P83510 (TNIK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Traf2 and NCK-interacting protein kinase
EC=2.7.11.1

Gene names

Name:	Tnik
Synonyms:	Kiaa0551

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1323 AA.
Sequence status	Complete.
Protein existence	Evidence 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.7 Ref.8
Subcellular location	Nucleus. Cytoplasm. Recycling endosome By similarity. Cytoplasm › cytoskeleton By similarity. Note: Associated with recycling endosomes and the cytoskeletal fraction upon RAP2A overexpression By similarity. Ref.7
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 process	Neurogenesis Wnt signaling pathway
Cellular component	Cytoplasm Cytoskeleton Endosome Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor 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 protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of dendrite morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	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_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1323	1323	Traf2 and NCK-interacting protein kinase		PRO_0000086762
Regions
	Domain	25 – 289	265	Protein kinase
	Domain	1010 – 1297	288	CNH
	Nucleotide binding	31 – 39	9	ATP By similarity UniProtKB O00506
	Region	290 – 1010	721	Mediates interaction with NEDD4 By similarity
Sites
	Active site	153	1	Proton acceptor By similarity UniProtKB O00506
	Binding site	54	1	ATP By similarity UniProtKB O00506
Amino acid modifications
	Modified residue	326	1	Phosphoserine By similarity
	Modified residue	531	1	Phosphoserine By similarity
	Modified residue	611	1	Phosphoserine By similarity
	Modified residue	649	1	Phosphoserine By similarity
	Modified residue	651	1	Phosphoserine By similarity
	Modified residue	659	1	Phosphoserine By similarity
	Modified residue	678	1	Phosphoserine By similarity
	Modified residue	691	1	Phosphoserine By similarity
	Modified residue	737	1	Phosphoserine By similarity
	Modified residue	740	1	Phosphoserine Ref.6
	Modified residue	950	1	Phosphothreonine Ref.5
Natural variations
	Alternative sequence	926 – 962	37	YGIGS…ESSAA → SLK in isoform 2.		VSP_007351
Experimental info
	Sequence conflict	735	1	S → C in BAC40365. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 24, 2007. Version 2. Checksum: B8289189530251D2	FASTA	1,323	150,367
	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
	Isoform 2 [UniParc]. Checksum: A41F95CC9AC436D8	FASTA	1,289	146,713
	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 DSGAESLKAL FTSELLRQEQ AKLNEARKIS VVNVNPTNIR 970 980 990 1000 1010 1020 PHSDTPEIRK YKKRFNSEIL CAALWGVNLL VGTENGLMLL DRSGQGKVYN LINRRRFQQM 1030 1040 1050 1060 1070 1080 DVLEGLNVLV TISGKKNKLR VYYLSWLRNR ILHNDPEVEK KQGWITVGDL EGCIHYKVVK 1090 1100 1110 1120 1130 1140 YERIKFLVIA LKNAVEIYAW APKPYHKFMA FKSFADLQHK PLLVDLTVEE GQRLKVIFGS 1150 1160 1170 1180 1190 1200 HTGFHVIDVD SGNSYDIYIP SHIQGNITPH AIVILPKTDG MEMLVCYEDE GVYVNTYGRI 1210 1220 1230 1240 1250 1260 TKDVVLQWGE MPTSVAYIHS NQIMGWGEKA IEIRSVETGH LDGVFMHKRA QRLKFLCERN 1270 1280 DKVFFASVRS GGSSQVFFMT LNRNSMMNW

References

	« Hide 'large scale' referencesShow '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. , 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]	"Phosphoproteomic analysis of the developing mouse brain." Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P. Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-950, MASS SPECTROMETRY. Tissue: Embryonic brain.
[6]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-740, MASS SPECTROMETRY. Tissue: Melanoma.
[7]	"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.
[8]	"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.
IPI	IPI00187510. IPI00989691.
RefSeq	NP_001156480.1. NM_001163008.1.
UniGene	Mm.126193. Mm.483052.
3D structure databases
ProteinModelPortal	P83510.
SMR	P83510. Positions 13-313.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-57467N.
PTM databases
PhosphoSite	P83510.
Proteomic databases
PaxDb	P83510.
PRIDE	P83510.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000159236; ENSMUSP00000124681; ENSMUSG00000027692.
GeneID	665113.
KEGG	mmu:665113.
UCSC	uc008oty.1. mouse.
Organism-specific databases
CTD	23043.
MGI	MGI:1916264. Tnik.
Rouge	Search...
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00680000099778.
HOGENOM	HOG000290708.
HOVERGEN	HBG036506.
KO	K08840.
Gene expression databases
ArrayExpress	P83510.
Bgee	P83510.
CleanEx	MM_TNIK.
Genevestigator	P83510.
GermOnline	ENSMUSG00000027692. Mus musculus.
Family and domain databases
InterPro	IPR001180. Citron. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00780. CNH. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00036. CNH. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50219. CNH. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TNIK. mouse.
NextBio	426671.
SOURCE	Search...

Entry information

Entry name

TNIK_MOUSE

Accession

Primary (citable) accession number: P83510

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 30, 2003
Last sequence update:	July 24, 2007
Last modified:	April 3, 2013
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program