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UniProtKB - Q9UKE5 (TNIK_HUMAN)

Protein

TRAF2 and NCK-interacting protein kinase

Gene

TNIK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Phosphorylates SMAD1 on Thr-322.6 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei54ATPPROSITE-ProRule annotation1
Active sitei153Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi31 – 39ATPPROSITE-ProRule annotation9

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processNeurogenesis, Wnt signaling pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
SignaLinkiQ9UKE5
SIGNORiQ9UKE5

Names & Taxonomyi

Protein namesi
Recommended name:
TRAF2 and NCK-interacting protein kinase (EC:2.7.11.1)
Gene namesi
Name:TNIK
Synonyms:KIAA0551
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000154310.16
HGNCiHGNC:30765 TNIK
MIMi610005 gene
neXtProtiNX_Q9UKE5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Endosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

Mental retardation, autosomal recessive 54 (MRT54)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT54 patients manifest intellectual disability, delayed speech and hyperactivity.
See also OMIM:617028

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi54K → A: Kinase dead. Loss of autophosphorylation and loss of function in cytoskeleton regulation. 2 Publications1
Mutagenesisi152 – 153RD → AA: Loss of autophosphorylation. 1 Publication2
Mutagenesisi171 – 172DF → AA: Loss of autophosphorylation. 1 Publication2

Keywords - Diseasei

Mental retardation

Organism-specific databases

DisGeNETi23043
MalaCardsiTNIK
MIMi617028 phenotype
OpenTargetsiENSG00000154310
PharmGKBiPA134893180

Chemistry databases

ChEMBLiCHEMBL4527
GuidetoPHARMACOLOGYi2244

Polymorphism and mutation databases

BioMutaiTNIK
DMDMi29840818

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000867611 – 1360TRAF2 and NCK-interacting protein kinaseAdd BLAST1360

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei187PhosphothreonineBy similarity1
Modified residuei324PhosphoserineBy similarity1
Modified residuei326PhosphoserineCombined sources1
Modified residuei560PhosphoserineCombined sources1
Modified residuei570PhosphoserineCombined sources1
Modified residuei581PhosphothreonineBy similarity1
Modified residuei600PhosphoserineCombined sources1
Modified residuei608PhosphoserineCombined sources1
Modified residuei610PhosphoserineCombined sources1
Modified residuei640PhosphoserineCombined sources1
Modified residuei678PhosphoserineCombined sources1
Modified residuei680PhosphoserineCombined sources1
Modified residuei688PhosphoserineCombined sources1
Modified residuei701PhosphoserineCombined sources1
Modified residuei707PhosphoserineCombined sources1
Modified residuei720PhosphoserineCombined sources1
Modified residuei764PhosphoserineCombined sources1
Modified residuei766PhosphoserineCombined sources1
Modified residuei769PhosphoserineCombined sources1
Modified residuei959PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylated. Autophosphorylation is activated by RAP2A and induces association to the cytoskeletal fraction.

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UKE5
PaxDbiQ9UKE5
PeptideAtlasiQ9UKE5
PRIDEiQ9UKE5
ProteomicsDBi84769
84770 [Q9UKE5-2]
84771 [Q9UKE5-3]
84772 [Q9UKE5-4]
84773 [Q9UKE5-5]
84774 [Q9UKE5-6]
84775 [Q9UKE5-7]
84776 [Q9UKE5-8]

PTM databases

iPTMnetiQ9UKE5
PhosphoSitePlusiQ9UKE5

Miscellaneous databases

PMAP-CutDBiQ9UKE5

Expressioni

Tissue specificityi

Expressed ubiquitously. Highest levels observed in heart, brain and skeletal muscle. Expressed in normal colonic epithelia and colorectal cancer tissues.2 Publications

Gene expression databases

BgeeiENSG00000154310 Expressed in 210 organ(s), highest expression level in corpus callosum
ExpressionAtlasiQ9UKE5 baseline and differential
GenevisibleiQ9UKE5 HS

Organism-specific databases

HPAiHPA012128
HPA012297

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 TANC1.5 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi116682, 52 interactors
DIPiDIP-37562N
IntActiQ9UKE5, 32 interactors
MINTiQ9UKE5
STRINGi9606.ENSP00000399511

Chemistry databases

BindingDBiQ9UKE5

Structurei

Secondary structure

11360
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UKE5
SMRiQ9UKE5
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UKE5

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 289Protein kinasePROSITE-ProRule annotationAdd BLAST265
Domaini1047 – 1334CNHPROSITE-ProRule annotationAdd BLAST288

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni290 – 1047Mediates interaction with NEDD41 PublicationAdd BLAST758

