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Protein

Serine/threonine-protein kinase tousled-like 2

Gene

Tlk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation. Phosphorylates the chromatin assembly factors ASF1A AND ASF1B. Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (By similarity). Negative regulator of amino acid starvation-induced autophagy (By similarity).By similarity
Testis-specific isoforms may play a role in spermatogenesis. Highly expressed in embryos throughout development.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity

Cofactori

Mg2+By similarity

Enzyme regulationi

Cell cycle-regulated, with maximal activity in the S-phase. Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase, probably by CHEK1, possibly at Ser-696. This inhibition is cell cycle checkpoint- and ATM-dependent (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei437 – 4371ATPPROSITE-ProRule annotation
Active sitei538 – 5381Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi414 – 4229ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Cell cycle, Differentiation, DNA damage, Spermatogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase tousled-like 2 (EC:2.7.11.1)
Alternative name(s):
PKU-alpha
Tousled-like kinase 2
Gene namesi
Name:Tlk2
Synonyms:Tlk
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1346023. Tlk2.

Subcellular locationi

  • Nucleus 1 Publication
  • Cytoplasmperinuclear region 1 Publication
  • Cytoplasmcytoskeleton 1 Publication

  • Note: Colocalizes with the cytoplasmic intermediate filament system during the G1 phase of the cell cycle. Present in the perinuclear region at S phase and in the nucleus at late G2.

GO - Cellular componenti

  • cell junction Source: MGI
  • intermediate filament Source: UniProtKB
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 718718Serine/threonine-protein kinase tousled-like 2PRO_0000086755Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei73 – 731PhosphoserineBy similarity
Modified residuei102 – 1021PhosphoserineBy similarity
Modified residuei696 – 6961Phosphoserine; by CHEK1By similarity
Isoform 2Curated (identifier: O55047-2)
Modified residuei94 – 941PhosphoserineCombined sourcesCurated
Modified residuei99 – 991PhosphoserineCombined sourcesCurated

Post-translational modificationi

Phosphorylated at Ser-696, probably by CHEK1.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO55047.
MaxQBiO55047.
PaxDbiO55047.
PeptideAtlasiO55047.
PRIDEiO55047.

PTM databases

iPTMnetiO55047.
PhosphoSiteiO55047.

Expressioni

Tissue specificityi

Ubiquitously expressed in all tissues examined, with high levels in heart and testis, in particular the pachytene spermatocytes and in round spermatids. Some evidence for the existence of a testis-specific isoform suggesting a role in spermatogenesis.1 Publication3 Publications

Gene expression databases

BgeeiENSMUSG00000020694.
CleanExiMM_TLK2.
ExpressionAtlasiO55047. baseline and differential.
GenevisibleiO55047. MM.

Interactioni

Subunit structurei

Monomer and heterodimer with TLK1. Interacts with ASF1A and ASF1B. May also interact with FEZ1/LZTS1 and FEZ2 (By similarity). Association with 14-3-3 proteins such as YWHAZ regulates subcellular location.By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000102554.

Structurei

3D structure databases

ProteinModelPortaliO55047.
SMRiO55047. Positions 316-684.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini408 – 687280Protein kinasePROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili193 – 24452Sequence analysisAdd
BLAST
Coiled coili285 – 31531Sequence analysisAdd
BLAST
Coiled coili349 – 39749Sequence analysisAdd
BLAST

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.
InParanoidiO55047.
KOiK08864.
PhylomeDBiO55047.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR027086. TLK2.
[Graphical view]
PANTHERiPTHR22974:SF20. PTHR22974:SF20. 2 hits.
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

