O76039 (CDKL5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase-like 5
EC=2.7.11.22

Alternative name(s):
Serine/threonine-protein kinase 9

Gene names

Name:	CDKL5
Synonyms:	STK9

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1030 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates phosphorylation of MECP2. Ref.6 Ref.7
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with MECP2. Ref.6
Subcellular location	Nucleus Ref.7.
Tissue specificity	Expressed in brain, lung, kidney, prostate, ovary, placenta, pancreas and testis.
Post-translational modification	Autophosphorylated. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10
Involvement in disease	Note=Chromosomal aberrations involving CDKL5 are found in patients manifesting early-onset seizures and spams and psychomotor impairment. Translocation t(X;6)(p22.3;q14); translocation t(X;7)(p22.3;p15). Defects in CDKL5 are a cause of epileptic encephalopathy early infantile type 2 (EIEE2) [MIM:300672]; also known as atypical CDKL5-related Rett syndrome. EIEE2 is a severe form of epilepsy characterized by seizures or spasms beginning in infancy. Patients manifest features resembling Rett syndrome such as microcephaly, lack of speech development, stereotypic hand movements. Ref.2 Ref.5 Ref.6 Ref.7 Ref.11 Ref.12 Ref.13 Ref.14 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. Contains 1 protein kinase domain.
Caution	It is uncertain whether Met-1 or Met-10 is the initiator.
Sequence caution	The sequence CAA61445.1 differs from that shown. Reason: Frameshift at position 415.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Disease mutation Epilepsy Mental retardation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	neuron migration Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of Rac GTPase activity Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of axon extension Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of dendrite morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL protein autophosphorylation Inferred from direct assay Ref.7. Source: HGNC
Cellular component	dendrite cytoplasm Inferred from sequence or structural similarity. Source: BHF-UCL dendritic growth cone Inferred from sequence or structural similarity. Source: BHF-UCL nucleus Inferred from direct assay Ref.7. Source: HGNC
Molecular function	ATP binding Inferred from direct assay Ref.7. Source: HGNC Rac GTPase binding Inferred from sequence or structural similarity. Source: BHF-UCL cyclin-dependent protein kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1030	1030	Cyclin-dependent kinase-like 5		PRO_0000085826
Regions
	Domain	13 – 297	285	Protein kinase
	Nucleotide binding	19 – 27	9	ATP By similarity
	Compositional bias	784 – 789	6	Poly-Lys
Sites
	Active site	135	1	Proton acceptor By similarity
	Binding site	42	1	ATP By similarity
Amino acid modifications
	Modified residue	171	1	Phosphotyrosine Ref.8 Ref.10
	Modified residue	306	1	Phosphoserine Ref.8 Ref.10
	Modified residue	375	1	Phosphoserine Ref.10
	Modified residue	377	1	Phosphoserine Ref.10
	Modified residue	407	1	Phosphoserine Ref.8 Ref.9 Ref.10
	Modified residue	476	1	Phosphoserine Ref.10
	Modified residue	488	1	Phosphoserine Ref.10
	Modified residue	529	1	Phosphoserine Ref.10
	Modified residue	646	1	Phosphoserine Ref.8
	Modified residue	681	1	Phosphoserine Ref.10
	Modified residue	720	1	Phosphoserine Ref.8 Ref.10
	Modified residue	726	1	Phosphoserine Ref.8 Ref.10
	Modified residue	761	1	Phosphoserine Ref.8
Natural variations
	Natural variant	40	1	A → V in EIEE2; causes mislocalization of the protein in the cytoplasm. Ref.17 Ref.18		VAR_058022
	Natural variant	72	1	I → N in EIEE2. Ref.13		VAR_058023
	Natural variant	72	1	I → T in EIEE2. Ref.21		VAR_058024
	Natural variant	127	1	H → R in EIEE2. Ref.21		VAR_058025
	Natural variant	152	1	C → F in EIEE2; affect activity; causes mislocalization of the protein in the cytoplasm. Ref.7 Ref.11		VAR_023560
	Natural variant	175	1	R → S in EIEE2; affect activity; does not affect the cellular distribution of the protein. Ref.7 Ref.11		VAR_023561
	Natural variant	178	1	R → P in EIEE2. Ref.19		VAR_058026
