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Protein

Serine/threonine-protein kinase TAO3

Gene

TAOK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Inhibits basal activity of MAPK8/JNK cascade and diminishes its activation in response epidermal growth factor (EGF).3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei53ATPPROSITE-ProRule annotation1
Active sitei147Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi30 – 38ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • MAP kinase kinase kinase activity Source: GO_Central
  • protein kinase inhibitor activity Source: ProtInc
  • protein serine/threonine kinase activity Source: HGNC
  • transferase activity Source: HGNC

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • DNA repair Source: UniProtKB-KW
  • MAPK cascade Source: HGNC
  • mitotic G2 DNA damage checkpoint Source: UniProtKB
  • negative regulation of JNK cascade Source: HGNC
  • nervous system development Source: GO_Central
  • positive regulation of JNK cascade Source: HGNC
  • positive regulation of JUN kinase activity Source: UniProtKB
  • positive regulation of stress-activated MAPK cascade Source: UniProtKB
  • protein autophosphorylation Source: HGNC
  • protein phosphorylation Source: HGNC
  • regulation of apoptotic process Source: GO_Central

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processDNA damage, DNA repair
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ9H2K8
SIGNORiQ9H2K8

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase TAO3 (EC:2.7.11.1)
Alternative name(s):
Cutaneous T-cell lymphoma-associated antigen HD-CL-09
Short name:
CTCL-associated antigen HD-CL-09
Dendritic cell-derived protein kinase
JNK/SAPK-inhibitory kinase
Jun kinase-inhibitory kinase
Kinase from chicken homolog A
Short name:
hKFC-A
Thousand and one amino acid protein 3
Gene namesi
Name:TAOK3
Synonyms:DPK, JIK, KDS, MAP3K18
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000135090.13
HGNCiHGNC:18133 TAOK3
MIMi616711 gene
neXtProtiNX_Q9H2K8

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

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi165D → A: Loss of serine/threonine-protein kinase activity. 1 Publication1
Mutagenesisi181T → A: No autophosphorylation and no kinase activity; when associated with F-183. 1 Publication1
Mutagenesisi183Y → F: No autophosphorylation and no kinase activity; when associated with A-181. 1 Publication1
Mutagenesisi324S → A: Inhibits activation of the p38/MAPK14 stress-activated MAPK cascade in response to DNA damage. 1 Publication1

Organism-specific databases

DisGeNETi51347
OpenTargetsiENSG00000135090
PharmGKBiPA134975064

Chemistry databases

ChEMBLiCHEMBL5701
GuidetoPHARMACOLOGYi2235

Polymorphism and mutation databases

BioMutaiTAOK3
DMDMi78099183

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000867371 – 898Serine/threonine-protein kinase TAO3Add BLAST898

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei324Phosphoserine; by ATMCombined sources1 Publication1
Modified residuei331PhosphoserineCombined sources1
Modified residuei343PhosphoserineBy similarity1
Modified residuei346PhosphoserineBy similarity1
Modified residuei349PhosphoserineBy similarity1
Modified residuei357PhosphothreonineBy similarity1
Modified residuei359PhosphoserineBy similarity1
Modified residuei442PhosphoserineCombined sources1
Modified residuei830N6-acetyllysineBy similarity1

Post-translational modificationi

Autophosphorylated. Phosphorylation at Ser-324 by ATM following DNA damage is required for activation of the p38/MAPK14 stress-activated MAPK cascade. Phosphorylated by LRRK2.3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9H2K8
MaxQBiQ9H2K8
PaxDbiQ9H2K8
PeptideAtlasiQ9H2K8
PRIDEiQ9H2K8

PTM databases

iPTMnetiQ9H2K8
PhosphoSitePlusiQ9H2K8

Expressioni

Tissue specificityi

Ubiquitously expressed at a low level, and highly expressed in peripheral blood leukocytes (PBLs), thymus, spleen, kidney, skeletal muscle, heart and liver.2 Publications

Gene expression databases

BgeeiENSG00000135090
CleanExiHS_TAOK3
ExpressionAtlasiQ9H2K8 baseline and differential
GenevisibleiQ9H2K8 HS

Organism-specific databases

HPAiHPA017160

Interactioni

Subunit structurei

Self-associates. Interacts with ERN1 and TRAF2. Interaction with TRAF2 is facilitated under ER stress conditions, such as treatment with tunicamycin, and may promote TRAF2 phosphorylation.1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi119490, 11 interactors
IntActiQ9H2K8, 7 interactors
STRINGi9606.ENSP00000376317

Chemistry databases

BindingDBiQ9H2K8

Structurei

3D structure databases

ProteinModelPortaliQ9H2K8
SMRiQ9H2K8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 277Protein kinasePROSITE-ProRule annotationAdd BLAST254

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili452 – 502Sequence analysisAdd BLAST51
Coiled coili548 – 649Sequence analysisAdd BLAST102
Coiled coili754 – 879Sequence analysisAdd BLAST126

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi343 – 393Ser-richAdd BLAST51

