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Protein

Troponin I, cardiac muscle

Gene

TNNI3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei80Involved in TNI-TNT interactions1
Sitei97Involved in TNI-TNT interactions1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi137 – 148By similarityAdd BLAST12

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • actin filament binding Source: CAFA
  • calcium channel inhibitor activity Source: UniProtKB
  • calcium-dependent protein binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein domain specific binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • troponin C binding Source: UniProtKB
  • troponin T binding Source: UniProtKB

GO - Biological processi

  • cardiac muscle contraction Source: UniProtKB
  • cellular calcium ion homeostasis Source: UniProtKB
  • heart contraction Source: UniProtKB
  • heart development Source: UniProtKB
  • muscle filament sliding Source: Reactome
  • negative regulation of ATPase activity Source: UniProtKB
  • regulation of cardiac muscle contraction by calcium ion signaling Source: CAFA
  • regulation of smooth muscle contraction Source: Ensembl
  • regulation of systemic arterial blood pressure by ischemic conditions Source: UniProtKB
  • skeletal muscle contraction Source: GO_Central
  • vasculogenesis Source: UniProtKB
  • ventricular cardiac muscle tissue morphogenesis Source: HGNC

Keywordsi

Molecular functionActin-binding, Muscle protein
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-390522 Striated Muscle Contraction
R-HSA-5578775 Ion homeostasis
SIGNORiP19429

Names & Taxonomyi

Protein namesi
Recommended name:
Troponin I, cardiac muscle
Alternative name(s):
Cardiac troponin I
Gene namesi
Name:TNNI3
Synonyms:TNNC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000129991.12
HGNCiHGNC:11947 TNNI3
MIMi191044 gene
neXtProtiNX_P19429

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, familial hypertrophic 7 (CMH7)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
See also OMIM:613690
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019872141R → Q in CMH7. 1 PublicationCorresponds to variant dbSNP:rs397516347EnsemblClinVar.1
Natural variantiVAR_007603145R → G in CMH7. 1 PublicationCorresponds to variant dbSNP:rs104894724EnsemblClinVar.1
Natural variantiVAR_019873157A → V in CMH7. 1 PublicationCorresponds to variant dbSNP:rs397516353EnsemblClinVar.1
Natural variantiVAR_019874162R → P in CMH7. 2 PublicationsCorresponds to variant dbSNP:rs397516354EnsemblClinVar.1
Natural variantiVAR_042745162R → Q in CMH7. 1 PublicationCorresponds to variant dbSNP:rs397516354EnsemblClinVar.1
Natural variantiVAR_029454166S → F in CMH7. 1 PublicationCorresponds to variant dbSNP:rs727504242EnsemblClinVar.1
Natural variantiVAR_019875177Missing in CMH7. 1 Publication1
Natural variantiVAR_019876186R → Q in CMH7. 1 PublicationCorresponds to variant dbSNP:rs397516357EnsemblClinVar.1
Natural variantiVAR_016085196D → N in CMH7. 2 PublicationsCorresponds to variant dbSNP:rs104894727EnsemblClinVar.1
Natural variantiVAR_042746204R → H in CMH7. 1 PublicationCorresponds to variant dbSNP:rs727504275EnsemblClinVar.1
Natural variantiVAR_007604206K → Q in CMH7. 1 PublicationCorresponds to variant dbSNP:rs104894725EnsemblClinVar.1
Cardiomyopathy, familial restrictive 1 (RCM1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function.
See also OMIM:115210
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_016079144L → Q in RCM1. 1 PublicationCorresponds to variant dbSNP:rs121917760EnsemblClinVar.1
Natural variantiVAR_016080145R → W in RCM1. 1 PublicationCorresponds to variant dbSNP:rs104894724EnsemblClinVar.1
Natural variantiVAR_016081171A → T in RCM1. 1 PublicationCorresponds to variant dbSNP:rs121917761EnsemblClinVar.1
Natural variantiVAR_016082178K → E in RCM1. 1 PublicationCorresponds to variant dbSNP:rs104894730EnsemblClinVar.1
Natural variantiVAR_016084192R → H in RCM1. 1 PublicationCorresponds to variant dbSNP:rs104894729EnsemblClinVar.1
Cardiomyopathy, dilated 2A (CMD2A)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
See also OMIM:611880
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0439892A → V in CMD2A. 1 PublicationCorresponds to variant dbSNP:rs397516359EnsemblClinVar.1
Cardiomyopathy, dilated 1FF (CMD1FF)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
See also OMIM:613286
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06354836K → Q in CMD1FF. 1 PublicationCorresponds to variant dbSNP:rs267607130EnsemblClinVar.1
Natural variantiVAR_067264116A → G in CMD1FF. 1 PublicationCorresponds to variant dbSNP:rs777177571Ensembl.1
Natural variantiVAR_063549185N → K in CMD1FF. 1 PublicationCorresponds to variant dbSNP:rs267607129EnsemblClinVar.1

