ID TLK2_HUMAN Reviewed; 772 AA. AC Q86UE8; D3DU07; Q9UKI7; Q9Y4F7; DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot. DT 22-AUG-2003, sequence version 2. DT 27-MAR-2024, entry version 196. DE RecName: Full=Serine/threonine-protein kinase tousled-like 2; DE EC=2.7.11.1 {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:9427565}; DE AltName: Full=HsHPK; DE AltName: Full=PKU-alpha {ECO:0000303|PubMed:9427565}; DE AltName: Full=Tousled-like kinase 2 {ECO:0000303|PubMed:10523312}; GN Name=TLK2 {ECO:0000312|HGNC:HGNC:11842}; 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; RN [1] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANT ARG-6, FUNCTION, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Placenta {ECO:0000269|PubMed:9427565}, and Testis RC {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 2), FUNCTION, MUTAGENESIS OF ASP-613, RP SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH TLK1, AND ACTIVITY RP REGULATION. RC TISSUE=Placenta {ECO:0000269|PubMed:10523312}; 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] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 189-772 (ISOFORM 2/3), AND TISSUE RP SPECIFICITY. RX PubMed=9662073; DOI=10.1007/bf02258367; RA Huang A.M., Chang T.J., Cho W.L., Chou C.K.; RT "From mosquito to man: identification of a novel protein kinase, HsHPK, RT which is highly expressed in human hepatoma tissues."; RL J. Biomed. Sci. 5:135-140(1998). RN [6] RP SUBCELLULAR LOCATION, AND INTERACTION WITH YWHAZ. RX PubMed=10455159; DOI=10.1074/jbc.274.35.24865; RA Zhang S., Xing H., Muslin A.J.; RT "Nuclear localization of protein kinase U-alpha is regulated by 14-3-3."; RL J. Biol. Chem. 274:24865-24872(1999). RN [7] RP FUNCTION, AND MUTAGENESIS OF ASP-613. 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 [8] {ECO:0000305} RP FUNCTION, AND ACTIVITY 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 [9] RP PHOSPHORYLATION AT SER-750, FUNCTION, AND ACTIVITY REGULATION. RX PubMed=12955071; DOI=10.1038/sj.onc.1206691; RA Krause D.R., Jonnalagadda J.C., Gatei M.H., Sillje H.H.W., Zhou B.-B., RA Nigg E.A., Khanna K.; RT "Suppression of tousled-like kinase activity after DNA damage or RT replication block requires ATM, NBS1 and Chk1."; RL Oncogene 22:5927-5937(2003). RN [10] RP INTERACTION WITH FEZ1 AND FEZ2. RX PubMed=16484223; DOI=10.1074/jbc.m513280200; RA Assmann E.M., Alborghetti M.R., Camargo M.E.R., Kobarg J.; RT "FEZ1 dimerization and interaction with transcription regulatory proteins RT involves its coiled-coil region."; RL J. Biol. Chem. 281:9869-9881(2006). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, AND IDENTIFICATION BY RP 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=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94 AND SER-134, AND 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 [15] RP FUNCTION AS ASF1A AND ASF1B KINASE, AND ACTIVITY REGULATION. RX PubMed=20016786; DOI=10.1371/journal.pone.0008328; RA Pilyugin M., Demmers J., Verrijzer C.P., Karch F., Moshkin Y.M.; RT "Phosphorylation-mediated control of histone chaperone ASF1 levels by RT Tousled-like kinases."; RL PLoS ONE 4:E8328-E8328(2009). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, 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 [17] 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 [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [19] RP FUNCTION. RX PubMed=22354037; DOI=10.1038/emboj.2012.36; RA McKnight N.C., Jefferies H.B., Alemu E.A., Saunders R.E., Howell M., RA Johansen T., Tooze S.A.; RT "Genome-wide siRNA screen reveals amino acid starvation-induced autophagy RT requires SCOC and WAC."; RL EMBO J. 31:1931-1946(2012). