CDKL5_HUMAN
ID CDKL5_HUMAN Reviewed; 960 AA.
AC O76039; G9B9X4; Q14198; Q5H985; Q8IYC7; Q9UJL6;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 07-OCT-2020, sequence version 2.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Cyclin-dependent kinase-like 5 {ECO:0000305};
DE EC=2.7.11.22;
DE AltName: Full=Serine/threonine-protein kinase 9;
GN Name=CDKL5 {ECO:0000312|HGNC:HGNC:11411}; Synonyms=STK9;
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 2).
RX PubMed=9721213; DOI=10.1006/geno.1998.5391;
RA Montini E., Andolfi G., Caruso A., Buchner G., Walpole S.M., Mariani M.,
RA Consalez G.G., Trump D., Ballabio A., Franco B.;
RT "Identification and characterization of a novel serine-threonine kinase
RT gene from the Xp22 region.";
RL Genomics 51:427-433(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INVOLVEMENT IN DEE2, CHROMOSOMAL
RP TRANSLOCATION, AND VARIANT PRO-791.
RX PubMed=12736870; DOI=10.1086/375538;
RA Kalscheuer V.M., Tao J., Donnelly A., Hollway G., Schwinger E., Kuebart S.,
RA Menzel C., Hoeltzenbein M., Tommerup N., Eyre H., Harbord M., Haan E.,
RA Sutherland G.R., Ropers H.-H., Gecz J.;
RT "Disruption of the serine/threonine kinase 9 gene causes severe X-linked
RT infantile spasms and mental retardation.";
RL Am. J. Hum. Genet. 72:1401-1411(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, AND TISSUE
RP SPECIFICITY.
RX PubMed=21748340; DOI=10.1007/s00439-011-1058-x;
RA Williamson S.L., Giudici L., Kilstrup-Nielsen C., Gold W., Pelka G.J.,
RA Tam P.P., Grimm A., Prodi D., Landsberger N., Christodoulou J.;
RT "A novel transcript of cyclin-dependent kinase-like 5 (CDKL5) has an
RT alternative C-terminus and is the predominant transcript in brain.";
RL Hum. Genet. 131:187-200(2012).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 339-789.
RX PubMed=8864140; DOI=10.1002/jlb.60.4.540;
RA Krause S.W., Rehli M., Kreutz M., Schwarzfischer L., Paulauskis J.D.,
RA Andreesen J.D.;
RT "Differential screening leads to novel genetic markers of monocyte to
RT macrophage maturation.";
RL J. Leukoc. Biol. 60:540-545(1996).
RN [6]
RP INVOLVEMENT IN DEE2.
RX PubMed=15492925; DOI=10.1086/426462;
RA Weaving L.S., Christodoulou J., Williamson S.L., Friend K.L.,
RA McKenzie O.L.D., Archer H., Evans J., Clarke A., Pelka G.J., Tam P.P.L.,
RA Watson C., Lahooti H., Ellaway C.J., Bennetts B., Leonard H., Gecz J.;
RT "Mutations of CDKL5 cause a severe neurodevelopmental disorder with
RT infantile spasms and mental retardation.";
RL Am. J. Hum. Genet. 75:1079-1093(2004).
RN [7]
RP INTERACTION WITH MECP2, FUNCTION, AUTOPHOSPHORYLATION, AND INVOLVEMENT IN
RP DEE2.
RX PubMed=15917271; DOI=10.1093/hmg/ddi198;
RA Mari F., Azimonti S., Bertani I., Bolognese F., Colombo E., Caselli R.,
RA Scala E., Longo I., Grosso S., Pescucci C., Ariani F., Hayek G.,
RA Balestri P., Bergo A., Badaracco G., Zappella M., Broccoli V., Renieri A.,
RA Kilstrup-Nielsen C., Landsberger N.;
RT "CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible
RT for the early-onset seizure variant of Rett syndrome.";
RL Hum. Mol. Genet. 14:1935-1946(2005).
RN [8]
RP FUNCTION, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, AND CHARACTERIZATION
RP OF VARIANTS DEE2 PHE-152 AND SER-175.
