ID MELK_HUMAN Reviewed; 651 AA. AC Q14680; A6P3A7; A6P3A8; B1AMQ6; B7Z1E6; B7Z5M5; B7Z6Q7; B7Z6R8; AC B7Z6Y0; B7Z7Q1; D3DRP8; F5H0Y0; F5H2R4; F5H689; Q7L3C3; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 19-JUL-2004, sequence version 3. DT 11-NOV-2015, entry version 149. DE RecName: Full=Maternal embryonic leucine zipper kinase; DE Short=hMELK; DE EC=2.7.11.1; DE AltName: Full=Protein kinase Eg3; DE Short=pEg3 kinase; DE AltName: Full=Protein kinase PK38; DE Short=hPK38; DE AltName: Full=Tyrosine-protein kinase MELK; DE EC=2.7.10.2; GN Name=MELK; Synonyms=KIAA0175; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6). RA Katagiri T., Lin M.; RT "Identification of MELK whose expression was highly up-regulated in RT breast cancers."; RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND TISSUE RP SPECIFICITY. RC TISSUE=Bone marrow; RX PubMed=8724849; DOI=10.1093/dnares/3.1.17; RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.; RT "Prediction of the coding sequences of unidentified human genes. V. RT The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by RT analysis of cDNA clones from human cell line KG-1."; RL DNA Res. 3:17-24(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4; 5; 7 AND 8). RC TISSUE=Spleen, 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., RA Rogers J., Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP INTERACTION WITH ZNF622, AND FUNCTION IN PHOSPHORYLATION OF ZNF622. RC TISSUE=Keratinocyte; RX PubMed=11802789; DOI=10.1042/0264-6021:3610597; RA Seong H.-A., Gil M., Kim K.-T., Kim S.-J., Ha H.; RT "Phosphorylation of a novel zinc-finger-like protein, ZPR9, by murine RT protein serine/threonine kinase 38 (MPK38)."; RL Biochem. J. 361:597-604(2002). RN [8] RP FUNCTION IN PHOSPHORYLATION OF CDC25B. RX PubMed=12400006; DOI=10.1038/sj.onc.1205870; RA Davezac N., Baldin V., Blot J., Ducommun B., Tassan J.P.; RT "Human pEg3 kinase associates with and phosphorylates CDC25B RT phosphatase: a potential role for pEg3 in cell cycle regulation."; RL Oncogene 21:7630-7641(2002). RN [9] RP INTERACTION WITH PPP1R8, AUTOPHOSPHORYLATION, MUTAGENESIS OF ASP-150; RP THR-345; THR-387; THR-409; THR-415; THR-428; THR-446; THR-460; RP THR-466; THR-478 AND THR-518, PHOSPHORYLATION AT THR-478, AND RP FUNCTION. RX PubMed=14699119; DOI=10.1074/jbc.M311466200; RA Vulsteke V., Beullens M., Boudrez A., Keppens S., Van Eynde A., RA Rider M.H., Stalmans W., Bollen M.; RT "Inhibition of spliceosome assembly by the cell cycle-regulated RT protein kinase MELK and involvement of splicing factor NIPP1."; RL J. Biol. Chem. 279:8642-8647(2004). RN [10] RP PHOSPHORYLATION AT THR-167, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF RP THR-167. RX PubMed=14976552; DOI=10.1038/sj.emboj.7600110; RA Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., RA Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., RA Alessi D.R.; RT "LKB1 is a master kinase that activates 13 kinases of the AMPK RT subfamily, including MARK/PAR-1."; RL EMBO J. 23:833-843(2004). RN [11] RP INVOLVEMENT IN CANCER. RX PubMed=16266996; DOI=10.1158/0008-5472.CAN-04-4531; RA Gray D., Jubb A.M., Hogue D., Dowd P., Kljavin N., Yi S., Bai W., RA Frantz G., Zhang Z., Koeppen H., de Sauvage F.J., Davis D.P.; RT "Maternal embryonic leucine zipper kinase/murine protein serine- RT threonine kinase 38 is a promising therapeutic target for multiple RT cancers."; RL Cancer Res. 65:9751-9761(2005). RN [12] RP FUNCTION IN PHOSPHORYLATION OF CDC25B. RX PubMed=15908796; RA Mirey G., Chartrain I., Froment C., Quaranta M., Bouche J.P., RA Monsarrat B., Tassan J.P., Ducommun B.; RT "CDC25B phosphorylated by pEg3 localizes to the centrosome and the RT spindle poles at mitosis."; RL Cell Cycle 4:806-811(2005). