TLK1_MOUSE
ID TLK1_MOUSE Reviewed; 766 AA.
AC Q8C0V0;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2003, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Serine/threonine-protein kinase tousled-like 1;
DE EC=2.7.11.1;
DE AltName: Full=Tousled-like kinase 1;
GN Name=Tlk1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:BAC26610.1};
RN [1] {ECO:0000312|EMBL:AAH51641.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Limb {ECO:0000312|EMBL:AAH51641.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 43-766.
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=10523312; DOI=10.1093/emboj/18.20.5691;
RA Sillje H.H.W., Takahashi K., Tanaka K., Van Houwe G., Nigg E.A.;
RT "Mammalian homologues of the plant tousled gene code for cell-cycle-
RT regulated kinases with maximal activities linked to ongoing DNA
RT replication.";
RL EMBO J. 18:5691-5702(1999).
RN [4]
RP FUNCTION.
RX PubMed=16156902; DOI=10.1186/1471-2199-6-19;
RA Sunavala-Dossabhoy G., Balakrishnan S.K., Sen S., Nuthalapaty S.,
RA De Benedetti A.;
RT "The radioresistance kinase TLK1B protects the cells by promoting repair of
RT double strand breaks.";
RL BMC Mol. Biol. 6:19-19(2005).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80 AND SER-159, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Rapidly and transiently inhibited by phosphorylation
CC following the generation of DNA double-stranded breaks during S-phase.
CC This is cell cycle checkpoint and ATM-pathway dependent and appears to
CC regulate processes involved in chromatin assembly (By similarity).
CC Isoform 3 protects the cells from the ionizing radiation by
CC facilitating the repair of DSBs. In vitro, phosphorylates histone H3 at
CC 'Ser-10' (By similarity). {ECO:0000250, ECO:0000269|PubMed:16156902}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q9UKI8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q9UKI8};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9UKI8};
CC -!- ACTIVITY REGULATION: Cell-cycle regulated, maximal activity in S-phase.
CC Inactivated by phosphorylation at Ser-743, potentially by CHEK1 (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Heterodimerizes with TLK2. Interacts with ASF1A and ASF1B (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissues examined.
CC {ECO:0000269|PubMed:10523312}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH51641.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; BC051641; AAH51641.1; ALT_INIT; mRNA.
DR EMBL; AK029773; BAC26610.1; ALT_SEQ; mRNA.
DR CCDS; CCDS50599.1; -.
DR RefSeq; NP_766252.2; NM_172664.3.
DR RefSeq; XP_006499253.1; XM_006499190.3.
DR AlphaFoldDB; Q8C0V0; -.
DR SMR; Q8C0V0; -.
DR BioGRID; 230704; 1.
DR STRING; 10090.ENSMUSP00000035961; -.
DR iPTMnet; Q8C0V0; -.
DR PhosphoSitePlus; Q8C0V0; -.
DR EPD; Q8C0V0; -.
DR jPOST; Q8C0V0; -.
DR MaxQB; Q8C0V0; -.
DR PaxDb; Q8C0V0; -.
DR PeptideAtlas; Q8C0V0; -.
DR PRIDE; Q8C0V0; -.
DR ProteomicsDB; 259200; -.
DR Antibodypedia; 19345; 396 antibodies from 35 providers.
DR DNASU; 228012; -.
DR Ensembl; ENSMUST00000038584; ENSMUSP00000035961; ENSMUSG00000041997.
DR GeneID; 228012; -.
DR KEGG; mmu:228012; -.
DR UCSC; uc008jzt.1; mouse.
DR CTD; 9874; -.
DR MGI; MGI:2441683; Tlk1.
DR VEuPathDB; HostDB:ENSMUSG00000041997; -.
DR eggNOG; KOG1151; Eukaryota.
DR GeneTree; ENSGT00950000182984; -.
DR HOGENOM; CLU_000288_85_1_1; -.
DR InParanoid; Q8C0V0; -.
DR OMA; YKHACRE; -.
DR OrthoDB; 693214at2759; -.
DR PhylomeDB; Q8C0V0; -.
DR TreeFam; TF315233; -.
DR BioGRID-ORCS; 228012; 3 hits in 77 CRISPR screens.
DR ChiTaRS; Tlk1; mouse.
DR PRO; PR:Q8C0V0; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8C0V0; protein.
DR Bgee; ENSMUSG00000041997; Expressed in manus and 228 other tissues.
DR Genevisible; Q8C0V0; MM.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:1902275; P:regulation of chromatin organization; ISS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Chromatin regulator; Coiled coil; DNA damage;
KW Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..766
FT /note="Serine/threonine-protein kinase tousled-like 1"
FT /id="PRO_0000086753"
FT DOMAIN 456..734
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 344..381
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 745..766
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 229..280
FT /evidence="ECO:0000255"
FT COILED 397..445
FT /evidence="ECO:0000255"
FT COMPBIAS 1..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..63
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 70..106
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 107..131
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 169..190
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 351..370
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 586
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 462..470
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 485
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 38
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKI8"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKI8"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKI8"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86UE8"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86UE8"
FT MOD_RES 176
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86UE8"
FT MOD_RES 743
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86UE8"
SQ SEQUENCE 766 AA; 86624 MW; 19634346118E6551 CRC64;
MSVQSSSGSL EGPPSWSRLS TSPTPGSAAA ARSLLNHTPP SGRPREGAMD ELHSLDPRRQ
ELLEARFTGV ATGSTGSTGS CSVGAKASTN NESSNHSFGS LGSLSDKESE TPEKKQSESS
RGRKRKAESQ NESSQGKSIG GRGHKISDYF EYQGGNGSSP VRGIPPAIRS PQNSHSHSTP
SSSVRPNSPS PTALAFGDHP VVQPKQLSFK ITQTDLTMLK LAALESTKNQ DLEKKEGRID
DLLRANCDLR RQIDDQQKLL EKYKERLNKC ISMSKKLLIE KSTQEKLSSR EKSMQDRLRL
GHFTTVRHGA SFTEQWTDGF AFQNLVKQQE WVNQQREDIE RQRKLLGKRK PPTANNSQAP
ATNSEAKQRK TKAVNGAEND PFVRPNLPQL LTLAEYHEQE EIFKLRLGHL KKEEAEIQAE
LERLERVRNL HIRELKRINN EDNSQFKDHP TLNERYLLLH LLGRGGFSEV YKAFDLYEQR
YAAVKIHQLN KSWRDEKKEN YHKHACREYR IHKELDHPRI VKLYDYFSLD TDTFCTVLEY
CEGNDLDFYL KQHKLMSEKE ARSIVMQIVN ALRYLNEIKP PIIHYDLKPG NILLVDGTAC
GEIKITDFGL SKIMDDDSYG VDGMDLTSQG AGTYWYLPPE CFVVGKEPPK ISNKVDVWSV
GVIFFQCLYG RKPFGHNQSQ QDILQENTIL KATEVQFPVK PVVSSEAKAF IRRCLAYRKE
DRFDVHQLAN DPYLLPHMRR SNSSGNLHMS GLTATPTPPS SSIITY
