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Protein

Serine/threonine-protein kinase TNNI3K

Gene

TNNI3K

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

Functioni

May play a role in cardiac physiology.1 Publication

Caution

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei490ATP1
Active sitei588Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi469 – 477ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • protein C-terminus binding Source: UniProtKB
  • protein kinase activity Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB-KW
  • signal transducer activity Source: GO_Central
  • troponin I binding Source: UniProtKB

GO - Biological processi

  • bundle of His cell to Purkinje myocyte communication Source: BHF-UCL
  • intracellular signal transduction Source: GO_Central
  • protein phosphorylation Source: UniProtKB
  • regulation of cardiac conduction Source: BHF-UCL
  • regulation of cardiac muscle contraction Source: BHF-UCL
  • regulation of heart rate Source: BHF-UCL

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase TNNI3K (EC:2.7.11.1)
Alternative name(s):
Cardiac ankyrin repeat kinase
Cardiac troponin I-interacting kinase
TNNI3-interacting kinase
Gene namesi
Name:TNNI3KImported
Synonyms:CARK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000116783.14
HGNCiHGNC:19661 TNNI3K
MIMi613932 gene
neXtProtiNX_Q59H18

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Cardiac conduction disease with or without dilated cardiomyopathy (CCDD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA cardiac disorder characterized by atrial tachyarrhythmia and conduction system disease. Some patients have dilated cardiomyopathy.
See also OMIM:616117
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072650526G → D in CCDD; the mutation results in decreased protein solubility; causes abnormal aggregation; markedly reduced protein expression is observed in the sarcoplasm and nuclei of patient cardiomyocytes. 1 PublicationCorresponds to variant dbSNP:rs606231469Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi490K → R: Loss of autophosphorylation activity. 1 Publication1

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi51086
MalaCardsiTNNI3K
MIMi616117 phenotype
OpenTargetsiENSG00000116783
ENSG00000259030
PharmGKBiPA134976654

Chemistry databases

ChEMBLiCHEMBL5260
GuidetoPHARMACOLOGYi2247

Polymorphism and mutation databases

BioMutaiTNNI3K
DMDMi300669705

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000867571 – 835Serine/threonine-protein kinase TNNI3KAdd BLAST835

Post-translational modificationi

Autophosphorylated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ59H18
PeptideAtlasiQ59H18
PRIDEiQ59H18

PTM databases

iPTMnetiQ59H18
PhosphoSitePlusiQ59H18

Expressioni

Tissue specificityi

Highly expressed in both adult and fetal heart.1 Publication

Gene expression databases

BgeeiENSG00000116783
CleanExiHS_TNNI3K
ExpressionAtlasiQ59H18 baseline and differential
GenevisibleiQ59H18 HS

Organism-specific databases

HPAiHPA072331

Interactioni

Subunit structurei

Interacts with TNNI3, ACTC, ACTA1, MYBPC3, AIP, BABP3 and HADHB.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
TNNI3P194292EBI-10762055,EBI-704146

GO - Molecular functioni

  • protein C-terminus binding Source: UniProtKB
  • troponin I binding Source: UniProtKB

Protein-protein interaction databases

BioGridi11927611 interactors.
IntActiQ59H18 8 interactors.
STRINGi9606.ENSP00000450895

Chemistry databases

BindingDBiQ59H18

Structurei

Secondary structure

1835
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi442 – 451Combined sources10
Helixi454 – 456Combined sources3
Helixi460 – 462Combined sources3
Beta strandi463 – 470Combined sources8
Beta strandi473 – 482Combined sources10
Beta strandi485 – 492Combined sources8
Helixi502 – 515Combined sources14
Beta strandi524 – 528Combined sources5
Helixi532 – 534Combined sources3
Beta strandi536 – 540Combined sources5
Helixi547 – 552Combined sources6
Helixi560 – 578Combined sources19
Beta strandi580 – 582Combined sources3
Helixi591 – 593Combined sources3
Beta strandi594 – 596Combined sources3
Beta strandi602 – 604Combined sources3
Helixi628 – 630Combined sources3
Helixi633 – 636Combined sources4
Helixi637 – 639Combined sources3
Helixi645 – 660Combined sources16
Turni664 – 667Combined sources4
Helixi670 – 678Combined sources9
Helixi692 – 701Combined sources10
Helixi706 – 708Combined sources3
Helixi712 – 725Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4YFFX-ray3.07A/B/C/D420-730[»]
4YFIX-ray2.70A/B/C/D402-730[»]
ProteinModelPortaliQ59H18
SMRiQ59H18
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati66 – 96ANK 1Add BLAST31
Repeati100 – 129ANK 2Add BLAST30
Repeati133 – 162ANK 3Add BLAST30
Repeati166 – 195ANK 4Add BLAST30
Repeati199 – 228ANK 5Add BLAST30
Repeati234 – 263ANK 6Add BLAST30
Repeati269 – 298ANK 7Add BLAST30
Repeati304 – 335ANK 8Add BLAST32
Repeati339 – 368ANK 9Add BLAST30
Repeati381 – 410ANK 10Add BLAST30
Domaini463 – 723Protein kinasePROSITE-ProRule annotationAdd BLAST261