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-73; SER-94; SER-99; SER-115; RP SER-117 AND SER-134, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [22] {ECO:0007744|PDB:5O0Y} RP X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 191-755 IN COMPLEX WITH ATP, RP FUNCTION, SUBUNIT, INTERACTION WITH DYNLL1/LC8 AND TLK1, SUBCELLULAR RP LOCATION, PHOSPHORYLATION, CHARACTERIZATION OF VARIANTS MRD57 ARG-493; RP ARG-518 AND ASN-629, AND MUTAGENESIS OF HIS-518; ASP-613; SER-617; SER-659; RP SER-686; THR-695 AND ARG-720. RX PubMed=29955062; DOI=10.1038/s41467-018-04941-y; RA Mortuza G.B., Hermida D., Pedersen A.K., Segura-Bayona S., Lopez-Mendez B., RA Redondo P., Ruther P., Pozdnyakova I., Garrote A.M., Munoz I.G., RA Villamor-Paya M., Jauset C., Olsen J.V., Stracker T.H., Montoya G.; RT "Molecular basis of Tousled-Like Kinase 2 activation."; RL Nat. Commun. 9:2535-2535(2018). RN [23] {ECO:0007744|PDB:7LO0} RP X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) OF 3-23 IN COMPLEX WITH ASF1A, AND RP FUNCTION. RX PubMed=35136069; DOI=10.1038/s41467-022-28427-0; RA Simon B., Lou H.J., Huet-Calderwood C., Shi G., Boggon T.J., Turk B.E., RA Calderwood D.A.; RT "Tousled-like kinase 2 targets ASF1 histone chaperones through client RT mimicry."; RL Nat. Commun. 13:749-749(2022). RN [24] RP VARIANTS [LARGE SCALE ANALYSIS] ARG-6; ASP-54; GLY-95; GLY-108; LEU-109; RP LEU-173 AND GLN-262. 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). RN [25] RP VARIANT MRD57 LEU-617. RX PubMed=21572417; DOI=10.1038/ng.835; RA O'Roak B.J., Deriziotis P., Lee C., Vives L., Schwartz J.J., Girirajan S., RA Karakoc E., Mackenzie A.P., Ng S.B., Baker C., Rieder M.J., Nickerson D.A., RA Bernier R., Fisher S.E., Shendure J., Eichler E.E.; RT "Exome sequencing in sporadic autism spectrum disorders identifies severe RT de novo mutations."; RL Nat. Genet. 43:585-589(2011). RN [26] RP VARIANT MRD57 720-ARG--ASN-772 DEL, AND INVOLVEMENT IN MRD57. RX PubMed=27479843; DOI=10.1038/nn.4352; RA Lelieveld S.H., Reijnders M.R., Pfundt R., Yntema H.G., Kamsteeg E.J., RA de Vries P., de Vries B.B., Willemsen M.H., Kleefstra T., Loehner K., RA Vreeburg M., Stevens S.J., van der Burgt I., Bongers E.M., Stegmann A.P., RA Rump P., Rinne T., Nelen M.R., Veltman J.A., Vissers L.E., Brunner H.G., RA Gilissen C.; RT "Meta-analysis of 2,104 trios provides support for 10 new genes for RT intellectual disability."; RL Nat. Neurosci. 19:1194-1196(2016). RN [27] RP VARIANTS MRD57 13-GLN--ASN-772 DEL; 61-ARG--ASN-772 DEL; 68-GLU--ASN-772 RP DEL; 259-TYR--ASN-772 DEL; 262-ARG--ASN-772 DEL; ASP-297; 303-ARG--ASN-772 RP DEL; 330-SER--ASN-772 DEL; GLN-339; TRP-339; LYS-447; ARG-493; ARG-518; RP TRP-568; 573-GLN--ASN-772 DEL; ASN-629; ARG-680; 720-ARG--ASN-772 DEL AND RP 746-ARG--ASN-772 DEL, AND INVOLVEMENT IN MRD57. RX PubMed=29861108; DOI=10.1016/j.ajhg.2018.04.014; RG Deciphering Developmental Disorders Study; RA Reijnders M.R.F., Miller K.A., Alvi M., Goos J.A.C., Lees M.M., RA de Burca A., Henderson A., Kraus A., Mikat B., de Vries B.B.A., Isidor B., RA Kerr B., Marcelis C., Schluth-Bolard C., Deshpande C., Ruivenkamp C.A.L., RA Wieczorek D., Baralle D., Blair E.M., Engels H., Luedecke H.J., Eason J., RA Santen G.W.E., Clayton-Smith J., Chandler K., Tatton-Brown K., Payne K., RA Helbig K., Radtke K., Nugent K.M., Cremer K., Strom T.M., Bird L.M., RA Sinnema M., Bitner-Glindzicz M., van Dooren M.F., Alders M., Koopmans M., RA Brick L., Kozenko M., Harline M.L., Klaassens M., Steinraths M., RA Cooper N.S., Edery P., Yap P., Terhal P.A., van der Spek P.J., Lakeman P., RA Taylor R.L., Littlejohn R.O., Pfundt R., Mercimek-Andrews S., RA Stegmann A.P.A., Kant S.G., McLean S., Joss S., Swagemakers S.M.A., RA Douzgou S., Wall S.A., Kuery S., Calpena E., Koelling N., McGowan S.J., RA Twigg S.R.F., Mathijssen I.M.J., Nellaker C., Brunner H.G., Wilkie A.O.M.; RT "De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and RT Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder."; RL Am. J. Hum. Genet. 