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Q59H18 (TNI3K_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 112. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:TNNI3K
Synonyms:CARK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length835 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May play a role in cardiac physiology. Ref.1

Catalytic activity

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

Cofactor

Magnesium. Ref.1

Subunit structure

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

Subcellular location

Nucleus. Cytoplasm. Note: Expressed at lower levels in the cytoplasm. Ref.1

Tissue specificity

Highly expressed in both adult and fetal heart. Ref.1

Post-translational modification

Autophosphorylated. Ref.1

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.

Contains 10 ANK repeats.

Contains 1 protein kinase domain.

Sequence caution

The sequence BAD92178.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence CAE45949.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TNNI3P194292EBI-704142,EBI-704146

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 Ref.1 (identifier: Q59H18-2)

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.
Isoform 1 (identifier: Q59H18-1)

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.
Isoform 3 (identifier: Q59H18-3)

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.
Isoform 4 (identifier: Q59H18-4)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 835835Serine/threonine-protein kinase TNNI3K
PRO_0000086757

Regions

Repeat66 – 9631ANK 1
Repeat100 – 12930ANK 2
Repeat133 – 16230ANK 3
Repeat166 – 19530ANK 4
Repeat199 – 22830ANK 5
Repeat234 – 26330ANK 6
Repeat269 – 29830ANK 7
Repeat304 – 33532ANK 8
Repeat339 – 36830ANK 9
Repeat381 – 41030ANK 10
Domain463 – 723261Protein kinase
Nucleotide binding469 – 4779ATP By similarity
Coiled coil21 – 5131 Potential
Compositional bias733 – 74614Poly-Ser

Sites

Active site5881Proton acceptor By similarity
Binding site4901ATP

Natural variations

Alternative sequence1 – 1313MGNYK…TQTCT → MAAARDPPEVSLREATQRKL RRFSELRGKLVARGEFWDIV AITAADEKQELAYNQQLSEK LKRKELPLGVQYHVFVDPAG AKIGNGGSTLCALQCLEKLY GDKWNSFTILLIHS in isoform 1, isoform 3 and isoform 4.
VSP_039403
Alternative sequence591 – 5966SHNILL → RYFFPK in isoform 3.
VSP_051882
Alternative sequence597 – 835239Missing in isoform 3.
VSP_051883
Alternative sequence708 – 74235GRPEF…GSLSP → AKSRPSHYPVSSVYTETLKK KNEDRFGMWIEYLRR in isoform 4.
VSP_051884
Alternative sequence743 – 83593Missing in isoform 4.
VSP_051885
Natural variant1511D → H. Ref.10
Corresponds to variant rs34874695 [ dbSNP | Ensembl ].
VAR_041223
Natural variant2631P → L. Ref.10
Corresponds to variant rs34521608 [ dbSNP | Ensembl ].
VAR_041224
Natural variant3091F → L. Ref.10
VAR_041225
Natural variant4301S → L in a colorectal adenocarcinoma sample; somatic mutation. Ref.10
VAR_041226
Natural variant5101V → L. Ref.10
Corresponds to variant rs34335537 [ dbSNP | Ensembl ].
VAR_041227
Natural variant6291R → G in a colorectal cancer sample; somatic mutation. Ref.9
VAR_035639
Natural variant6371T → M. Ref.10
Corresponds to variant rs2274260 [ dbSNP | Ensembl ].
VAR_041228
Natural variant6861I → T. Ref.10
Corresponds to variant rs3737564 [ dbSNP | Ensembl ].
VAR_041229
Natural variant7851A → G. Ref.5
Corresponds to variant rs45578635 [ dbSNP | Ensembl ].
VAR_038821
Natural variant7981M → I in a head & Neck squamous cell carcinoma sample; somatic mutation. Ref.10
VAR_041230
Natural variant8331D → Y. Ref.5
Corresponds to variant rs45614933 [ dbSNP | Ensembl ].
VAR_038822

Experimental info

Mutagenesis4901K → R: Loss of autophosphorylation activity. Ref.1
Sequence conflict1271I → V in AAH32865. Ref.8
Sequence conflict2501I → M in CAE45949. Ref.4
Sequence conflict3671N → S in CAE45949. Ref.4
Sequence conflict6291R → L in AAH32865. Ref.8

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 [UniParc].

Last modified July 13, 2010. Version 3.
Checksum: 3B21484B434F46E8

FASTA83592,851
        10         20         30         40         50         60 
MGNYKSRPTQ TCTDEWKKKV SESYVITIER LEDDLQIKEK ELTELRNIFG SDEAFSKVNL 

        70         80         90        100        110        120 
NYRTENGLSL LHLCCICGGK KSHIRTLMLK GLRPSRLTRN GFTALHLAVY KDNAELITSL 

       130        140        150        160        170        180 
LHSGADIQQV GYGGLTALHI ATIAGHLEAA DVLLQHGANV NIQDAVFFTP LHIAAYYGHE 

       190        200        210        220        230        240 
QVTRLLLKFG ADVNVSGEVG DRPLHLASAK GFLNIAKLLM EEGSKADVNA QDNEDHVPLH 

       250        260        270        280        290        300 
FCSRFGHHDI VKYLLQSDLE VQPHVVNIYG DTPLHLACYN GKFEVAKEII QISGTESLTK 

