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P19429 (TNNI3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Troponin I, cardiac muscle
Alternative name(s):
Cardiac troponin I
Gene names
Name:TNNI3
Synonyms:TNNC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length210 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

Binds to actin and tropomyosin. Interacts with TRIM63. Interacts with STK4/MST1. Ref.9 Ref.10

Post-translational modification

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). Ref.5 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11

Involvement in disease

Cardiomyopathy, familial hypertrophic 7 (CMH7) [MIM:613690]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.15 Ref.17 Ref.19 Ref.21

Cardiomyopathy, familial restrictive 1 (RCM1) [MIM:115210]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16

Cardiomyopathy, dilated 2A (CMD2A) [MIM:611880]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20

Cardiomyopathy, dilated 1FF (CMD1FF) [MIM:613286]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.22 Ref.23

Sequence similarities

Belongs to the troponin I family.

Ontologies

Keywords
   DiseaseCardiomyopathy
Disease mutation
   LigandActin-binding
Calcium
Metal-binding
   Molecular functionMuscle protein
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcardiac muscle contraction

Inferred from mutant phenotype PubMed 11735257. Source: UniProtKB

cellular calcium ion homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

heart contraction

Inferred from mutant phenotype Ref.16. Source: UniProtKB

heart development

Inferred from sequence or structural similarity. Source: UniProtKB

muscle filament sliding

Traceable author statement. Source: Reactome

negative regulation of ATPase activity

Inferred from direct assay PubMed 11735257PubMed 7957210. Source: UniProtKB

regulation of smooth muscle contraction

Inferred from electronic annotation. Source: Ensembl

regulation of systemic arterial blood pressure by ischemic conditions

Inferred from sequence or structural similarity. Source: UniProtKB

vasculogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

ventricular cardiac muscle tissue morphogenesis

Inferred from mutant phenotype PubMed 16754800. Source: BHF-UCL

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

sarcomere

Traceable author statement PubMed 16754800. Source: BHF-UCL

troponin complex

Inferred from direct assay PubMed 10806205PubMed 10850966PubMed 12093807PubMed 7957210. Source: UniProtKB

   Molecular_functionactin binding

Inferred from direct assay PubMed 10806205. Source: UniProtKB

calcium channel inhibitor activity

Inferred from physical interaction PubMed 12809519. Source: UniProtKB

calcium-dependent protein binding

Inferred from physical interaction PubMed 7957210. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein domain specific binding

Inferred from physical interaction PubMed 11984006. Source: UniProtKB

protein kinase binding

Inferred from physical interaction PubMed 12721663. Source: UniProtKB

troponin C binding

Inferred from physical interaction PubMed 11735257PubMed 15542288PubMed 7957210. Source: UniProtKB

troponin T binding

Inferred from physical interaction PubMed 15542288. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TNNI3KQ59H182EBI-704146,EBI-704142

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 210209Troponin I, cardiac muscle
PRO_0000186151

Regions

Calcium binding137 – 14812 By similarity
Region32 – 7948Involved in binding TNC
Region129 – 14921Involved in binding TNC and actin

Sites

Site801Involved in TNI-TNT interactions
Site971Involved in TNI-TNT interactions

Amino acid modifications

Modified residue21N-acetylalanine Ref.5
Modified residue51Phosphoserine Ref.11
Modified residue61Phosphoserine Ref.11
Modified residue231Phosphoserine; by PKA and PKD/PRKD1 Ref.5 Ref.6 Ref.8 Ref.11
Modified residue241Phosphoserine; by PKA and PKD/PRKD1 Ref.5 Ref.6 Ref.8 Ref.11
Modified residue261Phosphotyrosine Ref.11
Modified residue311Phosphothreonine; by STK4/MST1 Ref.10
Modified residue421Phosphoserine; by PKC/PRKCE By similarity
Modified residue441Phosphoserine; by PKC/PRKCE By similarity
Modified residue511Phosphothreonine; by STK4/MST1 Ref.10 Ref.11
Modified residue771Phosphoserine Ref.11
Modified residue781Phosphothreonine Ref.11
Modified residue1291Phosphothreonine; by STK4/MST1 Ref.10
Modified residue1431Phosphothreonine; by STK4/MST1 Ref.10 Ref.11
Modified residue1501Phosphoserine; by PAK3 Ref.7
Modified residue1661Phosphoserine Ref.11
Modified residue1811Phosphothreonine Ref.11
Modified residue1991Phosphoserine Ref.11