RX PubMed=16935860; DOI=10.1074/jbc.m606325200;
RA Bertani I., Rusconi L., Bolognese F., Forlani G., Conca B., De Monte L.,
RA Badaracco G., Landsberger N., Kilstrup-Nielsen C.;
RT "Functional consequences of mutations in CDKL5, an X-linked gene involved
RT in infantile spasms and mental retardation.";
RL J. Biol. Chem. 281:32048-32056(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-761, AND
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-720, 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-479 AND SER-720, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [14] {ECO:0007744|PDB:4BGQ}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1-303 IN COMPLEX WITH SYNTHETIC
RP INHIBITOR, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=29420175; DOI=10.1016/j.celrep.2017.12.083;
RA Canning P., Park K., Goncalves J., Li C., Howard C.J., Sharpe T.D.,
RA Holt L.J., Pelletier L., Bullock A.N., Leroux M.R.;
RT "CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary
RT Function.";
RL Cell Rep. 22:885-894(2018).
RN [15]
RP VARIANTS DEE2 PHE-152 AND SER-175, AND VARIANT PRO-791.
RX PubMed=15499549; DOI=10.1086/426460;
RA Tao J., Van Esch H., Hagedorn-Greiwe M., Hoffmann K., Moser B., Raynaud M.,
RA Sperner J., Fryns J.-P., Schwinger E., Gecz J., Ropers H.-H.,
RA Kalscheuer V.M.;
RT "Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene
RT are associated with severe neurodevelopmental retardation.";
RL Am. J. Hum. Genet. 75:1149-1154(2004).
RN [16]
RP INVOLVEMENT IN DEE2.
RX PubMed=15689447; DOI=10.1136/jmg.2004.026237;
RA Scala E., Ariani F., Mari F., Caselli R., Pescucci C., Longo I., Meloni I.,
RA Giachino D., Bruttini M., Hayek G., Zappella M., Renieri A.;
RT "CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms.";
RL J. Med. Genet. 42:103-107(2005).
RN [17]
RP VARIANT DEE2 ASN-72, AND VARIANT CYS-444.
RX PubMed=16015284; DOI=10.1038/sj.ejhg.5201451;
RA Evans J.C., Archer H.L., Colley J.P., Ravn K., Nielsen J.B., Kerr A.,
RA Williams E., Christodoulou J., Gecz J., Jardine P.E., Wright M.J.,
RA Pilz D.T., Lazarou L., Cooper D.N., Sampson J.R., Butler R., Whatley S.D.,
RA Clarke A.J.;
RT "Early onset seizures and Rett-like features associated with mutations in
RT CDKL5.";
RL Eur. J. Hum. Genet. 13:1113-1120(2005).
RN [18]
RP VARIANTS DEE2 LEU-180 AND ALA-793.
RX PubMed=16611748; DOI=10.1136/jmg.2006.041467;
RA Archer H.L., Evans J., Edwards S., Colley J., Newbury-Ecob R.,
RA O'Callaghan F., Huyton M., O'Regan M., Tolmie J., Sampson J., Clarke A.,
RA Osborne J.;
RT "CDKL5 mutations cause infantile spasms, early onset seizures, and severe
RT mental retardation in female patients.";
RL J. Med. Genet. 43:729-734(2006).
RN [19]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-368.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [20]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-374; GLN-574; ALA-734; PRO-791 AND
RP GLY-1023 (ISOFORM 2).
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 [21]
RP VARIANTS DEE2 VAL-40; PRO-220 AND MET-718.
RX PubMed=18790821; DOI=10.1093/brain/awn197;
RA Bahi-Buisson N., Nectoux J., Rosas-Vargas H., Milh M., Boddaert N.,
RA Girard B., Cances C., Ville D., Afenjar A., Rio M., Heron D.,
RA N'guyen Morel M.A., Arzimanoglou A., Philippe C., Jonveaux P., Chelly J.,
RA Bienvenu T.;
RT "Key clinical features to identify girls with CDKL5 mutations.";
RL Brain 131:2647-2661(2008).
RN [22]
RP VARIANTS DEE2 VAL-40 AND PRO-220, AND CHARACTERIZATION OF VARIANTS DEE2
RP VAL-40 AND PRO-220.