Note: Additional isoforms seem to exist.1 Publication
Isoform 11 Publication (identifier: O55047-1) [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
MMEELHSLDP RRQELLEARF TGVGVSKGPL NSESSNQSLC SVGSLSDKEV
60 70 80 90 100
ETPEKKQNDQ RNRKRKAEPY DTSQGKGTPR GHKISDYFER RAEQPLYGLD
110 120 130 140 150
GSAAKEASEE QSALPTLMSV MLAKPRLDTE QLAPRGAGLC FTFVSAQQNS
160 170 180 190 200
PSSTGSGNTE HSCSSQKQIS IQHRQTQSDL TIEKISALEN SKNSDLEKKE
210 220 230 240 250
GRIDDLLRAN CDLRRQIDEQ QKMLEKYKER LNRCVTMSKK LLIEKSKQEK
260 270 280 290 300
MACRDKSMQD RLRLGHFTTV RHGASFTEQW TDGYAFQNLI KQQERINSQR
310 320 330 340 350
EEIERQRKML AKRKPPAMGQ APPATNEQKQ RKSKTNGAEN ETLTLAEYHE
360 370 380 390 400
QEEIFKLRLG HLKKEEAEIQ AELERLERVR NLHIRELKRI HNEDNSQFKD
410 420 430 440 450
HPTLNDRYLL LHLLGRGGFS EVYKAFDLTE QRYVAVKIHQ LNKNWRDEKK
460 470 480 490 500
ENYHKHACRE YRIHKELDHP RIVKLYDYFS LDTDSFCTVL EYCEGNDLDF
510 520 530 540 550
YLKQHKLMSE KEARSIIMQI VNALKYLNEI KPPIIHYDLK PGNILLVNGT
560 570 580 590 600
ACGEIKITDF GLSKIMDDDS YNSVDGMELT SQGAGTYWYL PPECFVVGKE
610 620 630 640 650
PPKISNKVDV WSVGVIFYQC LYGRKPFGHN QSQQDILQEN TILKATEVQF
660 670 680 690 700
PPKPVVTPEA KAFIRRCLAY RKEDRIDVQQ LACDPYLLPH IRKSVSTSSP
710
AGAAIASTSG ASNNSSSN
Length:718
Mass (Da):82,261
Last modified:August 22, 2003 - v2
Checksum:i60009617C162BB05
GO
Isoform 2Curated (identifier: O55047-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     89-89: E → EFAGGSGPGTSPGRSVPPVARSSPQHSLSNPLP
     626-718: PFGHNQSQQD...SGASNNSSSN → VRKKAVEQPG...SGLKKIQTSQ

Note: No experimental confirmation available.Combined sourcesCurated
Show »
Length:697
Mass (Da):79,634
Checksum:iC87D35DC2BEA0437
GO
Isoform 31 Publication (identifier: O55047-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     2-117: Missing.

Show »
Length:602
Mass (Da):69,388
Checksum:i7D2AD2A4D0A12C80
GO

Sequence cautioni

The sequence AAC02225 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti520 – 5201I → M in BAB29570 (PubMed:16141072).Curated
Sequence conflicti525 – 5251K → T in BAB29570 (PubMed:16141072).Curated
Sequence conflicti535 – 5351I → T in BAB29570 (PubMed:16141072).Curated
Sequence conflicti540 – 5401K → E in BAB29570 (PubMed:16141072).Curated
Sequence conflicti543 – 5431N → D in BAB29570 (PubMed:16141072).Curated
Sequence conflicti548 – 5481N → D in BAB29570 (PubMed:16141072).Curated
Sequence conflicti555 – 5551I → M in BAB29570 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei2 – 117116Missing in isoform 3. 1 PublicationVSP_050574Add
BLAST
Alternative sequencei89 – 891E → EFAGGSGPGTSPGRSVPPVA RSSPQHSLSNPLP in isoform 2. 1 PublicationVSP_050575
Alternative sequencei626 – 71893PFGHN…NSSSN → VRKKAVEQPGAIPTTSLGFF FAVNHWNPESSGLKKIQTSQ in isoform 2. 1 PublicationVSP_050576Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045252 mRNA. Translation: AAC02225.1. Different initiation.
AF045254 mRNA. Translation: AAC02227.1.
AF045253 mRNA. Translation: AAC02226.1.
AK014829 mRNA. Translation: BAB29570.2.
AL645471 Genomic DNA. Translation: CAM24828.1.
AL645471 Genomic DNA. Translation: CAM24830.1.
CCDSiCCDS36356.2. [O55047-1]
CCDS79062.1. [O55047-2]
RefSeqiNP_001281260.1. NM_001294331.1. [O55047-1]
NP_001281263.1. NM_001294334.1. [O55047-2]
XP_006533378.2. XM_006533315.2. [O55047-1]
XP_011247316.1. XM_011249014.1. [O55047-1]
XP_011247317.1. XM_011249015.1. [O55047-1]
UniGeneiMm.126976.