Natural variations

Natural variant21A → V in CMD2A. Ref.20
VAR_043989
Natural variant361K → Q in CMD1FF. Ref.22
VAR_063548
Natural variant791R → C.
Corresponds to variant rs3729712 [ dbSNP | Ensembl ].
VAR_029453
Natural variant821P → S in CMH7. Ref.15
Corresponds to variant rs77615401 [ dbSNP | Ensembl ].
VAR_016078
Natural variant1161A → G in CMD1FF. Ref.23
VAR_067264
Natural variant1411R → Q in CMH7. Ref.17
VAR_019872
Natural variant1441L → Q in RCM1. Ref.16
VAR_016079
Natural variant1451R → G in CMH7. Ref.14
VAR_007603
Natural variant1451R → W in RCM1. Ref.16
Corresponds to variant rs28934871 [ dbSNP | Ensembl ].
VAR_016080
Natural variant1571A → V in CMH7. Ref.17
VAR_019873
Natural variant1621R → P in CMH7. Ref.17 Ref.21
VAR_019874
Natural variant1621R → Q in CMH7. Ref.21
VAR_042745
Natural variant1661S → F in CMH7. Ref.19
VAR_029454
Natural variant1711A → T in RCM1. Ref.16
VAR_016081
Natural variant1771Missing in CMH7. Ref.17
VAR_019875
Natural variant1781K → E in RCM1. Ref.16
Corresponds to variant rs28934870 [ dbSNP | Ensembl ].
VAR_016082
Natural variant1851N → K in CMD1FF. Ref.22
VAR_063549
Natural variant1861R → Q in CMH7. Ref.17
VAR_019876
Natural variant1901D → H in CMH7 and RCM1. Ref.16
VAR_016083
Natural variant1921R → H in RCM1. Ref.16
VAR_016084
Natural variant1961D → N in CMH7. Ref.15 Ref.17
VAR_016085
Natural variant2041R → H in CMH7. Ref.21
VAR_042746
Natural variant2061K → Q in CMH7. Ref.14
VAR_007604

Secondary structure

.......... 210
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P19429 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 20A804F8C24AE1B0

FASTA21024,008
        10         20         30         40         50         60 
MADGSSDAAR EPRPAPAPIR RRSSNYRAYA TEPHAKKKSK ISASRKLQLK TLLLQIAKQE 

        70         80         90        100        110        120 
LEREAEERRG EKGRALSTRC QPLELAGLGF AELQDLCRQL HARVDKVDEE RYDIEAKVTK 

       130        140        150        160        170        180 
NITEIADLTQ KIFDLRGKFK RPTLRRVRIS ADAMMQALLG ARAKESLDLR AHLKQVKKED 