RX PubMed=17993579; DOI=10.1136/jmg.2007.053504;
RA Rosas-Vargas H., Bahi-Buisson N., Philippe C., Nectoux J., Girard B.,
RA N'Guyen Morel M.A., Gitiaux C., Lazaro L., Odent S., Jonveaux P.,
RA Chelly J., Bienvenu T.;
RT "Impairment of CDKL5 nuclear localisation as a cause for severe infantile
RT encephalopathy.";
RL J. Med. Genet. 45:172-178(2008).
RN [23]
RP VARIANTS DEE2 PRO-178; ILE-288 AND TYR-291.
RX PubMed=18809835; DOI=10.1212/01.wnl.0000326592.37105.88;
RA Elia M., Falco M., Ferri R., Spalletta A., Bottitta M., Calabrese G.,
RA Carotenuto M., Musumeci S.A., Lo Giudice M., Fichera M.;
RT "CDKL5 mutations in boys with severe encephalopathy and early-onset
RT intractable epilepsy.";
RL Neurology 71:997-999(2008).
RN [24]
RP VARIANT DEE2 THR-399.
RX PubMed=19253388; DOI=10.1002/ajmg.a.32711;
RA Sprovieri T., Conforti F.L., Fiumara A., Mazzei R., Ungaro C., Citrigno L.,
RA Muglia M., Arena A., Quattrone A.;
RT "A novel mutation in the X-linked cyclin-dependent kinase-like 5 (CDKL5)
RT gene associated with a severe Rett phenotype.";
RL Am. J. Med. Genet. A 149:722-725(2009).
RN [25]
RP VARIANTS DEE2 THR-72 AND ARG-127, AND VARIANTS PRO-791 AND CYS-923 (ISOFORM
RP 2).
RX PubMed=19241098; DOI=10.1007/s10048-009-0177-1;
RA Russo S., Marchi M., Cogliati F., Bonati M.T., Pintaudi M., Veneselli E.,
RA Saletti V., Balestrini M., Ben-Zeev B., Larizza L.;
RT "Novel mutations in the CDKL5 gene, predicted effects and associated
RT phenotypes.";
RL Neurogenetics 10:241-250(2009).
RN [26]
RP VARIANT DEE2 GLN-178.
RX PubMed=23662938; DOI=10.1111/epi.12203;
RA Kodera H., Kato M., Nord A.S., Walsh T., Lee M., Yamanaka G., Tohyama J.,
RA Nakamura K., Nakagawa E., Ikeda T., Ben-Zeev B., Lev D., Lerman-Sagie T.,
RA Straussberg R., Tanabe S., Ueda K., Amamoto M., Ohta S., Nonoda Y.,
RA Nishiyama K., Tsurusaki Y., Nakashima M., Miyake N., Hayasaka K.,
RA King M.C., Matsumoto N., Saitsu H.;
RT "Targeted capture and sequencing for detection of mutations causing early
RT onset epileptic encephalopathy.";
RL Epilepsia 54:1262-1269(2013).
RN [27]
RP VARIANTS DEE2 TYR-145; GLN-178; PRO-182; GLU-207; TYR-581 AND CYS-858, AND
RP VARIANT 855-SER--LYS-960 DEL.
RX PubMed=23708187; DOI=10.1038/ng.2646;
RA Carvill G.L., Heavin S.B., Yendle S.C., McMahon J.M., O'Roak B.J., Cook J.,
RA Khan A., Dorschner M.O., Weaver M., Calvert S., Malone S., Wallace G.,
RA Stanley T., Bye A.M., Bleasel A., Howell K.B., Kivity S., Mackay M.T.,
RA Rodriguez-Casero V., Webster R., Korczyn A., Afawi Z., Zelnick N.,
RA Lerman-Sagie T., Lev D., Moeller R.S., Gill D., Andrade D.M., Freeman J.L.,
RA Sadleir L.G., Shendure J., Berkovic S.F., Scheffer I.E., Mefford H.C.;
RT "Targeted resequencing in epileptic encephalopathies identifies de novo
RT mutations in CHD2 and SYNGAP1.";
RL Nat. Genet. 45:825-830(2013).
RN [28]
RP VARIANT DEE2 GLN-178.