       310        320        330        340        350        360 
ENIFSETAFH SACTYGKSID LVKFLLDQNV ININHQGRDG HTGLHSACYH GHIRLVQFLL 

       370        380        390        400        410        420 
DNGADMNLVA CDPSRSSGEK DEQTCLMWAY EKGHDAIVTL LKHYKRPQDE LPCNEYSQPG 

       430        440        450        460        470        480 
GDGSYVSVPS PLGKIKSMTK EKADILLLRA GLPSHFHLQL SEIEFHEIIG SGSFGKVYKG 

       490        500        510        520        530        540 
RCRNKIVAIK RYRANTYCSK SDVDMFCREV SILCQLNHPC VIQFVGACLN DPSQFAIVTQ 

       550        560        570        580        590        600 
YISGGSLFSL LHEQKRILDL QSKLIIAVDV AKGMEYLHNL TQPIIHRDLN SHNILLYEDG 

       610        620        630        640        650        660 
HAVVADFGES RFLQSLDEDN MTKQPGNLRW MAPEVFTQCT RYTIKADVFS YALCLWEILT 

       670        680        690        700        710        720 
GEIPFAHLKP AAAAADMAYH HIRPPIGYSI PKPISSLLIR GWNACPEGRP EFSEVVMKLE 

       730        740        750        760        770        780 
ECLCNIELMS PASSNSSGSL SPSSSSDCLV NRGGPGRSHV AALRSRFELE YALNARSYAA 

       790        800        810        820        830 
LSQSAGQYSS QGLSLEEMKR SLQYTPIDKY GYVSDPMSSM HFHSCRNSSS FEDSS 

« Hide

Isoform 1 [UniParc].

Checksum: 081220549646863F
Show »

FASTA936104,179
Isoform 3 [UniParc].

Checksum: 7567E27D45485C9C
Show »

FASTA69777,957
Isoform 4 [UniParc].

Checksum: 3001399FAEAD7B24
Show »

FASTA84394,517

References

« Hide 'large scale' references
[1]"Cloning and characterization of a novel cardiac-specific kinase that interacts specifically with cardiac troponin I."
Zhao Y., Meng X.-M., Wei Y.-J., Zhao X.-W., Liu D.-Q., Cao H.-Q., Liew C.-C., Ding J.-F.
J. Mol. Med. 81:297-304(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, INTERACTION WITH TNNI3; ACTC; ACTA1; MYBPC3; AIP; BABP3 AND HADHB, MUTAGENESIS OF LYS-490.
Tissue: Heart.
[2]"Cardiac ankyrin repeat kinase (CARK)."
Jeyaseelan R.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Fetal kidney.
[5]SeattleSNPs variation discovery resource
Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-785 AND TYR-833.
[6]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
Tissue: Brain.
[9]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLY-629.
[10]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] HIS-151; LEU-263; LEU-309; LEU-430; LEU-510; MET-637; THR-686 AND ILE-798.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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 expand/collapse EMBL AC list , 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.
CCDSCCDS664.1. [Q59H18-2]
RefSeqNP_001186256.2. NM_001199327.1.
NP_057062.1. NM_015978.2. [Q59H18-2]
UniGeneHs.480085.

3D structure databases

ProteinModelPortalQ59H18.
SMRQ59H18. Positions 41-720.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119276. 8 interactions.
IntActQ59H18. 7 interactions.

Chemistry

BindingDBQ59H18.
ChEMBLCHEMBL5260.
GuidetoPHARMACOLOGY2247.

PTM databases

PhosphoSiteQ59H18.

Polymorphism databases

DMDM300669705.

Proteomic databases

MaxQBQ59H18.
PRIDEQ59H18.

Protocols and materials databases

DNASU51086.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000326637; ENSP00000322251; ENSG00000116783. [Q59H18-2]
ENST00000370891; ENSP00000359928; ENSG00000116783. [Q59H18-1]
GeneID100526835.
51086.
KEGGhsa:100526835.
hsa:51086.
UCSCuc001dgc.2. human. [Q59H18-3]
uc001dgd.3. human. [Q59H18-4]
uc001dge.2. human. [Q59H18-1]
uc001dgf.2. human. [Q59H18-2]

Organism-specific databases

CTD100526835.
51086.
GeneCardsGC01P074669.
HGNCHGNC:19661. TNNI3K.
MIM613932. gene.
neXtProtNX_Q59H18.
PharmGKBPA134976654.
GenAtlasSearch...

Phylogenomic databases

HOGENOMHOG000234421.
HOVERGENHBG079513.
InParanoidQ59H18.
KOK17535.
OMAQPHVVNI.
OrthoDBEOG7XDBF3.
PhylomeDBQ59H18.

Gene expression databases

BgeeQ59H18.
CleanExHS_TNNI3K.
GenevestigatorQ59H18.

Family and domain databases

Gene3D1.25.40.20. 3 hits.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
[Graphical view]
PfamPF12796. Ank_2. 3 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
SMARTSM00248. ANK. 10 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 6 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio53751.
PROQ59H18.
SOURCESearch...

Entry information

Entry nameTNI3K_HUMAN
AccessionPrimary (citable) accession number: Q59H18
Secondary accession number(s): Q17RN0 expand/collapse secondary AC list , Q49AR1, Q6MZS9, Q9Y2V6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: July 13, 2010
Last modified: July 9, 2014
This is version 112 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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

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 1

Human chromosome 1: entries, gene names and cross-references to MIM