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P83510

- TNIK_MOUSE

UniProt

P83510 - TNIK_MOUSE

Protein

Traf2 and NCK-interacting protein kinase

Gene

Tnik

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 2 (24 Jul 2007)
      Previous versions | rss
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    Functioni

    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.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei54 – 541ATPPROSITE-ProRule annotation
    Active sitei153 – 1531Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi31 – 399ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. protein serine/threonine kinase activity Source: UniProtKB
    4. small GTPase regulator activity Source: InterPro

    GO - Biological processi

    1. actin cytoskeleton reorganization Source: UniProtKB
    2. activation of JNKK activity Source: UniProtKB
    3. intracellular signal transduction Source: UniProtKB
    4. protein autophosphorylation Source: UniProtKB
    5. protein phosphorylation Source: UniProtKB
    6. regulation of dendrite morphogenesis Source: UniProtKB
    7. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Neurogenesis, Wnt signaling pathway

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Traf2 and NCK-interacting protein kinase (EC:2.7.11.1)
    Gene namesi
    Name:Tnik
    Synonyms:Kiaa0551
    OrganismiMus musculus (Mouse)Imported
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 3

    Organism-specific databases

    MGIiMGI:1916264. Tnik.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasm 1 Publication. Recycling endosome By similarity. Cytoplasmcytoskeleton By similarity
    Note: Associated with recycling endosomes and the cytoskeletal fraction upon RAP2A overexpression.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytoskeleton Source: UniProtKB
    3. nucleus Source: UniProtKB-SubCell
    4. perinuclear region of cytoplasm Source: MGI
    5. recycling endosome Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Endosome, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 13231323Traf2 and NCK-interacting protein kinasePRO_0000086762Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei326 – 3261PhosphoserineBy similarity
    Modified residuei531 – 5311PhosphoserineBy similarity
    Modified residuei611 – 6111PhosphoserineBy similarity
    Modified residuei649 – 6491PhosphoserineBy similarity
    Modified residuei651 – 6511PhosphoserineBy similarity
    Modified residuei659 – 6591PhosphoserineBy similarity
    Modified residuei678 – 6781PhosphoserineBy similarity
    Modified residuei691 – 6911PhosphoserineBy similarity
    Modified residuei737 – 7371PhosphoserineBy similarity
    Modified residuei740 – 7401PhosphoserineBy similarity

    Post-translational modificationi

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

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP83510.
    PaxDbiP83510.
    PRIDEiP83510.

    PTM databases

    PhosphoSiteiP83510.

    Expressioni

    Gene expression databases

    ArrayExpressiP83510.
    BgeeiP83510.
    CleanExiMM_TNIK.
    GenevestigatoriP83510.

    Interactioni

    Subunit structurei

    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 TANC1.2 Publications

    Protein-protein interaction databases

    BioGridi576981. 1 interaction.
    DIPiDIP-57467N.
    IntActiP83510. 3 interactions.
    MINTiMINT-4138101.

    Structurei

    3D structure databases

    ProteinModelPortaliP83510.
    SMRiP83510. Positions 13-313.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini25 – 289265Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini1010 – 1297288CNHPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni290 – 1010721Mediates interaction with NEDD4By similarityAdd
    BLAST

    Sequence similaritiesi

    Contains 1 CNH domain.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00740000115097.
    HOGENOMiHOG000290708.
    HOVERGENiHBG036506.
    KOiK08840.
    OrthoDBiEOG73803V.

    Family and domain databases

    InterProiIPR001180. 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]
    PfamiPF00780. CNH. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00036. CNH. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS50219. CNH. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P83510-1) [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