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0577 Eukaryota
ENOG410Y259 LUCA
GeneTreeiENSGT00900000140838
HOGENOMiHOG000236358
HOVERGENiHBG088996
InParanoidiQ9H2K8
KOiK04429
OMAiNHSIPSM
OrthoDBiEOG091G01CN
PhylomeDBiQ9H2K8
TreeFamiTF351444

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

Q9H2K8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRKGVLKDPE IADLFYKDDP EELFIGLHEI GHGSFGAVYF ATNAHTSEVV
60 70 80 90 100
AIKKMSYSGK QTHEKWQDIL KEVKFLRQLK HPNTIEYKGC YLKEHTAWLV
110 120 130 140 150
MEYCLGSASD LLEVHKKPLQ EVEIAAITHG ALHGLAYLHS HALIHRDIKA
160 170 180 190 200
GNILLTEPGQ VKLADFGSAS MASPANSFVG TPYWMAPEVI LAMDEGQYDG
210 220 230 240 250
KVDIWSLGIT CIELAERKPP LFNMNAMSAL YHIAQNDSPT LQSNEWTDSF
260 270 280 290 300
RRFVDYCLQK IPQERPTSAE LLRHDFVRRD RPLRVLIDLI QRTKDAVREL
310 320 330 340 350
DNLQYRKMKK ILFQETRNGP LNESQEDEED SEHGTSLNRE MDSLGSNHSI
360 370 380 390 400
PSMSVSTGSQ SSSVNSMQEV MDESSSELVM MHDDESTINS SSSVVHKKDH
410 420 430 440 450
VFIRDEAGHG DPRPEPRPTQ SVQSQALHYR NRERFATIKS ASLVTRQIHE
460 470 480 490 500
HEQENELREQ MSGYKRMRRQ HQKQLIALEN KLKAEMDEHR LKLQKEVETH
510 520 530 540 550
ANNSSIELEK LAKKQVAIIE KEAKVAAADE KKFQQQILAQ QKKDLTTFLE
560 570 580 590 600
SQKKQYKICK EKIKEEMNED HSTPKKEKQE RISKHKENLQ HTQAEEEAHL
610 620 630 640 650
LTQQRLYYDK NCRFFKRKIM IKRHEVEQQN IREELNKKRT QKEMEHAMLI
660 670 680 690 700
RHDESTRELE YRQLHTLQKL RMDLIRLQHQ TELENQLEYN KRRERELHRK
710 720 730 740 750
HVMELRQQPK NLKAMEMQIK KQFQDTCKVQ TKQYKALKNH QLEVTPKNEH
760 770 780 790 800
KTILKTLKDE QTRKLAILAE QYEQSINEMM ASQALRLDEA QEAECQALRL
810 820 830 840 850
QLQQEMELLN AYQSKIKMQT EAQHERELQK LEQRVSLRRA HLEQKIEEEL
860 870 880 890
AALQKERSER IKNLLERQER EIETFDMESL RMGFGNLVTL DFPKEDYR
Length:898
Mass (Da):105,406
Last modified:October 25, 2005 - v2
Checksum:iAE7E30745B09763C
GO

Sequence cautioni

The sequence AAN09723 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti136A → T in AAG38501 (PubMed:13679851).Curated1
Sequence conflicti173S → P in AAG38501 (PubMed:13679851).Curated1
Sequence conflicti356 – 378STGSQ…SSSEL → TWNQPEQGNGQPGQQPFHSK HVR in AAF14559 (PubMed:10559204).CuratedAdd BLAST23
Sequence conflicti668Q → R in AAG38501 (PubMed:13679851).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04120520P → T in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_02369147S → N3 PublicationsCorresponds to variant dbSNP:rs428073Ensembl.1
Natural variantiVAR_041206392S → Y in a lung small cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041207727C → Y1 PublicationCorresponds to variant dbSNP:rs55857273Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF179867 mRNA Translation: AAF14559.1
AF135158 mRNA Translation: AAG09131.1
AF263311 mRNA Translation: AAG38501.1
AF181985 mRNA Translation: AAF25817.1
BT007185 mRNA Translation: AAP35849.1
AC026366 Genomic DNA No translation available.
BC002756 mRNA Translation: AAH02756.1
AL833731 mRNA Translation: CAH56239.1
AF328731 mRNA Translation: AAN09723.1 Different initiation.
CCDSiCCDS9188.1
RefSeqiNP_001333417.1, NM_001346488.1
NP_001333418.1, NM_001346489.1
NP_057365.3, NM_016281.3
UniGeneiHs.644420

Genome annotation databases

EnsembliENST00000392533; ENSP00000376317; ENSG00000135090
ENST00000419821; ENSP00000416374; ENSG00000135090
GeneIDi51347
KEGGihsa:51347
UCSCiuc001twx.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTAOK3_HUMAN
AccessioniPrimary (citable) accession number: Q9H2K8
Secondary accession number(s): Q658N1
, Q8IUM4, Q9HC79, Q9NZM9, Q9UHG7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: October 25, 2005
Last modified: April 25, 2018
This is version 152 of the entry and version 2 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

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health