TNI3K_HUMAN
ID TNI3K_HUMAN Reviewed; 835 AA.
AC Q59H18; Q17RN0; Q49AR1; Q6MZS9; Q9Y2V6;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 3.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Serine/threonine-protein kinase TNNI3K;
DE EC=2.7.11.1;
DE AltName: Full=Cardiac ankyrin repeat kinase;
DE AltName: Full=Cardiac troponin I-interacting kinase;
DE AltName: Full=TNNI3-interacting kinase;
GN Name=TNNI3K {ECO:0000312|EMBL:AAH32865.1}; Synonyms=CARK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAD29632.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, INTERACTION WITH TNNI3; ACTC1;
RP ACTA1; MYBPC3; AIP; FABP3 AND HADHB, AND MUTAGENESIS OF LYS-490.
RC TISSUE=Heart {ECO:0000312|EMBL:AAD29632.1};
RX PubMed=12721663; DOI=10.1007/s00109-003-0427-x;
RA Zhao Y., Meng X.-M., Wei Y.-J., Zhao X.-W., Liu D.-Q., Cao H.-Q.,
RA Liew C.-C., Ding J.-F.;
RT "Cloning and characterization of a novel cardiac-specific kinase that
RT interacts specifically with cardiac troponin I.";
RL J. Mol. Med. 81:297-304(2003).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAP72030.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Jeyaseelan R.;
RT "Cardiac ankyrin repeat kinase (CARK).";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAP72030.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain {ECO:0000312|EMBL:BAD92178.1};
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Fetal kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAP72030.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-785 AND TYR-833.
RG SeattleSNPs variation discovery resource;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7] {ECO:0000305, ECO:0000312|EMBL:AAP72030.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8] {ECO:0000305, ECO:0000312|EMBL:AAH32865.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Brain {ECO:0000312|EMBL:AAH32865.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP VARIANT [LARGE SCALE ANALYSIS] GLY-629.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [10]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-151; LEU-263; LEU-309; LEU-430;
RP LEU-510; MET-637; THR-686 AND ILE-798.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [11]
RP INVOLVEMENT IN CCDD, VARIANT CCDD ASP-526, AND CHARACTERIZATION OF VARIANT
RP CCDD ASP-526.
RX PubMed=24925317; DOI=10.1093/hmg/ddu297;
RA Theis J.L., Zimmermann M.T., Larsen B.T., Rybakova I.N., Long P.A.,
RA Evans J.M., Middha S., de Andrade M., Moss R.L., Wieben E.D., Michels V.V.,
RA Olson T.M.;
RT "TNNI3K mutation in familial syndrome of conduction system disease, atrial
RT tachyarrhythmia and dilated cardiomyopathy.";
RL Hum. Mol. Genet. 23:5793-5804(2014).
CC -!- FUNCTION: May play a role in cardiac physiology.
CC {ECO:0000303|PubMed:12721663}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:12721663};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:12721663};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12721663};
CC -!- SUBUNIT: Interacts with TNNI3, ACTC1, ACTA1, MYBPC3, AIP, FABP3 and
CC HADHB. {ECO:0000269|PubMed:12721663}.
CC -!- INTERACTION:
CC Q59H18; Q9UKT5: FBXO4; NbExp=3; IntAct=EBI-704142, EBI-960409;
CC Q59H18; P19429: TNNI3; NbExp=2; IntAct=EBI-704142, EBI-704146;
CC Q59H18-2; P19429: TNNI3; NbExp=2; IntAct=EBI-10762055, EBI-704146;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12721663}. Cytoplasm
CC {ECO:0000269|PubMed:12721663}. Note=Expressed at lower levels in the
CC cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=2 {ECO:0000269|PubMed:12721663};
CC IsoId=Q59H18-2; Sequence=Displayed;
CC Name=1 {ECO:0000305};
CC IsoId=Q59H18-1; Sequence=VSP_039403;
CC Name=3 {ECO:0000305};
CC IsoId=Q59H18-3; Sequence=VSP_039403, VSP_051882, VSP_051883;
CC Name=4 {ECO:0000305};
CC IsoId=Q59H18-4; Sequence=VSP_039403, VSP_051884, VSP_051885;
CC -!- TISSUE SPECIFICITY: Highly expressed in both adult and fetal heart.
CC {ECO:0000269|PubMed:12721663}.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:12721663}.