    MASDSPARSL DEIDLSALRD PAGIFELVEL VGNGTYGQVY KGRHVKTGQL     50
    AAIKVMDVTG DEEEEIKQEI NMLKKYSHHR NIATYYGAFI KKNPPGMDDQ 100
    LWLVMEFCGA GSVTDLIKNT KGNTLKEEWI AYICREILRG LSHLHQHKVI 150
    HRDIKGQNVL LTENAEVKLV DFGVSAQLDR TVGRRNTFIG TPYWMAPEVI 200
    ACDENPDATY DFKSDLWSLG ITAIEMAEGA PPLCDMHPMR ALFLIPRNPA 250
    PRLKSKKWSK KFQSFIESCL VKNHSQRPAT EQLMKHPFIR DQPNERQVRI 300
    QLKDHIDRTK KKRGEKDETE YEYSGSEEEE EENDSGEPSS ILNLPGESTL 350
    RRDFLRLQLA NKERSEALRR QQLEQQQREN EEHKRQLLAE RQKRIEEQKE 400
    QRRRLEEQQR REKELRKQQE REQRRHYEEQ MRREEERRRA EHEQEYKRKQ 450
    LEEQRQAERL QRQLKQERDY LVSLQHQRQE QRPLEKKPLY HYKEGMSPSE 500
    KPAWAKEVEE RSRLNRQSSP AMPHKVANRI SDPNLPPRSE SFSISGVQPA 550
    RTPPMLRPVD PQIPQLVAVK SQGPALTASQ SVHEQPTKGL SGFQEALNVT 600
    SHRVEMPRQN SDPTSENPPL PTRIEKFDRS SWLRQEEDIP PKVPQRTTSI 650
    SPALARKNSP GNGSALGPRL GSQPIRASNP DLRRTEPVLE SSLQRTSSGS 700
    SSSSSTPSSQ PSSQGGSQPG SQAGSSERSR VRANSKSEGS PVLPHEPSKV 750
    KPEESRDITR PSRPADLTAL AKELRELRIE ETNRPLKKVT DYSSSSEESE 800
    SSEEEEEDGE SETHDGTVAV SDIPRLIPTG APGNNEQYNM GMVGTHGLET 850
    SHADTFGGSI SREGTLMIRE TAEEKKRSGH SDSNGFAGHI NLPDLVQQSH 900
    SPAGTPTEGL GRVSTHSQEM DSGAEYGIGS STKASFTPFV DPRVYQTSPT 950
    DEDEEDDESS AAALFTSELL RQEQAKLNEA RKISVVNVNP TNIRPHSDTP 1000
    EIRKYKKRFN SEILCAALWG VNLLVGTENG LMLLDRSGQG KVYNLINRRR 1050
    FQQMDVLEGL NVLVTISGKK NKLRVYYLSW LRNRILHNDP EVEKKQGWIT 1100
    VGDLEGCIHY KVVKYERIKF LVIALKNAVE IYAWAPKPYH KFMAFKSFAD 1150
    LQHKPLLVDL TVEEGQRLKV IFGSHTGFHV IDVDSGNSYD IYIPSHIQGN 1200
    ITPHAIVILP KTDGMEMLVC YEDEGVYVNT YGRITKDVVL QWGEMPTSVA 1250
    YIHSNQIMGW GEKAIEIRSV ETGHLDGVFM HKRAQRLKFL CERNDKVFFA 1300
    SVRSGGSSQV FFMTLNRNSM MNW 1323

    Note: No experimental confirmation available.

    Length:1,323
    Mass (Da):150,367
    Last modified:July 24, 2007 - v2
    Checksum:iB8289189530251D2
    GO
    Isoform 2 (identifier: P83510-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         926-962: YGIGSSTKASFTPFVDPRVYQTSPTDEDEEDDESSAA → SLK

    Note: No experimental confirmation available.

    Show »
    Length:1,289
    Mass (Da):146,713
    Checksum:iA41F95CC9AC436D8
    GO

    Sequence cautioni

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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti735 – 7351S → C in BAC40365. (PubMed:16141072)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei926 – 96237YGIGS…ESSAA → SLK in isoform 2. 1 PublicationVSP_007351Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS50879.1. [P83510-1]
    RefSeqiNP_001156480.1. NM_001163008.1. [P83510-1]
    UniGeneiMm.126193.
    Mm.483052.

    Genome annotation databases

    EnsembliENSMUST00000159236; ENSMUSP00000124681; ENSMUSG00000027692. [P83510-1]
    GeneIDi665113.
    KEGGimmu:665113.
    UCSCiuc008oty.1. mouse. [P83510-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSi CCDS50879.1. [P83510-1 ]
    RefSeqi NP_001156480.1. NM_001163008.1. [P83510-1 ]
    UniGenei Mm.126193.
    Mm.483052.

    3D structure databases

    ProteinModelPortali P83510.
    SMRi P83510. Positions 13-313.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 576981. 1 interaction.
    DIPi DIP-57467N.
    IntActi P83510. 3 interactions.
    MINTi MINT-4138101.

    PTM databases

    PhosphoSitei P83510.

    Proteomic databases

    MaxQBi P83510.
    PaxDbi P83510.
    PRIDEi P83510.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000159236 ; ENSMUSP00000124681 ; ENSMUSG00000027692 . [P83510-1 ]
    GeneIDi 665113.
    KEGGi mmu:665113.
    UCSCi uc008oty.1. mouse. [P83510-1 ]

    Organism-specific databases

    CTDi 23043.
    MGIi MGI:1916264. Tnik.
    Rougei Search...

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00740000115097.
    HOGENOMi HOG000290708.
    HOVERGENi HBG036506.
    KOi K08840.
    OrthoDBi EOG73803V.

    Miscellaneous databases

    ChiTaRSi TNIK. mouse.
    NextBioi 426671.
    PROi P83510.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P83510.
    Bgeei P83510.
    CleanExi MM_TNIK.
    Genevestigatori P83510.

    Family and domain databases

    InterProi IPR001180. 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 ]
    Pfami PF00780. CNH. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00036. CNH. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50219. CNH. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. Cited for: INTERACTION WITH NEDD4 AND RAP2A.

    Entry informationi

    Entry nameiTNIK_MOUSE
    AccessioniPrimary (citable) accession number: P83510
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 30, 2003
    Last sequence update: July 24, 2007
    Last modified: October 1, 2014
    This is version 114 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3