RX PubMed=24564546; DOI=10.1186/1471-2350-15-24;
RA Zhao Y., Zhang X., Bao X., Zhang Q., Zhang J., Cao G., Zhang J., Li J.,
RA Wei L., Pan H., Wu X.;
RT "Clinical features and gene mutational spectrum of CDKL5-related diseases
RT in a cohort of Chinese patients.";
RL BMC Med. Genet. 15:24-24(2014).
RN [29]
RP VARIANT LEU-647.
RX PubMed=25969726; DOI=10.1186/s13229-015-0017-0;
RA Codina-Sola M., Rodriguez-Santiago B., Homs A., Santoyo J., Rigau M.,
RA Aznar-Lain G., Del Campo M., Gener B., Gabau E., Botella M.P.,
RA Gutierrez-Arumi A., Antinolo G., Perez-Jurado L.A., Cusco I.;
RT "Integrated analysis of whole-exome sequencing and transcriptome profiling
RT in males with autism spectrum disorders.";
RL Mol. Autism 6:21-21(2015).
RN [30]
RP VARIANTS DEE2 TRP-178; MET-718 AND 726-SER--LYS-1030 DEL.
RX PubMed=26993267; DOI=10.1136/jmedgenet-2015-103263;
RA Trump N., McTague A., Brittain H., Papandreou A., Meyer E., Ngoh A.,
RA Palmer R., Morrogh D., Boustred C., Hurst J.A., Jenkins L., Kurian M.A.,
RA Scott R.H.;
RT "Improving diagnosis and broadening the phenotypes in early-onset seizure
RT and severe developmental delay disorders through gene panel analysis.";
RL J. Med. Genet. 53:310-317(2016).
RN [31]
RP VARIANTS DEE2 LEU-196 AND ARG-994 (ISOFORM 2).
RX PubMed=27864847; DOI=10.1002/humu.23149;
RG Clinical Study Group;
RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT pediatric epilepsies identifies causative mutations in 30 different
RT genes.";
RL Hum. Mutat. 38:216-225(2017).
CC -!- FUNCTION: Mediates phosphorylation of MECP2 (PubMed:15917271,
CC PubMed:16935860). May regulate ciliogenesis (PubMed:29420175).
CC {ECO:0000269|PubMed:15917271, ECO:0000269|PubMed:16935860,
CC ECO:0000269|PubMed:29420175}.
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=2.7.11.22;
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=2.7.11.22;
CC -!- SUBUNIT: Interacts with MECP2. {ECO:0000269|PubMed:15917271}.
CC -!- INTERACTION:
CC O76039; Q08379: GOLGA2; NbExp=3; IntAct=EBI-1752465, EBI-618309;
CC O76039; P40692: MLH1; NbExp=4; IntAct=EBI-1752465, EBI-744248;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16935860}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000269|PubMed:29420175}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:29420175}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O76039-2; Sequence=Displayed;
CC Name=2;
CC IsoId=O76039-1; Sequence=VSP_060755;
CC -!- TISSUE SPECIFICITY: Expressed in brain, lung, kidney, prostate, ovary,
CC placenta, pancreas and testis.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Predominant transcript in brain.
CC {ECO:0000269|PubMed:21748340}.
CC -!- PTM: Autophosphorylated.
CC -!- DISEASE: Note=Chromosomal aberrations involving CDKL5 are found in
CC patients manifesting early-onset seizures and spams and psychomotor
CC impairment. Translocation t(X;6)(p22.3;q14); translocation
CC t(X;7)(p22.3;p15).
CC -!- DISEASE: Developmental and epileptic encephalopathy 2 (DEE2)
CC [MIM:300672]: A severe form of epilepsy characterized by seizures or
CC spasms beginning in infancy. Patients with epileptic encephalopathy
CC early infantile type 2 manifest features resembling Rett syndrome such
CC as microcephaly, lack of speech development, stereotypic hand
CC movements. However, DEE2 and Rett syndrome are considered two distinct
CC entities. {ECO:0000269|PubMed:12736870, ECO:0000269|PubMed:15492925,
CC ECO:0000269|PubMed:15499549, ECO:0000269|PubMed:15689447,
CC ECO:0000269|PubMed:15917271, ECO:0000269|PubMed:16015284,
CC ECO:0000269|PubMed:16611748, ECO:0000269|PubMed:16935860,
CC ECO:0000269|PubMed:17993579, ECO:0000269|PubMed:18790821,
CC ECO:0000269|PubMed:18809835, ECO:0000269|PubMed:19241098,
CC ECO:0000269|PubMed:19253388, ECO:0000269|PubMed:23662938,
CC ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:24564546,
CC ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-10 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA61445.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; Y15057; CAA75342.1; -; mRNA.