CC -!- DISEASE: Cardiac conduction disease with or without dilated
CC cardiomyopathy (CCDD) [MIM:616117]: A cardiac disorder characterized by
CC atrial tachyarrhythmia and conduction system disease. Some patients
CC have dilated cardiomyopathy. {ECO:0000269|PubMed:24925317}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: [Isoform 1]: Based on a naturally occurring readthrough
CC transcript which produces a FPGT-TNNI3K fusion protein. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Based on a naturally occurring readthrough
CC transcript which produces a FPGT-TNNI3K fusion protein. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Based on a naturally occurring readthrough
CC transcript which produces a FPGT-TNNI3K fusion protein. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. MAP kinase kinase kinase subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92178.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAE45949.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/tnni3k/";
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DR EMBL; AF116826; AAD29632.1; -; mRNA.
DR EMBL; AY303691; AAP72030.1; -; mRNA.
DR EMBL; AB208941; BAD92178.1; ALT_INIT; Transcribed_RNA.
DR EMBL; BX640903; CAE45949.1; ALT_INIT; mRNA.
DR EMBL; DQ822519; ABG46944.1; -; Genomic_DNA.
DR EMBL; AC093158; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC098692; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC105271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC119672; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX470253; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06415.1; -; Genomic_DNA.
DR EMBL; BC032865; AAH32865.1; -; mRNA.
DR EMBL; BC113539; AAI13540.1; -; mRNA.
DR EMBL; BC117262; AAI17263.1; -; mRNA.
DR CCDS; CCDS664.1; -. [Q59H18-2]
DR RefSeq; NP_001186256.2; NM_001199327.1. [Q59H18-4]
DR RefSeq; NP_057062.1; NM_015978.2. [Q59H18-2]
DR PDB; 4YFF; X-ray; 3.07 A; A/B/C/D=420-730.
DR PDB; 4YFI; X-ray; 2.70 A; A/B/C/D=402-730.
DR PDB; 6B5J; X-ray; 2.97 A; A/B/C/D=420-730.
DR PDB; 7MGJ; X-ray; 2.95 A; A/B/C/D=402-730.
DR PDB; 7MGK; X-ray; 3.10 A; A/B/C/D=420-730.
DR PDBsum; 4YFF; -.
DR PDBsum; 4YFI; -.
DR PDBsum; 6B5J; -.
DR PDBsum; 7MGJ; -.
DR PDBsum; 7MGK; -.
DR AlphaFoldDB; Q59H18; -.
DR SMR; Q59H18; -.
DR BioGRID; 119276; 13.
DR IntAct; Q59H18; 16.
DR STRING; 9606.ENSP00000322251; -.
DR BindingDB; Q59H18; -.
DR ChEMBL; CHEMBL5260; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q59H18; -.
DR GuidetoPHARMACOLOGY; 2247; -.
DR iPTMnet; Q59H18; -.
DR PhosphoSitePlus; Q59H18; -.
DR BioMuta; TNNI3K; -.
DR DMDM; 300669705; -.
DR jPOST; Q59H18; -.
DR MassIVE; Q59H18; -.
DR MaxQB; Q59H18; -.
DR PaxDb; Q59H18; -.
DR PeptideAtlas; Q59H18; -.
DR PRIDE; Q59H18; -.
DR ProteomicsDB; 62665; -. [Q59H18-2]
DR ProteomicsDB; 62666; -. [Q59H18-1]
DR ProteomicsDB; 62667; -. [Q59H18-3]
DR ProteomicsDB; 62668; -. [Q59H18-4]
DR Antibodypedia; 2103; 155 antibodies from 21 providers.
DR DNASU; 51086; -.
DR Ensembl; ENST00000326637.8; ENSP00000322251.3; ENSG00000116783.15. [Q59H18-2]
DR GeneID; 100526835; -.
DR GeneID; 51086; -.
DR KEGG; hsa:100526835; -.
DR KEGG; hsa:51086; -.
DR MANE-Select; ENST00000326637.8; ENSP00000322251.3; NM_015978.3; NP_057062.1.
DR UCSC; uc001dgf.3; human. [Q59H18-2]
DR CTD; 100526835; -.
DR CTD; 51086; -.
DR DisGeNET; 100526835; -.
DR DisGeNET; 51086; -.
DR GeneCards; TNNI3K; -.
DR HGNC; HGNC:19661; TNNI3K.
DR HPA; ENSG00000116783; Tissue enriched (heart).
DR MalaCards; TNNI3K; -.
DR MIM; 613932; gene.
DR MIM; 616117; phenotype.
DR neXtProt; NX_Q59H18; -.
DR OpenTargets; ENSG00000116783; -.
DR OpenTargets; ENSG00000259030; -.
DR Orphanet; 436242; Familial atrial tachyarrhythmia-infra-Hisian cardiac conduction disease.
