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Identification
HMDB Protein ID HMDBP01211
Secondary Accession Numbers
  • 6507
Name Cyclin-dependent kinase-like 5
Synonyms
  1. Serine/threonine-protein kinase 9
Gene Name CDKL5
Protein Type Enzyme
Biological Properties
General Function Involved in protein kinase activity
Specific Function Mediates phosphorylation of MECP2
Pathways Not Available
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Nucleus
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs CDKL5
Gene Sequence
>3093 bp
ATGAAGATTCCTAACATTGGTAATGTGATGAATAAATTTGAGATCCTTGGGGTTGTAGGT
GAAGGAGCCTATGGAGTTGTACTTAAATGCAGACACAAGGAAACACATGAAATTGTGGCG
ATCAAGAAATTCAAGGACAGTGAAGAAAATGAAGAAGTCAAAGAAACGACTTTACGAGAG
CTTAAAATGCTTCGGACTCTCAAGCAGGAAAACATTGTGGAGTTGAAGGAAGCATTTCGT
CGGAGGGGAAAGTTGTACTTGGTGTTTGAGTATGTTGAAAAAAATATGCTCGAATTGCTG
GAAGAAATGCCAAATGGAGTTCCACCTGAGAAAGTAAAAAGCTACATCTATCAGCTAATC
AAGGCTATTCACTGGTGCCATAAGAATGATATTGTCCATCGAGATATAAAACCAGAAAAT
CTCTTAATCAGCCACAATGATGTCCTAAAACTGTGTGACTTTGGTTTTGCTCGTAATCTG
TCAGAAGGCAATAATGCTAATTACACAGAGTACGTTGCCACCAGATGGTATCGGTCCCCA
GAACTCTTACTTGGCGCTCCCTATGGAAAGTCCGTGGACATGTGGTCGGTGGGCTGTATT
CTTGGGGAGCTTAGCGATGGACAGCCTTTATTTCCTGGAGAAAGTGAAATTGACCAACTT
TTTACTATTCAGAAGGTGCTAGGACCACTTCCATCTGAGCAGATGAAGCTTTTCTACAGT
AATCCTCGCTTCCATGGGCTCCGGTTTCCAGCTGTTAACCATCCTCAGTCCTTGGAAAGA
AGATACCTTGGAATTTTGAATAGTGTTCTACTTGACCTAATGAAGAATTTACTGAAGTTG
GACCCAGCTGACAGATACTTGACAGAACAGTGTTTGAATCACCCTACATTTCAAACCCAG
AGACTTCTGGATCGTTCTCCTTCAAGGTCAGCAAAAAGAAAACCTTACCATGTGGAAAGC
AGCACATTGTCTAATAGAAACCAAGCCGGCAAAAGTACTGCTTTGCAGTCTCACCACAGA
TCTAACAGCAAGGACATCCAGAACCTGAGTGTAGGCCTGCCCCGGGCTGACGAAGGTCTC
CCTGCCAATGAAAGCTTCCTAAATGGAAACCTTGCTGGAGCTAGTCTTAGTCCACTGCAC
ACCAAAACCTACCAAGCAAGCAGCCAGCCTGGGTCTACCAGCAAAGATCTCACCAACAAC
AACATACCACACCTTCTTAGCCCAAAAGAAGCCAAGTCAAAAACAGAGTTTGATTTTAAT
ATTGACCCAAAGCCTTCAGAAGGCCCAGGGACAAAGTACCTCAAGTCAAACAGCAGATCT
CAGCAGAACCGCCACTCATTCATGGAAAGCTCTCAAAGCAAAGCTGGGACACTGCAGCCC
AATGAAAAGCAGAGTCGGCATAGCTATATTGACACAATTCCCCAGTCCTCTAGGAGTCCC
TCCTACAGGACCAAGGCCAAAAGCCATGGGGCACTGAGTGACTCCAAGTCTGTGAGCAAC
CTTTCTGAAGCCAGGGCCCAAATTGCGGAGCCCAGTACCAGTAGGTACTTCCCATCTAGC
TGCTTAGACTTGAATTCTCCCACCAGCCCAACCCCCACCAGACACAGTGACACGAGAACT
TTGCTCAGCCCTTCTGGAAGAAATAACCGAAATGAGGGAACGCTGGACTCACGTCGAACC
ACAACCAGACATTCTAAGACGATGGAGGAATTGAAGCTGCCGGAGCACATGGACAGTAGC
CATTCCCATTCACTGTCTGCACCTCACGAATCTTTTTCTTATGGACTGGGCTACACCAGC
CCCTTTTCTTCCCAGCAACGTCCTCATAGGCATTCTATGTATGTGACCCGTGACAAAGTG
AGAGCCAAGGGCTTGGATGGAAGCTTGAGCATAGGGCAAGGGATGGCAGCTAGAGCCAAC
AGCCTGCAACTCTTGTCACCCCAGCCTGGAGAACAGCTCCCTCCAGAGATGACTGTGGCA
AGATCTTCGGTCAAAGAGACCTCCAGAGAAGGCACCTCTTCCTTCCATACACGCCAGAAG
TCTGAGGGTGGAGTGTATCATGACCCACACTCTGATGATGGCACAGCCCCCAAAGAAAAT
AGACACCTATACAATGATCCTGTGCCAAGGAGAGTTGGTAGCTTTTACAGAGTGCCATCT
CCACGTCCAGACAATTCTTTCCATGAAAATAATGTGTCAACTAGAGTTTCTTCTCTACCA
TCAGAGAGCAGTTCTGGAACCAACCACTCAAAAAGACAACCAGCATTCGATCCATGGAAA
AGTCCTGAAAATATTAGTCATTCAGAGCAACTCAAGGAAAAAGAGAAGCAAGGATTTTTC
AGGTCAATGAAAAAGAAAAAGAAGAAATCTCAAACAGTACCCAATTCCGACAGCCCTGAT
CTTCTGACGTTGCAGAAATCCATTCATTCTGCTAGCACTCCAAGCAGCAGACCAAAGGAG
TGGCGCCCCGAGAAGATCTCAGATCTGCAGACCCAAAGCCAGCCATTAAAATCACTGCGC
AAGTTGTTACATCTCTCTTCGGCCTCAAATCACCCGGCTTCCTCAGATCCCCGCTTCCAG
CCCTTAACAGCTCAACAAACCAAAAATTCCTTCTCAGAAATTCGGATTCACCCCCTGAGC
CAGGCCTCTGGCGGGAGCAGCAACATCCGGCAGGAACCCGCACCGAAGGGCAGGCCAGCC
CTCCAGCTGCCAGACGGTGGATGTGATGGCAGAAGACAGAGACACCATTCTGGACCCCAA