Genome annotation databases

EnsembliENSMUST00000015107; ENSMUSP00000015107; ENSMUSG00000020694. [O55047-1]
ENSMUST00000092537; ENSMUSP00000090198; ENSMUSG00000020694. [O55047-2]
ENSMUST00000106939; ENSMUSP00000102552; ENSMUSG00000020694. [O55047-1]
GeneIDi24086.
KEGGimmu:24086.
UCSCiuc007lxd.3. mouse. [O55047-2]
uc007lxg.3. mouse. [O55047-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045252 mRNA. Translation: AAC02225.1. Different initiation.
AF045254 mRNA. Translation: AAC02227.1.
AF045253 mRNA. Translation: AAC02226.1.
AK014829 mRNA. Translation: BAB29570.2.
AL645471 Genomic DNA. Translation: CAM24828.1.
AL645471 Genomic DNA. Translation: CAM24830.1.
CCDSiCCDS36356.2. [O55047-1]
CCDS79062.1. [O55047-2]
RefSeqiNP_001281260.1. NM_001294331.1. [O55047-1]
NP_001281263.1. NM_001294334.1. [O55047-2]
XP_006533378.2. XM_006533315.2. [O55047-1]
XP_011247316.1. XM_011249014.1. [O55047-1]
XP_011247317.1. XM_011249015.1. [O55047-1]
UniGeneiMm.126976.

3D structure databases

ProteinModelPortaliO55047.
SMRiO55047. Positions 316-684.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000102554.

PTM databases

iPTMnetiO55047.
PhosphoSiteiO55047.

Proteomic databases

EPDiO55047.
MaxQBiO55047.
PaxDbiO55047.
PeptideAtlasiO55047.
PRIDEiO55047.

Protocols and materials databases

DNASUi24086.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000015107; ENSMUSP00000015107; ENSMUSG00000020694. [O55047-1]
ENSMUST00000092537; ENSMUSP00000090198; ENSMUSG00000020694. [O55047-2]
ENSMUST00000106939; ENSMUSP00000102552; ENSMUSG00000020694. [O55047-1]
GeneIDi24086.
KEGGimmu:24086.
UCSCiuc007lxd.3. mouse. [O55047-2]
uc007lxg.3. mouse. [O55047-1]

Organism-specific databases

CTDi11011.
MGIiMGI:1346023. Tlk2.

Phylogenomic databases

eggNOGiKOG1151. Eukaryota.
ENOG410Y3FX. LUCA.
GeneTreeiENSGT00790000123008.
HOGENOMiHOG000259522.
HOVERGENiHBG007938.
InParanoidiO55047.
KOiK08864.
PhylomeDBiO55047.

Miscellaneous databases

ChiTaRSiTlk2. mouse.
PROiO55047.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020694.
CleanExiMM_TLK2.
ExpressionAtlasiO55047. baseline and differential.
GenevisibleiO55047. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR027086. TLK2.
[Graphical view]
PANTHERiPTHR22974:SF20. PTHR22974:SF20. 2 hits.
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 nameiTLK2_MOUSE
AccessioniPrimary (citable) accession number: O55047
Secondary accession number(s): B1ASU7, B1ASU8, Q9D5Y5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 22, 2003
Last sequence update: August 22, 2003
Last modified: September 7, 2016
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.