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 27-MAR-2024, entry version 184. 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 18. DR IntAct; Q59H18; 17. 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; 9606-ENSP00000322251; -. DR PeptideAtlas; Q59H18; -. DR ProteomicsDB; 62665; -. [Q59H18-2] DR ProteomicsDB; 62666; -. [Q59H18-1] DR ProteomicsDB; 62667; -. [Q59H18-3] DR ProteomicsDB; 62668; -. [Q59H18-4] DR Antibodypedia; 2103; 173 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 AGR; HGNC:19661; -. DR AGR; HGNC:42952; -. 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; IHFVGAC; -. DR OrthoDB; 3020493at2759; -. DR PhylomeDB; Q59H18; -. DR PathwayCommons; Q59H18; -. DR SignaLink; Q59H18; -. DR BioGRID-ORCS; 100526835; 43 hits in 928 CRISPR screens. DR BioGRID-ORCS; 51086; 14 hits in 781 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 97 other cell types or tissues. DR ExpressionAtlas; Q59H18; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. 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: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: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 CDD; cd14064; PKc_TNNI3K; 1. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 3. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24203:SF83; ANKYRIN REPEAT AND SOCS BOX PROTEIN 15-RELATED; 1. DR PANTHER; PTHR24203; ANKYRIN REPEAT FAMILY PROTEIN; 1. 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; Ankyrin repeat; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; Q59H18; HS. 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 //