TLK1_HUMAN
ID TLK1_HUMAN Reviewed; 766 AA.
AC Q9UKI8; B3KR15; B4DX87; Q14150; Q8N591; Q9NYH2; Q9Y4F6;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2003, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Serine/threonine-protein kinase tousled-like 1;
DE EC=2.7.11.1;
DE AltName: Full=PKU-beta;
DE AltName: Full=Tousled-like kinase 1;
GN Name=TLK1; Synonyms=KIAA0137;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000312|EMBL:AAF03094.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Placenta {ECO:0000269|PubMed:9427565}, and
RC Testis {ECO:0000269|PubMed:9427565};
RX PubMed=9427565; DOI=10.1016/s0378-1119(97)00495-2;
RA Yamakawa A., Kameoka Y., Hashimoto K., Yoshitake Y., Nishikawa K.,
RA Tanihara K., Date T.;
RT "cDNA cloning and chromosomal mapping of genes encoding novel protein
RT kinases termed PKU-alpha and PKU-beta, which have nuclear localization
RT signal.";
RL Gene 202:193-201(1997).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, MUTAGENESIS OF ASP-607,
RP SUBCELLULAR LOCATION, INTERACTION WITH TLK2, AND ACTIVITY REGULATION.
RC TISSUE=Placenta {ECO:0000312|EMBL:AAF03094.1};
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 [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Placenta {ECO:0000269|PubMed:10588641};
RX PubMed=10588641; DOI=10.1091/mbc.10.12.4033;
RA Cabaniols J.-P., Ravichandran V., Roche P.A.;
RT "Phosphorylation of SNAP-23 by the novel kinase SNAK regulates t-SNARE
RT complex assembly.";
RL Mol. Biol. Cell 10:4033-4041(1999).
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow {ECO:0000269|PubMed:8590280};
RX PubMed=8590280; DOI=10.1093/dnares/2.4.167;
RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. IV. The
RT coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 2:167-174(1995).
RN [5]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5).
RC TISSUE=Amygdala, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [8] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus {ECO:0000312|EMBL:AAH32657.1};
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 [9]
RP FUNCTION, INTERACTION WITH ASF1A AND ASF1B, AND MUTAGENESIS OF ASP-607.
RX PubMed=11470414; DOI=10.1016/s0960-9822(01)00298-6;
RA Sillje H.H.W., Nigg E.A.;
RT "Identification of human Asf1 chromatin assembly factors as substrates of
RT Tousled-like kinases.";
RL Curr. Biol. 11:1068-1073(2001).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION OF HISTONE H3.
RX PubMed=11314006; DOI=10.1038/sj.onc.1204147;
RA Li Y., DeFatta R., Anthony C., Sunavala G., De Benedetti A.;
RT "A translationally regulated Tousled kinase phosphorylates histone H3 and
RT confers radioresistance when overexpressed.";
RL Oncogene 20:726-738(2001).
RN [11] {ECO:0000305}
RP FUNCTION, MUTAGENESIS OF SER-743, PHOSPHORYLATION AT SER-743, AND ACTIVITY
RP REGULATION.
RX PubMed=12660173; DOI=10.1093/emboj/cdg151;
RA Groth A., Lukas J., Nigg E.A., Sillje H.H.W., Wernstedt C., Bartek J.,
RA Hansen K.;
RT "Human tousled like kinases are targeted by an ATM- and Chk1-dependent DNA
RT damage checkpoint.";
RL EMBO J. 22:1676-1687(2003).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-159, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-159, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORM 3), AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-38; SER-54; SER-77 AND
RP SER-159, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-121.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
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. Isoform 3
CC phosphorylates and enhances the stability of the t-SNARE SNAP23,
CC augmenting its assembly with syntaxin. Isoform 3 protects the cells
CC from the ionizing radiation by facilitating the repair of DSBs. In
CC vitro, phosphorylates histone H3 at 'Ser-10'.
CC {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:10588641,
CC ECO:0000269|PubMed:11314006, ECO:0000269|PubMed:11470414,
CC ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:9427565}.