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0587 Eukaryota
ENOG410XPHR LUCA
GeneTreeiENSGT00920000148966
HOVERGENiHBG036506
InParanoidiQ9UKE5
KOiK08840
OMAiFKIVRYE
OrthoDBiEOG091G018A
PhylomeDBiQ9UKE5
TreeFamiTF105138

Family and domain databases

InterProiView protein in InterPro
IPR001180 CNH_dom
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00780 CNH, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00036 CNH, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50219 CNH, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (8+)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 8 described isoforms and 2 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q9UKE5-1) [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 EHEQEYIRRQ 
       460        470        480        490        500
LEEEQRQLEI LQQQLLHEQA LLLEYKRKQL EEQRQAERLQ RQLKQERDYL 
       510        520        530        540        550
VSLQHQRQEQ RPVEKKPLYH YKEGMSPSEK PAWAKEVEER SRLNRQSSPA 
       560        570        580        590        600
MPHKVANRIS DPNLPPRSES FSISGVQPAR TPPMLRPVDP QIPHLVAVKS 
       610        620        630        640        650
QGPALTASQS VHEQPTKGLS GFQEALNVTS HRVEMPRQNS DPTSENPPLP 
       660        670        680        690        700
TRIEKFDRSS WLRQEEDIPP KVPQRTTSIS PALARKNSPG NGSALGPRLG 
       710        720        730        740        750
SQPIRASNPD LRRTEPILES PLQRTSSGSS SSSSTPSSQP SSQGGSQPGS 
       760        770        780        790        800
QAGSSERTRV RANSKSEGSP VLPHEPAKVK PEESRDITRP SRPASYKKAI 
       810        820        830        840        850
DEDLTALAKE LRELRIEETN RPMKKVTDYS SSSEESESSE EEEEDGESET 
       860        870        880        890        900
HDGTVAVSDI PRLIPTGAPG SNEQYNVGMV GTHGLETSHA DSFSGSISRE 
       910        920        930        940        950
GTLMIRETSG EKKRSGHSDS NGFAGHINLP DLVQQSHSPA GTPTEGLGRV 
       960        970        980        990       1000
STHSQEMDSG TEYGMGSSTK ASFTPFVDPR VYQTSPTDED EEDEESSAAA 
      1010       1020       1030       1040       1050
LFTSELLRQE QAKLNEARKI SVVNVNPTNI RPHSDTPEIR KYKKRFNSEI 
      1060       1070       1080       1090       1100
LCAALWGVNL LVGTENGLML LDRSGQGKVY NLINRRRFQQ MDVLEGLNVL 
      1110       1120       1130       1140       1150
VTISGKKNKL RVYYLSWLRN RILHNDPEVE KKQGWITVGD LEGCIHYKVV 
      1160       1170       1180       1190       1200
KYERIKFLVI ALKNAVEIYA WAPKPYHKFM AFKSFADLQH KPLLVDLTVE 
      1210       1220       1230       1240       1250
EGQRLKVIFG SHTGFHVIDV DSGNSYDIYI PSHIQGNITP HAIVILPKTD 
      1260       1270       1280       1290       1300
GMEMLVCYED EGVYVNTYGR ITKDVVLQWG EMPTSVAYIH SNQIMGWGEK 
      1310       1320       1330       1340       1350
AIEIRSVETG HLDGVFMHKR AQRLKFLCER NDKVFFASVR SGGSSQVFFM 
      1360
TLNRNSMMNW
Length:1,360
Mass (Da):154,943
Last modified:May 1, 2000 - v1
Checksum:i3590BC2905A72C3D
GO
Isoform 2 (identifier: Q9UKE5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     445-473: Missing.

Show »
Length:1,331
Mass (Da):151,300
Checksum:i85378CBC98631411
GO
Isoform 3 (identifier: Q9UKE5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     537-591: Missing.

Show »
Length:1,305
Mass (Da):148,829
Checksum:i209230BB15712DFC
GO
Isoform 4 (identifier: Q9UKE5-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     795-802: Missing.

Show »
Length:1,352
Mass (Da):154,008
Checksum:iF4708A71FF26C54F
GO
Isoform 5 (identifier: Q9UKE5-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     445-473: Missing.
     537-591: Missing.

Show »
Length:1,276
Mass (Da):145,186
Checksum:i9B85E462E4FAE9F0
GO
Isoform 6 (identifier: Q9UKE5-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     445-473: Missing.
     795-802: Missing.

Show »
Length:1,323
Mass (Da):150,365
Checksum:i93B2E73EF75034B9
GO
Isoform 7 (identifier: Q9UKE5-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     537-591: Missing.
     795-802: Missing.

Show »
Length:1,297
Mass (Da):147,894
Checksum:iEED944B571948D3F
GO
Isoform 8 (identifier: Q9UKE5-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     445-473: Missing.
     537-591: Missing.
     795-802: Missing.

