ID PLK4_HUMAN Reviewed; 970 AA. AC O00444; B2RAL0; B7Z837; B7Z8G7; Q8IYF0; Q96Q95; Q9UD84; Q9UDE2; DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 13-NOV-2007, sequence version 3. DT 27-MAR-2024, entry version 204. DE RecName: Full=Serine/threonine-protein kinase PLK4 {ECO:0000305}; DE EC=2.7.11.21 {ECO:0000269|PubMed:16244668, ECO:0000269|PubMed:18239451, ECO:0000269|PubMed:19164942}; DE AltName: Full=Polo-like kinase 4; DE Short=PLK-4; DE AltName: Full=Serine/threonine-protein kinase 18; DE AltName: Full=Serine/threonine-protein kinase Sak; GN Name=PLK4 {ECO:0000312|HGNC:HGNC:11397}; Synonyms=SAK, STK18; 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] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS THR-232 AND ASP-830. RC TISSUE=Lung; RA Karn T., Holtrich U., Wolf G., Hock B., Strebhardt K., RA Ruebsamen-Waigmann H.; RT "Human SAK related to the PLK/polo family of cell cycle kinases shows high RT mRNA expression in testis."; RL Oncol. Rep. 4:505-510(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION BY TEC, AND RP VARIANTS THR-232 AND ASP-830. RC TISSUE=Blood; RX PubMed=11489907; DOI=10.1074/jbc.m106249200; RA Yamashita Y., Kajigaya S., Yoshida K., Ueno S., Ota J., Ohmine K., Ueda M., RA Miyazato A., Ohya K., Kitamura T., Ozawa K., Mano H.; RT "Sak serine-threonine kinase acts as an effector of Tec tyrosine kinase."; RL J. Biol. Chem. 276:39012-39020(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANTS RP THR-232 AND ASP-830. RC TISSUE=Testis, and Thymus; 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 [4] 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 134-196. RX PubMed=8260651; DOI=10.1006/smim.1993.1041; RA Mills G.B., Schmandt R., Gibson S., Leung B., Hill M., May C., Shi Y.F., RA Branch D.R., Radvanyi L., Truitt K.E., Imboden J.; RT "Transmembrane signaling by the interleukin-2 receptor: progress and RT conundrums."; RL Semin. Immunol. 5:345-364(1993). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 135-196. RC TISSUE=Mammary carcinoma; RX PubMed=1311287; DOI=10.1002/ijc.2910500419; RA Lehtola L., Partanen J., Sistonen L., Korhonen J., Warri A., Harkonen P., RA Clarke R., Alitalo K.; RT "Analysis of tyrosine kinase mRNAs including four FGF receptor mRNAs RT expressed in MCF-7 breast-cancer cells."; RL Int. J. Cancer 50:598-603(1992). RN [7] RP FUNCTION. RX PubMed=16326102; DOI=10.1016/j.cub.2005.11.042; RA Bettencourt-Dias M., Rodrigues-Martins A., Carpenter L., Riparbelli M., RA Lehmann L., Gatt M.K., Carmo N., Balloux F., Callaini G., Glover D.M.; RT "SAK/PLK4 is required for centriole duplication and flagella development."; RL Curr. Biol. 15:2199-2207(2005). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP ASP-154. RX PubMed=16244668; DOI=10.1038/ncb1320; RA Habedanck R., Stierhof Y.-D., Wilkinson C.J., Nigg E.A.; RT "The Polo kinase Plk4 functions in centriole duplication."; RL Nat. Cell Biol. 7:1140-1146(2005). RN [9] RP INDUCTION BY TP53. RX PubMed=15967108; DOI=10.1593/neo.04325; RA Li J., Tan M., Li L., Pamarthy D., Lawrence T.S., Sun Y.; RT "SAK, a new polo-like kinase, is transcriptionally repressed by p53 and RT induces apoptosis upon RNAi silencing."; RL Neoplasia 7:312-323(2005). RN [10] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=17681131; DOI=10.1016/j.devcel.2007.07.002; RA Kleylein-Sohn J., Westendorf J., Le Clech M., Habedanck R., Stierhof Y.-D., RA Nigg E.A.; RT "Plk4-induced centriole biogenesis in human cells."; RL Dev. Cell 13:190-202(2007). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-41 AND THR-170. RX PubMed=18239451; DOI=10.4161/cc.7.4.5387; RA Bonni S., Ganuelas M.L., Petrinac S., Hudson J.W.; RT "Human Plk4 phosphorylates Cdc25C."; RL Cell Cycle 7:545-547(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401, AND IDENTIFICATION BY RP 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 [13] 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 [14] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-41 AND THR-170. RX PubMed=19164942; DOI=10.4161/cc.8.2.7355; RA Petrinac S., Ganuelas M.L., Bonni S., Nantais J., Hudson J.W.; RT "Polo-like kinase 4 phosphorylates Chk2."; RL Cell Cycle 8:327-329(2009). RN [15] RP INDUCTION. RX PubMed=19454482; DOI=10.1242/jcs.036715; RA Kuriyama R., Bettencourt-Dias M., Hoffmann I., Arnold M., Sandvig L.; RT "Gamma-tubulin-containing abnormal centrioles are induced by insufficient RT Plk4 in human HCT116 colorectal cancer cells."; RL J. Cell Sci. 122:2014-2023(2009). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401 AND SER-817, 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 [17] RP INTERACTION WITH CEP152. RX PubMed=21059844; DOI=10.1083/jcb.201007107; RA Cizmecioglu O., Arnold M., Bahtz R., Settele F., Ehret L., RA Haselmann-Weiss U., Antony C., Hoffmann I.; RT "Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the RT centrosome."; RL J. Cell Biol. 191:731-739(2010). RN [18] RP INTERACTION WITH CEP152. RX PubMed=20852615; DOI=10.1038/nature09445; RA Dzhindzhev N.S., Yu Q.D., Weiskopf K., Tzolovsky G., Cunha-Ferreira I., RA Riparbelli M., Rodrigues-Martins A., Bettencourt-Dias M., Callaini G., RA Glover D.M.; RT "Asterless is a scaffold for the onset of centriole assembly."; RL Nature 467:714-718(2010). RN [19] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=22020124; DOI=10.1038/emboj.2011.378; RA Tang C.J., Lin S.Y., Hsu W.B., Lin Y.N., Wu C.T., Lin Y.C., Chang C.W., RA Wu K.S., Tang T.K.; RT "The human microcephaly protein STIL interacts with CPAP and is required RT for procentriole formation."; RL EMBO J. 30:4790-4804(2011). RN [20] RP FUNCTION IN PHOSPHORYLATION OF FBXW5. RX PubMed=21725316; DOI=10.1038/ncb2282; RA Puklowski A., Homsi Y., Keller D., May M., Chauhan S., Kossatz U., RA Grunwald V., Kubicka S., Pich A., Manns M.P., Hoffmann I., Gonczy P., RA Malek N.P.; RT "The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 RT to control centrosome duplication."; RL Nat. Cell Biol. 13:1004-1009(2011). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-665, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [22] RP INVOLVEMENT IN MCPHCR. RX PubMed=25344692; DOI=10.1038/ng.3122; RA Martin C.A., Ahmad I., Klingseisen A., Hussain M.S., Bicknell L.S., RA Leitch A., Nuernberg G., Toliat M.R., Murray J.E., Hunt D., Khan F., RA Ali Z., Tinschert S., Ding J., Keith C., Harley M.E., Heyn P., Mueller R., RA Hoffmann I., Daire V.C., Dollfus H., Dupuis L., Bashamboo A., RA McElreavey K., Kariminejad A., Mendoza-Londono R., Moore A.T., Saggar A., RA Schlechter C., Weleber R., Thiele H., Altmueller J., Hoehne W., RA Hurles M.E., Noegel A.A., Baig S.M., Nuernberg P., Jackson A.P.; RT "Mutations in PLK4, encoding a master regulator of centriole biogenesis, RT cause microcephaly, growth failure and retinopathy."; RL Nat. Genet. 46:1283-1292(2014). RN [23] RP INTERACTION WITH CEP78, AND SUBCELLULAR LOCATION. RX PubMed=27246242; DOI=10.1242/jcs.184093; RA Brunk K., Zhu M., Baerenz F., Kratz A.S., Haselmann-Weiss U., Antony C., RA Hoffmann I.; RT "Cep78 is a new centriolar protein involved in Plk4-induced centriole RT overduplication."; RL J. Cell Sci. 129:2713-2718(2016). RN [24] RP FUNCTION, SUBCELLULAR LOCATION, AND ACETYLATION AT LYS-45 AND LYS-46. RX PubMed=27796307; DOI=10.1038/ncomms13227; RA Fournier M., Orpinell M., Grauffel C., Scheer E., Garnier J.M., Ye T., RA Chavant V., Joint M., Esashi F., Dejaegere A., Goenczy P., Tora L.; RT "KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in RT preventing centrosome amplification."; RL Nat. Commun. 