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi7137
GeneReviewsiTNNI3
MalaCardsiTNNI3
MIMi115210 phenotype
611880 phenotype
613286 phenotype
613690 phenotype
OpenTargetsiENSG00000129991
Orphaneti154 Familial isolated dilated cardiomyopathy
155 Familial isolated hypertrophic cardiomyopathy
75249 Familial isolated restrictive cardiomyopathy
PharmGKBiPA36636

Chemistry databases

ChEMBLiCHEMBL2095202
DrugBankiDB04513 N-(6-Aminohexyl)-5-Chloro-1-Naphthalenesulfonamide

Polymorphism and mutation databases

BioMutaiTNNI3
DMDMi136213

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001861512 – 210Troponin I, cardiac muscleAdd BLAST209

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei5Phosphoserine1 Publication1
Modified residuei6Phosphoserine1 Publication1
Modified residuei23Phosphoserine; by PKA and PKD/PRKD14 Publications1
Modified residuei24Phosphoserine; by PKA and PKD/PRKD14 Publications1
Modified residuei26Phosphotyrosine1 Publication1
Modified residuei31Phosphothreonine; by STK4/MST11 Publication1
Modified residuei42Phosphoserine; by PKC/PRKCEBy similarity1
Modified residuei44Phosphoserine; by PKC/PRKCEBy similarity1
Modified residuei51Phosphothreonine; by STK4/MST12 Publications1
Modified residuei77Phosphoserine1 Publication1
Modified residuei78Phosphothreonine1 Publication1
Modified residuei129Phosphothreonine; by STK4/MST11 Publication1
Modified residuei143Phosphothreonine; by STK4/MST12 Publications1
Modified residuei150Phosphoserine; by PAK31 Publication1
Modified residuei166Phosphoserine1 Publication1
Modified residuei181Phosphothreonine1 Publication1
Modified residuei199Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylated at Ser-42 and Ser-44 by PRKCE; phosphorylation increases myocardium contractile dysfunction (By similarity). Phosphorylated at Ser-23 and Ser-24 by PRKD1; phosphorylation reduces myofilament calcium sensitivity. Phosphorylated preferentially at Thr-31. Phosphorylation by STK4/MST1 alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T).By similarity6 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP19429
PeptideAtlasiP19429
PRIDEiP19429
ProteomicsDBi53658

PTM databases

iPTMnetiP19429
PhosphoSitePlusiP19429

Expressioni

Gene expression databases

BgeeiENSG00000129991
CleanExiHS_TNNC1
HS_TNNI3
ExpressionAtlasiP19429 baseline and differential
GenevisibleiP19429 HS

Organism-specific databases

HPAiCAB009349
HPA046428

Interactioni

Subunit structurei

Binds to actin and tropomyosin. Interacts with TRIM63. Interacts with STK4/MST1.3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • actin filament binding Source: CAFA
  • calcium-dependent protein binding Source: UniProtKB
  • protein domain specific binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • troponin C binding Source: UniProtKB
  • troponin T binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112991, 16 interactors
ComplexPortaliCPX-3280 Cardiac Troponin complex
DIPiDIP-34065N
IntActiP19429, 19 interactors
MINTiP19429
STRINGi9606.ENSP00000341838

Structurei

Secondary structure

1210
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi43 – 79Combined sources37
Helixi85 – 87Combined sources3
Helixi90 – 136Combined sources47
Turni144 – 146Combined sources3
Helixi151 – 159Combined sources9
Helixi160 – 162Combined sources3
Helixi163 – 188Combined sources26

3D structure databases

DisProtiDP00166
ProteinModelPortaliP19429
SMRiP19429
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP19429

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni32 – 79Involved in binding TNCAdd BLAST48
Regioni129 – 149Involved in binding TNC and actinAdd BLAST21

Sequence similaritiesi

Belongs to the troponin I family.Curated

Phylogenomic databases

eggNOGiKOG3977 Eukaryota
ENOG410Y9IX LUCA
GeneTreeiENSGT00390000002746
HOGENOMiHOG000293300
HOVERGENiHBG052737
InParanoidiP19429
KOiK12044
OMAiKMFDTGG
OrthoDBiEOG091G0NOD
PhylomeDBiP19429
TreeFamiTF313374

