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Protein

Serine/threonine-protein kinase tousled-like 1

Gene

TLK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly. Isoform 3 phosphorylates and enhances the stability of the t-SNARE SNAP23, augmenting its assembly with syntaxin. Isoform 3 protects the cells from the ionizing radiation by facilitating the repair of DSBs. In vitro, phosphorylates histone H3 at 'Ser-10'.6 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.3 Publications

Cofactori

Mg2+3 Publications

Enzyme regulationi

Cell-cycle regulated, maximal activity in S-phase. Inactivated by phosphorylation at Ser-743, potentially by CHEK1.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei485ATPPROSITE-ProRule annotation1
Active sitei586Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi462 – 470ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB-KW
  • chromatin modification Source: UniProtKB-KW
  • intracellular protein transport Source: UniProtKB
  • intracellular signal transduction Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of chromatin assembly or disassembly Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, DNA damage

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01042-MONOMER.
SignaLinkiQ9UKI8.
SIGNORiQ9UKI8.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase tousled-like 1 (EC:2.7.11.1)
Alternative name(s):
PKU-beta
Tousled-like kinase 1
Gene namesi
Name:TLK1
Synonyms:KIAA0137
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:11841. TLK1.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi607D → A: Loss of kinase activity. 2 Publications1
Mutagenesisi743S → A: Loss of kinase inhibition in response to DNA damage. 1 Publication1
Mutagenesisi743S → D: Loss of kinase inhibition in response to DNA damage. 1 Publication1
Mutagenesisi743S → E: Loss of kinase inhibition in response to DNA damage. 1 Publication1

Organism-specific databases

DisGeNETi9874.
OpenTargetsiENSG00000198586.
PharmGKBiPA36543.

Chemistry databases

ChEMBLiCHEMBL5388.
GuidetoPHARMACOLOGYi2242.

Polymorphism and mutation databases

BioMutaiTLK1.
DMDMi34223086.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000867521 – 766Serine/threonine-protein kinase tousled-like 1Add BLAST766

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei38PhosphothreonineCombined sources1
Modified residuei54PhosphoserineCombined sources1
Modified residuei77PhosphoserineCombined sources1
Modified residuei80PhosphoserineBy similarity1
Modified residuei134PhosphoserineBy similarity1
Modified residuei159PhosphoserineCombined sources1
Modified residuei174PhosphoserineBy similarity1
Modified residuei176PhosphoserineBy similarity1
Modified residuei743Phosphoserine1 Publication1
Isoform 31 Publication (identifier: Q9UKI8-3)
Modified residuei1N-acetylmethionineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9UKI8.
PaxDbiQ9UKI8.
PeptideAtlasiQ9UKI8.
PRIDEiQ9UKI8.

PTM databases

iPTMnetiQ9UKI8.

Expressioni

Tissue specificityi

Widely expressed. Present in fetal placenta, liver, kidney and pancreas but not heart or skeletal muscle. Also found in adult cell lines. Isoform 3 is ubiquitously expressed in all tissues examined.2 Publications

Gene expression databases

BgeeiENSG00000198586.
CleanExiHS_TLK1.
ExpressionAtlasiQ9UKI8. baseline and differential.
GenevisibleiQ9UKI8. HS.

Organism-specific databases

HPAiHPA016043.

Interactioni

Subunit structurei

Heterodimerizes with TLK2. Interacts with ASF1A and ASF1B.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LUZP4Q9P1273EBI-740492,EBI-10198848
TPM3Q5VU623EBI-740492,EBI-10184033

Protein-protein interaction databases

BioGridi115206. 20 interactors.
IntActiQ9UKI8. 18 interactors.
MINTiMINT-112025.
STRINGi9606.ENSP00000411099.

Chemistry databases

BindingDBiQ9UKI8.

Structurei

3D structure databases

ProteinModelPortaliQ9UKI8.
SMRiQ9UKI8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini456 – 734Protein kinasePROSITE-ProRule annotationAdd BLAST279

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili230 – 281Sequence analysisAdd BLAST52
Coiled coili397 – 445Sequence analysisAdd BLAST49

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG1151. Eukaryota.
ENOG410Y3FX. LUCA.
GeneTreeiENSGT00790000123008.
HOGENOMiHOG000259522.
HOVERGENiHBG007938.
InParanoidiQ9UKI8.
KOiK08864.
OMAiDVQFPVK.
OrthoDBiEOG091G02XG.
PhylomeDBiQ9UKI8.
TreeFamiTF315233.