102:1195-1203(2018). RN [28] RP VARIANTS MRD57 475-GLU--ASN-772 DEL AND GLY-551, CHARACTERIZATION OF RP VARIANTS MRD57 GLY-551 AND LEU-617, FUNCTION, SUBCELLULAR LOCATION, RP INTERACTION WITH TLK1; CHD7; CHD8 AND DYNLL1/LC8, AND MUTAGENESIS OF RP ASP-592. RX PubMed=33323470; DOI=10.1136/jmedgenet-2020-107281; RA Pavinato L., Villamor-Paya M., Sanchiz-Calvo M., Andreoli C., Gay M., RA Vilaseca M., Arauz-Garofalo G., Ciolfi A., Bruselles A., Pippucci T., RA Prota V., Carli D., Giorgio E., Radio F.C., Antona V., Giuffre M., RA Ranguin K., Colson C., De Rubeis S., Dimartino P., Buxbaum J.D., RA Ferrero G.B., Tartaglia M., Martinelli S., Stracker T.H., Brusco A.; RT "Functional analysis of TLK2 variants and their proximal interactomes RT implicates impaired kinase activity and chromatin maintenance defects in RT their pathogenesis."; RL J. Med. Genet. 59:170-179(2022). CC -!- FUNCTION: Serine/threonine-protein kinase involved in the process of CC chromatin assembly and probably also DNA replication, transcription, CC repair, and chromosome segregation (PubMed:9427565, PubMed:10523312, CC PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, CC PubMed:33323470). Phosphorylates the chromatin assembly factors ASF1A CC and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, CC PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome- CC mediated degradation, thereby enhancing chromatin assembly CC (PubMed:20016786). Negative regulator of amino acid starvation-induced CC autophagy (PubMed:22354037). {ECO:0000269|PubMed:10523312, CC ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, CC ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786, CC ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:29955062, CC ECO:0000269|PubMed:33323470, ECO:0000269|PubMed:35136069, CC 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:12660173, 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:12660173, ECO:0000269|PubMed:9427565}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:12660173, CC ECO:0000269|PubMed:9427565}; CC -!- ACTIVITY REGULATION: Cell cycle-regulated, with maximal activity in the CC S-phase (PubMed:10523312, PubMed:20016786). Rapidly and transiently CC inhibited by phosphorylation following the generation of DNA double- CC stranded breaks during S-phase, probably by CHEK1, possibly at Ser-750 CC (PubMed:12660173, PubMed:12955071). This inhibition is cell cycle CC checkpoint- and ATM-dependent (PubMed:12955071). CC {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:12660173, CC ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786}. CC -!- SUBUNIT: Monomer (PubMed:29955062). May form homodimers; CC homodimerization may enhance autophosphoylation and enzymatic activity CC (PubMed:29955062). Heterodimer with TLK1 (PubMed:10523312, CC PubMed:29955062, PubMed:33323470). Interacts with YWHAZ; association CC with 14-3-3 proteins such as YWHAZ regulates subcellular location CC (PubMed:10455159). May also interact with FEZ1/LZTS1 and FEZ2 CC (PubMed:16484223). Interacts with CHD7 and CHD8 (PubMed:33323470). CC Interacts with DYNLL1/LC8 (PubMed:29955062). CC {ECO:0000269|PubMed:10455159, ECO:0000269|PubMed:10523312, CC ECO:0000269|PubMed:16484223, ECO:0000269|PubMed:29955062, CC ECO:0000269|PubMed:33323470}. CC -!