Family and domain databases

Gene3Di1.20.5.350, 1 hit
InterProiView protein in InterPro
IPR001978 Troponin
IPR021666 Troponin-I_N
IPR038077 Troponin_sf
PfamiView protein in Pfam
PF00992 Troponin, 1 hit
PF11636 Troponin-I_N, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P19429-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADGSSDAAR EPRPAPAPIR RRSSNYRAYA TEPHAKKKSK ISASRKLQLK
60 70 80 90 100
TLLLQIAKQE LEREAEERRG EKGRALSTRC QPLELAGLGF AELQDLCRQL
110 120 130 140 150
HARVDKVDEE RYDIEAKVTK NITEIADLTQ KIFDLRGKFK RPTLRRVRIS
160 170 180 190 200
ADAMMQALLG ARAKESLDLR AHLKQVKKED TEKENREVGD WRKNIDALSG
210
MEGRKKKFES
Length:210
Mass (Da):24,008
Last modified:January 23, 2007 - v3
Checksum:i20A804F8C24AE1B0
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0439892A → V in CMD2A. 1 PublicationCorresponds to variant dbSNP:rs397516359EnsemblClinVar.1
Natural variantiVAR_06354836K → Q in CMD1FF. 1 PublicationCorresponds to variant dbSNP:rs267607130EnsemblClinVar.1
Natural variantiVAR_02945379R → C. Corresponds to variant dbSNP:rs3729712EnsemblClinVar.1
Natural variantiVAR_01607882P → S Polymorphism; risk factor for CMH7. 1 PublicationCorresponds to variant dbSNP:rs77615401EnsemblClinVar.1
Natural variantiVAR_067264116A → G in CMD1FF. 1 PublicationCorresponds to variant dbSNP:rs777177571Ensembl.1
Natural variantiVAR_019872141R → Q in CMH7. 1 PublicationCorresponds to variant dbSNP:rs397516347EnsemblClinVar.1
Natural variantiVAR_016079144L → Q in RCM1. 1 PublicationCorresponds to variant dbSNP:rs121917760EnsemblClinVar.1
Natural variantiVAR_007603145R → G in CMH7. 1 PublicationCorresponds to variant dbSNP:rs104894724EnsemblClinVar.1
Natural variantiVAR_016080145R → W in RCM1. 1 PublicationCorresponds to variant dbSNP:rs104894724EnsemblClinVar.1
Natural variantiVAR_019873157A → V in CMH7. 1 PublicationCorresponds to variant dbSNP:rs397516353EnsemblClinVar.1
Natural variantiVAR_019874162R → P in CMH7. 2 PublicationsCorresponds to variant dbSNP:rs397516354EnsemblClinVar.1
Natural variantiVAR_042745162R → Q in CMH7. 1 PublicationCorresponds to variant dbSNP:rs397516354EnsemblClinVar.1
Natural variantiVAR_029454166S → F in CMH7. 1 PublicationCorresponds to variant dbSNP:rs727504242EnsemblClinVar.1
Natural variantiVAR_016081171A → T in RCM1. 1 PublicationCorresponds to variant dbSNP:rs121917761EnsemblClinVar.1
Natural variantiVAR_019875177Missing in CMH7. 1 Publication1
Natural variantiVAR_016082178K → E in RCM1. 1 PublicationCorresponds to variant dbSNP:rs104894730EnsemblClinVar.1
Natural variantiVAR_063549185N → K in CMD1FF. 1 PublicationCorresponds to variant dbSNP:rs267607129EnsemblClinVar.1
Natural variantiVAR_019876186R → Q in CMH7. 1 PublicationCorresponds to variant dbSNP:rs397516357EnsemblClinVar.1
Natural variantiVAR_016083190D → H in CMH7 and RCM1. 1 Publication1
Natural variantiVAR_016084192R → H in RCM1. 1 PublicationCorresponds to variant dbSNP:rs104894729EnsemblClinVar.1
Natural variantiVAR_016085196D → N in CMH7. 2 PublicationsCorresponds to variant dbSNP:rs104894727EnsemblClinVar.1
Natural variantiVAR_042746204R → H in CMH7. 1 PublicationCorresponds to variant dbSNP:rs727504275EnsemblClinVar.1
Natural variantiVAR_007604206K → Q in CMH7. 1 PublicationCorresponds to variant dbSNP:rs104894725EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54163 mRNA Translation: CAA38102.1
M64247 mRNA Translation: AAA16157.1
X90780 Genomic DNA Translation: CAA62301.1
CCDSiCCDS42628.1
PIRiA61229 TPHUIC
RefSeqiNP_000354.4, NM_000363.4
UniGeneiHs.709179

Genome annotation databases

EnsembliENST00000344887; ENSP00000341838; ENSG00000129991
GeneIDi7137
KEGGihsa:7137

Similar proteinsi

Entry informationi

Entry nameiTNNI3_HUMAN
AccessioniPrimary (citable) accession number: P19429
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 185 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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