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 (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q9UKI8-1) [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
MSVQSSSGSL EGPPSWSQLS TSPTPGSAAA ARSLLNHTPP SGRPREGAMD
60 70 80 90 100
ELHSLDPRRQ ELLEARFTGV ASGSTGSTGS CSVGAKASTN NESSNHSFGS
110 120 130 140 150
LGSLSDKESE TPEKKQSESS RGRKRKAENQ NESSQGKSIG GRGHKISDYF
160 170 180 190 200
EYQGGNGSSP VRGIPPAIRS PQNSHSHSTP SSSVRPNSPS PTALAFGDHP
210 220 230 240 250
IVQPKQLSFK IIQTDLTMLK LAALESNKIQ DLEKKEGRID DLLRANCDLR
260 270 280 290 300
RQIDEQQKLL EKYKERLNKC ISMSKKLLIE KSTQEKLSSR EKSMQDRLRL
310 320 330 340 350
GHFTTVRHGA SFTEQWTDGF AFQNLVKQQE WVNQQREDIE RQRKLLAKRK
360 370 380 390 400
PPTANNSQAP STNSEPKQRK NKAVNGAEND PFVRPNLPQL LTLAEYHEQE
410 420 430 440 450
EIFKLRLGHL KKEEAEIQAE LERLERVRNL HIRELKRINN EDNSQFKDHP
460 470 480 490 500
TLNERYLLLH LLGRGGFSEV YKAFDLYEQR YAAVKIHQLN KSWRDEKKEN
510 520 530 540 550
YHKHACREYR IHKELDHPRI VKLYDYFSLD TDTFCTVLEY CEGNDLDFYL
560 570 580 590 600
KQHKLMSEKE ARSIVMQIVN ALRYLNEIKP PIIHYDLKPG NILLVDGTAC
610 620 630 640 650
GEIKITDFGL SKIMDDDSYG VDGMDLTSQG AGTYWYLPPE CFVVGKEPPK
660 670 680 690 700
ISNKVDVWSV GVIFFQCLYG RKPFGHNQSQ QDILQENTIL KATEVQFPVK
710 720 730 740 750
PVVSSEAKAF IRRCLAYRKE DRFDVHQLAN DPYLLPHMRR SNSSGNLHMA
760
GLTASPTPPS SSIITY
Length:766
Mass (Da):86,700
Last modified:August 22, 2003 - v2
Checksum:iA65AE0A2A7C7FF2F
GO
Isoform 21 Publication (identifier: Q9UKI8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     136-136: G → GFPNLPVFQSLAYWEMGRTAGG

Show »
Length:787
Mass (Da):89,023
Checksum:i87275865796F5A54
GO
Isoform 31 Publication (identifier: Q9UKI8-3) [UniParc]FASTAAdd to basket
Also known as: SNAK1 Publication, TLK1B

The sequence of this isoform differs from the canonical sequence as follows:
     1-217: Missing.

Show »
Length:549
Mass (Da):63,994
Checksum:iED6FBF1F77E7E90F
GO
Isoform 4 (identifier: Q9UKI8-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MSVQSSSGSLEGPP → MAVLFLYDLKTTGK
     15-110: Missing.

Note: No experimental confirmation available.
Show »
Length:670
Mass (Da):77,110
Checksum:iBFA0D9CF3CEFB7C1
GO
Isoform 5 (identifier: Q9UKI8-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-48: Missing.

Note: No experimental confirmation available.
Show »
Length:718
Mass (Da):81,927
Checksum:i73E77AF8D34C531D
GO

Sequence cautioni

The sequence AAF03094 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAA09486 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti88S → T in AAF03094 (PubMed:10523312).Curated1
Sequence conflicti102G → E in BAA20562 (PubMed:9427565).Curated1
Sequence conflicti230Q → L in BAA20562 (PubMed:9427565).Curated1
Sequence conflicti261E → D in BAA20562 (PubMed:9427565).Curated1
Sequence conflicti416E → G in BAA20562 (PubMed:9427565).Curated1
Sequence conflicti439N → H in BAA20562 (PubMed:9427565).Curated1
Sequence conflicti471Y → D in BAA20562 (PubMed:9427565).Curated1
Sequence conflicti477Y → S in BAA20562 (PubMed:9427565).Curated1
Sequence conflicti625D → V in BAA20562 (PubMed:9427565).Curated1
Sequence conflicti665F → Y in BAA20562 (PubMed:9427565).Curated1
Sequence conflicti730N → C in BAA20562 (PubMed:9427565).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041215121R → C.1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0505701 – 217Missing in isoform 3. 1 PublicationAdd BLAST217
Alternative sequenceiVSP_0435041 – 48Missing in isoform 5. 1 PublicationAdd BLAST48
Alternative sequenceiVSP_0435051 – 14MSVQS…LEGPP → MAVLFLYDLKTTGK in isoform 4. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_04350615 – 110Missing in isoform 4. 1 PublicationAdd BLAST96
Alternative sequenceiVSP_050571136G → GFPNLPVFQSLAYWEMGRTA GG in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB004885 mRNA. Translation: BAA20562.1.
AF162666 mRNA. Translation: AAF03094.1. Different initiation.
AF246219 mRNA. Translation: AAF71263.1.
D50927 mRNA. Translation: BAA09486.2. Different initiation.
AK090779 mRNA. Translation: BAG52227.1.
AK301857 mRNA. Translation: BAG63299.1.
AC007739 Genomic DNA. No translation available.
AC009953 Genomic DNA. No translation available.
AC010092 Genomic DNA. No translation available.
BC032657 mRNA. Translation: AAH32657.1.
CCDSiCCDS2241.1. [Q9UKI8-1]
CCDS46447.1. [Q9UKI8-5]
CCDS46448.1. [Q9UKI8-4]
RefSeqiNP_001130026.1. NM_001136554.1. [Q9UKI8-5]
NP_001130027.1. NM_001136555.1. [Q9UKI8-4]
NP_036422.3. NM_012290.4. [Q9UKI8-1]
XP_016860910.1. XM_017005421.1. [Q9UKI8-3]
XP_016860911.1. XM_017005422.1. [Q9UKI8-3]
UniGeneiHs.744917.