DR EMBL; AY217744; AAO64440.1; -; mRNA.
DR EMBL; HQ171445; ADN38258.1; -; mRNA.
DR EMBL; Z92542; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL109798; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X89059; CAA61445.1; ALT_FRAME; mRNA.
DR CCDS; CCDS14186.1; -. [O76039-1]
DR CCDS; CCDS83458.1; -. [O76039-2]
DR PIR; S58296; S58296.
DR RefSeq; NP_001032420.1; NM_001037343.1. [O76039-1]
DR RefSeq; NP_001310218.1; NM_001323289.1. [O76039-2]
DR RefSeq; NP_003150.1; NM_003159.2. [O76039-1]
DR PDB; 4BGQ; X-ray; 2.00 A; A=1-303.
DR PDBsum; 4BGQ; -.
DR AlphaFoldDB; O76039; -.
DR SMR; O76039; -.
DR BioGRID; 112668; 25.
DR IntAct; O76039; 23.
DR MINT; O76039; -.
DR STRING; 9606.ENSP00000369325; -.
DR BindingDB; O76039; -.
DR ChEMBL; CHEMBL1163112; -.
DR DrugCentral; O76039; -.
DR iPTMnet; O76039; -.
DR PhosphoSitePlus; O76039; -.
DR BioMuta; CDKL5; -.
DR EPD; O76039; -.
DR jPOST; O76039; -.
DR MassIVE; O76039; -.
DR MaxQB; O76039; -.
DR PaxDb; O76039; -.
DR PeptideAtlas; O76039; -.
DR PRIDE; O76039; -.
DR ProteomicsDB; 50359; -. [O76039-1]
DR Antibodypedia; 481; 239 antibodies from 32 providers.
DR DNASU; 6792; -.
DR Ensembl; ENST00000379989.6; ENSP00000369325.3; ENSG00000008086.13. [O76039-1]
DR Ensembl; ENST00000379996.7; ENSP00000369332.3; ENSG00000008086.13. [O76039-1]
DR Ensembl; ENST00000623535.2; ENSP00000485244.1; ENSG00000008086.13. [O76039-2]
DR GeneID; 6792; -.
DR KEGG; hsa:6792; -.
DR MANE-Select; ENST00000623535.2; ENSP00000485244.1; NM_001323289.2; NP_001310218.1.
DR UCSC; uc004cym.4; human. [O76039-2]
DR CTD; 6792; -.
DR DisGeNET; 6792; -.
DR GeneCards; CDKL5; -.
DR HGNC; HGNC:11411; CDKL5.
DR HPA; ENSG00000008086; Low tissue specificity.
DR MalaCards; CDKL5; -.
DR MIM; 300203; gene.
DR MIM; 300672; phenotype.
DR neXtProt; NX_O76039; -.
DR OpenTargets; ENSG00000008086; -.
DR PharmGKB; PA36218; -.
DR VEuPathDB; HostDB:ENSG00000008086; -.
DR eggNOG; KOG0593; Eukaryota.
DR GeneTree; ENSGT00940000157355; -.
DR InParanoid; O76039; -.
DR OMA; YHENLRH; -.
DR OrthoDB; 398098at2759; -.
DR PhylomeDB; O76039; -.
DR TreeFam; TF101032; -.
DR BRENDA; 2.7.11.22; 2681.
DR PathwayCommons; O76039; -.
DR SignaLink; O76039; -.
DR SIGNOR; O76039; -.
DR BioGRID-ORCS; 6792; 10 hits in 732 CRISPR screens.
DR ChiTaRS; CDKL5; human.
DR GeneWiki; CDKL5; -.
DR GenomeRNAi; 6792; -.