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [14] RP PHOSPHORYLATION AT THR-167; SER-343; SER-356; TYR-367; THR-398; RP THR-409; SER-431; THR-494; SER-505 AND SER-529. RX PubMed=16628004; RA Badouel C., Korner R., Frank-Vaillant M., Couturier A., Nigg E.A., RA Tassan J.P.; RT "M-phase MELK activity is regulated by MPF and MAPK."; RL Cell Cycle 5:883-889(2006). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, AUTOPHOSPHORYLATION, RP CALCIUM-BINDING, PHOSPHORYLATION AT THR-56; TYR-163; THR-167; SER-171; RP SER-253; SER-336; SER-343; SER-356; SER-391; THR-398; SER-407; RP SER-431; THR-494; SER-505; SER-529 AND THR-539, AND MUTAGENESIS OF RP CYS-29; CYS-70; CYS-89; ASP-150; CYS-154; TYR-163; CYS-168; CYS-169; RP SER-171; CYS-204; 283-ASP--ASP-285; CYS-286 AND CYS-339. RX PubMed=16216881; DOI=10.1074/jbc.M507274200; RA Beullens M., Vancauwenbergh S., Morrice N., Derua R., Ceulemans H., RA Waelkens E., Bollen M.; RT "Substrate specificity and activity regulation of protein kinase RT MELK."; RL J. Biol. Chem. 280:40003-40011(2005). RN [16] RP SUBCELLULAR LOCATION. RX PubMed=16159311; DOI=10.1042/BC20050041; RA Chartrain I., Couturier A., Tassan J.P.; RT "Cell-cycle-dependent cortical localization of pEg3 protein kinase in RT Xenopus and human cells."; RL Biol. Cell 98:253-263(2006). RN [17] RP FUNCTION IN PHOSPHORYLATION OF BCL2L14, AND MUTAGENESIS OF ASP-150. RX PubMed=17280616; DOI=10.1186/bcr1650; RA Lin M.L., Park J.H., Nishidate T., Nakamura Y., Katagiri T.; RT "Involvement of maternal embryonic leucine zipper kinase (MELK) in RT mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic RT member of the Bcl-2 family."; RL Breast Cancer Res. 9:R17-R17(2007). RN [18] RP INVOLVEMENT IN CANCER. RX PubMed=17960622; DOI=10.1002/ijc.23189; RA Marie S.K., Okamoto O.K., Uno M., Hasegawa A.P., Oba-Shinjo S.M., RA Cohen T., Camargo A.A., Kosoy A., Carlotti C.G. Jr., Toledo S., RA Moreira-Filho C.A., Zago M.A., Simpson A.J., Caballero O.L.; RT "Maternal embryonic leucine zipper kinase transcript abundance RT correlates with malignancy grade in human astrocytomas."; RL Int. J. Cancer 122:807-815(2008). RN [19] RP INVOLVEMENT IN CANCER. RX PubMed=17722061; DOI=10.1002/jnr.21471; RA Nakano I., Masterman-Smith M., Saigusa K., Paucar A.A., Horvath S., RA Shoemaker L., Watanabe M., Negro A., Bajpai R., Howes A., Lelievre V., RA Waschek J.A., Lazareff J.A., Freije W.A., Liau L.M., Gilbertson R.J., RA Cloughesy T.F., Geschwind D.H., Nelson S.F., Mischel P.S., RA Terskikh A.V., Kornblum H.I.; RT "Maternal embryonic leucine zipper kinase is a key regulator of the RT proliferation of malignant brain tumors, including brain tumor stem RT cells."; RL J. Neurosci. Res. 86:48-60(2008). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356; SER-498; SER-505; RP THR-518 AND SER-529, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP 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 RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-431 AND SER-505, AND 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 [22] RP INVOLVEMENT IN CANCER. RX PubMed=19671159; DOI=10.1186/bcr2350; RA Pickard M.R., Green A.R., Ellis I.O., Caldas C., Hedge V.L., RA Mourtada-Maarabouni M., Williams G.T.; RT "Dysregulated expression of Fau and MELK is associated with poor RT prognosis in breast cancer."; RL Breast Cancer Res. 11:R60-R60(2009). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356; SER-498; SER-505 RP AND SER-529, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356, AND IDENTIFICATION RP BY 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 [25] RP INVOLVEMENT IN CANCER. RX PubMed=20861186; DOI=10.1158/0008-5472.CAN-10-1295; RA Hebbard L.W., Maurer J., Miller A., Lesperance J., Hassell J., RA Oshima R.G., Terskikh A.V.; RT "Maternal embryonic leucine zipper kinase is upregulated and required RT in mammary tumor-initiating cells in vivo."; RL Cancer Res. 70:8863-8873(2010). RN [26] RP SUBCELLULAR LOCATION. RX PubMed=21145462; DOI=10.1016/j.cell.2010.11.028; RA Moravcevic K., Mendrola J.M., Schmitz K.R., Wang Y.H., Slochower D., RA Janmey P.A., Lemmon M.A.; RT "Kinase associated-1 domains drive MARK/PAR1 kinases to membrane RT targets by binding acidic phospholipids."; RL Cell 143:966-977(2010). RN [27] RP DEVELOPMENTAL STAGE, AND PHOSPHORYLATION. RX PubMed=20420823; DOI=10.1016/j.yexcr.2010.04.019; RA Badouel C., Chartrain I., Blot J., Tassan J.P.; RT "Maternal embryonic leucine zipper kinase is stabilized in mitosis by RT phosphorylation and is partially degraded upon mitotic exit."; RL Exp. Cell Res. 316:2166-2173(2010). RN [28] RP INDUCTION. RX PubMed=21806965; DOI=10.1016/j.bbrc.2011.07.060; RA Choi S., Ku J.L.; RT "Resistance of colorectal cancer cells to radiation and 5-FU is RT associated with MELK expression."; RL Biochem. Biophys. Res. Commun. 412:207-213(2011). RN [29] RP INDUCTION. RX PubMed=21558073; DOI=10.1093/neuonc/nor023; RA Nakano I., Joshi K., Visnyei K., Hu B., Watanabe M., Lam D., RA Wexler E., Saigusa K., Nakamura Y., Laks D.R., Mischel P.S., RA Viapiano M., Kornblum H.I.; RT "Siomycin A targets brain tumor stem cells partially through a MELK- RT mediated pathway."; RL Neuro-oncol. 13:622-634(2011). RN [30] RP VARIANTS [LARGE SCALE ANALYSIS] MET-56; ARG-219; LYS-333; ILE-348 AND RP MET-460. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., 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 involved in various CC processes such as cell cycle regulation, self-renewal of stem CC cells, apoptosis and splicing regulation. Has a broad substrate CC specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and CC ZNF622. Acts as an activator of apoptosis by phosphorylating and CC activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably CC by mediating phosphorylation of CDC25B, promoting localization of CC CDC25B to the centrosome and the spindle poles during mitosis. CC Plays a key role in cell proliferation and carcinogenesis. CC Required for proliferation of embryonic and postnatal multipotent CC neural progenitors. Phosphorylates and inhibits BCL2L14, possibly CC leading to affect mammary carcinogenesis by mediating inhibition CC of the pro-apoptotic function of BCL2L14. Also involved in the CC inhibition of spliceosome assembly during mitosis by CC phosphorylating ZNF622, thereby contributing to its redirection to CC the nucleus. May also play a role in primitive hematopoiesis. CC {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:12400006, CC ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:15908796, CC ECO:0000269|PubMed:16216881, ECO:0000269|PubMed:17280616}. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- CC ProRule:PRU10027, ECO:0000269|PubMed:16216881}. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC {ECO:0000269|PubMed:16216881}. CC -!- ENZYME REGULATION: Activated by autophosphorylation of the T-loop CC at Thr-167 and Ser-171: in contrast to other members of the SNF1 CC subfamily, phosphorylation at Thr-167 is not mediated by CC STK11/LKB1 but via autophosphorylation instead. Inhibited by CC calcium-binding. Kinase activity is also regulated by reducing CC agents: dithiothreitol (DTT) or reduced glutathione are required CC for kinase activity in vitro; such dependence is however not due CC to the presence of disulfide bonds. {ECO:0000269|PubMed:16216881}. CC -!- SUBUNIT: Monomer. Interacts with ZNF622 and PPP1R8. CC {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:14699119}. CC -!