Genome annotation databases

EnsembliENST00000360843; ENSP00000354089; ENSG00000198586. [Q9UKI8-2]
ENST00000431350; ENSP00000411099; ENSG00000198586. [Q9UKI8-1]
ENST00000434911; ENSP00000409222; ENSG00000198586. [Q9UKI8-4]
ENST00000521943; ENSP00000428113; ENSG00000198586. [Q9UKI8-5]
GeneIDi9874.
KEGGihsa:9874.
UCSCiuc002ugn.3. human. [Q9UKI8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB004885 mRNA. Translation: BAA20562.1.
AF162666 mRNA. Translation: AAF03094.1. Different initiation.
AF246219 mRNA. Translation: AAF71263.1.
D50927 mRNA. Translation: BAA09486.2. Different initiation.
AK090779 mRNA. Translation: BAG52227.1.
AK301857 mRNA. Translation: BAG63299.1.
AC007739 Genomic DNA. No translation available.
AC009953 Genomic DNA. No translation available.
AC010092 Genomic DNA. No translation available.
BC032657 mRNA. Translation: AAH32657.1.
CCDSiCCDS2241.1. [Q9UKI8-1]
CCDS46447.1. [Q9UKI8-5]
CCDS46448.1. [Q9UKI8-4]
RefSeqiNP_001130026.1. NM_001136554.1. [Q9UKI8-5]
NP_001130027.1. NM_001136555.1. [Q9UKI8-4]
NP_036422.3. NM_012290.4. [Q9UKI8-1]
XP_016860910.1. XM_017005421.1. [Q9UKI8-3]
XP_016860911.1. XM_017005422.1. [Q9UKI8-3]
UniGeneiHs.744917.

3D structure databases

ProteinModelPortaliQ9UKI8.
SMRiQ9UKI8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115206. 20 interactors.
IntActiQ9UKI8. 18 interactors.
MINTiMINT-112025.
STRINGi9606.ENSP00000411099.

Chemistry databases

BindingDBiQ9UKI8.
ChEMBLiCHEMBL5388.
GuidetoPHARMACOLOGYi2242.

PTM databases

iPTMnetiQ9UKI8.

Polymorphism and mutation databases

BioMutaiTLK1.
DMDMi34223086.

Proteomic databases

EPDiQ9UKI8.
PaxDbiQ9UKI8.
PeptideAtlasiQ9UKI8.
PRIDEiQ9UKI8.

Protocols and materials databases

DNASUi9874.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000360843; ENSP00000354089; ENSG00000198586. [Q9UKI8-2]
ENST00000431350; ENSP00000411099; ENSG00000198586. [Q9UKI8-1]
ENST00000434911; ENSP00000409222; ENSG00000198586. [Q9UKI8-4]
ENST00000521943; ENSP00000428113; ENSG00000198586. [Q9UKI8-5]
GeneIDi9874.
KEGGihsa:9874.
UCSCiuc002ugn.3. human. [Q9UKI8-1]

Organism-specific databases

CTDi9874.
DisGeNETi9874.
GeneCardsiTLK1.
HGNCiHGNC:11841. TLK1.
HPAiHPA016043.
MIMi608438. gene.
neXtProtiNX_Q9UKI8.
OpenTargetsiENSG00000198586.
PharmGKBiPA36543.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1151. Eukaryota.
ENOG410Y3FX. LUCA.
GeneTreeiENSGT00790000123008.
HOGENOMiHOG000259522.
HOVERGENiHBG007938.
InParanoidiQ9UKI8.
KOiK08864.
OMAiDVQFPVK.
OrthoDBiEOG091G02XG.
PhylomeDBiQ9UKI8.
TreeFamiTF315233.

Enzyme and pathway databases

BioCyciZFISH:HS01042-MONOMER.
SignaLinkiQ9UKI8.
SIGNORiQ9UKI8.

Miscellaneous databases

ChiTaRSiTLK1. human.
GeneWikiiTLK1.
GenomeRNAii9874.
PROiQ9UKI8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198586.
CleanExiHS_TLK1.
ExpressionAtlasiQ9UKI8. baseline and differential.
GenevisibleiQ9UKI8. 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 nameiTLK1_HUMAN
AccessioniPrimary (citable) accession number: Q9UKI8
Secondary accession number(s): B3KR15
, B4DX87, Q14150, Q8N591, Q9NYH2, Q9Y4F6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 22, 2003
Last sequence update: August 22, 2003
Last modified: November 30, 2016
This is version 162 of the entry and version 2 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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.