       190        200        210 
TEKENREVGD WRKNIDALSG MEGRKKKFES 

« Hide

References

[1]"Molecular cloning of human cardiac troponin I using polymerase chain reaction."
Vallins W.J., Brand N.J., Dabhade N., Butler-Browne G., Yacoub M.H., Barton P.J.R.
FEBS Lett. 270:57-61(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart muscle.
[2]"Cloning and expression in Escherichia coli of the cDNA encoding human cardiac troponin I."
Armour K.L., Harris W.J., Tempest P.R.
Gene 131:287-292(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION TO 85, NUCLEOTIDE SEQUENCE [MRNA].
[3]"Troponin I isoform expression in human heart."
Hunkeler N.M., Kullman J., Murphy A.M.
Circ. Res. 69:1409-1414(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Isolation and characterization of the human cardiac troponin I gene (TNNI3)."
Bhavsar P.K., Brand N.J., Yacoub M.H., Barton P.J.R.
Genomics 35:11-23(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"A common motif of two adjacent phosphoserines in bovine, rabbit and human cardiac troponin I."
Mittmann K., Jaquet K., Heilmeyer L.M.G. Jr.
FEBS Lett. 273:41-45(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 11-36, ACETYLATION AT ALA-2, PHOSPHORYLATION AT SER-23 AND SER-24.
[6]"The ordered phosphorylation of cardiac troponin I by the cAMP-dependent protein kinase -- structural consequences and functional implications."
Keane N.E., Quirk P.G., Gao Y., Patchell V.B., Perry S.V., Levine B.A.
Eur. J. Biochem. 248:329-337(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-23 AND SER-24.
[7]"p21-activated kinase increases the calcium sensitivity of rat triton-skinned cardiac muscle fiber bundles via a mechanism potentially involving novel phosphorylation of troponin I."
Buscemi N., Foster D.B., Neverova I., Van Eyk J.E.
Circ. Res. 91:509-516(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-150 BY PAK3.
[8]"Protein kinase D is a novel mediator of cardiac troponin I phosphorylation and regulates myofilament function."
Haworth R.S., Cuello F., Herron T.J., Franzen G., Kentish J.C., Gautel M., Avkiran M.
Circ. Res. 95:1091-1099(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-23 AND SER-24.
[9]"Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I."
Kedar V., McDonough H., Arya R., Li H.-H., Rockman H.A., Patterson C.
Proc. Natl. Acad. Sci. U.S.A. 101:18135-18140(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRIM63.
[10]"Phosphorylation of cardiac troponin I by mammalian sterile 20-like kinase 1."
You B., Yan G., Zhang Z., Yan L., Li J., Ge Q., Jin J.P., Sun J.
Biochem. J. 418:93-101(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STK4/MST1, PHOSPHORYLATION AT THR-31; THR-51; THR-129 AND THR-143.
[11]"Multiple reaction monitoring to identify site-specific troponin I phosphorylated residues in the failing human heart."
Zhang P., Kirk J.A., Ji W., dos Remedios C.G., Kass D.A., Van Eyk J.E., Murphy A.M.
Circulation 126:1828-1837(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-5; SER-6; SER-23; SER-24; TYR-26; SER-42; SER-44; THR-51; SER-77; THR-78; THR-143; SER-166; THR-181 AND SER-199.
[12]"Binding of cardiac troponin-I147-163 induces a structural opening in human cardiac troponin-C."
Li M.X., Spyracopoulos L., Sykes B.D.
Biochemistry 38:8289-8298(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 148-164.
[13]"Structure of the regulatory N-domain of human cardiac troponin C in complex with human cardiac troponin I147-163 and bepridil."
Wang X., Li M.X., Sykes B.D.
J. Biol. Chem. 277:31124-31133(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 149-165 IN COMPLEX WITH CARDIAC TROPONIN C.
[14]"Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy."
Kimura A., Harada H., Park J.-E., Nishi H., Satoh M., Takahashi M., Hiroi S., Sasaoka T., Ohbuchi N., Nakamura T., Koyanagi T., Hwang T.-H., Choo J., Chung K.-S., Hasegawa A., Nagai R., Okazaki O., Nakamura H. expand/collapse author list , Matsuzaki M., Sakamoto T., Toshima H., Koga Y., Imaizumi T., Sasazuki T.
Nat. Genet. 16:379-382(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMH7 GLY-145 AND GLN-206.
[15]"Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly."
Niimura H., Patton K.K., McKenna W.J., Soults J., Maron B.J., Seidman J.G., Seidman C.E.
Circulation 105:446-451(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMH7 SER-82 AND ASN-196.
[16]"Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations."
Mogensen J., Kubo T., Duque M., Uribe W., Shaw A., Murphy R., Gimeno J.R., Elliott P., McKenna W.J.
J. Clin. Invest. 111:209-216(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS RCM1 GLN-144; TRP-145; THR-171; GLU-178; HIS-190 AND HIS-192.
[17]"Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy."
Richard P., Charron P., Carrier L., Ledeuil C., Cheav T., Pichereau C., Benaiche A., Isnard R., Dubourg O., Burban M., Gueffet J.-P., Millaire A., Desnos M., Schwartz K., Hainque B., Komajda M.
Circulation 107:2227-2232(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMH7 GLN-141; VAL-157; PRO-162; LYS-177 DEL; GLN-186 AND ASN-196.
[18]Erratum
Richard P., Charron P., Carrier L., Ledeuil C., Cheav T., Pichereau C., Benaiche A., Isnard R., Dubourg O., Burban M., Gueffet J.-P., Millaire A., Desnos M., Schwartz K., Hainque B., Komajda M.
Circulation 109:3258-3258(2004)
[19]"Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy."
Erdmann J., Daehmlow S., Wischke S., Senyuva M., Werner U., Raible J., Tanis N., Dyachenko S., Hummel M., Hetzer R., Regitz-Zagrosek V.
Clin. Genet. 64:339-349(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMH7 PHE-166.
[20]"Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy."
Murphy R.T., Mogensen J., Shaw A., Kubo T., Hughes S., McKenna W.J.
Lancet 363:371-372(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMD2A VAL-2.
[21]"Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling."
Ingles J., Doolan A., Chiu C., Seidman J., Seidman C., Semsarian C.
J. Med. Genet. 42:E59-E59(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMH7 PRO-162; GLN-162 AND HIS-204.
[22]"Identification and functional characterization of cardiac troponin I as a novel disease gene in autosomal dominant dilated cardiomyopathy."
Carballo S., Robinson P., Otway R., Fatkin D., Jongbloed J.D., de Jonge N., Blair E., van Tintelen J.P., Redwood C., Watkins H.
Circ. Res. 105:375-382(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMD1FF GLN-36 AND LYS-185.
[23]"Clinical and mutational spectrum in a cohort of 105 unrelated patients with dilated cardiomyopathy."
Millat G., Bouvagnet P., Chevalier P., Sebbag L., Dulac A., Dauphin C., Jouk P.S., Delrue M.A., Thambo J.B., Le Metayer P., Seronde M.F., Faivre L., Eicher J.C., Rousson R.
Eur. J. Med. Genet. 54:E570-E575(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMD1FF GLY-116.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X54163 mRNA. Translation: CAA38102.1.
M64247 mRNA. Translation: AAA16157.1.
X90780 Genomic DNA. Translation: CAA62301.1.
PIRTPHUIC. A61229.
RefSeqNP_000354.4. NM_000363.4.
UniGeneHs.709179.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1J1DX-ray2.61C/F32-162[»]
1J1EX-ray3.30C/F32-209[»]
1LXFNMR-I148-164[»]
1MXLNMR-I148-164[»]
1OZSNMR-B129-148[»]
2KGBNMR-I145-164[»]
2KRDNMR-I148-164[»]
2L1RNMR-B145-164[»]
DisProtDP00166.
ProteinModelPortalP19429.
SMRP19429. Positions 35-191.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112991. 7 interactions.
DIPDIP-34065N.
IntActP19429. 4 interactions.
MINTMINT-2801556.
STRING9606.ENSP00000341838.