Show »
Length:1,268
Mass (Da):144,251
Checksum:i55AD5F59B7A08A2A
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J338C9J338_HUMAN
TRAF2 and NCK-interacting protein k...
TNIK
350Annotation score:
C9JVV1C9JVV1_HUMAN
TRAF2 and NCK-interacting protein k...
TNIK
45Annotation score:

Sequence cautioni

The sequence BAA25477 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041231778K → E1 PublicationCorresponds to variant dbSNP:rs55778284Ensembl.1
Natural variantiVAR_041232910G → E1 PublicationCorresponds to variant dbSNP:rs35090763Ensembl.1
Natural variantiVAR_041233999A → T1 PublicationCorresponds to variant dbSNP:rs17857452Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004889445 – 473Missing in isoform 2, isoform 5, isoform 6 and isoform 8. 2 PublicationsAdd BLAST29
Alternative sequenceiVSP_004890537 – 591Missing in isoform 3, isoform 5, isoform 7 and isoform 8. 2 PublicationsAdd BLAST55
Alternative sequenceiVSP_004891795 – 802Missing in isoform 4, isoform 6, isoform 7 and isoform 8. 1 Publication8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF172264 mRNA Translation: AAF03782.1
AF172268 mRNA Translation: AAF03786.1
AF172267 mRNA Translation: AAF03785.1
AF172266 mRNA Translation: AAF03784.1
AF172265 mRNA Translation: AAF03783.1
AF172270 mRNA Translation: AAF03788.1
AF172271 mRNA Translation: AAF03789.1
AF172269 mRNA Translation: AAF03787.1
AB011123 mRNA Translation: BAA25477.2 Different initiation.
AK291056 mRNA Translation: BAF83745.1
AC026315 Genomic DNA No translation available.
AC078793 Genomic DNA No translation available.
AC092919 Genomic DNA No translation available.
AC137517 Genomic DNA No translation available.
CH471052 Genomic DNA Translation: EAW78484.1
CH471052 Genomic DNA Translation: EAW78489.1
CH471052 Genomic DNA Translation: EAW78492.1
CH471052 Genomic DNA Translation: EAW78493.1
BC019081 mRNA Translation: AAH19081.2
BC150256 mRNA Translation: AAI50257.1
CCDSiCCDS46956.1 [Q9UKE5-1]
CCDS54673.1 [Q9UKE5-8]
CCDS54674.1 [Q9UKE5-5]
CCDS54675.1 [Q9UKE5-6]
CCDS54676.1 [Q9UKE5-2]
CCDS54677.1 [Q9UKE5-7]
CCDS54678.1 [Q9UKE5-3]
CCDS54679.1 [Q9UKE5-4]
RefSeqiNP_001155032.1, NM_001161560.2 [Q9UKE5-4]
NP_001155033.1, NM_001161561.2 [Q9UKE5-2]
NP_001155034.1, NM_001161562.2 [Q9UKE5-6]
NP_001155035.1, NM_001161563.2 [Q9UKE5-3]
NP_001155036.1, NM_001161564.2 [Q9UKE5-7]
NP_001155037.1, NM_001161565.2 [Q9UKE5-5]
NP_001155038.1, NM_001161566.2 [Q9UKE5-8]
NP_055843.1, NM_015028.3 [Q9UKE5-1]
UniGeneiHs.34024
Hs.723245

Genome annotation databases

EnsembliENST00000284483; ENSP00000284483; ENSG00000154310 [Q9UKE5-4]
ENST00000341852; ENSP00000345352; ENSG00000154310 [Q9UKE5-5]
ENST00000357327; ENSP00000349880; ENSG00000154310 [Q9UKE5-2]
ENST00000436636; ENSP00000399511; ENSG00000154310 [Q9UKE5-1]
ENST00000460047; ENSP00000418916; ENSG00000154310 [Q9UKE5-7]
ENST00000470834; ENSP00000419990; ENSG00000154310 [Q9UKE5-6]
ENST00000475336; ENSP00000418156; ENSG00000154310 [Q9UKE5-8]
ENST00000488470; ENSP00000418378; ENSG00000154310 [Q9UKE5-3]
GeneIDi23043
KEGGihsa:23043
UCSCiuc003fhh.3 human [Q9UKE5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTNIK_HUMAN
AccessioniPrimary (citable) accession number: Q9UKE5
Secondary accession number(s): A7E2A3
, A8K4U1, D3DNQ6, O60298, Q8WUY7, Q9UKD8, Q9UKD9, Q9UKE0, Q9UKE1, Q9UKE2, Q9UKE3, Q9UKE4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: May 1, 2000
Last modified: September 12, 2018
This is version 180 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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