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:0000269|PubMed:10523312, ECO:0000269|PubMed:10588641,
CC ECO:0000269|PubMed:9427565};
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:0000269|PubMed:10523312,
CC ECO:0000269|PubMed:10588641, ECO:0000269|PubMed:9427565};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:10588641,
CC ECO:0000269|PubMed:9427565};
CC -!- ACTIVITY REGULATION: Cell-cycle regulated, maximal activity in S-phase.
CC Inactivated by phosphorylation at Ser-743, potentially by CHEK1.
CC {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:12660173}.
CC -!- SUBUNIT: Heterodimerizes with TLK2. Interacts with ASF1A and ASF1B.
CC {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:11470414}.
CC -!- INTERACTION:
CC Q9UKI8; Q8N7W2-2: BEND7; NbExp=3; IntAct=EBI-740492, EBI-10181188;
CC Q9UKI8; Q6PI77: BHLHB9; NbExp=3; IntAct=EBI-740492, EBI-11519926;
CC Q9UKI8; Q7L190: DPPA4; NbExp=3; IntAct=EBI-740492, EBI-710457;
CC Q9UKI8; Q96FJ2: DYNLL2; NbExp=4; IntAct=EBI-740492, EBI-742371;
CC Q9UKI8; P50458: LHX2; NbExp=3; IntAct=EBI-740492, EBI-12179869;
CC Q9UKI8; Q9P127: LUZP4; NbExp=3; IntAct=EBI-740492, EBI-10198848;
CC Q9UKI8; P26367: PAX6; NbExp=3; IntAct=EBI-740492, EBI-747278;
CC Q9UKI8; Q96BK5: PINX1; NbExp=3; IntAct=EBI-740492, EBI-721782;
CC Q9UKI8; Q06124-2: PTPN11; NbExp=3; IntAct=EBI-740492, EBI-17635971;
CC Q9UKI8; Q12800: TFCP2; NbExp=3; IntAct=EBI-740492, EBI-717422;
CC Q9UKI8; Q5VU62: TPM3; NbExp=3; IntAct=EBI-740492, EBI-10184033;
CC Q9UKI8; Q8IY57-5: YAF2; NbExp=3; IntAct=EBI-740492, EBI-12111538;
CC Q9UKI8; Q8N720: ZNF655; NbExp=3; IntAct=EBI-740492, EBI-625509;
CC Q9UKI8; Q6PK81: ZNF773; NbExp=3; IntAct=EBI-740492, EBI-2686307;
CC Q9UKI8; Q3KNS6-3: ZNF829; NbExp=3; IntAct=EBI-740492, EBI-18036029;
CC Q9UKI8; P10073: ZSCAN22; NbExp=3; IntAct=EBI-740492, EBI-10178224;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10523312,
CC ECO:0000269|PubMed:10588641, ECO:0000269|PubMed:11314006,
CC ECO:0000269|PubMed:9427565}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1 {ECO:0000269|PubMed:10523312};
CC IsoId=Q9UKI8-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:9427565};
CC IsoId=Q9UKI8-2; Sequence=VSP_050571;
CC Name=3 {ECO:0000269|PubMed:10588641}; Synonyms=SNAK
CC {ECO:0000269|PubMed:10588641}, TLK1B;
CC IsoId=Q9UKI8-3; Sequence=VSP_050570;
CC Name=4;
CC IsoId=Q9UKI8-4; Sequence=VSP_043505, VSP_043506;
CC Name=5;
CC IsoId=Q9UKI8-5; Sequence=VSP_043504;
CC -!- TISSUE SPECIFICITY: Widely expressed. Present in fetal placenta, liver,
CC kidney and pancreas but not heart or skeletal muscle. Also found in
CC adult cell lines. Isoform 3 is ubiquitously expressed in all tissues
CC examined. {ECO:0000269|PubMed:10588641, ECO:0000269|PubMed:9427565}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF03094.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA09486.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB004885; BAA20562.1; -; mRNA.
DR EMBL; AF162666; AAF03094.1; ALT_INIT; mRNA.
DR EMBL; AF246219; AAF71263.1; -; mRNA.
DR EMBL; D50927; BAA09486.2; ALT_INIT; mRNA.
DR EMBL; AK090779; BAG52227.1; -; mRNA.
DR EMBL; AK301857; BAG63299.1; -; mRNA.
DR EMBL; AC007739; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC009953; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010092; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032657; AAH32657.1; -; mRNA.