DR Pharos; O76039; Tchem.
DR PRO; PR:O76039; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O76039; protein.
DR Bgee; ENSG00000008086; Expressed in frontal pole and 176 other tissues.
DR ExpressionAtlas; O76039; baseline and differential.
DR Genevisible; O76039; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0097542; C:ciliary tip; IDA:UniProtKB.
DR GO; GO:0032839; C:dendrite cytoplasm; ISS:BHF-UCL.
DR GO; GO:0044294; C:dendritic growth cone; ISS:BHF-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HGNC-UCL.
DR GO; GO:0005524; F:ATP binding; IDA:HGNC-UCL.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0016301; F:kinase activity; IDA:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:HGNC-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:ProtInc.
DR GO; GO:0031267; F:small GTPase binding; ISS:BHF-UCL.
DR GO; GO:0001764; P:neuron migration; ISS:BHF-UCL.
DR GO; GO:0045773; P:positive regulation of axon extension; ISS:BHF-UCL.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; ISS:BHF-UCL.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:BHF-UCL.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:HGNC-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:1902017; P:regulation of cilium assembly; IMP:UniProtKB.
DR GO; GO:0050773; P:regulation of dendrite development; ISS:BHF-UCL.
DR GO; GO:0099175; P:regulation of postsynapse organization; IDA:SynGO.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell projection;
KW Chromosomal rearrangement; Cytoplasm; Cytoskeleton; Disease variant;
KW Epilepsy; Intellectual disability; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..960
FT /note="Cyclin-dependent kinase-like 5"
FT /id="PRO_0000085826"
FT DOMAIN 13..297
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 300..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 382..566
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 646..834
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 848..960
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 317..349
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 382..406
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 431..551
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 552..566
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 671..706
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 724..754
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 766..780
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 794..817
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 848..890
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 912..952
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 135
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 19..27
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 42
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 407
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 479
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 720
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 761
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT VAR_SEQ 905..960
FT /note="GQMDPGWHVSSVTRSATEGPSYSEQLGAKSGPNGHPYNRTNRSRMPNLNDLK
FT ETAL -> DGGCDGRRQRHHSGPQDRRFMLRTTEQQGEYFCCGDPKKPHTPCVPNRALH
FT RPISSPAPYPVLQVRGTSMCPTLQVRGTDAFSCPTQQSGFSFFVRHVMREALIHRAQVN
FT QAALLTYHENAALTGK (in isoform 2)"
FT /evidence="ECO:0000269|PubMed:21748340"
FT /id="VSP_060755"
FT VARIANT 40
FT /note="A -> V (in DEE2; causes mislocalization of the
FT protein in the cytoplasm; dbSNP:rs122460159)"
FT /evidence="ECO:0000269|PubMed:17993579,
FT ECO:0000269|PubMed:18790821"
FT /id="VAR_058022"
FT VARIANT 72
FT /note="I -> N (in DEE2; dbSNP:rs62641235)"
FT /evidence="ECO:0000269|PubMed:16015284"