DR PharmGKB; PA134976654; -.
DR VEuPathDB; HostDB:ENSG00000116783; -.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00940000159131; -.
DR HOGENOM; CLU_017658_0_0_1; -.
DR InParanoid; Q59H18; -.
DR OMA; NCEEAFS; -.
DR OrthoDB; 173077at2759; -.
DR PhylomeDB; Q59H18; -.
DR PathwayCommons; Q59H18; -.
DR SignaLink; Q59H18; -.
DR BioGRID-ORCS; 100526835; 41 hits in 885 CRISPR screens.
DR BioGRID-ORCS; 51086; 13 hits in 705 CRISPR screens.
DR Pharos; Q59H18; Tchem.
DR PRO; PR:Q59H18; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q59H18; protein.
DR Bgee; ENSG00000116783; Expressed in apex of heart and 95 other tissues.
DR ExpressionAtlas; Q59H18; baseline and differential.
DR Genevisible; Q59H18; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0031013; F:troponin I binding; IPI:UniProtKB.
DR GO; GO:0086069; P:bundle of His cell to Purkinje myocyte communication; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:1903779; P:regulation of cardiac conduction; IGI:BHF-UCL.
DR GO; GO:0055117; P:regulation of cardiac muscle contraction; IMP:BHF-UCL.
DR GO; GO:0002027; P:regulation of heart rate; IMP:BHF-UCL.
DR GO; GO:0099175; P:regulation of postsynapse organization; IBA:GO_Central.
DR Gene3D; 1.25.40.20; -; 3.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR Pfam; PF12796; Ank_2; 3.
DR Pfam; PF13637; Ank_4; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 10.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 6.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ANK repeat; ATP-binding;
KW Cardiomyopathy; Coiled coil; Cytoplasm; Disease variant; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..835
FT /note="Serine/threonine-protein kinase TNNI3K"
FT /id="PRO_0000086757"
FT REPEAT 66..96
FT /note="ANK 1"
FT REPEAT 100..129
FT /note="ANK 2"
FT REPEAT 133..162
FT /note="ANK 3"
FT REPEAT 166..195
FT /note="ANK 4"
FT REPEAT 199..228
FT /note="ANK 5"
FT REPEAT 234..263
FT /note="ANK 6"
FT REPEAT 269..298
FT /note="ANK 7"
FT REPEAT 304..335
FT /note="ANK 8"
FT REPEAT 339..368
FT /note="ANK 9"
FT REPEAT 381..410
FT /note="ANK 10"
FT DOMAIN 463..723
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 732..751
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 21..51
FT /evidence="ECO:0000255"
FT ACT_SITE 588
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 469..477
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 490
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT VAR_SEQ 1..13
FT /note="MGNYKSRPTQTCT -> MAAARDPPEVSLREATQRKLRRFSELRGKLVARGE
FT FWDIVAITAADEKQELAYNQQLSEKLKRKELPLGVQYHVFVDPAGAKIGNGGSTLCALQ
FT CLEKLYGDKWNSFTILLIHS (in isoform 1, isoform 3 and isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005, ECO:0000303|Ref.3"
FT /id="VSP_039403"
FT VAR_SEQ 591..596
FT /note="SHNILL -> RYFFPK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_051882"
FT VAR_SEQ 597..835
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_051883"
FT VAR_SEQ 708..742
FT /note="GRPEFSEVVMKLEECLCNIELMSPASSNSSGSLSP -> AKSRPSHYPVSSV
FT YTETLKKKNEDRFGMWIEYLRR (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_051884"
FT VAR_SEQ 743..835
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_051885"
FT VARIANT 151
FT /note="D -> H (in dbSNP:rs34874695)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041223"
FT VARIANT 263
FT /note="P -> L (in dbSNP:rs34521608)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041224"
FT VARIANT 309
FT /note="F -> L"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041225"
FT VARIANT 430
FT /note="S -> L (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041226"
FT VARIANT 510
FT /note="V -> L (in dbSNP:rs34335537)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041227"
FT VARIANT 526
FT /note="G -> D (in CCDD; the mutation results in decreased
FT protein solubility; causes abnormal aggregation; markedly
FT reduced protein expression is observed in the sarcoplasm
FT and nuclei of patient cardiomyocytes; dbSNP:rs606231469)"
FT /evidence="ECO:0000269|PubMed:24925317"
FT /id="VAR_072650"
FT VARIANT 629
FT /note="R -> G (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035639"
FT VARIANT 637
FT /note="T -> M (in dbSNP:rs2274260)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041228"
FT VARIANT 686
FT /note="I -> T (in dbSNP:rs3737564)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041229"
FT VARIANT 785
FT /note="A -> G (in dbSNP:rs45578635)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_038821"
FT VARIANT 798
FT /note="M -> I (in a head & Neck squamous cell carcinoma
FT sample; somatic mutation; dbSNP:rs201613442)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041230"
FT VARIANT 833
FT /note="D -> Y (in dbSNP:rs45614933)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_038822"
FT MUTAGEN 490
FT /note="K->R: Loss of autophosphorylation activity."