7:13227-13227(2016). RN [25] RP FUNCTION, INTERACTION WITH CEP131, AND SUBCELLULAR LOCATION. RX PubMed=30804208; DOI=10.1074/jbc.ra118.004867; RA Denu R.A., Sass M.M., Johnson J.M., Potts G.K., Choudhary A., Coon J.J., RA Burkard M.E.; RT "Polo-like kinase 4 maintains centriolar satellite integrity by RT phosphorylation of centrosomal protein 131 (CEP131)."; RL J. Biol. Chem. 294:6531-6549(2019). RN [26] RP INTERACTION WITH CEP85. RX PubMed=32107292; DOI=10.1242/jcs.238352; RA Liu Y., Kim J., Philip R., Sridhar V., Chandrashekhar M., Moffat J., RA van Breugel M., Pelletier L.; RT "Direct interaction between CEP85 and STIL mediates PLK4-driven directed RT cell migration."; RL J. Cell Sci. 133:0-0(2020). RN [27] {ECO:0007744|PDB:6W38, ECO:0007744|PDB:6W3I, ECO:0007744|PDB:6W3J} RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 585-807 IN COMPLEXES WITH TENT5C RP AND CEP192, INTERACTION WITH TENT5C, MUTAGENESIS OF ASN-669 AND ILE-670, RP AND SUBCELLULAR LOCATION. RX PubMed=32433990; DOI=10.1016/j.str.2020.04.023; RA Chen H., Lu D., Shang G., Gao G., Zhang X.; RT "Structural and Functional Analyses of the FAM46C/Plk4 Complex."; RL Structure 28:910-921.e4(2020). RN [28] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 2-275. RG New York structural genomix research consortium (NYSGXRC); RT "Crystal structure of PLK4 kinase."; RL Submitted (JUN-2009) to the PDB data bank. RN [29] RP VARIANTS [LARGE SCALE ANALYSIS] CYS-86; HIS-146; THR-226; THR-232; LEU-317; RP ASP-449; SER-519 AND ASP-830. 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: Serine/threonine-protein kinase that plays a central role in CC centriole duplication. Able to trigger procentriole formation on the CC surface of the parental centriole cylinder, leading to the recruitment CC of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CC CEP135 and gamma-tubulin. When overexpressed, it is able to induce CC centrosome amplification through the simultaneous generation of CC multiple procentrioles adjoining each parental centriole during S CC phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, CC leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central CC role in centriole replication suggests a possible role in CC tumorigenesis, centrosome aberrations being frequently observed in CC tumors. Also involved in deuterosome-mediated centriole amplification CC in multiciliated that can generate more than 100 centrioles. Also CC involved in trophoblast differentiation by phosphorylating HAND1, CC leading to disrupt the interaction between HAND1 and MDFIC and activate CC HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of CC STIL to the centriole and for STIL-mediated centriole amplification CC (PubMed:22020124). Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser- CC 372' which is essential for proper organization and integrity of CC centriolar satellites (PubMed:30804208). {ECO:0000269|PubMed:16244668, CC ECO:0000269|PubMed:16326102, ECO:0000269|PubMed:17681131, CC ECO:0000269|PubMed:18239451, ECO:0000269|PubMed:19164942, CC ECO:0000269|PubMed:21725316, ECO:0000269|PubMed:22020124, CC ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:30804208}. 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=2.7.11.21; CC Evidence={ECO:0000269|PubMed:16244668, ECO:0000269|PubMed:18239451, CC ECO:0000269|PubMed:19164942}; 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=2.7.11.21; Evidence={ECO:0000269|PubMed:16244668, CC ECO:0000269|PubMed:18239451, ECO:0000269|PubMed:19164942}; CC -!- SUBUNIT: Homodimer (By similarity). Interacts with CEP152 (via N- CC terminus). Interacts with CEP78; this interaction may be important for CC proper PLK4 localization to the centriole and PLK4-induced CC overduplication of centrioles (PubMed:27246242). Interacts with CEP131 CC (PubMed:30804208). Interacts simultaneously with TENT5C and CEP192 CC (PubMed:32433990). Interacts with TENT5C; this interaction leads to the CC TENT5C recruitment in the centrosome (PubMed:32433990). Interacts with CC CEP85; this interaction may be important in cell migration and CC centriole assembly (PubMed:32107292). {ECO:0000250|UniProtKB:Q64702, CC ECO:0000269|PubMed:20852615, ECO:0000269|PubMed:21059844, CC ECO:0000269|PubMed:27246242, ECO:0000269|PubMed:30804208, CC ECO:0000269|PubMed:32107292, ECO:0000269|PubMed:32433990}. CC -!