TNNI3

Protein identityUniProt · HPA

UniProt accession

P19429

Gene

TNNI3

Ensembl

ENSG00000129991

Chromosome

19

Canonical length

210 aa

Protein class

Candidate cardiovascular disease genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Vesicles,Cytosol

OverviewNCBI Gene

Troponin I (TnI), along with troponin T (TnT) and troponin C (TnC), is one of 3 subunits that form the troponin complex of the thin filaments of striated muscle. TnI is the inhibitory subunit; blocking actin-myosin interactions and thereby mediating striated muscle relaxation. The TnI subfamily contains three genes: TnI-skeletal-fast-twitch, TnI-skeletal-slow-twitch, and TnI-cardiac. This gene encodes the TnI-cardiac protein and is exclusively expressed in cardiac muscle tissues. Mutations in this gene cause familial hypertrophic cardiomyopathy type 7 (CMH7) and familial restrictive cardiomyopathy (RCM). Troponin I is useful in making a diagnosis of heart failure, and of ischemic heart disease. An elevated level of troponin is also now used as indicator of acute myocardial injury in patients hospitalized with moderate/severe Coronavirus Disease 2019 (COVID-19). Such elevation has also been associated with higher risk of mortality in cardiovascular disease patients hospitalized due to COVID-19. [provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

210 residues, UniProt reviewed canonical sequence.

>P19429|TNNI3
     1  MADGSSDAAR EPRPAPAPIR RRSSNYRAYA TEPHAKKKSK ISASRKLQLK TLLLQIAKQE
    61  LEREAEERRG EKGRALSTRC QPLELAGLGF AELQDLCRQL HARVDKVDEE RYDIEAKVTK
   121  NITEIADLTQ KIFDLRGKFK RPTLRRVRIS ADAMMQALLG ARAKESLDLR AHLKQVKKED
   181  TEKENREVGD WRKNIDALSG MEGRKKKFES

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNNI3 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)

0.57

Highest tissue expression

10,359 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TNNI3.

Disease | AllUniProt

Conditions TNNI3 is implicated in, by any mechanism.

• Cardiomyopathy, familial hypertrophic, 7 (CMH7) MIM:613690
• Cardiomyopathy, familial restrictive 1 (RCM1) MIM:115210
• Cardiomyopathy, dilated, 2A (CMD2A) MIM:611880
• Cardiomyopathy, dilated, 1FF (CMD1FF) MIM:613286

Disease | GeneticClinVar

80 pathogenic / likely-pathogenic of 848 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hypertrophic cardiomyopathy
• Hypertrophic cardiomyopathy 7
• Cardiovascular phenotype
• Cardiomyopathy
• Cardiomyopathy, familial restrictive, 1

Disease | AutoantibodyPubMed

Conditions in which antibodies against TNNI3 are reported. Each links to that disease's full target list.

• Myocardial Infarction 5

Showing 1 of 3 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for TNNI3 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.69

gnomAD pLI

0.1

gnomAD missense Z

1.28

DepMap mean gene effect

0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cardiac muscle contraction
• heart contraction
• heart development
• intracellular calcium ion homeostasis
• muscle filament sliding
• negative regulation of ATP-dependent activity
• regulation of cardiac muscle contraction by calcium ion signaling
• regulation of smooth muscle contraction
• skeletal muscle contraction
• vasculogenesis
• ventricular cardiac muscle tissue morphogenesis
• regulation of systemic arterial blood pressure by ischemic conditions

Molecular functions

• actin binding
• actin filament binding
• calcium channel inhibitor activity
• calcium-dependent protein binding
• protein domain specific binding
• protein kinase binding
• troponin C binding
• troponin T binding

Cellular components

• cardiac myofibril
• cardiac Troponin complex
• cytosol
• sarcomere
• troponin complex

Protein domainsUniProt · Pfam · InterPro

• Troponin
• Troponin domain superfamily
• Troponin I
• Troponin
• Troponin I residues 1-32
• Troponin I residues 1-32

KeywordsUniProt

• Acetylation
• Actin-binding
• Cardiomyopathy
• Muscle protein
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of TNNI3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TRIM63
• TNNI3K
• STK4
• TNNC1