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili21 – 51Sequence analysisAdd BLAST31

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi733 – 746Poly-SerAdd BLAST14

Sequence similaritiesi

Keywords - Domaini

ANK repeat, Coiled coil, Repeat

Phylogenomic databases

eggNOGiENOG410IT5N Eukaryota
COG0666 LUCA
GeneTreeiENSGT00900000140790
HOGENOMiHOG000234421
HOVERGENiHBG079513
InParanoidiQ59H18
KOiK17535
OrthoDBiEOG091G01QL
PhylomeDBiQ59H18

Family and domain databases

CDDicd00204 ANK, 5 hits
Gene3Di1.25.40.204 hits
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF12796 Ank_2, 3 hits
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR01415 ANKYRIN
SMARTiView protein in SMART
SM00248 ANK, 10 hits
SUPFAMiSSF48403 SSF48403, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 6 hits
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 21 Publication (identifier: Q59H18-2) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGNYKSRPTQ TCTDEWKKKV SESYVITIER LEDDLQIKEK ELTELRNIFG
60 70 80 90 100
SDEAFSKVNL NYRTENGLSL LHLCCICGGK KSHIRTLMLK GLRPSRLTRN
110 120 130 140 150
GFTALHLAVY KDNAELITSL LHSGADIQQV GYGGLTALHI ATIAGHLEAA
160 170 180 190 200
DVLLQHGANV NIQDAVFFTP LHIAAYYGHE QVTRLLLKFG ADVNVSGEVG
210 220 230 240 250
DRPLHLASAK GFLNIAKLLM EEGSKADVNA QDNEDHVPLH FCSRFGHHDI
260 270 280 290 300
VKYLLQSDLE VQPHVVNIYG DTPLHLACYN GKFEVAKEII QISGTESLTK
310 320 330 340 350
ENIFSETAFH SACTYGKSID LVKFLLDQNV ININHQGRDG HTGLHSACYH
360 370 380 390 400
GHIRLVQFLL DNGADMNLVA CDPSRSSGEK DEQTCLMWAY EKGHDAIVTL
410 420 430 440 450
LKHYKRPQDE LPCNEYSQPG GDGSYVSVPS PLGKIKSMTK EKADILLLRA
460 470 480 490 500
GLPSHFHLQL SEIEFHEIIG SGSFGKVYKG RCRNKIVAIK RYRANTYCSK
510 520 530 540 550
SDVDMFCREV SILCQLNHPC VIQFVGACLN DPSQFAIVTQ YISGGSLFSL
560 570 580 590 600
LHEQKRILDL QSKLIIAVDV AKGMEYLHNL TQPIIHRDLN SHNILLYEDG
610 620 630 640 650
HAVVADFGES RFLQSLDEDN MTKQPGNLRW MAPEVFTQCT RYTIKADVFS
660 670 680 690 700
YALCLWEILT GEIPFAHLKP AAAAADMAYH HIRPPIGYSI PKPISSLLIR
710 720 730 740 750
GWNACPEGRP EFSEVVMKLE ECLCNIELMS PASSNSSGSL SPSSSSDCLV
760 770 780 790 800
NRGGPGRSHV AALRSRFELE YALNARSYAA LSQSAGQYSS QGLSLEEMKR
810 820 830
SLQYTPIDKY GYVSDPMSSM HFHSCRNSSS FEDSS
Length:835
Mass (Da):92,851
Last modified:July 13, 2010 - v3
Checksum:i3B21484B434F46E8
GO
Isoform 1Curated (identifier: Q59H18-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: MGNYKSRPTQTCT → MAAARDPPEV...NSFTILLIHS

Note: Based on a naturally occurring readthrough transcript which produces a FPGT-TNNI3K fusion protein.
Show »
Length:936
Mass (Da):104,179
Checksum:i081220549646863F
GO
Isoform 3Curated (identifier: Q59H18-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: MGNYKSRPTQTCT → MAAARDPPEV...NSFTILLIHS
     591-596: SHNILL → RYFFPK
     597-835: Missing.

