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Protein

Troponin I, cardiac muscle

Gene

TNNI3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • 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 conduction Source: Reactome
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Muscle protein

Keywords - Ligandi

Actin-binding, Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000129991-MONOMER.
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

HGNCiHGNC:11947. TNNI3.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • sarcomere Source: BHF-UCL
  • troponin complex Source: UniProtKB
Complete GO annotation...

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_01607882P → S in CMH7. 1 PublicationCorresponds to variant rs77615401dbSNPEnsembl.1
Natural variantiVAR_019872141R → Q in CMH7. 1 PublicationCorresponds to variant rs397516347dbSNPEnsembl.1
Natural variantiVAR_007603145R → G in CMH7. 1 PublicationCorresponds to variant rs104894724dbSNPEnsembl.1
Natural variantiVAR_019873157A → V in CMH7. 1 PublicationCorresponds to variant rs397516353dbSNPEnsembl.1
Natural variantiVAR_019874162R → P in CMH7. 2 PublicationsCorresponds to variant rs397516354dbSNPEnsembl.1
Natural variantiVAR_042745162R → Q in CMH7. 1 PublicationCorresponds to variant rs397516354dbSNPEnsembl.1
Natural variantiVAR_029454166S → F in CMH7. 1 PublicationCorresponds to variant rs727504242dbSNPEnsembl.1
Natural variantiVAR_019875177Missing in CMH7. 1 Publication1
Natural variantiVAR_019876186R → Q in CMH7. 1 PublicationCorresponds to variant rs397516357dbSNPEnsembl.1
Natural variantiVAR_016083190D → H in CMH7 and RCM1. 1 Publication1
Natural variantiVAR_016085196D → N in CMH7. 2 PublicationsCorresponds to variant rs104894727dbSNPEnsembl.1
Natural variantiVAR_042746204R → H in CMH7. 1 PublicationCorresponds to variant rs727504275dbSNPEnsembl.1
Natural variantiVAR_007604206K → Q in CMH7. 1 PublicationCorresponds to variant rs104894725dbSNPEnsembl.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 rs121917760dbSNPEnsembl.1
Natural variantiVAR_016080145R → W in RCM1. 1 PublicationCorresponds to variant rs28934871dbSNPEnsembl.1
Natural variantiVAR_016081171A → T in RCM1. 1 PublicationCorresponds to variant rs121917761dbSNPEnsembl.1
Natural variantiVAR_016082178K → E in RCM1. 1 PublicationCorresponds to variant rs28934870dbSNPEnsembl.1
Natural variantiVAR_016083190D → H in CMH7 and RCM1. 1 Publication1
Natural variantiVAR_016084192R → H in RCM1. 1 PublicationCorresponds to variant rs104894729dbSNPEnsembl.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 rs397516359dbSNPEnsembl.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 rs267607130dbSNPEnsembl.1
Natural variantiVAR_067264116A → G in CMD1FF. 1 PublicationCorresponds to variant rs777177571dbSNPEnsembl.1
Natural variantiVAR_063549185N → K in CMD1FF. 1 PublicationCorresponds to variant rs267607129dbSNPEnsembl.1

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi7137.
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.

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.

PTM databases

iPTMnetiP19429.
PhosphoSitePlusiP19429.

Expressioni

Gene expression databases

BgeeiENSG00000129991.
CleanExiHS_TNNC1.
HS_TNNI3.
ExpressionAtlasiP19429. baseline and differential.
GenevisibleiP19429. HS.

Organism-specific databases

HPAiCAB009349.
HPA046428.
HPA063258.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
PDE4DIPQ5VU43-114EBI-704146,EBI-10769071
RCAN3Q9UKA8-13EBI-704146,EBI-10762111
RCAN3Q9UKA8-42EBI-704146,EBI-10762136
TNNI3KQ59H182EBI-704146,EBI-704142
TNNI3KQ59H18-22EBI-704146,EBI-10762055

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • 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. 15 interactors.
DIPiDIP-34065N.
IntActiP19429. 16 interactors.
MINTiMINT-2801556.
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
Helixi151 – 159Combined sources9
Helixi160 – 162Combined sources3
Helixi163 – 188Combined sources26

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J1DX-ray2.61C/F31-163[»]
1J1EX-ray3.30C/F31-210[»]
1LXFNMR-I148-164[»]
1MXLNMR-I148-164[»]
1OZSNMR-B129-148[»]
2KGBNMR-I145-164[»]
2KRDNMR-I148-164[»]
2L1RNMR-B145-164[»]
2MZPNMR-I145-171[»]
2N7LNMR-C145-174[»]
4Y99X-ray2.00C1-210[»]
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.
OMAiCRQLHTR.
OrthoDBiEOG091G0NOD.
PhylomeDBiP19429.
TreeFamiTF313374.