GATAGACGCTTCATGTTAAGGACGACAGAACAACAAGGAGAATACTTCTGCTGTGGTGAC
CCAAAGAAGCCTCACACTCCGTGCGTCCCAAACCGAGCCCTTCATCGTCCAATCTCCAGT
CCTGCTCCCTATCCAGTACTCCAGGTCCGAGGCACTTCCATGTGCCCGACACTCCAGGTC
CGAGGCACTGATGCTTTCAGCTGCCCAACCCAGCAATCCGGGTTCTCTTTCTTCGTGAGA
CACGTTATGAGGGAAGCCCTGATTCACAGGGCCCAGGTAAACCAAGCTGCGCTCCTGACA
TACCATGAGAATGCGGCACTGACGGGCAAGTGA
Protein Properties
Number of Residues 1030
Molecular Weight 115536.8
Theoretical pI 10.08
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Cyclin-dependent kinase-like 5
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRE
LKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLI
KAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSP
ELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYS
NPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQ
RLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTALQSHHRSNSKDIQNLSVGLPRADEGL
PANESFLNGNLAGASLSPLHTKTYQASSQPGSTSKDLTNNNIPHLLSPKEAKSKTEFDFN
IDPKPSEGPGTKYLKSNSRSQQNRHSFMESSQSKAGTLQPNEKQSRHSYIDTIPQSSRSP
SYRTKAKSHGALSDSKSVSNLSEARAQIAEPSTSRYFPSSCLDLNSPTSPTPTRHSDTRT
LLSPSGRNNRNEGTLDSRRTTTRHSKTMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTS
PFSSQQRPHRHSMYVTRDKVRAKGLDGSLSIGQGMAARANSLQLLSPQPGEQLPPEMTVA
RSSVKETSREGTSSFHTRQKSEGGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPS
PRPDNSFHENNVSTRVSSLPSESSSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFF
RSMKKKKKKSQTVPNSDSPDLLTLQKSIHSASTPSSRPKEWRPEKISDLQTQSQPLKSLR
KLLHLSSASNHPASSDPRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPA
LQLPDGGCDGRRQRHHSGPQDRRFMLRTTEQQGEYFCCGDPKKPHTPCVPNRALHRPISS
PAPYPVLQVRGTSMCPTLQVRGTDAFSCPTQQSGFSFFVRHVMREALIHRAQVNQAALLT
YHENAALTGK
GenBank ID Protein 57208543
UniProtKB/Swiss-Prot ID O76039
UniProtKB/Swiss-Prot Entry Name CDKL5_HUMAN
PDB IDs Not Available
GenBank Gene ID AL109798
GeneCard ID CDKL5
GenAtlas ID CDKL5
HGNC ID HGNC:11411
References
General References
  1. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  2. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  3. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
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  5. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
  6. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846 ]
  7. Montini E, Andolfi G, Caruso A, Buchner G, Walpole SM, Mariani M, Consalez G, Trump D, Ballabio A, Franco B: Identification and characterization of a novel serine-threonine kinase gene from the Xp22 region. Genomics. 1998 Aug 1;51(3):427-33. [PubMed:9721213 ]
  8. Kalscheuer VM, Tao J, Donnelly A, Hollway G, Schwinger E, Kubart S, Menzel C, Hoeltzenbein M, Tommerup N, Eyre H, Harbord M, Haan E, Sutherland GR, Ropers HH, Gecz J: Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation. Am J Hum Genet. 2003 Jun;72(6):1401-11. Epub 2003 May 7. [PubMed:12736870 ]
  9. Krause SW, Rehli M, Kreutz M, Schwarzfischer L, Paulauskis JD, Andreesen R: Differential screening identifies genetic markers of monocyte to macrophage maturation. J Leukoc Biol. 1996 Oct;60(4):540-5. [PubMed:8864140 ]
  10. Weaving LS, Christodoulou J, Williamson SL, Friend KL, McKenzie OL, Archer H, Evans J, Clarke A, Pelka GJ, Tam PP, Watson C, Lahooti H, Ellaway CJ, Bennetts B, Leonard H, Gecz J: Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation. Am J Hum Genet. 2004 Dec;75(6):1079-93. Epub 2004 Oct 18. [PubMed:15492925 ]