- INTERACTION: CC Q9BZR8:BCL2L14; NbExp=4; IntAct=EBI-1046702, EBI-1385773; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16159311, CC ECO:0000269|PubMed:21145462}; Peripheral membrane protein CC {ECO:0000269|PubMed:16159311, ECO:0000269|PubMed:21145462}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Name=1; CC IsoId=Q14680-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14680-2; Sequence=VSP_044715; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=Q14680-3; Sequence=VSP_045208; CC Name=4; CC IsoId=Q14680-4; Sequence=VSP_045209; CC Name=5; CC IsoId=Q14680-5; Sequence=VSP_045430; CC Name=6; CC IsoId=Q14680-6; Sequence=VSP_045431; CC Name=7; CC IsoId=Q14680-7; Sequence=VSP_046760; CC Note=No experimental confirmation available.; CC Name=8; CC IsoId=Q14680-8; Sequence=VSP_046759; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed in placenta, kidney, thymus, testis, CC ovary and intestine. {ECO:0000269|PubMed:8724849}. CC -!- DEVELOPMENTAL STAGE: Increases during G2/M phase compared to CC interphase. Protein level decreases when cells exit mitosis, CC probably due to degradation. {ECO:0000269|PubMed:20420823}. CC -!- INDUCTION: Up-regulated in many cancers cells. Up-regulated upon CC treatment with radiation or 5-fluorouracil (5-FU) in colorectal CC cancer cells, suggesting that it might be associated with CC increased resistance of colorectal cells against radiation and 5- CC FU. Down-regulated upon siomycin A, a thiazole antibiotic, CC treatment, leading to inhibit tumor growth in vivo. CC {ECO:0000269|PubMed:21558073, ECO:0000269|PubMed:21806965}. CC -!- DOMAIN: The KA1 domain mediates binding to phospholipids and CC targeting to membranes. {ECO:0000250}. CC -!- PTM: Autophosphorylated: autophosphorylation of the T-loop at Thr- CC 167 and Ser-171 is required for activation. Thr-478 CC phosphorylation during mitosis promotes interaction with PPP1R8 CC (Probable). {ECO:0000305|PubMed:14699119, CC ECO:0000305|PubMed:14976552, ECO:0000305|PubMed:16216881, CC ECO:0000305|PubMed:16628004, ECO:0000305|PubMed:20420823}. CC -!- DISEASE: Note=Defects in MELK are associated with some cancers, CC such as brain or breast cancers. Expression is dramatically CC increased in aggressive undifferentiated tumors, correlating with CC poor patient outcome in breast and brain cancers, suggesting a CC role in tumor-initiating cells and proliferation via its function CC in cell proliferation regulation. CC -!- MISCELLANEOUS: Potential therapeutic target for treatment of CC somatic tumors, such as brain and breast cancers, down-regulation CC of MELK inhibiting tumorigenesis (PubMed:17960622, CC PubMed:20861186). {ECO:0000305|PubMed:17960622, CC ECO:0000305|PubMed:20861186}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK CC Ser/Thr protein kinase family. SNF1 subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 KA1 (kinase-associated) domain. CC {ECO:0000255|PROSITE-ProRule:PRU00565}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA11492.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/MELKID43360ch9p13.html"; 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; AB183427; BAF73615.1; -; mRNA. DR EMBL; AB183428; BAF73616.1; -; mRNA. DR EMBL; D79997; BAA11492.2; ALT_INIT; mRNA. DR EMBL; AK293284; BAH11482.1; -; mRNA. DR EMBL; AK293447; BAH11508.1; -; mRNA. DR EMBL; AK299164; BAH12961.1; -; mRNA. DR EMBL; AK300761; BAH13343.1; -; mRNA. DR EMBL; AK300821; BAH13354.1; -; mRNA. DR EMBL; AK301131; BAH13416.1; -; mRNA. DR EMBL; AK302374; BAH13687.1; -; mRNA. DR EMBL; AL354932; CAI11034.2; -; Genomic_DNA. DR EMBL; AL442063; CAI11034.2; JOINED; Genomic_DNA. DR EMBL; AL442063; CAI16995.2; -; Genomic_DNA. DR EMBL; AL354932; CAI16995.2; JOINED; Genomic_DNA. DR EMBL; CH471071; EAW58303.1; -; Genomic_DNA. DR EMBL; CH471071; EAW58304.1; -; Genomic_DNA. DR EMBL; BC014039; AAH14039.1; -; mRNA. DR