DR CCDS; CCDS2241.1; -. [Q9UKI8-1]
DR CCDS; CCDS46447.1; -. [Q9UKI8-5]
DR CCDS; CCDS46448.1; -. [Q9UKI8-4]
DR RefSeq; NP_001130026.1; NM_001136554.1. [Q9UKI8-5]
DR RefSeq; NP_001130027.1; NM_001136555.1. [Q9UKI8-4]
DR RefSeq; NP_036422.3; NM_012290.4. [Q9UKI8-1]
DR RefSeq; XP_016860910.1; XM_017005421.1.
DR RefSeq; XP_016860911.1; XM_017005422.1. [Q9UKI8-3]
DR AlphaFoldDB; Q9UKI8; -.
DR SMR; Q9UKI8; -.
DR BioGRID; 115206; 50.
DR IntAct; Q9UKI8; 38.
DR MINT; Q9UKI8; -.
DR STRING; 9606.ENSP00000411099; -.
DR BindingDB; Q9UKI8; -.
DR ChEMBL; CHEMBL5388; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9UKI8; -.
DR iPTMnet; Q9UKI8; -.
DR PhosphoSitePlus; Q9UKI8; -.
DR BioMuta; TLK1; -.
DR DMDM; 34223086; -.
DR EPD; Q9UKI8; -.
DR jPOST; Q9UKI8; -.
DR MassIVE; Q9UKI8; -.
DR MaxQB; Q9UKI8; -.
DR PaxDb; Q9UKI8; -.
DR PeptideAtlas; Q9UKI8; -.
DR PRIDE; Q9UKI8; -.
DR ProteomicsDB; 84791; -. [Q9UKI8-1]
DR ProteomicsDB; 84792; -. [Q9UKI8-2]
DR ProteomicsDB; 84793; -. [Q9UKI8-3]
DR ProteomicsDB; 84794; -. [Q9UKI8-4]
DR ProteomicsDB; 84795; -. [Q9UKI8-5]
DR Antibodypedia; 19345; 396 antibodies from 35 providers.
DR DNASU; 9874; -.
DR Ensembl; ENST00000360843.7; ENSP00000354089.3; ENSG00000198586.14. [Q9UKI8-2]
DR Ensembl; ENST00000431350.7; ENSP00000411099.2; ENSG00000198586.14. [Q9UKI8-1]
DR Ensembl; ENST00000434911.6; ENSP00000409222.2; ENSG00000198586.14. [Q9UKI8-4]
DR Ensembl; ENST00000521943.5; ENSP00000428113.1; ENSG00000198586.14. [Q9UKI8-5]
DR GeneID; 9874; -.
DR KEGG; hsa:9874; -.
DR MANE-Select; ENST00000431350.7; ENSP00000411099.2; NM_012290.5; NP_036422.3.
DR UCSC; uc002ugn.3; human. [Q9UKI8-1]
DR CTD; 9874; -.
DR DisGeNET; 9874; -.
DR GeneCards; TLK1; -.
DR HGNC; HGNC:11841; TLK1.
DR HPA; ENSG00000198586; Low tissue specificity.
DR MIM; 608438; gene.
DR neXtProt; NX_Q9UKI8; -.
DR OpenTargets; ENSG00000198586; -.
DR PharmGKB; PA36543; -.
DR VEuPathDB; HostDB:ENSG00000198586; -.
DR eggNOG; KOG1151; Eukaryota.
DR GeneTree; ENSGT00950000182984; -.
DR InParanoid; Q9UKI8; -.
DR OMA; YKHACRE; -.
DR OrthoDB; 693214at2759; -.
DR PhylomeDB; Q9UKI8; -.
DR TreeFam; TF315233; -.
DR PathwayCommons; Q9UKI8; -.
DR SignaLink; Q9UKI8; -.
DR SIGNOR; Q9UKI8; -.
DR BioGRID-ORCS; 9874; 27 hits in 1114 CRISPR screens.
DR ChiTaRS; TLK1; human.
DR GeneWiki; TLK1; -.
DR GenomeRNAi; 9874; -.
DR Pharos; Q9UKI8; Tchem.
DR PRO; PR:Q9UKI8; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9UKI8; protein.
DR Bgee; ENSG00000198586; Expressed in lateral nuclear group of thalamus and 207 other tissues.