FT /id="VAR_058023"
FT VARIANT 72
FT /note="I -> T (in DEE2; dbSNP:rs62641235)"
FT /evidence="ECO:0000269|PubMed:19241098"
FT /id="VAR_058024"
FT VARIANT 127
FT /note="H -> R (in DEE2; dbSNP:rs267608468)"
FT /evidence="ECO:0000269|PubMed:19241098"
FT /id="VAR_058025"
FT VARIANT 145
FT /note="H -> Y (in DEE2; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078625"
FT VARIANT 152
FT /note="C -> F (in DEE2; affect activity; causes
FT mislocalization of the protein in the cytoplasm;
FT dbSNP:rs122460157)"
FT /evidence="ECO:0000269|PubMed:15499549,
FT ECO:0000269|PubMed:16935860"
FT /id="VAR_023560"
FT VARIANT 175
FT /note="R -> S (in DEE2; affect activity; does not affect
FT the cellular distribution of the protein;
FT dbSNP:rs61749700)"
FT /evidence="ECO:0000269|PubMed:15499549,
FT ECO:0000269|PubMed:16935860"
FT /id="VAR_023561"
FT VARIANT 178
FT /note="R -> P (in DEE2; dbSNP:rs267606715)"
FT /evidence="ECO:0000269|PubMed:18809835"
FT /id="VAR_058026"
FT VARIANT 178
FT /note="R -> Q (in DEE2; dbSNP:rs267606715)"
FT /evidence="ECO:0000269|PubMed:23662938,
FT ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:24564546"
FT /id="VAR_071103"
FT VARIANT 178
FT /note="R -> W (in DEE2; dbSNP:rs267608493)"
FT /evidence="ECO:0000269|PubMed:26993267"
FT /id="VAR_078712"
FT VARIANT 180
FT /note="P -> L (in DEE2; dbSNP:rs61749704)"
FT /evidence="ECO:0000269|PubMed:16611748"
FT /id="VAR_037635"
FT VARIANT 182
FT /note="L -> P (in DEE2)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078626"
FT VARIANT 196
FT /note="S -> L (in DEE2; dbSNP:rs267608501)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078219"
FT VARIANT 207
FT /note="G -> E (in DEE2)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078627"
FT VARIANT 220
FT /note="L -> P (in DEE2; causes mislocalization of the
FT protein in the cytoplasm; dbSNP:rs267608511)"
FT /evidence="ECO:0000269|PubMed:17993579,
FT ECO:0000269|PubMed:18790821"
FT /id="VAR_058027"
FT VARIANT 288
FT /note="T -> I (in DEE2; dbSNP:rs267606713)"
FT /evidence="ECO:0000269|PubMed:18809835"
FT /id="VAR_058028"
FT VARIANT 291
FT /note="C -> Y (in DEE2; dbSNP:rs267606714)"
FT /evidence="ECO:0000269|PubMed:18809835"
FT /id="VAR_058029"
FT VARIANT 368
FT /note="N -> H (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036578"
FT VARIANT 374
FT /note="A -> T (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041997"
FT VARIANT 399
FT /note="N -> T (in DEE2; dbSNP:rs267608611)"
FT /evidence="ECO:0000269|PubMed:19253388"
FT /id="VAR_058030"
FT VARIANT 444
FT /note="R -> C (in dbSNP:rs61753977)"
FT /evidence="ECO:0000269|PubMed:16015284"
FT /id="VAR_058031"
FT VARIANT 574
FT /note="P -> Q (in an ovarian serous carcinoma sample;
FT somatic mutation; dbSNP:rs199897804)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041998"
FT VARIANT 581
FT /note="H -> Y (in DEE2; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078628"
FT VARIANT 647
FT /note="P -> L (probable disease-associated variant found in
FT a patient with autism spectrum disorder)"
FT /evidence="ECO:0000269|PubMed:25969726"
FT /id="VAR_078713"
FT VARIANT 718
FT /note="V -> M (in DEE2; dbSNP:rs267608653)"
FT /evidence="ECO:0000269|PubMed:18790821,
FT ECO:0000269|PubMed:26993267"
FT /id="VAR_058032"
FT VARIANT 726..960
FT /note="Missing (in DEE2)"
FT /evidence="ECO:0000269|PubMed:26993267"
FT /id="VAR_078714"
FT VARIANT 734
FT /note="T -> A (in dbSNP:rs55803460)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041999"
FT VARIANT 791
FT /note="Q -> P (in dbSNP:rs35478150)"
FT /evidence="ECO:0000269|PubMed:12736870,
FT ECO:0000269|PubMed:15499549, ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:19241098"
