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Protein

Serine/threonine-protein kinase TAO1

Gene

TAOK1

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

Functioni

Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability. Phosphorylates MAP2K3, MAP2K6 and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade by mediating phosphorylation and subsequent activation of the upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled receptor signaling to p38/MAPK14. 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 MAP2K3 and MAP2K6. Acts as a regulator of cytoskeleton stability by phosphorylating 'Thr-208' of MARK2, leading to activate MARK2 kinase activity and subsequent phosphorylation and detachment of MAPT/TAU from microtubules. Also acts as a regulator of apoptosis: regulates apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation via activation of the MAPK8/JNK cascade.5 Publications

Caution

Was initially thought to play a role in the spindle checkpoint (PubMed:17417629). However, it was later shown that it is not the case and that phenotypes initially observed are the cause of the siRNA used that has an off-target effect resulting in MAD2L1 inhibition (PubMed:19904549 and PubMed:20162290).1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Serine/threonine-protein kinase activity is inhibited by SPRED1.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei57ATPCurated1
Active sitei151Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi34 – 42ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: HGNC
  • kinase activity Source: HGNC
  • MAP kinase kinase kinase activity Source: GO_Central
  • protein kinase activity Source: ARUK-UCL
  • protein serine/threonine kinase activator activity Source: ARUK-UCL
  • protein serine/threonine kinase activity Source: UniProtKB
  • transferase activity Source: HGNC

GO - Biological processi

  • activation of JUN kinase activity Source: ARUK-UCL
  • activation of MAPK activity Source: ARUK-UCL
  • cellular response to DNA damage stimulus Source: UniProtKB
  • DNA repair Source: UniProtKB-KW
  • execution phase of apoptosis Source: UniProtKB
  • mitotic G2 DNA damage checkpoint Source: UniProtKB
  • nervous system development Source: GO_Central
  • positive regulation of JNK cascade Source: UniProtKB
  • positive regulation of stress-activated MAPK cascade Source: UniProtKB
  • protein autophosphorylation Source: ARUK-UCL
  • protein phosphorylation Source: HGNC
  • regulation of actin cytoskeleton organization Source: ARUK-UCL
  • regulation of apoptotic process Source: GO_Central
  • regulation of cytoskeleton organization Source: UniProtKB
  • regulation of microtubule cytoskeleton organization Source: ARUK-UCL
  • regulation of mitotic cell cycle Source: GO_Central

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-68877 Mitotic Prometaphase
SignaLinkiQ7L7X3
SIGNORiQ7L7X3

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase TAO1 (EC:2.7.11.1)
Alternative name(s):
Kinase from chicken homolog B
Short name:
hKFC-B
MARK Kinase
Short name:
MARKK
Prostate-derived sterile 20-like kinase 2
Short name:
PSK-2
Short name:
PSK2
Short name:
Prostate-derived STE20-like kinase 2
Thousand and one amino acid protein kinase 1
Short name:
TAOK1
Short name:
hTAOK1
Gene namesi
Name:TAOK1
Synonyms:KIAA1361, MAP3K16, MARKK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000160551.9
HGNCiHGNC:29259 TAOK1
MIMi610266 gene
neXtProtiNX_Q7L7X3

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi57K → A: Abolishes kinase activity, ability to activate the MAPK8/JNK cascade and cleavage by caspase-3 (CASP3). 1 Publication1
Mutagenesisi169D → A: Loss of serine/threonine-protein kinase activity. 1 Publication1
Mutagenesisi376D → N: Does not abolish cleavage by caspase-3 (CASP3). 1 Publication1
Mutagenesisi643T → A: Abolishes phosphorylation by ATM; when associated with A-785 and A-990. 1 Publication1
Mutagenesisi785T → A: Abolishes phosphorylation by ATM; when associated with A-643 and A-990. 1 Publication1
Mutagenesisi990S → A: Abolishes phosphorylation by ATM; when associated with A-643 and A-785. 1 Publication1

Organism-specific databases

DisGeNETi57551
OpenTargetsiENSG00000160551
PharmGKBiPA134872946

Chemistry databases

ChEMBLiCHEMBL5261
GuidetoPHARMACOLOGYi2233

Polymorphism and mutation databases

BioMutaiTAOK1
DMDMi74759012

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000867281 – 1001Serine/threonine-protein kinase TAO1Add BLAST1001