- INTERACTION: CC O00444; Q9NX04: AIRIM; NbExp=3; IntAct=EBI-746202, EBI-8643161; CC O00444; P36575: ARR3; NbExp=3; IntAct=EBI-746202, EBI-718116; CC O00444; Q9Y297: BTRC; NbExp=4; IntAct=EBI-746202, EBI-307461; CC O00444; O94986: CEP152; NbExp=7; IntAct=EBI-746202, EBI-311012; CC O00444; O94986-3: CEP152; NbExp=16; IntAct=EBI-746202, EBI-15878364; CC O00444; Q8TEP8: CEP192; NbExp=2; IntAct=EBI-746202, EBI-2339778; CC O00444; Q8TEP8-3: CEP192; NbExp=13; IntAct=EBI-746202, EBI-16111881; CC O00444; P59910: DNAJB13; NbExp=3; IntAct=EBI-746202, EBI-11514233; CC O00444; Q9H8V3: ECT2; NbExp=3; IntAct=EBI-746202, EBI-1054039; CC O00444; Q14241: ELOA; NbExp=6; IntAct=EBI-746202, EBI-742350; CC O00444; O95995: GAS8; NbExp=3; IntAct=EBI-746202, EBI-1052570; CC O00444; Q9H4L5: OSBPL3; NbExp=3; IntAct=EBI-746202, EBI-1051317; CC O00444; P07237: P4HB; NbExp=3; IntAct=EBI-746202, EBI-395883; CC O00444; O00444: PLK4; NbExp=10; IntAct=EBI-746202, EBI-746202; CC O00444; P31947: SFN; NbExp=3; IntAct=EBI-746202, EBI-476295; CC O00444; Q96R06: SPAG5; NbExp=3; IntAct=EBI-746202, EBI-413317; CC O00444; Q15468: STIL; NbExp=11; IntAct=EBI-746202, EBI-7488405; CC O00444; Q96A09: TENT5B; NbExp=3; IntAct=EBI-746202, EBI-752030; CC O00444; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-746202, EBI-1105213; CC O00444; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-746202, EBI-2130429; CC O00444; P62258: YWHAE; NbExp=2; IntAct=EBI-746202, EBI-356498; CC O00444; O15060: ZBTB39; NbExp=3; IntAct=EBI-746202, EBI-9995672; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing CC center, centrosome, centriole {ECO:0000269|PubMed:22020124, CC ECO:0000269|PubMed:27246242, ECO:0000269|PubMed:27796307}. Nucleus, CC nucleolus {ECO:0000250|UniProtKB:Q64702}. Cleavage furrow CC {ECO:0000250|UniProtKB:Q64702}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:30804208, CC ECO:0000269|PubMed:32433990}. Note=Component of the deuterosome, a CC structure that promotes de novo centriole amplification in CC multiciliated cells that can generate more than 100 centrioles. CC Associates with centrioles throughout the cell cycle. According to CC PubMed:16244668, it is not present at cleavage furrows. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O00444-1; Sequence=Displayed; CC Name=2; CC IsoId=O00444-2; Sequence=VSP_038117; CC Name=3; CC IsoId=O00444-3; Sequence=VSP_038116; CC -!- INDUCTION: Down-regulated in HCT 116 colorectal cancer cells, leading CC to aberrant centrioles composed of disorganized cylindrical CC microtubules and displaced appendages. Down-regulated by p53/TP53. CC {ECO:0000269|PubMed:15967108, ECO:0000269|PubMed:19454482}. CC -!- DOMAIN: Cryptic POLO box 1 (CPB1) and Cryptic POLO box 2 (CPB2) domains CC can simultaneously bind to both TENT5C and CEP192. CC {ECO:0000269|PubMed:32433990}. CC -!- PTM: Acetylation by KAT2A and KAT2B impairs kinase activity by shifting CC the kinase to an inactive conformation. {ECO:0000269|PubMed:27796307}. CC -!- PTM: Ubiquitinated; leading to its degradation by the proteasome. CC {ECO:0000250}. CC -!- PTM: Tyrosine-phosphorylated by TEC. {ECO:0000269|PubMed:11489907}. CC -!- DISEASE: Microcephaly and chorioretinopathy, autosomal recessive, 2 CC (MCCRP2) [MIM:616171]: A severe disorder characterized by microcephaly, CC delayed psychomotor development, growth retardation with dwarfism, and CC ocular abnormalities. {ECO:0000269|PubMed:25344692}. Note=The disease CC is caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein CC kinase family. CDC5/Polo subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU01328, CC ECO:0000255|PROSITE-ProRule:PRU01329}. 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; Y13115; CAA73575.1; -; mRNA. DR EMBL; AB006972; BAB69958.1; -; mRNA. DR EMBL; AK302858; BAH13823.1; -; mRNA. DR EMBL; AK303399; BAH13953.1; -; mRNA. DR EMBL; AK314238; BAG36907.1; -; mRNA. DR EMBL; BC036023; AAH36023.1; -; mRNA. DR CCDS; CCDS3735.1; -. [O00444-1] DR CCDS; CCDS54803.1; -. [O00444-2] DR CCDS; CCDS54804.1; -. [O00444-3] DR RefSeq; NP_001177728.1; NM_001190799.1. [O00444-2] DR RefSeq; NP_001177730.1; NM_001190801.1. [O00444-3] DR RefSeq; NP_055079.3; NM_014264.4. [O00444-1] DR PDB; 2N19; NMR; -; A=884-970. DR PDB; 3COK; X-ray; 2.25 A; A/B=2-275. DR PDB; 4JXF; X-ray; 2.40 A; A=4-269. DR PDB; 4N7V; X-ray; 2.76 A; A/B=580-808. DR PDB; 4N7Z; X-ray; 2.85 A; A=580-808. DR PDB; 4N9J; X-ray; 2.60 A; A/B=581-808. DR PDB; 4YUR; X-ray; 2.65 A; A=2-275. DR PDB; 4YYP; X-ray; 2.60 A; A=884-970. DR PDB; 5LHY; X-ray; 3.31 A; 1/2/3/4/5/6/7/8/9/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U=884-970. DR PDB; 5LHZ; X-ray; 2.51 A; A/B/C=884-970. DR PDB; 6N45; X-ray; 2.64 A; A/B=581-808. DR PDB; 6N46; X-ray; 3.71 A; A/B/C/D/E/F/G/H=581-808. DR PDB; 6W38; X-ray; 4.48 A; B=585-807. DR PDB; 6W3I; X-ray; 3.80 A; B=585-807. DR PDB; 6W3J; X-ray; 4.38 A; B=585-807. DR PDBsum; 2N19; -. DR PDBsum; 3COK; -. DR PDBsum; 4JXF; -. DR PDBsum; 4N7V; -. DR PDBsum; 4N7Z; -. DR PDBsum; 4N9J; -. DR PDBsum; 4YUR; -. DR PDBsum; 4YYP; -. DR PDBsum; 5LHY; -. DR PDBsum; 5LHZ; -. DR PDBsum; 6N45; -. DR PDBsum; 6N46; -. DR PDBsum; 6W38; -. DR PDBsum; 6W3I; -. DR PDBsum; 6W3J; -. DR AlphaFoldDB; O00444; -. DR BMRB; O00444; -. DR SMR; O00444; -. DR BioGRID; 115956; 142. DR ComplexPortal; CPX-1161; CEP192-PLK4 complex. DR ComplexPortal; CPX-1299; CEP152-PLK4 complex. DR DIP; DIP-34467N; -. DR IntAct; O00444; 61. DR MINT; O00444; -. DR STRING; 9606.ENSP00000270861; -. DR BindingDB; O00444; -. DR ChEMBL; CHEMBL3788; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; O00444; -. DR GuidetoPHARMACOLOGY; 2171; -. DR iPTMnet; O00444; -. DR PhosphoSitePlus; O00444; -. DR BioMuta; PLK4; -. DR CPTAC; CPTAC-3076; -. DR CPTAC; CPTAC-3077; -. DR jPOST; O00444; -. DR MassIVE; O00444; -. DR MaxQB; O00444; -. DR PaxDb; 9606-ENSP00000270861; -. DR PeptideAtlas; O00444; -. DR ProteomicsDB; 47893; -. [O00444-1] DR ProteomicsDB; 47894; -. [O00444-2] DR ProteomicsDB; 47895; -. [O00444-3] DR Antibodypedia; 26934; 276 antibodies from 35 providers. DR DNASU; 10733; -. DR Ensembl; ENST00000270861.10; ENSP00000270861.5; ENSG00000142731.11. [O00444-1] DR Ensembl; ENST00000513090.5; ENSP00000427554.1; ENSG00000142731.11. [O00444-2] DR Ensembl; ENST00000514379.5; ENSP00000423582.1; ENSG00000142731.11. [O00444-3] DR GeneID; 10733; -. DR KEGG; hsa:10733; -. DR MANE-Select; ENST00000270861.10; ENSP00000270861.5; NM_014264.5; NP_055079.3. DR UCSC; uc003ifo.4; human. [O00444-1] DR AGR; HGNC:11397; -. DR CTD; 10733; -. DR DisGeNET; 10733; -. DR GeneCards; PLK4; -. DR HGNC; HGNC:11397; PLK4. DR HPA; ENSG00000142731; Group enriched (bone marrow, lymphoid tissue, testis). DR MalaCards; PLK4; -. DR MIM; 605031; gene. DR MIM; 616171; phenotype. DR neXtProt; NX_O00444; -. DR OpenTargets; ENSG00000142731; -. DR Orphanet; 2518; Autosomal recessive chorioretinopathy-microcephaly syndrome. DR Orphanet; 808; Seckel syndrome. DR PharmGKB; PA36205; -. DR VEuPathDB; HostDB:ENSG00000142731; -. DR eggNOG; KOG0575; Eukaryota. DR GeneTree; ENSGT00940000156316; -. DR InParanoid; O00444; -. DR OMA; NIVERCH; -. DR OrthoDB; 5471704at2759; -. DR PhylomeDB; O00444; -. DR TreeFam; TF101090; -. DR BRENDA; 2.7.11.21; 2681. DR PathwayCommons; O00444; -. DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition. DR