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P83510 (TNIK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Traf2 and NCK-interacting protein kinase

EC=2.7.11.1
Gene names
Name:Tnik
Synonyms:Kiaa0551
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1323 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. UniProtKB Q9UKE5

Subunit structure

Interacts (via the CNH domain) with RAP2A (GTP-bound form preferentially); the interaction is direct and required for the activation of TNIK by RAP2A. Interacts with NEDD4; recruits RAP2A to NEDD4. Interacts with TRAF2 and NCK. Interacts with TCF7L2/TCF4 and CTNNB1; the interaction is direct. Interacts with TANC1. Ref.5 Ref.6

Subcellular location

Nucleus. Cytoplasm. Recycling endosome By similarity. Cytoplasmcytoskeleton By similarity. Note: Associated with recycling endosomes and the cytoskeletal fraction upon RAP2A overexpression By similarity. Ref.5

Post-translational modification

Autophosphorylated. Autophosphorylation is activated by RAP2A and induces association to the cytoskeletal fraction. Phosphorylates SMAD1 on Thr-322 By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Contains 1 CNH domain.

Contains 1 protein kinase domain.

Sequence caution

The sequence BAC65588.2 differs from that shown. Reason: Probable cloning artifact.

Ontologies

Keywords
   Biological processNeurogenesis
Wnt signaling pathway
   Cellular componentCytoplasm
Cytoskeleton
Endosome
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

actin cytoskeleton reorganization

Inferred from sequence or structural similarity. Source: UniProtKB

activation of JNKK activity

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of dendrite morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytoskeleton

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from sequence orthology PubMed 19061864. Source: MGI

recycling endosome

Inferred from sequence orthology PubMed 19061864. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.6. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

receptor signaling protein serine/threonine kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

small GTPase regulator activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P83510-1)

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.
Note: No experimental confirmation available.
Isoform 2 (identifier: P83510-2)

The sequence of this isoform differs from the canonical sequence as follows:
     926-962: YGIGSSTKASFTPFVDPRVYQTSPTDEDEEDDESSAA → SLK
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13231323Traf2 and NCK-interacting protein kinase
PRO_0000086762

Regions

Domain25 – 289265Protein kinase
Domain1010 – 1297288CNH
Nucleotide binding31 – 399ATP By similarity UniProtKB O00506
Region290 – 1010721Mediates interaction with NEDD4 By similarity

Sites

Active site1531Proton acceptor By similarity UniProtKB O00506
Binding site541ATP By similarity UniProtKB O00506

Amino acid modifications

Modified residue3261Phosphoserine By similarity
Modified residue5311Phosphoserine By similarity
Modified residue6111Phosphoserine By similarity
Modified residue6491Phosphoserine By similarity
Modified residue6511Phosphoserine By similarity
Modified residue6591Phosphoserine By similarity
Modified residue6781Phosphoserine By similarity
Modified residue6911Phosphoserine By similarity
Modified residue7371Phosphoserine By similarity
Modified residue7401Phosphoserine By similarity

Natural variations

Alternative sequence926 – 96237YGIGS…ESSAA → SLK in isoform 2.
VSP_007351

Experimental info

Sequence conflict7351S → C in BAC40365. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 24, 2007. Version 2.
Checksum: B8289189530251D2

FASTA1,323150,367
        10         20         30         40         50         60 
MASDSPARSL DEIDLSALRD PAGIFELVEL VGNGTYGQVY KGRHVKTGQL AAIKVMDVTG 

        70         80         90        100        110        120 
DEEEEIKQEI NMLKKYSHHR NIATYYGAFI KKNPPGMDDQ LWLVMEFCGA GSVTDLIKNT 

       130        140        150        160        170        180 
KGNTLKEEWI AYICREILRG LSHLHQHKVI HRDIKGQNVL LTENAEVKLV DFGVSAQLDR 

       190        200        210        220        230        240 
TVGRRNTFIG TPYWMAPEVI ACDENPDATY DFKSDLWSLG ITAIEMAEGA PPLCDMHPMR 

       250        260        270        280        290        300 
ALFLIPRNPA PRLKSKKWSK KFQSFIESCL VKNHSQRPAT EQLMKHPFIR DQPNERQVRI 

       310        320        330        340        350        360 
QLKDHIDRTK KKRGEKDETE YEYSGSEEEE EENDSGEPSS ILNLPGESTL RRDFLRLQLA 

       370        380        390        400        410        420 
NKERSEALRR QQLEQQQREN EEHKRQLLAE RQKRIEEQKE QRRRLEEQQR REKELRKQQE 

       430        440        450        460        470        480 
REQRRHYEEQ MRREEERRRA EHEQEYKRKQ LEEQRQAERL QRQLKQERDY LVSLQHQRQE 

       490        500        510        520        530        540 
QRPLEKKPLY HYKEGMSPSE KPAWAKEVEE RSRLNRQSSP AMPHKVANRI SDPNLPPRSE 

       550        560        570        580        590        600 
SFSISGVQPA RTPPMLRPVD PQIPQLVAVK SQGPALTASQ SVHEQPTKGL SGFQEALNVT 

       610        620        630        640        650        660 
SHRVEMPRQN SDPTSENPPL PTRIEKFDRS SWLRQEEDIP PKVPQRTTSI SPALARKNSP 