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei9PhosphoserineCombined sources1
Modified residuei421PhosphoserineCombined sources1
Modified residuei445PhosphoserineCombined sources1
Modified residuei669PhosphothreonineCombined sources1
Modified residuei965PhosphoserineCombined sources1

Post-translational modificationi

Proteolytically processed by caspase-3 (CASP3).1 Publication
Autophosphorylated (By similarity). Phosphorylated by ATM in response to DNA damage. Phosphorylated by LRRK2.By similarity2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ7L7X3
MaxQBiQ7L7X3
PaxDbiQ7L7X3
PeptideAtlasiQ7L7X3
PRIDEiQ7L7X3
ProteomicsDBi68829
68830 [Q7L7X3-2]
68831 [Q7L7X3-3]

PTM databases

iPTMnetiQ7L7X3
PhosphoSitePlusiQ7L7X3

Expressioni

Tissue specificityi

Highly expressed in the testis, and to a lower extent also expressed in brain, placenta, colon and skeletal muscle.2 Publications

Inductioni

In response to DNA damage.1 Publication

Gene expression databases

BgeeiENSG00000160551
CleanExiHS_TAOK1
ExpressionAtlasiQ7L7X3 baseline and differential
GenevisibleiQ7L7X3 HS

Organism-specific databases

HPAiHPA007669

Interactioni

Subunit structurei

Self-associates. Interacts with MAP2K3 (By similarity). Interacts with SPRED1 and TESK1. Interacts with MAP3K7.By similarity1 Publication

Protein-protein interaction databases

BioGridi121607, 15 interactors
DIPiDIP-39709N
IntActiQ7L7X3, 11 interactors
MINTiQ7L7X3
STRINGi9606.ENSP00000261716

Chemistry databases

BindingDBiQ7L7X3

Structurei

3D structure databases

ProteinModelPortaliQ7L7X3
SMRiQ7L7X3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 281Protein kinasePROSITE-ProRule annotationAdd BLAST254

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili458 – 651Sequence analysisAdd BLAST194
Coiled coili754 – 877Sequence analysisAdd BLAST124

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi330 – 334Poly-Glu5
Compositional biasi347 – 379Ser-richAdd BLAST33

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0577 Eukaryota
ENOG410Y259 LUCA
GeneTreeiENSGT00920000148968
HOGENOMiHOG000236358
HOVERGENiHBG088996
InParanoidiQ7L7X3
KOiK04429
OMAiPQAMRRT
OrthoDBiEOG091G01CN
PhylomeDBiQ7L7X3
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

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7L7X3-1) [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
MPSTNRAGSL KDPEIAELFF KEDPEKLFTD LREIGHGSFG AVYFARDVRT
60 70 80 90 100
NEVVAIKKMS YSGKQSTEKW QDIIKEVKFL QRIKHPNSIE YKGCYLREHT
110 120 130 140 150
AWLVMEYCLG SASDLLEVHK KPLQEVEIAA ITHGALQGLA YLHSHTMIHR
160 170 180 190 200
DIKAGNILLT EPGQVKLADF GSASMASPAN SFVGTPYWMA PEVILAMDEG
210 220 230 240 250
QYDGKVDVWS LGITCIELAE RKPPLFNMNA MSALYHIAQN ESPTLQSNEW
260 270 280 290 300
SDYFRNFVDS CLQKIPQDRP TSEELLKHIF VLRERPETVL IDLIQRTKDA
310 320 330 340 350
VRELDNLQYR KMKKLLFQEA HNGPAVEAQE EEEEQDHGVG RTGTVNSVGS
360 370 380 390 400
NQSIPSMSIS ASSQSSSVNS LPDVSDDKSE LDMMEGDHTV MSNSSVIHLK
410 420 430 440 450
PEEENYREEG DPRTRASDPQ SPPQVSRHKS HYRNREHFAT IRTASLVTRQ
460 470 480 490 500
MQEHEQDSEL REQMSGYKRM RRQHQKQLMT LENKLKAEMD EHRLRLDKDL
510 520 530 540 550
ETQRNNFAAE MEKLIKKHQA AMEKEAKVMS NEEKKFQQHI QAQQKKELNS
560 570 580 590 600
FLESQKREYK LRKEQLKEEL NENQSTPKKE KQEWLSKQKE NIQHFQAEEE
610 620 630 640 650
ANLLRRQRQY LELECRRFKR RMLLGRHNLE QDLVREELNK RQTQKDLEHA
660 670 680 690 700
MLLRQHESMQ ELEFRHLNTI QKMRCELIRL QHQTELTNQL EYNKRREREL
710 720 730 740 750
RRKHVMEVRQ QPKSLKSKEL QIKKQFQDTC KIQTRQYKAL RNHLLETTPK
760 770 780 790 800
SEHKAVLKRL KEEQTRKLAI LAEQYDHSIN EMLSTQALRL DEAQEAECQV
810 820 830 840 850
LKMQLQQELE LLNAYQSKIK MQAEAQHDRE LRELEQRVSL RRALLEQKIE
860 870 880 890 900
EEMLALQNER TERIRSLLER QAREIEAFDS ESMRLGFSNM VLSNLSPEAF
910 920 930 940 950
SHSYPGASGW SHNPTGGPGP HWGHPMGGPP QAWGHPMQGG PQPWGHPSGP
960 970 980 990 1000
MQGVPRGSSM GVRNSPQALR RTASGGRTEQ GMSRSTSVTS QISNGSHMSY