- INTERACTION: CC Q86UE8; Q9Y294: ASF1A; NbExp=8; IntAct=EBI-1047967, EBI-749553; CC Q86UE8; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-1047967, EBI-739624; CC Q86UE8; Q9NPF5: DMAP1; NbExp=3; IntAct=EBI-1047967, EBI-399105; CC Q86UE8; Q96NE9-2: FRMD6; NbExp=3; IntAct=EBI-1047967, EBI-13213391; CC Q86UE8; Q96IK5: GMCL1; NbExp=3; IntAct=EBI-1047967, EBI-2548508; CC Q86UE8; Q15306: IRF4; NbExp=2; IntAct=EBI-1047967, EBI-751345; CC Q86UE8; Q92985: IRF7; NbExp=2; IntAct=EBI-1047967, EBI-968267; CC Q86UE8; Q02548: PAX5; NbExp=3; IntAct=EBI-1047967, EBI-296331; CC Q86UE8; P26367: PAX6; NbExp=3; IntAct=EBI-1047967, EBI-747278; CC Q86UE8; Q86UE8: TLK2; NbExp=3; IntAct=EBI-1047967, EBI-1047967; CC Q86UE8; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-1047967, EBI-10180829; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10455159, CC ECO:0000269|PubMed:29955062, ECO:0000269|PubMed:33323470, CC ECO:0000269|PubMed:9427565}. Nucleus, nucleoplasm CC {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:33323470}. Cytoplasm, CC perinuclear region {ECO:0000269|PubMed:10455159, CC ECO:0000269|PubMed:33323470}. Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:10455159}. Note=Colocalizes with the cytoplasmic CC intermediate filament system during the G1 phase of the cell cycle CC (PubMed:10455159). Present in the perinuclear region at S phase and in CC the nucleus at late G2 (PubMed:10455159). CC {ECO:0000269|PubMed:10455159}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1 {ECO:0000305}; CC IsoId=Q86UE8-1; Sequence=Displayed; CC Name=2 {ECO:0000269|PubMed:10523312}; CC IsoId=Q86UE8-2; Sequence=VSP_050573; CC Name=3 {ECO:0000269|PubMed:9427565}; CC IsoId=Q86UE8-3; Sequence=VSP_050572, VSP_050573; CC -!- TISSUE SPECIFICITY: Detected in placenta, fetal liver, kidney, CC pancreas, heart and skeletal muscle (PubMed:9427565). Highly expressed CC in testis (PubMed:9427565, PubMed:9662073). Detected in spleen, thymus, CC colon, ovary, small intestine, prostate and peripheral blood leukocytes CC (PubMed:9662073). Almost undetectable in liver and lung CC (PubMed:9662073). {ECO:0000269|PubMed:9427565, CC ECO:0000269|PubMed:9662073}. CC -!- PTM: Phosphorylated at Ser-750, probably by CHEK1. CC {ECO:0000269|PubMed:12955071}. CC -!- PTM: Autophosphorylated; phosphorylation promotes the assembly of CC higher order oligomers and enzymatic activity. CC {ECO:0000269|PubMed:29955062}. CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 57 CC (MRD57) [MIM:618050]: A disorder characterized by significantly below CC average general intellectual functioning associated with impairments in CC adaptive behavior and manifested during the developmental period. MRD57 CC is characterized by delayed psychomotor development apparent in infancy CC or early childhood, and a variety of behavioral abnormalities. Affected CC individuals may have severe gastro-intestinal problems, and facial CC dysmorphism. {ECO:0000269|PubMed:21572417, ECO:0000269|PubMed:27479843, CC ECO:0000269|PubMed:29861108, ECO:0000269|PubMed:29955062, CC ECO:0000269|PubMed:33323470}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF03095.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAH44925.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAA20561.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB004884; BAA20561.1; ALT_INIT; mRNA. DR EMBL; AF162667; AAF03095.1; ALT_INIT; mRNA. DR EMBL; CH471109; EAW94346.1; -; Genomic_DNA. DR EMBL; CH471109; EAW94348.1; -; Genomic_DNA. DR EMBL; BC044925; AAH44925.2; ALT_INIT; mRNA. DR CCDS; CCDS11633.1; -. [Q86UE8-2] DR CCDS; CCDS45753.1; -. [Q86UE8-3] DR CCDS; CCDS62283.1; -. [Q86UE8-1] DR RefSeq; NP_001271262.1; NM_001284333.1. [Q86UE8-1] DR RefSeq; NP_001271292.1; NM_001284363.1. [Q86UE8-3] DR RefSeq; NP_006843.2; NM_006852.3. [Q86UE8-2] DR RefSeq; XP_011522518.1; XM_011524216.2. [Q86UE8-1] DR RefSeq; XP_011522519.1; XM_011524217.2. DR RefSeq; XP_011522524.1; XM_011524222.2. [Q86UE8-1] DR RefSeq; XP_016879533.1; XM_017024044.1. DR RefSeq; XP_016879535.1; XM_017024046.1. DR RefSeq; XP_016879536.1; XM_017024047.1. DR RefSeq; XP_016879540.1; XM_017024051.1. [Q86UE8-3] DR RefSeq; XP_016879541.1; XM_017024052.1. DR RefSeq; XP_016879542.1; XM_017024053.1. [Q86UE8-3] DR PDB; 5O0Y; X-ray; 2.86 A; A=191-755. DR PDB; 7LO0; X-ray; 2.71 A; I/J/K/L/M/N/O/P/Q/R/T/U/V/W/X/Y=3-23. DR PDBsum; 5O0Y; -. DR PDBsum; 7LO0; -. DR AlphaFoldDB; Q86UE8; -. DR SMR; Q86UE8; -. DR BioGRID; 116201; 105. DR IntAct; Q86UE8; 146. DR MINT; Q86UE8; -. DR STRING; 9606.ENSP00000316512; -. DR BindingDB; Q86UE8; -. DR ChEMBL; CHEMBL5404; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; Q86UE8; -. DR GlyGen; Q86UE8; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q86UE8; -. DR PhosphoSitePlus; Q86UE8; -. DR BioMuta; TLK2; -. DR DMDM; 34222826; -. DR CPTAC; non-CPTAC-5682; -. DR CPTAC; non-CPTAC-5683; -. DR EPD; Q86UE8; -. DR jPOST; Q86UE8; -. DR MassIVE; Q86UE8; -. DR MaxQB; Q86UE8; -. DR PaxDb; 9606-ENSP00000316512; -. DR PeptideAtlas; Q86UE8; -. DR ProteomicsDB; 69811; -. [Q86UE8-1] DR ProteomicsDB; 69812; -. [Q86UE8-2] DR ProteomicsDB; 69813; -. [Q86UE8-3] DR Pumba; Q86UE8; -. DR Antibodypedia; 31236; 432 antibodies from 31 providers. DR DNASU; 11011; -. DR Ensembl; ENST00000326270.13; ENSP00000316512.9; ENSG00000146872.19. [Q86UE8-1] DR Ensembl; ENST00000343388.11; ENSP00000340800.7; ENSG00000146872.19. [Q86UE8-3] DR Ensembl; ENST00000346027.10; ENSP00000275780.7; ENSG00000146872.19. [Q86UE8-2] DR Ensembl; ENST00000682085.1; ENSP00000506744.1; ENSG00000146872.19. [Q86UE8-2] DR Ensembl; ENST00000683104.1; ENSP00000508242.1; ENSG00000146872.19. [Q86UE8-3] DR GeneID; 11011; -. DR KEGG; hsa:11011; -. DR MANE-Select; ENST00000346027.10; ENSP00000275780.7; NM_006852.6; NP_006843.2. [Q86UE8-2] DR UCSC; uc002izz.5; human. [Q86UE8-1] DR AGR; HGNC:11842; -. DR CTD; 11011; -. DR DisGeNET; 11011; -. DR GeneCards; TLK2; -. DR HGNC; HGNC:11842; TLK2. DR HPA; ENSG00000146872; Low tissue specificity. DR MalaCards; TLK2; -. DR MIM; 608439; gene. DR MIM; 618050; phenotype. DR neXtProt; NX_Q86UE8; -. DR OpenTargets; ENSG00000146872; -. DR PharmGKB; PA36544; -. DR VEuPathDB; HostDB:ENSG00000146872; -. DR eggNOG; KOG1151; Eukaryota. DR GeneTree; ENSGT00950000182984; -. DR InParanoid; Q86UE8; -. DR OMA; SSFNIGM; -. DR OrthoDB; 1523at2759; -. DR PhylomeDB; Q86UE8; -. DR TreeFam; TF315233; -. DR PathwayCommons; Q86UE8; -. DR SignaLink; Q86UE8; -. DR SIGNOR; Q86UE8; -. DR BioGRID-ORCS; 11011; 259 hits in 1157 CRISPR screens. DR ChiTaRS; TLK2; human. DR GeneWiki; TLK2; -. DR GenomeRNAi; 11011; -. DR Pharos; Q86UE8; Tchem. DR PRO; PR:Q86UE8; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q86UE8; Protein. DR Bgee; ENSG00000146872; Expressed in calcaneal tendon and 115 other cell types or tissues. DR ExpressionAtlas; Q86UE8; baseline and differential. DR GO; GO:0005882; C:intermediate filament; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. 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:0071480; P:cellular response to gamma radiation; IDA:UniProtKB. DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW. DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB. DR GO; GO:0010507; P:negative regulation of autophagy; NAS:BHF-UCL. DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0051647; P:nucleus localization; IMP:DisProt. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:1902275; P:regulation of chromatin organization; IDA:UniProtKB. DR CDD; cd14041; STKc_TLK2; 1. DR DisProt; DP02475; -. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR22974; MIXED LINEAGE PROTEIN KINASE; 1. DR PANTHER; PTHR22974:SF20; SERINE_THREONINE-PROTEIN KINASE TOUSLED-LIKE 2; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q86UE8; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle; KW Chromatin regulator; Coiled coil; Cytoplasm; Cytoskeleton; Disease variant; KW DNA damage; Intellectual disability; Kinase; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; KW Transferase. FT CHAIN 1..772 FT /note="Serine/threonine-protein kinase tousled-like 2" FT /id="PRO_0000086754" FT DOMAIN 462..741 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 24..126 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 180..208 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 225..276 FT /note="Required for interaction with TLK1 and DYNLL1/LC8" FT /evidence="ECO:0000269|PubMed:29955062" FT REGION 342..385 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 225..276 FT /evidence="ECO:0000255" FT COILED 317..347 FT /evidence="ECO:0000255" FT COILED 403..451 FT /evidence="ECO:0000255" FT COMPBIAS 27..45 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 48..71 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 104..120 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 355..383 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 592 FT /note="Proton acceptor" FT BINDING 468..476 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 491 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 73 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 94 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:23186163" FT MOD_RES 99 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 115 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 117 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 134 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:23186163" FT MOD_RES 750 FT /note="Phosphoserine; by CHEK1" FT /evidence="ECO:0000305|PubMed:12955071" FT VAR_SEQ 90..121 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9427565" FT /id="VSP_050572" FT VAR_SEQ 375..396 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:10523312, FT ECO:0000303|PubMed:9427565" FT /id="VSP_050573" FT VARIANT 6 FT /note="H -> R (in dbSNP:rs45550140)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:9427565" FT /id="VAR_041216" FT VARIANT 13..772 FT /note="Missing (in MRD57)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081017" FT VARIANT 54 FT /note="E -> D" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041217" FT VARIANT 61..772 FT /note="Missing (in MRD57)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081018" FT VARIANT 68..772 FT /note="Missing (in MRD57)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081019" FT VARIANT 95 FT /note="A -> G (in dbSNP:rs2598147)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041218" FT VARIANT 108 FT /note="A -> G" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041219" FT VARIANT 109 FT /note="R -> L (in dbSNP:rs1555617262)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041220" FT VARIANT 173 FT /note="F -> L (in a gastric adenocarcinoma sample; somatic FT mutation; dbSNP:rs1331331651)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041221" FT VARIANT 259..772 FT /note="Missing (in MRD57)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081020" FT