Family and domain databases

InterProiIPR001978. Troponin.
IPR021666. Troponin-I_N.
[Graphical view]
PfamiPF00992. Troponin. 1 hit.
PF11636. Troponin-I_N. 1 hit.
[Graphical view]

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 rs397516359dbSNPEnsembl.1
Natural variantiVAR_06354836K → Q in CMD1FF. 1 PublicationCorresponds to variant rs267607130dbSNPEnsembl.1
Natural variantiVAR_02945379R → C.Corresponds to variant rs3729712dbSNPEnsembl.1
Natural variantiVAR_01607882P → S in CMH7. 1 PublicationCorresponds to variant rs77615401dbSNPEnsembl.1
Natural variantiVAR_067264116A → G in CMD1FF. 1 PublicationCorresponds to variant rs777177571dbSNPEnsembl.1
Natural variantiVAR_019872141R → Q in CMH7. 1 PublicationCorresponds to variant rs397516347dbSNPEnsembl.1
Natural variantiVAR_016079144L → Q in RCM1. 1 PublicationCorresponds to variant rs121917760dbSNPEnsembl.1
Natural variantiVAR_007603145R → G in CMH7. 1 PublicationCorresponds to variant rs104894724dbSNPEnsembl.1
Natural variantiVAR_016080145R → W in RCM1. 1 PublicationCorresponds to variant rs28934871dbSNPEnsembl.1
Natural variantiVAR_019873157A → V in CMH7. 1 PublicationCorresponds to variant rs397516353dbSNPEnsembl.1
Natural variantiVAR_019874162R → P in CMH7. 2 PublicationsCorresponds to variant rs397516354dbSNPEnsembl.1
Natural variantiVAR_042745162R → Q in CMH7. 1 PublicationCorresponds to variant rs397516354dbSNPEnsembl.1
Natural variantiVAR_029454166S → F in CMH7. 1 PublicationCorresponds to variant rs727504242dbSNPEnsembl.1
Natural variantiVAR_016081171A → T in RCM1. 1 PublicationCorresponds to variant rs121917761dbSNPEnsembl.1
Natural variantiVAR_019875177Missing in CMH7. 1 Publication1
Natural variantiVAR_016082178K → E in RCM1. 1 PublicationCorresponds to variant rs28934870dbSNPEnsembl.1
Natural variantiVAR_063549185N → K in CMD1FF. 1 PublicationCorresponds to variant rs267607129dbSNPEnsembl.1
Natural variantiVAR_019876186R → Q in CMH7. 1 PublicationCorresponds to variant rs397516357dbSNPEnsembl.1
Natural variantiVAR_016083190D → H in CMH7 and RCM1. 1 Publication1
Natural variantiVAR_016084192R → H in RCM1. 1 PublicationCorresponds to variant rs104894729dbSNPEnsembl.1
Natural variantiVAR_016085196D → N in CMH7. 2 PublicationsCorresponds to variant rs104894727dbSNPEnsembl.1
Natural variantiVAR_042746204R → H in CMH7. 1 PublicationCorresponds to variant rs727504275dbSNPEnsembl.1
Natural variantiVAR_007604206K → Q in CMH7. 1 PublicationCorresponds to variant rs104894725dbSNPEnsembl.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.

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J1DX-ray2.61C/F31-163[»]
1J1EX-ray3.30C/F31-210[»]
1LXFNMR-I148-164[»]
1MXLNMR-I148-164[»]
1OZSNMR-B129-148[»]
2KGBNMR-I145-164[»]
2KRDNMR-I148-164[»]
2L1RNMR-B145-164[»]
2MZPNMR-I145-171[»]
2N7LNMR-C145-174[»]
4Y99X-ray2.00C1-210[»]
DisProtiDP00166.
ProteinModelPortaliP19429.
SMRiP19429.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112991. 15 interactors.
DIPiDIP-34065N.
IntActiP19429. 16 interactors.
MINTiMINT-2801556.
STRINGi9606.ENSP00000341838.

Chemistry databases

ChEMBLiCHEMBL2095202.

PTM databases

iPTMnetiP19429.
PhosphoSitePlusiP19429.

Polymorphism and mutation databases

BioMutaiTNNI3.
DMDMi136213.

Proteomic databases

PaxDbiP19429.
PeptideAtlasiP19429.
PRIDEiP19429.

Protocols and materials databases

DNASUi7137.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344887; ENSP00000341838; ENSG00000129991.
GeneIDi7137.
KEGGihsa:7137.

Organism-specific databases

CTDi7137.
DisGeNETi7137.
GeneCardsiTNNI3.
GeneReviewsiTNNI3.
HGNCiHGNC:11947. TNNI3.
HPAiCAB009349.
HPA046428.
HPA063258.
MalaCardsiTNNI3.
MIMi115210. phenotype.
191044. gene.
611880. phenotype.
613286. phenotype.
613690. phenotype.
neXtProtiNX_P19429.
OpenTargetsiENSG00000129991.
Orphaneti154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
75249. Familial isolated restrictive cardiomyopathy.
PharmGKBiPA36636.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000129991-MONOMER.
ReactomeiR-HSA-390522. Striated Muscle Contraction.
R-HSA-5578775. Ion homeostasis.
SIGNORiP19429.

Miscellaneous databases

ChiTaRSiTNNI3. human.
EvolutionaryTraceiP19429.
GeneWikiiTNNI3.
GenomeRNAii7137.
PROiP19429.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129991.
CleanExiHS_TNNC1.
HS_TNNI3.
ExpressionAtlasiP19429. baseline and differential.
GenevisibleiP19429. HS.

Family and domain databases

InterProiIPR001978. Troponin.
IPR021666. Troponin-I_N.
[Graphical view]
PfamiPF00992. Troponin. 1 hit.
PF11636. Troponin-I_N. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTNNI3_HUMAN
AccessioniPrimary (citable) accession number: P19429
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 171 of the entry and version 3 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.