T
Length:1,001
Mass (Da):116,070
Last modified:July 5, 2004 - v1
Checksum:i82941DEAEADC7651
GO
Isoform 2 (identifier: Q7L7X3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-174: Missing.
     569-572: ELNE → VLMS
     573-1001: Missing.

Note: No experimental confirmation available.
Show »
Length:398
Mass (Da):46,163
Checksum:iB2744BCA14C7E63F
GO
Isoform 3 (identifier: Q7L7X3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     569-716: Missing.

Note: No experimental confirmation available.
Show »
Length:853
Mass (Da):97,526
Checksum:i15DE595D707B9E34
GO

Sequence cautioni

The sequence BAA92599 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti251S → T in BAB14901 (PubMed:14702039).Curated1
Sequence conflicti257F → S in AAG38502 (PubMed:13679851).Curated1
Sequence conflicti860R → C in AAG38502 (PubMed:13679851).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041204855A → T1 PublicationCorresponds to variant dbSNP:rs34151057Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0159641 – 174Missing in isoform 2. 1 PublicationAdd BLAST174
Alternative sequenceiVSP_043706569 – 716Missing in isoform 3. 1 PublicationAdd BLAST148
Alternative sequenceiVSP_015965569 – 572ELNE → VLMS in isoform 2. 1 Publication4
Alternative sequenceiVSP_015966573 – 1001Missing in isoform 2. 1 PublicationAdd BLAST429

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF263312 mRNA Translation: AAG38502.1
AY049015 mRNA Translation: AAL12217.1
CQ834802 mRNA Translation: CAH05616.1
AB037782 mRNA Translation: BAA92599.1 Different initiation.
AK024376 mRNA Translation: BAB14901.1
AC068025 Genomic DNA No translation available.
AC068588 Genomic DNA No translation available.
AC090698 Genomic DNA No translation available.
CH471159 Genomic DNA Translation: EAW51188.1
BC133039 mRNA Translation: AAI33040.1
BC144067 mRNA Translation: AAI44068.1
CCDSiCCDS32601.1 [Q7L7X3-1]
CCDS56024.1 [Q7L7X3-3]
RefSeqiNP_065842.1, NM_020791.2 [Q7L7X3-1]
NP_079418.1, NM_025142.1 [Q7L7X3-3]
XP_011523362.1, XM_011525060.2 [Q7L7X3-1]
UniGeneiHs.597434
Hs.735869

Genome annotation databases

EnsembliENST00000261716; ENSP00000261716; ENSG00000160551 [Q7L7X3-1]
ENST00000536202; ENSP00000438819; ENSG00000160551 [Q7L7X3-3]
GeneIDi57551
KEGGihsa:57551
UCSCiuc002hdz.3 human [Q7L7X3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTAOK1_HUMAN
AccessioniPrimary (citable) accession number: Q7L7X3
Secondary accession number(s): A2RUT8
, B7ZLV6, Q96L75, Q9H2K7, Q9H7S5, Q9P2I6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: July 5, 2004
Last modified: June 20, 2018
This is version 143 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

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