Note: Based on a naturally occurring readthrough transcript which produces a FPGT-TNNI3K fusion protein.
Show »
Length:697
Mass (Da):77,957
Checksum:i7567E27D45485C9C
GO
Isoform 4Curated (identifier: Q59H18-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: MGNYKSRPTQTCT → MAAARDPPEV...NSFTILLIHS
     708-742: GRPEFSEVVMKLEECLCNIELMSPASSNSSGSLSP → AKSRPSHYPVSSVYTETLKKKNEDRFGMWIEYLRR
     743-835: Missing.

Note: Based on a naturally occurring readthrough transcript which produces a FPGT-TNNI3K fusion protein.
Show »
Length:843
Mass (Da):94,517
Checksum:i3001399FAEAD7B24
GO

Sequence cautioni

The sequence BAD92178 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAE45949 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti127I → V in AAH32865 (PubMed:15489334).Curated1
Sequence conflicti250I → M in CAE45949 (PubMed:17974005).Curated1
Sequence conflicti367N → S in CAE45949 (PubMed:17974005).Curated1
Sequence conflicti629R → L in AAH32865 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041223151D → H1 PublicationCorresponds to variant dbSNP:rs34874695Ensembl.1
Natural variantiVAR_041224263P → L1 PublicationCorresponds to variant dbSNP:rs34521608Ensembl.1
Natural variantiVAR_041225309F → L1 Publication1
Natural variantiVAR_041226430S → L in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041227510V → L1 PublicationCorresponds to variant dbSNP:rs34335537Ensembl.1
Natural variantiVAR_072650526G → D in CCDD; the mutation results in decreased protein solubility; causes abnormal aggregation; markedly reduced protein expression is observed in the sarcoplasm and nuclei of patient cardiomyocytes. 1 PublicationCorresponds to variant dbSNP:rs606231469Ensembl.1
Natural variantiVAR_035639629R → G in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_041228637T → M1 PublicationCorresponds to variant dbSNP:rs2274260Ensembl.1
Natural variantiVAR_041229686I → T1 PublicationCorresponds to variant dbSNP:rs3737564Ensembl.1
Natural variantiVAR_038821785A → G1 PublicationCorresponds to variant dbSNP:rs45578635Ensembl.1
Natural variantiVAR_041230798M → I in a head & Neck squamous cell carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs201613442Ensembl.1
Natural variantiVAR_038822833D → Y1 PublicationCorresponds to variant dbSNP:rs45614933Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0394031 – 13MGNYK…TQTCT → MAAARDPPEVSLREATQRKL RRFSELRGKLVARGEFWDIV AITAADEKQELAYNQQLSEK LKRKELPLGVQYHVFVDPAG AKIGNGGSTLCALQCLEKLY GDKWNSFTILLIHS in isoform 1, isoform 3 and isoform 4. 3 PublicationsAdd BLAST13
Alternative sequenceiVSP_051882591 – 596SHNILL → RYFFPK in isoform 3. 1 Publication6
Alternative sequenceiVSP_051883597 – 835Missing in isoform 3. 1 PublicationAdd BLAST239
Alternative sequenceiVSP_051884708 – 742GRPEF…GSLSP → AKSRPSHYPVSSVYTETLKK KNEDRFGMWIEYLRR in isoform 4. 1 PublicationAdd BLAST35
Alternative sequenceiVSP_051885743 – 835Missing in isoform 4. 1 PublicationAdd BLAST93

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF116826 mRNA Translation: AAD29632.1
AY303691 mRNA Translation: AAP72030.1
AB208941 Transcribed RNA Translation: BAD92178.1 Different initiation.
BX640903 mRNA Translation: CAE45949.1 Different initiation.
DQ822519 Genomic DNA Translation: ABG46944.1
BX470253
, AC093158, AC098692, AC105271, AC119672 Genomic DNA Translation: CAI16293.1
CH471059 Genomic DNA Translation: EAX06415.1
BC032865 mRNA Translation: AAH32865.1
BC113539 mRNA Translation: AAI13540.1
BC117262 mRNA Translation: AAI17263.1
CCDSiCCDS664.1 [Q59H18-2]
RefSeqiNP_001186256.2, NM_001199327.1
NP_057062.1, NM_015978.2 [Q59H18-2]
UniGeneiHs.480085

Genome annotation databases

EnsembliENST00000326637; ENSP00000322251; ENSG00000116783 [Q59H18-2]
GeneIDi100526835
51086
KEGGihsa:100526835
hsa:51086
UCSCiuc001dgf.3 human [Q59H18-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTNI3K_HUMAN
AccessioniPrimary (citable) accession number: Q59H18
Secondary accession number(s): Q17RN0
, Q49AR1, Q6MZS9, Q9Y2V6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: July 13, 2010
Last modified: March 28, 2018
This is version 147 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, Reference proteome