       670        680        690        700        710        720 
GNGSALGPRL GSQPIRASNP DLRRTEPVLE SSLQRTSSGS SSSSSTPSSQ PSSQGGSQPG 

       730        740        750        760        770        780 
SQAGSSERSR VRANSKSEGS PVLPHEPSKV KPEESRDITR PSRPADLTAL AKELRELRIE 

       790        800        810        820        830        840 
ETNRPLKKVT DYSSSSEESE SSEEEEEDGE SETHDGTVAV SDIPRLIPTG APGNNEQYNM 

       850        860        870        880        890        900 
GMVGTHGLET SHADTFGGSI SREGTLMIRE TAEEKKRSGH SDSNGFAGHI NLPDLVQQSH 

       910        920        930        940        950        960 
SPAGTPTEGL GRVSTHSQEM DSGAEYGIGS STKASFTPFV DPRVYQTSPT DEDEEDDESS 

       970        980        990       1000       1010       1020 
AAALFTSELL RQEQAKLNEA RKISVVNVNP TNIRPHSDTP EIRKYKKRFN SEILCAALWG 

      1030       1040       1050       1060       1070       1080 
VNLLVGTENG LMLLDRSGQG KVYNLINRRR FQQMDVLEGL NVLVTISGKK NKLRVYYLSW 

      1090       1100       1110       1120       1130       1140 
LRNRILHNDP EVEKKQGWIT VGDLEGCIHY KVVKYERIKF LVIALKNAVE IYAWAPKPYH 

      1150       1160       1170       1180       1190       1200 
KFMAFKSFAD LQHKPLLVDL TVEEGQRLKV IFGSHTGFHV IDVDSGNSYD IYIPSHIQGN 

      1210       1220       1230       1240       1250       1260 
ITPHAIVILP KTDGMEMLVC YEDEGVYVNT YGRITKDVVL QWGEMPTSVA YIHSNQIMGW 

      1270       1280       1290       1300       1310       1320 
GEKAIEIRSV ETGHLDGVFM HKRAQRLKFL CERNDKVFFA SVRSGGSSQV FFMTLNRNSM 


MNW 

« Hide

Isoform 2 [UniParc].

Checksum: A41F95CC9AC436D8
Show »

FASTA1,289146,713

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-327 AND 735-1323 (ISOFORM 1).
Strain: C57BL/6J and NOD.
Tissue: Hypothalamus and Thymus.
[2]"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] OF 311-1323 (ISOFORM 1).
Tissue: Embryo.
[3]"Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H.
DNA Res. 10:35-48(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 359-842 (ISOFORM 2).
Tissue: Brain.
[4]Okazaki N., Kikuno R., Nagase T., Ohara O., Koga H.
Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[5]"The kinase TNIK is an essential activator of Wnt target genes."
Mahmoudi T., Li V.S.W., Ng S.S., Taouatas N., Vries R.G.J., Mohammed S., Heck A.J., Clevers H.
EMBO J. 28:3329-3340(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TCF7L2 AND CTNNB1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]"Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development."
Kawabe H., Neeb A., Dimova K., Young S.M. Jr., Takeda M., Katsurabayashi S., Mitkovski M., Malakhova O.A., Zhang D.E., Umikawa M., Kariya K., Goebbels S., Nave K.A., Rosenmund C., Jahn O., Rhee J., Brose N.
Neuron 65:358-372(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NEDD4 AND RAP2A.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK039113 mRNA. Translation: BAC30241.1.
AK041777 mRNA. Translation: BAC31061.2.
AK088459 mRNA. Translation: BAC40365.1.
BC050866 mRNA. No translation available.
AK122306 Transcribed RNA. Translation: BAC65588.2. Sequence problems.
CCDSCCDS50879.1. [P83510-1]
RefSeqNP_001156480.1. NM_001163008.1. [P83510-1]
UniGeneMm.126193.
Mm.483052.

3D structure databases

ProteinModelPortalP83510.
SMRP83510. Positions 13-313.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid576981. 1 interaction.
DIPDIP-57467N.
IntActP83510. 3 interactions.
MINTMINT-4138101.

PTM databases

PhosphoSiteP83510.

Proteomic databases

MaxQBP83510.
PaxDbP83510.
PRIDEP83510.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000159236; ENSMUSP00000124681; ENSMUSG00000027692. [P83510-1]
GeneID665113.
KEGGmmu:665113.
UCSCuc008oty.1. mouse. [P83510-1]

Organism-specific databases

CTD23043.
MGIMGI:1916264. Tnik.
RougeSearch...

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115097.
HOGENOMHOG000290708.
HOVERGENHBG036506.
KOK08840.
OrthoDBEOG73803V.

Gene expression databases

ArrayExpressP83510.
BgeeP83510.
CleanExMM_TNIK.
GenevestigatorP83510.

Family and domain databases

InterProIPR001180. Citron.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTNIK. mouse.
NextBio426671.
PROP83510.
SOURCESearch...

Entry information

Entry nameTNIK_MOUSE
AccessionPrimary (citable) accession number: P83510
Entry history
Integrated into UniProtKB/Swiss-Prot: April 30, 2003
Last sequence update: July 24, 2007
Last modified: July 9, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot