Seroatlas · Human Serome Atlas

TNNI3K

Serine/threonine-protein kinase TNNI3K

Also known as: CARK, TNI3K_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q59H18
Gene: TNNI3K
Ensembl: ENSG00000116783
Chromosome: 1
Canonical length: 835 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

OverviewNCBI Gene

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. [provided by RefSeq, Sep 2012]

Canonical amino-acid sequenceUniProt

835 residues, UniProt reviewed canonical sequence.

>Q59H18|TNNI3K
     1  MGNYKSRPTQ TCTDEWKKKV SESYVITIER LEDDLQIKEK ELTELRNIFG SDEAFSKVNL
    61  NYRTENGLSL LHLCCICGGK KSHIRTLMLK GLRPSRLTRN GFTALHLAVY KDNAELITSL
   121  LHSGADIQQV GYGGLTALHI ATIAGHLEAA DVLLQHGANV NIQDAVFFTP LHIAAYYGHE
   181  QVTRLLLKFG ADVNVSGEVG DRPLHLASAK GFLNIAKLLM EEGSKADVNA QDNEDHVPLH
   241  FCSRFGHHDI VKYLLQSDLE VQPHVVNIYG DTPLHLACYN GKFEVAKEII QISGTESLTK
   301  ENIFSETAFH SACTYGKSID LVKFLLDQNV ININHQGRDG HTGLHSACYH GHIRLVQFLL
   361  DNGADMNLVA CDPSRSSGEK DEQTCLMWAY EKGHDAIVTL LKHYKRPQDE LPCNEYSQPG
   421  GDGSYVSVPS PLGKIKSMTK EKADILLLRA GLPSHFHLQL SEIEFHEIIG SGSFGKVYKG
   481  RCRNKIVAIK RYRANTYCSK SDVDMFCREV SILCQLNHPC VIQFVGACLN DPSQFAIVTQ
   541  YISGGSLFSL LHEQKRILDL QSKLIIAVDV AKGMEYLHNL TQPIIHRDLN SHNILLYEDG
   601  HAVVADFGES RFLQSLDEDN MTKQPGNLRW MAPEVFTQCT RYTIKADVFS YALCLWEILT
   661  GEIPFAHLKP AAAAADMAYH HIRPPIGYSI PKPISSLLIR GWNACPEGRP EFSEVVMKLE
   721  ECLCNIELMS PASSNSSGSL SPSSSSDCLV NRGGPGRSHV AALRSRFELE YALNARSYAA
   781  LSQSAGQYSS QGLSLEEMKR SLQYTPIDKY GYVSDPMSSM HFHSCRNSSS FEDSS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNNI3K can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.29
Highest tissue expression: 55 nTPM

Expression across tissuesHPA

Tissue

heart muscle: 55 nTPM
cerebellum: 12 nTPM
retina: 4.8 nTPM
cerebral cortex: 4.7 nTPM
testis: 3.6 nTPM
basal ganglia: 3.5 nTPM

Single-cell type

ependymal cells: 127 nCPM
bergmann glia: 85 nCPM
oligodendrocytes: 79 nCPM
astrocytes: 68 nCPM
oligodendrocyte progenitor cells: 58 nCPM
brain excitatory neurons: 57 nCPM

Immune cell

intermediate monocyte: 0.4 nTPM
plasmacytoid DC: 0.3 nTPM
memory CD8 T-cell: 0.1 nTPM
basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM

Brain region

cerebral cortex: 6.4 nTPM
cerebellum: 6.3 nTPM
white matter: 6 nTPM
hypothalamus: 4.3 nTPM
basal ganglia: 3.6 nTPM
pons: 3.6 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TNNI3K.

Disease | AllUniProt

Conditions TNNI3K is implicated in, by any mechanism.

Cardiac conduction disease with or without dilated cardiomyopathy (CCDD) MIM:616117

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 1,347 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Atrial conduction disease
Cardiovascular phenotype
Arrhythmogenic right ventricular dysplasia 2
TNNI3K-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 1.43
gnomAD pLI: 0
gnomAD missense Z: -0.55
DepMap mean gene effect: -0.04
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

peptidyl-serine autophosphorylation
protein phosphorylation
regulation of cardiac conduction
regulation of cardiac muscle contraction
regulation of heart rate
bundle of His cell to Purkinje myocyte communication

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of TNNI3K in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads TNNI3K as an antibody target. Whether an autoantibody or antibody against TNNI3K could matter depends on whether native TNNI3K is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

TNNI3K is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label TNNI3K as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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