FT /id="VAR_023562"
FT VARIANT 793
FT /note="V -> A (in DEE2; unknown pathological significance;
FT dbSNP:rs62643617)"
FT /evidence="ECO:0000269|PubMed:16611748"
FT /id="VAR_037636"
FT VARIANT 855..960
FT /note="Missing (probable disease-associated variant found
FT in a patient with infatile spasms)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078629"
FT VARIANT 858
FT /note="R -> C (in DEE2; unknown pathological significance;
FT dbSNP:rs773760466)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078630"
FT CONFLICT 339..340
FT /note="HR -> GT (in Ref. 5; CAA61445)"
FT /evidence="ECO:0000305"
FT CONFLICT 541
FT /note="L -> W (in Ref. 5; CAA61445)"
FT /evidence="ECO:0000305"
FT CONFLICT 731..764
FT /note="Missing (in Ref. 5; CAA61445)"
FT /evidence="ECO:0000305"
FT TURN 10..12
FT /evidence="ECO:0007829|PDB:4BGQ"
FT STRAND 13..24
FT /evidence="ECO:0007829|PDB:4BGQ"
FT STRAND 26..32
FT /evidence="ECO:0007829|PDB:4BGQ"
FT TURN 33..35
FT /evidence="ECO:0007829|PDB:4BGQ"
FT STRAND 38..43
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 55..66
FT /evidence="ECO:0007829|PDB:4BGQ"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:4BGQ"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:4BGQ"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 96..102
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 109..128
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:4BGQ"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:4BGQ"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 180..183
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 191..206
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 216..227
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 232..240
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 258..262
FT /evidence="ECO:0007829|PDB:4BGQ"
FT TURN 263..265
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 268..277
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 288..292
FT /evidence="ECO:0007829|PDB:4BGQ"
FT HELIX 295..298
FT /evidence="ECO:0007829|PDB:4BGQ"
FT VARIANT O76039-1:923
FT /note="R -> C (in dbSNP:rs267608664)"
FT /evidence="ECO:0000269|PubMed:19241098"
FT /id="VAR_083796"
FT VARIANT O76039-1:994
FT /note="G -> R (in DEE2; unknown pathological significance;
FT dbSNP:rs866859766)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_083797"
FT VARIANT O76039-1:999
FT /note="V -> M (in dbSNP:rs35693326)"
FT /id="VAR_083798"
FT VARIANT O76039-1:1023
FT /note="E -> G (in dbSNP:rs34166184)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_083799"
SQ SEQUENCE 960 AA; 107519 MW; 6E955E0B40DBC1B8 CRC64;
MKIPNIGNVM NKFEILGVVG EGAYGVVLKC RHKETHEIVA IKKFKDSEEN EEVKETTLRE
LKMLRTLKQE NIVELKEAFR RRGKLYLVFE YVEKNMLELL EEMPNGVPPE KVKSYIYQLI
KAIHWCHKND IVHRDIKPEN LLISHNDVLK LCDFGFARNL SEGNNANYTE YVATRWYRSP
ELLLGAPYGK SVDMWSVGCI LGELSDGQPL FPGESEIDQL FTIQKVLGPL PSEQMKLFYS
NPRFHGLRFP AVNHPQSLER RYLGILNSVL LDLMKNLLKL DPADRYLTEQ CLNHPTFQTQ
RLLDRSPSRS AKRKPYHVES STLSNRNQAG KSTALQSHHR SNSKDIQNLS VGLPRADEGL
PANESFLNGN LAGASLSPLH TKTYQASSQP GSTSKDLTNN NIPHLLSPKE AKSKTEFDFN
IDPKPSEGPG TKYLKSNSRS QQNRHSFMES SQSKAGTLQP NEKQSRHSYI DTIPQSSRSP
SYRTKAKSHG ALSDSKSVSN LSEARAQIAE PSTSRYFPSS CLDLNSPTSP TPTRHSDTRT
LLSPSGRNNR NEGTLDSRRT TTRHSKTMEE LKLPEHMDSS HSHSLSAPHE SFSYGLGYTS
PFSSQQRPHR HSMYVTRDKV RAKGLDGSLS IGQGMAARAN SLQLLSPQPG EQLPPEMTVA
RSSVKETSRE GTSSFHTRQK SEGGVYHDPH SDDGTAPKEN RHLYNDPVPR RVGSFYRVPS
PRPDNSFHEN NVSTRVSSLP SESSSGTNHS KRQPAFDPWK SPENISHSEQ LKEKEKQGFF
RSMKKKKKKS QTVPNSDSPD LLTLQKSIHS ASTPSSRPKE WRPEKISDLQ TQSQPLKSLR
KLLHLSSASN HPASSDPRFQ PLTAQQTKNS FSEIRIHPLS QASGGSSNIR QEPAPKGRPA
LQLPGQMDPG WHVSSVTRSA TEGPSYSEQL GAKSGPNGHP YNRTNRSRMP NLNDLKETAL
