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P83510

- TNIK_MOUSE

UniProt

P83510 - TNIK_MOUSE

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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

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 serine/threonine kinase activity Source: UniProtKB
  3. 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
Complete GO annotation...

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-KW
  4. perinuclear region of cytoplasm Source: MGI
  5. recycling endosome Source: MGI
Complete GO annotation...

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

BgeeiP83510.
CleanExiMM_TNIK.
ExpressionAtlasiP83510. baseline and differential.
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.
GeneTreeiENSGT00760000118848.
HOGENOMiHOG000290708.
HOVERGENiHBG036506.
InParanoidiP83510.
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.
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

        10         20         30         40         50
MASDSPARSL DEIDLSALRD PAGIFELVEL VGNGTYGQVY KGRHVKTGQL
60 70 80 90 100
AAIKVMDVTG DEEEEIKQEI NMLKKYSHHR NIATYYGAFI KKNPPGMDDQ
110 120 130 140 150
LWLVMEFCGA GSVTDLIKNT KGNTLKEEWI AYICREILRG LSHLHQHKVI
160 170 180 190 200
HRDIKGQNVL LTENAEVKLV DFGVSAQLDR TVGRRNTFIG TPYWMAPEVI
210 220 230 240 250
ACDENPDATY DFKSDLWSLG ITAIEMAEGA PPLCDMHPMR ALFLIPRNPA
260 270 280 290 300
PRLKSKKWSK KFQSFIESCL VKNHSQRPAT EQLMKHPFIR DQPNERQVRI
310 320 330 340 350
QLKDHIDRTK KKRGEKDETE YEYSGSEEEE EENDSGEPSS ILNLPGESTL
360 370 380 390 400
RRDFLRLQLA NKERSEALRR QQLEQQQREN EEHKRQLLAE RQKRIEEQKE
410 420 430 440 450
QRRRLEEQQR REKELRKQQE REQRRHYEEQ MRREEERRRA EHEQEYKRKQ
460 470 480 490 500
LEEQRQAERL QRQLKQERDY LVSLQHQRQE QRPLEKKPLY HYKEGMSPSE
510 520 530 540 550
KPAWAKEVEE RSRLNRQSSP AMPHKVANRI SDPNLPPRSE SFSISGVQPA
560 570 580 590 600
RTPPMLRPVD PQIPQLVAVK SQGPALTASQ SVHEQPTKGL SGFQEALNVT
610 620 630 640 650
SHRVEMPRQN SDPTSENPPL PTRIEKFDRS SWLRQEEDIP PKVPQRTTSI
660 670 680 690 700
SPALARKNSP GNGSALGPRL GSQPIRASNP DLRRTEPVLE SSLQRTSSGS
710 720 730 740 750
SSSSSTPSSQ PSSQGGSQPG SQAGSSERSR VRANSKSEGS PVLPHEPSKV
760 770 780 790 800
KPEESRDITR PSRPADLTAL AKELRELRIE ETNRPLKKVT DYSSSSEESE
810 820 830 840 850
SSEEEEEDGE SETHDGTVAV SDIPRLIPTG APGNNEQYNM GMVGTHGLET
860 870 880 890 900
SHADTFGGSI SREGTLMIRE TAEEKKRSGH SDSNGFAGHI NLPDLVQQSH
910 920 930 940 950
SPAGTPTEGL GRVSTHSQEM DSGAEYGIGS STKASFTPFV DPRVYQTSPT
960 970 980 990 1000
DEDEEDDESS AAALFTSELL RQEQAKLNEA RKISVVNVNP TNIRPHSDTP
1010 1020 1030 1040 1050
EIRKYKKRFN SEILCAALWG VNLLVGTENG LMLLDRSGQG KVYNLINRRR
1060 1070 1080 1090 1100
FQQMDVLEGL NVLVTISGKK NKLRVYYLSW LRNRILHNDP EVEKKQGWIT
1110 1120 1130 1140 1150
VGDLEGCIHY KVVKYERIKF LVIALKNAVE IYAWAPKPYH KFMAFKSFAD
1160 1170 1180 1190 1200
LQHKPLLVDL TVEEGQRLKV IFGSHTGFHV IDVDSGNSYD IYIPSHIQGN
1210 1220 1230 1240 1250
ITPHAIVILP KTDGMEMLVC YEDEGVYVNT YGRITKDVVL QWGEMPTSVA
1260 1270 1280 1290 1300
YIHSNQIMGW GEKAIEIRSV ETGHLDGVFM HKRAQRLKFL CERNDKVFFA
1310 1320
SVRSGGSSQV FFMTLNRNSM MNW

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 ENSGT00760000118848.
HOGENOMi HOG000290708.
HOVERGENi HBG036506.
InParanoidi P83510.
KOi K08840.
OrthoDBi EOG73803V.

Miscellaneous databases

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

Gene expression databases

Bgeei P83510.
CleanExi MM_TNIK.
ExpressionAtlasi P83510. baseline and differential.
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.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 115 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