Reactome; R-HSA-380259; Loss of Nlp from mitotic centrosomes. DR Reactome; R-HSA-380270; Recruitment of mitotic centrosome proteins and complexes. DR Reactome; R-HSA-380284; Loss of proteins required for interphase microtubule organization from the centrosome. DR Reactome; R-HSA-380320; Recruitment of NuMA to mitotic centrosomes. DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane. DR Reactome; R-HSA-8854518; AURKA Activation by TPX2. DR SignaLink; O00444; -. DR SIGNOR; O00444; -. DR BioGRID-ORCS; 10733; 761 hits in 1211 CRISPR screens. DR EvolutionaryTrace; O00444; -. DR GeneWiki; PLK4; -. DR GenomeRNAi; 10733; -. DR Pharos; O00444; Tchem. DR PRO; PR:O00444; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; O00444; Protein. DR Bgee; ENSG00000142731; Expressed in ventricular zone and 124 other cell types or tissues. DR ExpressionAtlas; O00444; baseline and differential. DR GO; GO:0005814; C:centriole; IDA:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:HPA. DR GO; GO:0032154; C:cleavage furrow; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0098536; C:deuterosome; ISS:UniProtKB. DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB. DR GO; GO:0120098; C:procentriole; IDA:ComplexPortal. DR GO; GO:0120099; C:procentriole replication complex; IPI:ComplexPortal. DR GO; GO:0001741; C:XY body; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. 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:0007099; P:centriole replication; IDA:ComplexPortal. DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB. DR GO; GO:0098535; P:de novo centriole assembly involved in multi-ciliated epithelial cell differentiation; ISS:UniProtKB. DR GO; GO:0046601; P:positive regulation of centriole replication; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0060707; P:trophoblast giant cell differentiation; ISS:UniProtKB. DR CDD; cd13114; POLO_box_Plk4_1; 1. DR CDD; cd13115; POLO_box_Plk4_2; 1. DR CDD; cd13116; POLO_box_Plk4_3; 1. DR CDD; cd14186; STKc_PLK4; 1. DR Gene3D; 2.40.50.930; -; 1. DR Gene3D; 3.30.1120.120; -; 1. DR Gene3D; 3.30.1120.130; -; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR047108; Plk4-like_POLO_box_2_sf. DR InterPro; IPR000959; POLO_box_dom. DR InterPro; IPR033699; POLO_box_Plk4_1. DR InterPro; IPR033698; POLO_box_Plk4_2. DR InterPro; IPR033696; POLO_box_Plk4_C. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR046437; Ser_Thr-PK_POLO_box_1_sf. DR InterPro; IPR008266; Tyr_kinase_AS. DR PANTHER; PTHR24345; SERINE/THREONINE-PROTEIN KINASE PLK; 1. DR PANTHER; PTHR24345:SF89; SERINE_THREONINE-PROTEIN KINASE PLK4; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF18190; Plk4_PB1; 1. DR Pfam; PF18409; Plk4_PB2; 1. DR SUPFAM; SSF82615; Polo-box domain; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS51984; CPB1; 1. DR PROSITE; PS51985; CPB2; 1. DR PROSITE; PS50078; POLO_BOX; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR Genevisible; O00444; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm; KW Cytoskeleton; Dwarfism; Kinase; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; KW Transferase; Ubl conjugation. FT CHAIN 1..970 FT /note="Serine/threonine-protein kinase PLK4" FT /id="PRO_0000086567" FT DOMAIN 12..265 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 586..699 FT /note="Cryptic POLO box 1 (CPB1)" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01328" FT DOMAIN 700..813 FT /note="Cryptic POLO box 2 (CPB2)" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01329" FT DOMAIN 886..964 FT /note="POLO box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00154" FT REGION 323..458 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 497..538 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 808..828 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 323..359 