FT /evidence="ECO:0000269|PubMed:12721663"
FT CONFLICT 127
FT /note="I -> V (in Ref. 8; AAH32865)"
FT /evidence="ECO:0000305"
FT CONFLICT 250
FT /note="I -> M (in Ref. 4; CAE45949)"
FT /evidence="ECO:0000305"
FT CONFLICT 367
FT /note="N -> S (in Ref. 4; CAE45949)"
FT /evidence="ECO:0000305"
FT CONFLICT 629
FT /note="R -> L (in Ref. 8; AAH32865)"
FT /evidence="ECO:0000305"
FT HELIX 442..451
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 454..456
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 460..462
FT /evidence="ECO:0007829|PDB:4YFI"
FT STRAND 463..470
FT /evidence="ECO:0007829|PDB:4YFI"
FT STRAND 473..482
FT /evidence="ECO:0007829|PDB:4YFI"
FT STRAND 485..492
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 502..515
FT /evidence="ECO:0007829|PDB:4YFI"
FT STRAND 524..528
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 532..534
FT /evidence="ECO:0007829|PDB:4YFI"
FT STRAND 536..540
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 547..552
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 560..578
FT /evidence="ECO:0007829|PDB:4YFI"
FT STRAND 580..582
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 591..593
FT /evidence="ECO:0007829|PDB:4YFI"
FT STRAND 594..596
FT /evidence="ECO:0007829|PDB:4YFI"
FT STRAND 602..604
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 628..630
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 633..636
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 637..639
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 645..660
FT /evidence="ECO:0007829|PDB:4YFI"
FT TURN 664..667
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 670..678
FT /evidence="ECO:0007829|PDB:4YFI"
FT STRAND 688..690
FT /evidence="ECO:0007829|PDB:7MGK"
FT HELIX 692..701
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 706..708
FT /evidence="ECO:0007829|PDB:4YFI"
FT HELIX 712..725
FT /evidence="ECO:0007829|PDB:4YFI"
SQ SEQUENCE 835 AA; 92851 MW; 3B21484B434F46E8 CRC64;
MGNYKSRPTQ TCTDEWKKKV SESYVITIER LEDDLQIKEK ELTELRNIFG SDEAFSKVNL
NYRTENGLSL LHLCCICGGK KSHIRTLMLK GLRPSRLTRN GFTALHLAVY KDNAELITSL
LHSGADIQQV GYGGLTALHI ATIAGHLEAA DVLLQHGANV NIQDAVFFTP LHIAAYYGHE
QVTRLLLKFG ADVNVSGEVG DRPLHLASAK GFLNIAKLLM EEGSKADVNA QDNEDHVPLH
FCSRFGHHDI VKYLLQSDLE VQPHVVNIYG DTPLHLACYN GKFEVAKEII QISGTESLTK
ENIFSETAFH SACTYGKSID LVKFLLDQNV ININHQGRDG HTGLHSACYH GHIRLVQFLL
DNGADMNLVA CDPSRSSGEK DEQTCLMWAY EKGHDAIVTL LKHYKRPQDE LPCNEYSQPG
GDGSYVSVPS PLGKIKSMTK EKADILLLRA GLPSHFHLQL SEIEFHEIIG SGSFGKVYKG
RCRNKIVAIK RYRANTYCSK SDVDMFCREV SILCQLNHPC VIQFVGACLN DPSQFAIVTQ
YISGGSLFSL LHEQKRILDL QSKLIIAVDV AKGMEYLHNL TQPIIHRDLN SHNILLYEDG
HAVVADFGES RFLQSLDEDN MTKQPGNLRW MAPEVFTQCT RYTIKADVFS YALCLWEILT
GEIPFAHLKP AAAAADMAYH HIRPPIGYSI PKPISSLLIR GWNACPEGRP EFSEVVMKLE
ECLCNIELMS PASSNSSGSL SPSSSSDCLV NRGGPGRSHV AALRSRFELE YALNARSYAA
LSQSAGQYSS QGLSLEEMKR SLQYTPIDKY GYVSDPMSSM HFHSCRNSSS FEDSS