DR ExpressionAtlas; Q9UKI8; baseline and differential.
DR Genevisible; Q9UKI8; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA: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; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:1902275; P:regulation of chromatin organization; IDA: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 Acetylation; Alternative splicing; ATP-binding; Cell cycle;
KW Chromatin regulator; Coiled coil; DNA damage; Kinase; Nucleotide-binding;
KW 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_0000086752"
FT DOMAIN 456..734
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..197
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 346..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 230..281
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 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:0007744|PubMed:23186163"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C0V0"
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:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
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:0000269|PubMed:12660173"
FT VAR_SEQ 1..217
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10588641"
FT /id="VSP_050570"
FT VAR_SEQ 1..48
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043504"
FT VAR_SEQ 1..14
FT /note="MSVQSSSGSLEGPP -> MAVLFLYDLKTTGK (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043505"
FT VAR_SEQ 15..110
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043506"
FT VAR_SEQ 136
FT /note="G -> GFPNLPVFQSLAYWEMGRTAGG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9427565"
FT /id="VSP_050571"
FT VARIANT 121
FT /note="R -> C"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041215"
FT MUTAGEN 607
FT /note="D->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:10523312,
FT ECO:0000269|PubMed:11470414"
FT MUTAGEN 743
FT /note="S->A: Loss of kinase inhibition in response to DNA
FT damage."
FT /evidence="ECO:0000269|PubMed:12660173"
FT MUTAGEN 743
FT /note="S->D: Loss of kinase inhibition in response to DNA
FT damage."
FT /evidence="ECO:0000269|PubMed:12660173"
FT MUTAGEN 743
FT /note="S->E: Loss of kinase inhibition in response to DNA
FT damage."
FT /evidence="ECO:0000269|PubMed:12660173"
FT CONFLICT 88
FT /note="S -> T (in Ref. 2; AAF03094)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="G -> E (in Ref. 1; BAA20562)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="Q -> L (in Ref. 1; BAA20562)"
FT /evidence="ECO:0000305"
FT CONFLICT 261
FT /note="E -> D (in Ref. 1; BAA20562)"
FT /evidence="ECO:0000305"
FT CONFLICT 416
FT /note="E -> G (in Ref. 1; BAA20562)"
FT /evidence="ECO:0000305"
FT CONFLICT 439
FT /note="N -> H (in Ref. 1; BAA20562)"
FT /evidence="ECO:0000305"
FT CONFLICT 471
FT /note="Y -> D (in Ref. 1; BAA20562)"
FT /evidence="ECO:0000305"
FT CONFLICT 477
FT /note="Y -> S (in Ref. 1; BAA20562)"
FT /evidence="ECO:0000305"
FT CONFLICT 625
FT /note="D -> V (in Ref. 1; BAA20562)"
FT /evidence="ECO:0000305"
FT CONFLICT 665
FT /note="F -> Y (in Ref. 1; BAA20562)"
FT /evidence="ECO:0000305"
FT CONFLICT 730
FT /note="N -> C (in Ref. 1; BAA20562)"
FT /evidence="ECO:0000305"
FT MOD_RES Q9UKI8-3:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
SQ SEQUENCE 766 AA; 86700 MW; A65AE0A2A7C7FF2F CRC64;
MSVQSSSGSL EGPPSWSQLS TSPTPGSAAA ARSLLNHTPP SGRPREGAMD ELHSLDPRRQ
ELLEARFTGV ASGSTGSTGS CSVGAKASTN NESSNHSFGS LGSLSDKESE TPEKKQSESS
RGRKRKAENQ NESSQGKSIG GRGHKISDYF EYQGGNGSSP VRGIPPAIRS PQNSHSHSTP
SSSVRPNSPS PTALAFGDHP IVQPKQLSFK IIQTDLTMLK LAALESNKIQ DLEKKEGRID
DLLRANCDLR RQIDEQQKLL EKYKERLNKC ISMSKKLLIE KSTQEKLSSR EKSMQDRLRL
GHFTTVRHGA SFTEQWTDGF AFQNLVKQQE WVNQQREDIE RQRKLLAKRK PPTANNSQAP
STNSEPKQRK NKAVNGAEND 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 SNSSGNLHMA GLTASPTPPS SSIITY
