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Protein

Serine/threonine-protein kinase TAO1

Gene

TAOK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei57 – 571ATPCurated
Active sitei151 – 1511Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi34 – 429ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: HGNC
  • kinase activity Source: HGNC
  • protein kinase activity Source: HGNC
  • protein serine/threonine kinase activity Source: UniProtKB
  • receptor signaling protein serine/threonine kinase activity Source: GO_Central
  • transferase activity Source: HGNC

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • DNA repair Source: UniProtKB-KW
  • execution phase of apoptosis Source: UniProtKB
  • G2 DNA damage checkpoint Source: UniProtKB
  • positive regulation of JNK cascade Source: UniProtKB
  • positive regulation of stress-activated MAPK cascade Source: UniProtKB
  • protein phosphorylation Source: HGNC
  • regulation of cytoskeleton organization Source: UniProtKB
  • sister chromatid cohesion Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, DNA damage, DNA repair

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-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

HGNCiHGNC:29259. TAOK1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi57 – 571K → A: Abolishes kinase activity, ability to activate the MAPK8/JNK cascade and cleavage by caspase-3 (CASP3). 1 Publication
Mutagenesisi169 – 1691D → A: Loss of serine/threonine-protein kinase activity. 1 Publication
Mutagenesisi376 – 3761D → N: Does not abolish cleavage by caspase-3 (CASP3). 1 Publication
Mutagenesisi643 – 6431T → A: Abolishes phosphorylation by ATM; when associated with A-785 and A-990. 1 Publication
Mutagenesisi785 – 7851T → A: Abolishes phosphorylation by ATM; when associated with A-643 and A-990. 1 Publication
Mutagenesisi990 – 9901S → A: Abolishes phosphorylation by ATM; when associated with A-643 and A-785. 1 Publication

Organism-specific databases

PharmGKBiPA134872946.

Chemistry

ChEMBLiCHEMBL5261.
GuidetoPHARMACOLOGYi2233.

Polymorphism and mutation databases

BioMutaiTAOK1.
DMDMi74759012.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10011001Serine/threonine-protein kinase TAO1PRO_0000086728Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei9 – 91PhosphoserineCombined sources
Modified residuei421 – 4211PhosphoserineCombined sources
Modified residuei445 – 4451PhosphoserineCombined sources
Modified residuei669 – 6691PhosphothreonineCombined sources
Modified residuei965 – 9651PhosphoserineCombined sources

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.

PTM databases

iPTMnetiQ7L7X3.
PhosphoSiteiQ7L7X3.

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. 13 interactions.
DIPiDIP-39709N.
IntActiQ7L7X3. 9 interactions.
MINTiMINT-5006389.
STRINGi9606.ENSP00000261716.

Chemistry

BindingDBiQ7L7X3.

Structurei

3D structure databases

ProteinModelPortaliQ7L7X3.
SMRiQ7L7X3. Positions 12-320.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini28 – 281254Protein kinasePROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili458 – 651194Sequence analysisAdd
BLAST
Coiled coili754 – 877124Sequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi330 – 3345Poly-Glu
Compositional biasi347 – 37933Ser-richAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0577. Eukaryota.
ENOG410Y259. LUCA.
GeneTreeiENSGT00840000129798.
HOGENOMiHOG000236358.
HOVERGENiHBG088996.
InParanoidiQ7L7X3.
KOiK04429.
OMAiAGPHWGH.
OrthoDBiEOG091G01CN.
PhylomeDBiQ7L7X3.
TreeFamiTF351444.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti251 – 2511S → T in BAB14901 (PubMed:14702039).Curated
Sequence conflicti257 – 2571F → S in AAG38502 (PubMed:13679851).Curated
Sequence conflicti860 – 8601R → C in AAG38502 (PubMed:13679851).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti855 – 8551A → T.1 Publication
Corresponds to variant rs34151057 [ dbSNP | Ensembl ].
VAR_041204

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 174174Missing in isoform 2. 1 PublicationVSP_015964Add
BLAST
Alternative sequencei569 – 716148Missing in isoform 3. 1 PublicationVSP_043706Add
BLAST
Alternative sequencei569 – 5724ELNE → VLMS in isoform 2. 1 PublicationVSP_015965
Alternative sequencei573 – 1001429Missing in isoform 2. 1 PublicationVSP_015966Add
BLAST

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ7L7X3.
SMRiQ7L7X3. Positions 12-320.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121607. 13 interactions.
DIPiDIP-39709N.
IntActiQ7L7X3. 9 interactions.
MINTiMINT-5006389.
STRINGi9606.ENSP00000261716.

Chemistry

BindingDBiQ7L7X3.
ChEMBLiCHEMBL5261.
GuidetoPHARMACOLOGYi2233.

PTM databases

iPTMnetiQ7L7X3.
PhosphoSiteiQ7L7X3.

Polymorphism and mutation databases

BioMutaiTAOK1.
DMDMi74759012.

Proteomic databases

EPDiQ7L7X3.
MaxQBiQ7L7X3.
PaxDbiQ7L7X3.
PeptideAtlasiQ7L7X3.
PRIDEiQ7L7X3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi57551.
GeneCardsiTAOK1.
HGNCiHGNC:29259. TAOK1.
HPAiHPA007669.
MIMi610266. gene.
neXtProtiNX_Q7L7X3.
PharmGKBiPA134872946.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0577. Eukaryota.
ENOG410Y259. LUCA.
GeneTreeiENSGT00840000129798.
HOGENOMiHOG000236358.
HOVERGENiHBG088996.
InParanoidiQ7L7X3.
KOiK04429.
OMAiAGPHWGH.
OrthoDBiEOG091G01CN.
PhylomeDBiQ7L7X3.
TreeFamiTF351444.

Enzyme and pathway databases

ReactomeiR-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.

Miscellaneous databases

ChiTaRSiTAOK1. human.
GeneWikiiTAOK1.
GenomeRNAii57551.
PROiQ7L7X3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160551.
CleanExiHS_TAOK1.
ExpressionAtlasiQ7L7X3. baseline and differential.
GenevisibleiQ7L7X3. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTAOK1_HUMAN
AccessioniPrimary (citable) accession number: Q7L7X3
Secondary accession number(s): A2RUT8
, B7ZLV6, Q96L75, Q9H2K7, Q9H7S5, Q9P2I6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: July 5, 2004
Last modified: September 7, 2016
This is version 129 of the entry and version 1 of the sequence. [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

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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.