  11. Mari F, Azimonti S, Bertani I, Bolognese F, Colombo E, Caselli R, Scala E, Longo I, Grosso S, Pescucci C, Ariani F, Hayek G, Balestri P, Bergo A, Badaracco G, Zappella M, Broccoli V, Renieri A, Kilstrup-Nielsen C, Landsberger N: CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Hum Mol Genet. 2005 Jul 15;14(14):1935-46. Epub 2005 May 25. [PubMed:15917271 ]
  12. Bertani I, Rusconi L, Bolognese F, Forlani G, Conca B, De Monte L, Badaracco G, Landsberger N, Kilstrup-Nielsen C: Functional consequences of mutations in CDKL5, an X-linked gene involved in infantile spasms and mental retardation. J Biol Chem. 2006 Oct 20;281(42):32048-56. Epub 2006 Aug 24. [PubMed:16935860 ]
  13. Tao J, Van Esch H, Hagedorn-Greiwe M, Hoffmann K, Moser B, Raynaud M, Sperner J, Fryns JP, Schwinger E, Gecz J, Ropers HH, Kalscheuer VM: Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are associated with severe neurodevelopmental retardation. Am J Hum Genet. 2004 Dec;75(6):1149-54. [PubMed:15499549 ]
  14. Scala E, Ariani F, Mari F, Caselli R, Pescucci C, Longo I, Meloni I, Giachino D, Bruttini M, Hayek G, Zappella M, Renieri A: CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms. J Med Genet. 2005 Feb;42(2):103-7. [PubMed:15689447 ]
  15. Evans JC, Archer HL, Colley JP, Ravn K, Nielsen JB, Kerr A, Williams E, Christodoulou J, Gecz J, Jardine PE, Wright MJ, Pilz DT, Lazarou L, Cooper DN, Sampson JR, Butler R, Whatley SD, Clarke AJ: Early onset seizures and Rett-like features associated with mutations in CDKL5. Eur J Hum Genet. 2005 Oct;13(10):1113-20. [PubMed:16015284 ]
  16. Archer HL, Evans J, Edwards S, Colley J, Newbury-Ecob R, O'Callaghan F, Huyton M, O'Regan M, Tolmie J, Sampson J, Clarke A, Osborne J: CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients. J Med Genet. 2006 Sep;43(9):729-34. Epub 2006 Apr 12. [PubMed:16611748 ]
  17. Bahi-Buisson N, Nectoux J, Rosas-Vargas H, Milh M, Boddaert N, Girard B, Cances C, Ville D, Afenjar A, Rio M, Heron D, N'guyen Morel MA, Arzimanoglou A, Philippe C, Jonveaux P, Chelly J, Bienvenu T: Key clinical features to identify girls with CDKL5 mutations. Brain. 2008 Oct;131(Pt 10):2647-61. doi: 10.1093/brain/awn197. Epub 2008 Sep 12. [PubMed:18790821 ]
  18. Rosas-Vargas H, Bahi-Buisson N, Philippe C, Nectoux J, Girard B, N'Guyen Morel MA, Gitiaux C, Lazaro L, Odent S, Jonveaux P, Chelly J, Bienvenu T: Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy. J Med Genet. 2008 Mar;45(3):172-8. Epub 2007 Nov 9. [PubMed:17993579 ]
  19. Elia M, Falco M, Ferri R, Spalletta A, Bottitta M, Calabrese G, Carotenuto M, Musumeci SA, Lo Giudice M, Fichera M: CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy. Neurology. 2008 Sep 23;71(13):997-9. doi: 10.1212/01.wnl.0000326592.37105.88. [PubMed:18809835 ]
  20. Sprovieri T, Conforti FL, Fiumara A, Mazzei R, Ungaro C, Citrigno L, Muglia M, Arena A, Quattrone A: A novel mutation in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene associated with a severe Rett phenotype. Am J Med Genet A. 2009 Feb 15;149A(4):722-5. doi: 10.1002/ajmg.a.32711. [PubMed:19253388 ]
  21. Russo S, Marchi M, Cogliati F, Bonati MT, Pintaudi M, Veneselli E, Saletti V, Balestrini M, Ben-Zeev B, Larizza L: Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes. Neurogenetics. 2009 Jul;10(3):241-50. doi: 10.1007/s10048-009-0177-1. Epub 2009 Feb 25. [PubMed:19241098 ]