VARIANT 262..772 FT /note="Missing (in MRD57)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081021" FT VARIANT 262 FT /note="R -> Q (in dbSNP:rs762409144)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041222" FT VARIANT 297 FT /note="G -> D (in MRD57; uncertain significance; FT dbSNP:rs1555639254)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081022" FT VARIANT 303..772 FT /note="Missing (in MRD57)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081023" FT VARIANT 330..772 FT /note="Missing (in MRD57)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081024" FT VARIANT 339 FT /note="R -> Q (in MRD57; uncertain significance; FT dbSNP:rs1567948287)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081025" FT VARIANT 339 FT /note="R -> W (in MRD57; uncertain significance; FT dbSNP:rs1567948262)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081026" FT VARIANT 447 FT /note="E -> K (in MRD57; uncertain significance; FT dbSNP:rs1567959483)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081027" FT VARIANT 475..772 FT /note="Missing (in MRD57; uncertain significance)" FT /evidence="ECO:0000269|PubMed:33323470" FT /id="VAR_087040" FT VARIANT 493 FT /note="H -> R (in MRD57; reduced kinase activity; FT dbSNP:rs1567974030)" FT /evidence="ECO:0000269|PubMed:29861108, FT ECO:0000269|PubMed:29955062" FT /id="VAR_081028" FT VARIANT 518 FT /note="H -> R (in MRD57; severely reduced kinase activity; FT dbSNP:rs1567995650)" FT /evidence="ECO:0000269|PubMed:29861108, FT ECO:0000269|PubMed:29955062" FT /id="VAR_081029" FT VARIANT 551 FT /note="D -> G (in MRD57; uncertain significance; exhibits FT abnormal perinuclear localization instead of diffuse FT nuclear localization; mildly impairs kinase activity; FT reduced phosphorylation of ASF1A; dbSNP:rs2082811958)" FT /evidence="ECO:0000269|PubMed:33323470" FT /id="VAR_087041" FT VARIANT 568 FT /note="R -> W (in MRD57; dbSNP:rs1283838287)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081030" FT VARIANT 573..772 FT /note="Missing (in MRD57)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081031" FT VARIANT 617 FT /note="S -> L (in MRD57; exhibits abnormal perinuclear FT localization instead of diffuse nuclear localization; FT impairs kinase activity; reduced phosphorylation of ASF1A; FT dbSNP:rs2082914686)" FT /evidence="ECO:0000269|PubMed:21572417, FT ECO:0000269|PubMed:33323470" FT /id="VAR_087042" FT VARIANT 629 FT /note="D -> N (in MRD57; reduced phosphorylation of ASF1A; FT dbSNP:rs1568006217)" FT /evidence="ECO:0000269|PubMed:29861108, FT ECO:0000269|PubMed:29955062" FT /id="VAR_081032" FT VARIANT 680 FT /note="P -> R (in MRD57; dbSNP:rs1568018905)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081033" FT VARIANT 720..772 FT /note="Missing (in MRD57; uncertain significance)" FT /evidence="ECO:0000269|PubMed:27479843, FT ECO:0000269|PubMed:29861108" FT /id="VAR_081034" FT VARIANT 746..772 FT /note="Missing (in MRD57; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29861108" FT /id="VAR_081035" FT MUTAGEN 518 FT /note="H->N: Reduced kinase activity." FT /evidence="ECO:0000269|PubMed:29955062" FT MUTAGEN 592 FT /note="D->V: Loss of kinase activity. No impact on FT interaction with ASF1A." FT /evidence="ECO:0000269|PubMed:33323470, FT ECO:0000269|PubMed:35136069" FT MUTAGEN 613 FT /note="D->A: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:10523312, FT ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:29955062" FT MUTAGEN 617 FT /note="S->A: Increase in autophosphorylation." FT /evidence="ECO:0000269|PubMed:29955062" FT MUTAGEN 617 FT /note="S->D: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:29955062" FT MUTAGEN 659 FT /note="S->A: Reduced kinase activity." FT /evidence="ECO:0000269|PubMed:29955062" FT MUTAGEN 686 FT /note="S->A: Reduced kinase activity." FT /evidence="ECO:0000269|PubMed:29955062" FT MUTAGEN 686 FT /note="S->D: Reduced kinase activity." FT /evidence="ECO:0000269|PubMed:29955062" FT MUTAGEN 695 FT /note="T->A: Reduced kinase activity." FT /evidence="ECO:0000269|PubMed:29955062" FT MUTAGEN 720 FT /note="R->A: Reduced phosphorylation of ASF1A." FT /evidence="ECO:0000269|PubMed:29955062" FT CONFLICT 1 FT /note="M -> I (in Ref. 1; BAA20561)" FT /evidence="ECO:0000305" FT CONFLICT 161 FT /note="T -> P (in Ref. 1; BAA20561)" FT /evidence="ECO:0000305" FT CONFLICT 207 FT /note="Q -> R (in Ref. 2; AAF03095)" FT /evidence="ECO:0000305" FT CONFLICT 562 FT /note="M -> I (in Ref. 1; BAA20561)" FT /evidence="ECO:0000305" FT CONFLICT 727 FT /note="E -> R (in Ref. 2; AAF03095)" FT /evidence="ECO:0000305" FT HELIX 10..21 FT /evidence="ECO:0007829|PDB:7LO0" FT STRAND 463..470 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 472..481 FT /evidence="ECO:0007829|PDB:5O0Y" FT TURN 482..485 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 486..494 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 497..499 FT /evidence="ECO:0007829|PDB:5O0Y" FT HELIX 502..519 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 529..534 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 539..545 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 549..551 FT /evidence="ECO:0007829|PDB:5O0Y" FT HELIX 552..559 FT /evidence="ECO:0007829|PDB:5O0Y" FT HELIX 564..581 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 584..586 FT /evidence="ECO:0007829|PDB:5O0Y" FT HELIX 595..597 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 598..600 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 603..607 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 609..611 FT /evidence="ECO:0007829|PDB:5O0Y" FT TURN 622..624 FT /evidence="ECO:0007829|PDB:5O0Y" FT TURN 627..629 FT /evidence="ECO:0007829|PDB:5O0Y" FT HELIX 641..643 FT /evidence="ECO:0007829|PDB:5O0Y" FT HELIX 646..649 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 652..654 FT /evidence="ECO:0007829|PDB:5O0Y" FT HELIX 661..676 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 680..682 FT /evidence="ECO:0007829|PDB:5O0Y" FT HELIX 687..693 FT /evidence="ECO:0007829|PDB:5O0Y" FT TURN 694..698 FT /evidence="ECO:0007829|PDB:5O0Y" FT STRAND 706..708 FT /evidence="ECO:0007829|PDB:5O0Y" FT HELIX 712..721 FT /evidence="ECO:0007829|PDB:5O0Y" FT HELIX 726..728 FT /evidence="ECO:0007829|PDB:5O0Y" FT HELIX 732..735 FT /evidence="ECO:0007829|PDB:5O0Y" FT HELIX 739..741 FT /evidence="ECO:0007829|PDB:5O0Y" SQ SEQUENCE 772 AA; 87661 MW; 765EE37ED4A4ADEC CRC64; MMEELHSLDP RRQELLEARF TGVGVSKGPL NSESSNQSLC SVGSLSDKEV ETPEKKQNDQ RNRKRKAEPY ETSQGKGTPR GHKISDYFEF AGGSAPGTSP GRSVPPVARS SPQHSLSNPL PRRVEQPLYG LDGSAAKEAT EEQSALPTLM SVMLAKPRLD TEQLAQRGAG LCFTFVSAQQ NSPSSTGSGN TEHSCSSQKQ ISIQHRQTQS DLTIEKISAL ENSKNSDLEK KEGRIDDLLR ANCDLRRQID EQQKMLEKYK ERLNRCVTMS KKLLIEKSKQ EKMACRDKSM QDRLRLGHFT TVRHGASFTE QWTDGYAFQN LIKQQERINS QREEIERQRK MLAKRKPPAM GQAPPATNEQ KQRKSKTNGA ENETPSSGNT ELKDTAPALG AHSLLRLTLA EYHEQEEIFK LRLGHLKKEE AEIQAELERL ERVRNLHIRE LKRIHNEDNS QFKDHPTLND RYLLLHLLGR GGFSEVYKAF DLTEQRYVAV KIHQLNKNWR DEKKENYHKH ACREYRIHKE LDHPRIVKLY DYFSLDTDSF CTVLEYCEGN DLDFYLKQHK LMSEKEARSI IMQIVNALKY LNEIKPPIIH YDLKPGNILL VNGTACGEIK ITDFGLSKIM DDDSYNSVDG MELTSQGAGT YWYLPPECFV VGKEPPKISN KVDVWSVGVI FYQCLYGRKP FGHNQSQQDI LQENTILKAT EVQFPPKPVV TPEAKAFIRR CLAYRKEDRI DVQQLACDPY LLPHIRKSVS TSSPAGAAIA STSGASNNSS SN //