CCDS; CCDS59123.1; -. [Q14680-7] DR CCDS; CCDS59124.1; -. [Q14680-8] DR CCDS; CCDS59125.1; -. [Q14680-2] DR CCDS; CCDS59126.1; -. [Q14680-6] DR CCDS; CCDS59127.1; -. [Q14680-5] DR CCDS; CCDS59128.1; -. [Q14680-4] DR CCDS; CCDS6606.1; -. [Q14680-1] DR RefSeq; NP_001243614.1; NM_001256685.1. [Q14680-7] DR RefSeq; NP_001243616.1; NM_001256687.1. [Q14680-8] DR RefSeq; NP_001243617.1; NM_001256688.1. [Q14680-2] DR RefSeq; NP_001243618.1; NM_001256689.1. [Q14680-6] DR RefSeq; NP_001243619.1; NM_001256690.1. [Q14680-5] DR RefSeq; NP_001243621.1; NM_001256692.1. [Q14680-4] DR RefSeq; NP_001243622.1; NM_001256693.1. [Q14680-3] DR RefSeq; NP_055606.1; NM_014791.3. [Q14680-1] DR RefSeq; XP_011516378.1; XM_011518076.1. [Q14680-1] DR RefSeq; XP_011516379.1; XM_011518077.1. [Q14680-1] DR RefSeq; XP_011516380.1; XM_011518078.1. [Q14680-1] DR RefSeq; XP_011516381.1; XM_011518079.1. [Q14680-1] DR RefSeq; XP_011516383.1; XM_011518081.1. [Q14680-6] DR RefSeq; XP_011516384.1; XM_011518082.1. [Q14680-6] DR RefSeq; XP_011516385.1; XM_011518083.1. [Q14680-6] DR RefSeq; XP_011516386.1; XM_011518084.1. [Q14680-6] DR UniGene; Hs.184339; -. DR PDB; 4BKY; X-ray; 1.83 A; A=2-340. DR PDB; 4BKZ; X-ray; 2.20 A; A=2-340. DR PDB; 4BL1; X-ray; 2.60 A; A=2-340. DR PDB; 4D2P; X-ray; 2.55 A; A/B/C/D=1-336. DR PDB; 4D2T; X-ray; 2.70 A; A/B/C/D=1-336. DR PDB; 4D2V; X-ray; 2.45 A; A/B/C/D=1-336. DR PDB; 4D2W; X-ray; 1.92 A; A/B/C/D=1-336. DR PDB; 4IXP; X-ray; 2.75 A; A=1-340. DR PDB; 4UMP; X-ray; 2.30 A; A/B/C/D=1-336. DR PDB; 4UMQ; X-ray; 2.60 A; A=1-336. DR PDB; 4UMR; X-ray; 3.00 A; A=1-336. DR PDB; 4UMT; X-ray; 1.98 A; A=1-336. DR PDB; 4UMU; X-ray; 2.02 A; A=1-336. DR PDBsum; 4BKY; -. DR PDBsum; 4BKZ; -. DR PDBsum; 4BL1; -. DR PDBsum; 4D2P; -. DR PDBsum; 4D2T; -. DR PDBsum; 4D2V; -. DR PDBsum; 4D2W; -. DR PDBsum; 4IXP; -. DR PDBsum; 4UMP; -. DR PDBsum; 4UMQ; -. DR PDBsum; 4UMR; -. DR PDBsum; 4UMT; -. DR PDBsum; 4UMU; -. DR ProteinModelPortal; Q14680; -. DR SMR; Q14680; 2-335, 554-651. DR BioGrid; 115171; 22. DR IntAct; Q14680; 3. DR MINT; MINT-7944803; -. DR STRING; 9606.ENSP00000298048; -. DR BindingDB; Q14680; -. DR ChEMBL; CHEMBL4578; -. DR GuidetoPHARMACOLOGY; 2102; -. DR PhosphoSite; Q14680; -. DR BioMuta; MELK; -. DR DMDM; 50400857; -. DR MaxQB; Q14680; -. DR PaxDb; Q14680; -. DR PRIDE; Q14680; -. DR DNASU; 9833; -. DR Ensembl; ENST00000298048; ENSP00000298048; ENSG00000165304. [Q14680-1] DR Ensembl; ENST00000536329; ENSP00000443550; ENSG00000165304. [Q14680-5] DR Ensembl; ENST00000536860; ENSP00000439792; ENSG00000165304. [Q14680-8] DR Ensembl; ENST00000536987; ENSP00000439184; ENSG00000165304. [Q14680-4] DR Ensembl; ENST00000541717; ENSP00000437804; ENSG00000165304. [Q14680-7] DR Ensembl; ENST00000543751; ENSP00000441596; ENSG00000165304. [Q14680-6] DR Ensembl; ENST00000545008; ENSP00000445452; ENSG00000165304. [Q14680-2] DR GeneID; 9833; -. DR KEGG; hsa:9833; -. DR UCSC; uc003zzn.4; human. [Q14680-1] DR UCSC; uc010mll.4; human. DR UCSC; uc010mlm.4; human. DR UCSC; uc011lpm.3; human. DR CTD; 9833; -. DR GeneCards; MELK; -. DR HGNC; HGNC:16870; MELK. DR HPA; HPA017214; -. DR MIM; 607025; gene. DR neXtProt; NX_Q14680; -. DR PharmGKB; PA134902874; -. DR eggNOG; KOG0583; Eukaryota. DR eggNOG; COG0515; LUCA. DR GeneTree; ENSGT00790000122960; -. DR HOGENOM; HOG000233023; -. DR HOVERGEN; HBG106273; -. DR InParanoid; Q14680; -. DR KO; K08799; -. DR OMA; YELHETI; -. DR OrthoDB; EOG7CK36C; -. DR PhylomeDB; Q14680; -. DR TreeFam; TF314032; -. DR SignaLink; Q14680; -. DR ChiTaRS; MELK; human. DR GeneWiki; MELK; -. DR GenomeRNAi; 9833; -. DR NextBio; 35480044; -. DR PRO; PR:Q14680; -. DR Proteomes; UP000005640; Chromosome 9. DR Bgee; Q14680; -. DR CleanEx; HS_MELK; -. DR Genevisible; Q14680; HS. DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB. DR GO; GO:0008283; P:cell proliferation; IDA:UniProtKB. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:UniProtKB. DR GO; GO:0030097; P:hemopoiesis; ISS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IEA:Ensembl. DR GO; GO:0061351; P:neural precursor cell proliferation; ISS:UniProtKB. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:GOC. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR Gene3D; 3.30.310.80; -; 1. DR InterPro; IPR028375; KA1/Ssp2_C. DR InterPro; IPR001772; KA1_dom. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR Pfam; PF02149; KA1; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF103243; SSF103243; 1. DR SUPFAM; SSF56112; SSF56112; 1. DR PROSITE; PS50032; KA1; 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 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Calcium; KW Cell cycle; Cell membrane; Complete proteome; Kinase; Lipid-binding; KW Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; KW Reference proteome; Serine/threonine-protein kinase; Transferase. FT CHAIN 1 651 Maternal embryonic leucine zipper kinase. FT /FTId=PRO_0000086323. FT DOMAIN 11 263 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT DOMAIN 602 651 KA1. {ECO:0000255|PROSITE- FT ProRule:PRU00565}. FT NP_BIND 17 25 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 282 321 UBA-like. FT REGION 326 651 Autoinhibitory region. FT ACT_SITE 132 132 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10027}. FT BINDING 40 40 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 56 56 Phosphothreonine; by autocatalysis. FT {ECO:0000269|PubMed:16216881}. FT MOD_RES 163 163 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:16216881}. FT MOD_RES 167 167 Phosphothreonine; by autocatalysis. FT {ECO:0000269|PubMed:14976552, FT ECO:0000269|PubMed:16216881, FT ECO:0000269|PubMed:16628004}. FT MOD_RES 171 171 Phosphoserine; by autocatalysis. FT {ECO:0000269|PubMed:16216881}. FT MOD_RES 253 253 Phosphoserine; by autocatalysis. FT {ECO:0000269|PubMed:16216881}. FT MOD_RES 336 336 Phosphoserine; by autocatalysis. FT {ECO:0000269|PubMed:16216881}. FT MOD_RES 343 343 Phosphoserine; by autocatalysis. FT {ECO:0000269|PubMed:16216881, FT ECO:0000269|PubMed:16628004}. FT MOD_RES 356 356 Phosphoserine; by autocatalysis. FT {ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:19690332, FT ECO:0000269|PubMed:16216881, FT ECO:0000269|PubMed:16628004}. FT MOD_RES 367 367 Phosphotyrosine. FT {ECO:0000269|PubMed:16628004}. FT MOD_RES 391 391 Phosphoserine; by autocatalysis. FT {ECO:0000269|PubMed:16216881}. FT MOD_RES 398 398 Phosphothreonine; by autocatalysis. FT {ECO:0000269|PubMed:16216881, FT ECO:0000269|PubMed:16628004}. FT MOD_RES 407 407 Phosphoserine; by autocatalysis. FT {ECO:0000269|PubMed:16216881}. FT MOD_RES 409 409 Phosphothreonine. FT {ECO:0000269|PubMed:16628004}. FT MOD_RES 431 431 Phosphoserine; by autocatalysis. FT {ECO:0000244|PubMed:18669648, FT ECO:0000269|PubMed:16216881, FT ECO:0000269|PubMed:16628004}. FT MOD_RES 478 478 Phosphothreonine. FT {ECO:0000269|PubMed:14699119}. FT MOD_RES 494 494 Phosphothreonine; by autocatalysis. FT {ECO:0000269|PubMed:16216881, FT ECO:0000269|PubMed:16628004}. FT MOD_RES 498 498 Phosphoserine. FT {ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195}. FT MOD_RES 505 505 Phosphoserine; by autocatalysis. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195, FT ECO:0000269|PubMed:16216881, FT ECO:0000269|PubMed:16628004}. FT MOD_RES 518 518 Phosphothreonine. FT {ECO:0000244|PubMed:18691976}. FT MOD_RES 529 529 Phosphoserine. FT {ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195, FT ECO:0000269|PubMed:16216881, FT ECO:0000269|PubMed:16628004}. FT MOD_RES 529 529 Phosphoserine; by autocatalysis. FT {ECO:0000269|PubMed:16216881, FT ECO:0000269|PubMed:16628004}. FT MOD_RES 539 539 Phosphothreonine; by autocatalysis. FT {ECO:0000269|PubMed:16216881}. FT VAR_SEQ 1 194 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_045208. FT VAR_SEQ 1 135 MKDYDELLKYYELHETIGTGGFAKVKLACHILTGEMVAIKI FT MDKNTLGSDLPRIKTEIEALKNLRHQHICQLYHVLETANKI FT FMVLEYCPGGELFDYIISQDRLSEEETRVVFRQIVSAVAYV FT HSQGYAHRDLKP -> MVLE (in isoform 4). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_045209. FT VAR_SEQ 1 87 MKDYDELLKYYELHETIGTGGFAKVKLACHILTGEMVAIKI FT MDKNTLGSDLPRIKTEIEALKNLRHQHICQLYHVLETANKI FT FMVLE -> MMNFSNIMNYMKLLGQ (in isoform 5). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|Ref.1}. FT /FTId=VSP_045430. FT VAR_SEQ 1 48 MKDYDELLKYYELHETIGTGGFAKVKLACHILTGEMVAIKI FT MDKNTLG -> MMNFSNIMNYMKLLGQ (in isoform FT 6). {ECO:0000303|Ref.1}. FT /FTId=VSP_045431. FT VAR_SEQ 88 158 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_044715. FT VAR_SEQ 88 135 Missing (in isoform 8). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_046759. FT VAR_SEQ 352 392 Missing (in isoform 7). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_046760. FT VARIANT 56 56 T -> M (in dbSNP:rs35233455). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_040794. FT VARIANT 219 219 K -> R (in dbSNP:rs35142210). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_040795. FT VARIANT 333 333 R -> K (in dbSNP:rs34655121). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_040796. FT VARIANT 348 348 T -> I (in dbSNP:rs55845414). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_040797. FT VARIANT 460 460 T -> M (in an ovarian mucinous carcinoma FT sample; somatic mutation). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_040798. FT MUTAGEN 29 29 C->V: Abolishes dependence to reducing FT agents; when associated with V-70; A-89; FT A-154; A-168; A-169; A-204; A-286 and A- FT 339. {ECO:0000269|PubMed:16216881}. FT MUTAGEN 70 70 C->V: Abolishes dependence to reducing FT agents; when associated with V-29; A-89; FT A-154; A-168; A-169; A-204; A-286 and A- FT 339. {ECO:0000269|PubMed:16216881}. FT MUTAGEN 89 89 C->A: Abolishes dependence to reducing FT agents; when associated with V-29; V-70; FT A-154; A-168; A-169; A-204; A-286 and A- FT 339. {ECO:0000269|PubMed:16216881}. FT MUTAGEN 150 150 D->A: Abolishes enzymatic activity. FT {ECO:0000269|PubMed:14699119, FT ECO:0000269|PubMed:16216881, FT ECO:0000269|PubMed:17280616}. FT MUTAGEN 154 154 C->A: Abolishes dependence to reducing FT agents; when associated with V-29; V-70; FT A-89; A-168; A-169; A-204; A-286 and A- FT 339. {ECO:0000269|PubMed:16216881}. FT MUTAGEN 163 163 Y->F: Abolishes autophosphorylation on FT tyrosine but still active on exogenous FT substrates. FT {ECO:0000269|PubMed:16216881}. FT MUTAGEN 167 167 T->A: Abolishes activation of FT serine/threonine-protein kinase activity FT and has only weak activity. FT {ECO:0000269|PubMed:14976552}. FT MUTAGEN 167 167 T->D,E: Phosphomimetic mutant that has FT similar kinase activity as wild-type. FT {ECO:0000269|PubMed:14976552}. FT MUTAGEN 168 168 C->A: Abolishes dependence to reducing FT agents; when associated with V-29; V-70; FT A-89; A-154; A-169; A-204; A-286 and A- FT 339. {ECO:0000269|PubMed:16216881}. FT MUTAGEN 169 169 C->A: Abolishes dependence to reducing FT agents; when associated with V-29; V-70; FT A-89; A-154; A-168; A-204; A-286 and A- FT 339. {ECO:0000269|PubMed:16216881}. FT MUTAGEN 171 171 S->A: Abolishes activation of FT serine/threonine-protein kinase activity FT and has only weak activity. FT {ECO:0000269|PubMed:16216881}. FT MUTAGEN 171 171 S->D: Inactive. FT {ECO:0000269|PubMed:16216881}. FT MUTAGEN 204 204 C->A: Abolishes dependence to reducing FT agents; when associated with V-29; V-70; FT A-89; A-154; A-168; A-169; A-286 and A- FT 