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 360..376 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 377..396 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 418..457 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 506..532 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 810..828 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 136 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 18..26 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 41 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305" FT MOD_RES 45 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:27796307" FT MOD_RES 46 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:27796307" FT MOD_RES 401 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195" FT MOD_RES 665 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 817 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT VAR_SEQ 1..41 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038116" FT VAR_SEQ 43..74 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038117" FT VARIANT 86 FT /note="Y -> C (in dbSNP:rs34156294)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041027" FT VARIANT 146 FT /note="R -> H (in dbSNP:rs35232579)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041028" FT VARIANT 226 FT /note="A -> T (in dbSNP:rs35448573)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041029" FT VARIANT 232 FT /note="S -> T (in dbSNP:rs3811740)" FT /evidence="ECO:0000269|PubMed:11489907, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:17344846, FT ECO:0000269|Ref.1" FT /id="VAR_019632" FT VARIANT 317 FT /note="P -> L (in dbSNP:rs35049837)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041030" FT VARIANT 449 FT /note="N -> D (in dbSNP:rs34906574)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041031" FT VARIANT 519 FT /note="W -> S (in dbSNP:rs56043017)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041032" FT VARIANT 830 FT /note="E -> D (in dbSNP:rs17012739)" FT /evidence="ECO:0000269|PubMed:11489907, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:17344846, FT ECO:0000269|Ref.1" FT /id="VAR_041033" FT MUTAGEN 41 FT /note="K->M: Abolishes ability to phosphorylate CDC25C and FT CHEK2." FT /evidence="ECO:0000269|PubMed:18239451, FT ECO:0000269|PubMed:19164942" FT MUTAGEN 154 FT /note="D->A: Catalytically inactive mutant that causes some FT centrosome amplification above background levels when FT overexpressed." FT /evidence="ECO:0000269|PubMed:16244668" FT MUTAGEN 170 FT /note="T->D: Activating mutant." FT /evidence="ECO:0000269|PubMed:18239451, FT ECO:0000269|PubMed:19164942" FT MUTAGEN 669 FT /note="N->R: Does not affect the interaction with TENT5C." FT /evidence="ECO:0000269|PubMed:32433990" FT MUTAGEN 670 FT /note="I->P: Decreases substantially the interaction with FT TENT5C. Does not affect localization to the centrosome. FT Loss of TENT5C recruitment to the centrosome." FT /evidence="ECO:0000269|PubMed:32433990" FT CONFLICT 34 FT /note="T -> S (in Ref. 2; BAB69958)" FT /evidence="ECO:0000305" FT CONFLICT 58 FT /note="Q -> K (in Ref. 1; CAA73575)" FT /evidence="ECO:0000305" FT CONFLICT 333 FT /note="D -> N (in Ref. 3; BAH13823)" FT /evidence="ECO:0000305" FT CONFLICT 387 FT /note="S -> R (in Ref. 2; BAB69958)" FT /evidence="ECO:0000305" FT CONFLICT 692 FT /note="F -> S (in Ref. 3; BAH13823)" FT /evidence="ECO:0000305" FT CONFLICT 696 FT /note="V -> L (in Ref. 2; BAB69958)" FT /evidence="ECO:0000305" FT CONFLICT 768 FT /note="Y -> F (in Ref. 1; CAA73575)" FT /evidence="ECO:0000305" FT CONFLICT 842 FT /note="A -> D (in Ref. 2; BAB69958)" FT /evidence="ECO:0000305" FT HELIX 2..5 FT /evidence="ECO:0007829|PDB:3COK" FT HELIX 9..11 FT /evidence="ECO:0007829|PDB:3COK" FT STRAND 12..20 FT /evidence="ECO:0007829|PDB:3COK" FT STRAND 22..31 FT /evidence="ECO:0007829|PDB:3COK" FT