Chemistry

ChEMBLCHEMBL2095202.

PTM databases

PhosphoSiteP19429.

Polymorphism databases

DMDM136213.

Proteomic databases

PaxDbP19429.
PRIDEP19429.

Protocols and materials databases

DNASU7137.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344887; ENSP00000341838; ENSG00000129991.
GeneID7137.
KEGGhsa:7137.
UCSCuc002qjg.4. human.

Organism-specific databases

CTD7137.
GeneCardsGC19M055663.
HGNCHGNC:11947. TNNI3.
HPAHPA046428.
MIM115210. phenotype.
191044. gene.
611880. phenotype.
613286. phenotype.
613690. phenotype.
neXtProtNX_P19429.
Orphanet154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
75249. Familial isolated restrictive cardiomyopathy.
PharmGKBPA36636.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG270363.
HOGENOMHOG000293300.
HOVERGENHBG052737.
InParanoidP19429.
KOK12044.
OMARMYTCEG.
OrthoDBEOG71G9WD.
PhylomeDBP19429.
TreeFamTF313374.

Enzyme and pathway databases

ReactomeREACT_17044. Muscle contraction.

Gene expression databases

ArrayExpressP19429.
BgeeP19429.
CleanExHS_TNNC1.
HS_TNNI3.
GenevestigatorP19429.

Family and domain databases

InterProIPR001978. Troponin.
IPR021666. Troponin-I_N.
[Graphical view]
PfamPF00992. Troponin. 1 hit.
PF11636. Troponin-I_N. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTNNI3. human.
EvolutionaryTraceP19429.
GeneWikiTNNI3.
GenomeRNAi7137.
NextBio27925.
PROP19429.
SOURCESearch...

Entry information

Entry nameTNNI3_HUMAN
AccessionPrimary (citable) accession number: P19429
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 145 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM