans is encoded by the MYL2 gene. This cardiac ventricular RLC isoform is distinct from that expressed in skeletal muscle (MYLPF), smooth muscle (MYL12B) and cardiac atrial muscle (MYL7).

Slow skeletal muscle troponin T (sTnT) is a protein that in humans is encoded by the TNNT1 gene.

Plakophilin-2 is a protein that in humans is encoded by the PKP2 gene. Plakophilin 2 is expressed in skin and cardiac muscle, where it functions to link cadherins to intermediate filaments in the cytoskeleton. In cardiac muscle, plakophilin-2 is found in desmosome structures located within intercalated discs. Mutations in PKP2 have been shown to be causal in arrhythmogenic right ventricular cardiomyopathy.

Serine/threonine-protein kinase PAK 5 is an enzyme that in humans is encoded by the PAK5 gene.

Obscurin is a protein that in humans is encoded by the OBSCN gene. Obscurin belongs to the family of giant sarcomeric signaling proteins that includes titin and nebulin. Obscurin is expressed in cardiac and skeletal muscle, and plays a role in the organization of myofibrils during sarcomere assembly. A mutation in the OBSCN gene has been associated with hypertrophic cardiomyopathy and altered obscurin protein properties have been associated with other muscle diseases.

Ankyrin Repeat, PEST sequence and Proline-rich region (ARPP), also known as Ankyrin repeat domain-containing protein 2 is a protein that in humans is encoded by the ANKRD2 gene. ARPP is a member of the muscle ankyrin repeat proteins (MARP), which also includes CARP and DARP, and is highly expressed in cardiac and skeletal muscle and in other tissues. Expression of ARPP has been shown to be altered in patients with dilated cardiomyopathy and amyotrophic lateral sclerosis. A role for Ankrd2 in tumor progression and metastases spreading has also been described.

Ankyrin repeat domain-containing protein 1, or Cardiac ankyrin repeat protein is a protein that in humans is encoded by the ANKRD1 gene also known as CARP. CARP is highly expressed in cardiac and skeletal muscle, and is a transcription factor involved in development and under conditions of stress. CARP has been implicated in several diseases, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and several skeletal muscle myopathies.

LIM domain binding 3 (LDB3), also known as Z-band alternatively spliced PDZ-motif (ZASP), is a protein which in humans is encoded by the LDB3 gene. ZASP belongs to the Enigma subfamily of proteins and stabilizes the sarcomere during contraction, through interactions with actin in cardiac and skeletal muscles. Mutations in the ZASP gene has been associated with several muscular diseases.

Atrial Light Chain-2 (ALC-2) also known as Myosin regulatory light chain 2, atrial isoform (MLC2a) is a protein that in humans is encoded by the MYL7 gene. ALC-2 expression is restricted to cardiac muscle atria in healthy individuals, where it functions to modulate cardiac development and contractility. In human diseases, including hypertrophic cardiomyopathy, dilated cardiomyopathy, ischemic cardiomyopathy and others, ALC-2 expression is altered.

Spondin 2, also known as mindin, is a protein that in humans is encoded by the SPON2 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000116783 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000040086 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 "Entrez Gene: TNNI3 interacting kinase".
↑ Theis JL, Zimmermann MT, Larsen BT, Rybakova IN, Long PA, Evans JM, Middha S, de Andrade M, Moss RL, Wieben ED, Michels VV, Olson TM (Nov 2014). "TNNI3K mutation in familial syndrome of conduction system disease, atrial tachyarrhythmia and dilated cardiomyopathy". Human Molecular Genetics. 23 (21): 5793–804. doi:10.1093/hmg/ddu297. PMC 4189907 . PMID 24925317.

Yang SW, Hitz MP, Andelfinger G (Oct 2010). "Ventricular septal defect and restrictive cardiomyopathy in a paediatric TNNI3 mutation carrier". Cardiology in the Young. 20 (5): 574–6. doi:10.1017/S1047951110000715. PMID 20569525. S2CID 20594665.
Wang L, Wang H, Ye J, Xu RX, Song L, Shi N, Zhang YW, Chen X, Meng XM (Apr 2011). "Adenovirus-mediated overexpression of cardiac troponin I-interacting kinase promotes cardiomyocyte hypertrophy". Clinical and Experimental Pharmacology & Physiology. 38 (4): 278–84. doi:10.1111/j.1440-1681.2011.05499.x. PMID 21314842. S2CID 32451541.
Wei YJ, Cui CJ, Huang YX, Zhang XL, Zhang H, Hu SS (Jun 2009). "Upregulated expression of cardiac ankyrin repeat protein in human failing hearts due to arrhythmogenic right ventricular cardiomyopathy". European Journal of Heart Failure. 11 (6): 559–66. doi: 10.1093/eurjhf/hfp049 . PMID 19359327.
Chen X, Li X, Wang P, Liu Y, Zhang Z, Zhao G, Xu H, Zhu J, Qin X, Chen S, Hu L, Kong X (2010). "Novel association strategy with copy number variation for identifying new risk Loci of human diseases". PLOS ONE. 5 (8): e12185. Bibcode:2010PLoSO...512185C. doi: 10.1371/journal.pone.0012185 . PMC 2924882 . PMID 20808825.
Tang H, Xiao K, Mao L, Rockman HA, Marchuk DA (Jan 2013). "Overexpression of TNNI3K, a cardiac-specific MAPKKK, promotes cardiac dysfunction". Journal of Molecular and Cellular Cardiology. 54: 101–11. doi:10.1016/j.yjmcc.2012.10.004. PMC 3535516 . PMID 23085512.
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, Kim-Mitsuyama S (Aug 2008). "Overexpression of TNNI3K, a cardiac-specific MAP kinase, promotes P19CL6-derived cardiac myogenesis and prevents myocardial infarction-induced injury". American Journal of Physiology. Heart and Circulatory Physiology. 295 (2): H708–16. doi:10.1152/ajpheart.00252.2008. PMID 18552163. S2CID 40248367.
Feng Y, Cao HQ, Liu Z, Ding JF, Meng XM (Jun 2007). "Identification of the dual specificity and the functional domains of the cardiac-specific protein kinase TNNI3K". General Physiology and Biophysics. 26 (2): 104–9. PMID 17660584.
Feng Y, Liu DQ, Wang Z, Liu Z, Cao HQ, Wang LY, Shi N, Meng XM (Nov 2007). "AOP-1 interacts with cardiac-specific protein kinase TNNI3K and down-regulates its kinase activity". Biochemistry. Biokhimiia. 72 (11): 1199–204. doi:10.1134/s0006297907110053. PMID 18205602. S2CID 32928443.
Cousminer DL, Berry DJ, Timpson NJ, Ang W, Thiering E, Byrne EM, et al. (Jul 2013). "Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity". Human Molecular Genetics. 22 (13): 2735–47. doi:10.1093/hmg/ddt104. PMC 3674797 . PMID 23449627.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000116783 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000040086 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] 1 2 "Entrez Gene: TNNI3 interacting kinase".

[6] Theis JL, Zimmermann MT, Larsen BT, Rybakova IN, Long PA, Evans JM, Middha S, de Andrade M, Moss RL, Wieben ED, Michels VV, Olson TM (Nov 2014). "TNNI3K mutation in familial syndrome of conduction system disease, atrial tachyarrhythmia and dilated cardiomyopathy". Human Molecular Genetics. 23 (21): 5793–804. doi:10.1093/hmg/ddu297. PMC 4189907 . PMID 24925317.

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TNNI3K

Contents

Function

Clinical significance

Related Research Articles

References

Further reading