TURN 32..34 FT /evidence="ECO:0007829|PDB:3COK" FT STRAND 37..44 FT /evidence="ECO:0007829|PDB:3COK" FT HELIX 45..50 FT /evidence="ECO:0007829|PDB:3COK" FT HELIX 54..64 FT /evidence="ECO:0007829|PDB:3COK" FT STRAND 75..80 FT /evidence="ECO:0007829|PDB:3COK" FT STRAND 82..90 FT /evidence="ECO:0007829|PDB:3COK" FT HELIX 97..102 FT /evidence="ECO:0007829|PDB:3COK" FT STRAND 104..106 FT /evidence="ECO:0007829|PDB:4JXF" FT HELIX 110..129 FT /evidence="ECO:0007829|PDB:3COK" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:3COK" FT STRAND 142..144 FT /evidence="ECO:0007829|PDB:3COK" FT STRAND 150..152 FT /evidence="ECO:0007829|PDB:3COK" FT TURN 158..161 FT /evidence="ECO:0007829|PDB:4JXF" FT HELIX 193..206 FT /evidence="ECO:0007829|PDB:3COK" FT HELIX 217..225 FT /evidence="ECO:0007829|PDB:4JXF" FT HELIX 236..245 FT /evidence="ECO:0007829|PDB:3COK" FT HELIX 250..252 FT /evidence="ECO:0007829|PDB:3COK" FT HELIX 256..259 FT /evidence="ECO:0007829|PDB:3COK" FT TURN 263..265 FT /evidence="ECO:0007829|PDB:3COK" FT HELIX 587..590 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 602..605 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 607..613 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 619..627 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 630..639 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 645..649 FT /evidence="ECO:0007829|PDB:4N9J" FT HELIX 651..654 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 671..674 FT /evidence="ECO:0007829|PDB:4N9J" FT HELIX 675..677 FT /evidence="ECO:0007829|PDB:4N9J" FT HELIX 680..682 FT /evidence="ECO:0007829|PDB:4N9J" FT HELIX 683..698 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 700..706 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 708..716 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 723..727 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 732..735 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 740..743 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 749..752 FT /evidence="ECO:0007829|PDB:4N9J" FT HELIX 755..759 FT /evidence="ECO:0007829|PDB:4N9J" FT HELIX 765..793 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 800..804 FT /evidence="ECO:0007829|PDB:4N9J" FT STRAND 887..893 FT /evidence="ECO:0007829|PDB:5LHZ" FT TURN 894..896 FT /evidence="ECO:0007829|PDB:5LHZ" FT STRAND 897..902 FT /evidence="ECO:0007829|PDB:5LHZ" FT STRAND 905..911 FT /evidence="ECO:0007829|PDB:5LHZ" FT STRAND 916..922 FT /evidence="ECO:0007829|PDB:5LHZ" FT STRAND 924..929 FT /evidence="ECO:0007829|PDB:5LHZ" FT TURN 931..933 FT /evidence="ECO:0007829|PDB:2N19" FT STRAND 935..939 FT /evidence="ECO:0007829|PDB:5LHZ" FT HELIX 946..961 FT /evidence="ECO:0007829|PDB:5LHZ" SQ SEQUENCE 970 AA; 108972 MW; 4D56F5FD983211A6 CRC64; MATCIGEKIE DFKVGNLLGK GSFAGVYRAE SIHTGLEVAI KMIDKKAMYK AGMVQRVQNE VKIHCQLKHP SILELYNYFE DSNYVYLVLE MCHNGEMNRY LKNRVKPFSE NEARHFMHQI ITGMLYLHSH GILHRDLTLS NLLLTRNMNI KIADFGLATQ LKMPHEKHYT LCGTPNYISP EIATRSAHGL ESDVWSLGCM FYTLLIGRPP FDTDTVKNTL NKVVLADYEM PSFLSIEAKD LIHQLLRRNP ADRLSLSSVL DHPFMSRNSS TKSKDLGTVE DSIDSGHATI STAITASSST SISGSLFDKR RLLIGQPLPN KMTVFPKNKS STDFSSSGDG NSFYTQWGNQ ETSNSGRGRV IQDAEERPHS RYLRRAYSSD RSGTSNSQSQ AKTYTMERCH SAEMLSVSKR SGGGENEERY SPTDNNANIF NFFKEKTSSS SGSFERPDNN QALSNHLCPG KTPFPFADPT PQTETVQQWF GNLQINAHLR KTTEYDSISP NRDFQGHPDL QKDTSKNAWT DTKVKKNSDA SDNAHSVKQQ NTMKYMTALH SKPEIIQQEC VFGSDPLSEQ SKTRGMEPPW GYQNRTLRSI TSPLVAHRLK PIRQKTKKAV VSILDSEEVC VELVKEYASQ EYVKEVLQIS SDGNTITIYY PNGGRGFPLA DRPPSPTDNI SRYSFDNLPE KYWRKYQYAS RFVQLVRSKS PKITYFTRYA KCILMENSPG ADFEVWFYDG VKIHKTEDFI QVIEKTGKSY TLKSESEVNS LKEEIKMYMD HANEGHRICL ALESIISEEE RKTRSAPFFP IIIGRKPGST SSPKALSPPP SVDSNYPTRE RASFNRMVMH SAASPTQAPI LNPSMVTNEG LGLTTTASGT DISSNSLKDC LPKSAQLLKS VFVKNVGWAT QLTSGAVWVQ FNDGSQLVVQ AGVSSISYTS PNGQTTRYGE NEKLPDYIKQ KLQCLSSILL MFSNPTPNFH //