339. {ECO:0000269|PubMed:16216881}. FT MUTAGEN 283 285 DDD->KKK: Inactive. FT {ECO:0000269|PubMed:16216881}. FT MUTAGEN 286 286 C->A: Abolishes dependence to reducing FT agents; when associated with V-29; V-70; FT A-89; A-154; A-168; A-169; A-204; and A- FT 339. {ECO:0000269|PubMed:16216881}. FT MUTAGEN 339 339 C->A: Abolishes dependence to reducing FT agents; when associated with V-29; V-70; FT A-89; A-154; A-168; A-169; A-204 and A- FT 286. {ECO:0000269|PubMed:16216881}. FT MUTAGEN 345 345 T->A: No effect on interaction with FT PPP1R8. {ECO:0000269|PubMed:14699119}. FT MUTAGEN 387 387 T->A: No effect on interaction with FT PPP1R8. {ECO:0000269|PubMed:14699119}. FT MUTAGEN 409 409 T->A: No effect on interaction with FT PPP1R8. {ECO:0000269|PubMed:14699119}. FT MUTAGEN 415 415 T->A: No effect on interaction with FT PPP1R8. {ECO:0000269|PubMed:14699119}. FT MUTAGEN 428 428 T->A: No effect on interaction with FT PPP1R8. {ECO:0000269|PubMed:14699119}. FT MUTAGEN 446 446 T->A: Inhibits interaction with PPP1R8. FT {ECO:0000269|PubMed:14699119}. FT MUTAGEN 460 460 T->A: Inhibits interaction with PPP1R8. FT {ECO:0000269|PubMed:14699119}. FT MUTAGEN 466 466 T->A: Inhibits interaction with PPP1R8. FT {ECO:0000269|PubMed:14699119}. FT MUTAGEN 478 478 T->A: Strongly inhibits interaction with FT PPP1R8. Enhances enzymatic activity. FT {ECO:0000269|PubMed:14699119}. FT MUTAGEN 518 518 T->A: No effect on interaction with FT PPP1R8. {ECO:0000269|PubMed:14699119}. FT CONFLICT 69 69 I -> M (in Ref. 3; BAH12961). FT {ECO:0000305}. FT CONFLICT 398 398 T -> A (in Ref. 3; BAH12961). FT {ECO:0000305}. FT CONFLICT 428 428 T -> A (in Ref. 3; BAH11482). FT {ECO:0000305}. FT CONFLICT 474 474 C -> R (in Ref. 3; BAH13343). FT {ECO:0000305}. FT CONFLICT 483 483 P -> L (in Ref. 3; BAH13354). FT {ECO:0000305}. FT TURN 4 6 {ECO:0000244|PDB:4BKY}. FT HELIX 7 9 {ECO:0000244|PDB:4BKY}. FT STRAND 11 19 {ECO:0000244|PDB:4BKY}. FT STRAND 21 30 {ECO:0000244|PDB:4BKY}. FT TURN 31 33 {ECO:0000244|PDB:4BKY}. FT STRAND 36 45 {ECO:0000244|PDB:4BKY}. FT HELIX 48 50 {ECO:0000244|PDB:4UMT}. FT HELIX 51 62 {ECO:0000244|PDB:4BKY}. FT STRAND 72 77 {ECO:0000244|PDB:4BKY}. FT STRAND 79 87 {ECO:0000244|PDB:4BKY}. FT HELIX 94 101 {ECO:0000244|PDB:4BKY}. FT HELIX 106 125 {ECO:0000244|PDB:4BKY}. FT HELIX 135 137 {ECO:0000244|PDB:4BKY}. FT STRAND 138 140 {ECO:0000244|PDB:4BKY}. FT STRAND 146 148 {ECO:0000244|PDB:4BKY}. FT STRAND 157 159 {ECO:0000244|PDB:4UMP}. FT STRAND 163 166 {ECO:0000244|PDB:4IXP}. FT HELIX 172 174 {ECO:0000244|PDB:4BKY}. FT HELIX 177 180 {ECO:0000244|PDB:4BKY}. FT HELIX 188 204 {ECO:0000244|PDB:4BKY}. FT HELIX 214 223 {ECO:0000244|PDB:4BKY}. FT HELIX 234 243 {ECO:0000244|PDB:4BKY}. FT TURN 248 250 {ECO:0000244|PDB:4BKY}. FT HELIX 254 258 {ECO:0000244|PDB:4BKY}. FT HELIX 261 264 {ECO:0000244|PDB:4BKY}. FT TURN 265 267 {ECO:0000244|PDB:4BKY}. FT STRAND 279 281 {ECO:0000244|PDB:4BKZ}. FT HELIX 284 293 {ECO:0000244|PDB:4BKY}. FT HELIX 298 305 {ECO:0000244|PDB:4BKY}. FT HELIX 312 325 {ECO:0000244|PDB:4BKY}. SQ SEQUENCE 651 AA; 74642 MW; 57F05CDC6122E570 CRC64; MKDYDELLKY YELHETIGTG GFAKVKLACH ILTGEMVAIK IMDKNTLGSD LPRIKTEIEA LKNLRHQHIC QLYHVLETAN KIFMVLEYCP GGELFDYIIS QDRLSEEETR VVFRQIVSAV AYVHSQGYAH RDLKPENLLF DEYHKLKLID FGLCAKPKGN KDYHLQTCCG SLAYAAPELI QGKSYLGSEA DVWSMGILLY VLMCGFLPFD DDNVMALYKK IMRGKYDVPK WLSPSSILLL QQMLQVDPKK RISMKNLLNH PWIMQDYNYP VEWQSKNPFI HLDDDCVTEL SVHHRNNRQT MEDLISLWQY DHLTATYLLL LAKKARGKPV RLRLSSFSCG QASATPFTDI KSNNWSLEDV TASDKNYVAG LIDYDWCEDD LSTGAATPRT SQFTKYWTES NGVESKSLTP ALCRTPANKL KNKENVYTPK SAVKNEEYFM FPEPKTPVNK NQHKREILTT PNRYTTPSKA RNQCLKETPI KIPVNSTGTD KLMTGVISPE RRCRSVELDL NQAHMEETPK RKGAKVFGSL ERGLDKVITV LTRSKRKGSA RDGPRRLKLH YNVTTTRLVN PDQLLNEIMS ILPKKHVDFV QKGYTLKCQT QSDFGKVTMQ FELEVCQLQK PDVVGIRRQR LKGDAWVYKR LVEDILSSCK V //