	Natural variant	180	1	P → L in EIEE2. Ref.14		VAR_037635
	Natural variant	220	1	L → P in EIEE2; causes mislocalization of the protein in the cytoplasm. Ref.17 Ref.18		VAR_058027
	Natural variant	288	1	T → I in EIEE2. Ref.19		VAR_058028
	Natural variant	291	1	C → Y in EIEE2. Ref.19		VAR_058029
	Natural variant	368	1	N → H in a colorectal cancer sample; somatic mutation. Ref.15		VAR_036578
	Natural variant	374	1	A → T in a metastatic melanoma sample; somatic mutation. Ref.16		VAR_041997
	Natural variant	399	1	N → T in EIEE2. Ref.20		VAR_058030
	Natural variant	444	1	R → C. Ref.13		VAR_058031
	Natural variant	574	1	P → Q in an ovarian serous carcinoma sample; somatic mutation. Ref.16		VAR_041998
	Natural variant	718	1	V → M in EIEE2. Ref.17		VAR_058032
	Natural variant	734	1	T → A. Ref.16 Corresponds to variant rs55803460 [ dbSNP | Ensembl ].		VAR_041999
	Natural variant	791	1	Q → P. Ref.2 Ref.11 Ref.16 Ref.21 Corresponds to variant rs35478150 [ dbSNP | Ensembl ].		VAR_023562
	Natural variant	793	1	V → A in EIEE2; uncertain pathogenicity. Ref.14		VAR_037636
	Natural variant	923	1	R → C. Ref.21		VAR_058033
	Natural variant	999	1	V → M. Corresponds to variant rs35693326 [ dbSNP | Ensembl ].		VAR_037637
	Natural variant	1023	1	E → G. Ref.16 Corresponds to variant rs34166184 [ dbSNP | Ensembl ].		VAR_042000
Experimental info
	Sequence conflict	339 – 340	2	HR → GT in CAA61445. Ref.4
	Sequence conflict	541	1	L → W in CAA61445. Ref.4
	Sequence conflict	731 – 764	34	Missing in CAA61445. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	O76039 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 8A1C9C438610EF08	FASTA	1,030	115,538
	10 20 30 40 50 60 MKIPNIGNVM NKFEILGVVG EGAYGVVLKC RHKETHEIVA IKKFKDSEEN EEVKETTLRE 70 80 90 100 110 120 LKMLRTLKQE NIVELKEAFR RRGKLYLVFE YVEKNMLELL EEMPNGVPPE KVKSYIYQLI 130 140 150 160 170 180 KAIHWCHKND IVHRDIKPEN LLISHNDVLK LCDFGFARNL SEGNNANYTE YVATRWYRSP 190 200 210 220 230 240 ELLLGAPYGK SVDMWSVGCI LGELSDGQPL FPGESEIDQL FTIQKVLGPL PSEQMKLFYS 250 260 270 280 290 300 NPRFHGLRFP AVNHPQSLER RYLGILNSVL LDLMKNLLKL DPADRYLTEQ CLNHPTFQTQ 310 320 330 340 350 360 RLLDRSPSRS AKRKPYHVES STLSNRNQAG KSTALQSHHR SNSKDIQNLS VGLPRADEGL 370 380 390 400 410 420 PANESFLNGN LAGASLSPLH TKTYQASSQP GSTSKDLTNN NIPHLLSPKE AKSKTEFDFN 430 440 450 460 470 480 IDPKPSEGPG TKYLKSNSRS QQNRHSFMES SQSKAGTLQP NEKQSRHSYI DTIPQSSRSP 490 500 510 520 530 540 SYRTKAKSHG ALSDSKSVSN LSEARAQIAE PSTSRYFPSS CLDLNSPTSP TPTRHSDTRT 550 560 570 580 590 600 LLSPSGRNNR NEGTLDSRRT TTRHSKTMEE LKLPEHMDSS HSHSLSAPHE SFSYGLGYTS 610 620 630 640 650 660 PFSSQQRPHR HSMYVTRDKV RAKGLDGSLS IGQGMAARAN SLQLLSPQPG EQLPPEMTVA 670 680 690 700 710 720 RSSVKETSRE GTSSFHTRQK SEGGVYHDPH SDDGTAPKEN RHLYNDPVPR RVGSFYRVPS 730 740 750 760 770 780 PRPDNSFHEN NVSTRVSSLP SESSSGTNHS KRQPAFDPWK SPENISHSEQ LKEKEKQGFF 790 800 810 820 830 840 RSMKKKKKKS QTVPNSDSPD LLTLQKSIHS ASTPSSRPKE WRPEKISDLQ TQSQPLKSLR 850 860 870 880 890 900 KLLHLSSASN HPASSDPRFQ PLTAQQTKNS FSEIRIHPLS QASGGSSNIR QEPAPKGRPA 910 920 930 940 950 960 LQLPDGGCDG RRQRHHSGPQ DRRFMLRTTE QQGEYFCCGD PKKPHTPCVP NRALHRPISS 970 980 990 1000 1010 1020 PAPYPVLQVR GTSMCPTLQV RGTDAFSCPT QQSGFSFFVR HVMREALIHR AQVNQAALLT 1030 YHENAALTGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of a novel serine-threonine kinase gene from the Xp22 region." Montini E., Andolfi G., Caruso A., Buchner G., Walpole S.M., Mariani M., Consalez G.G., Trump D., Ballabio A., Franco B. Genomics 51:427-433(1998) [PubMed: 9721213] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation." Kalscheuer V.M., Tao J., Donnelly A., Hollway G., Schwinger E., Kuebart S., Menzel C., Hoeltzenbein M., Tommerup N., Eyre H., Harbord M., Haan E., Sutherland G.R., Ropers H.-H., Gecz J. Am. J. Hum. Genet. 72:1401-1411(2003) [PubMed: 12736870] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN EIEE2, CHROMOSOMAL TRANSLOCATION, VARIANT PRO-791.
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Differential screening leads to novel genetic markers of monocyte to macrophage maturation." Krause S.W., Rehli M., Kreutz M., Schwarzfischer L., Paulauskis J.D., Andreesen J.D. J. Leukoc. Biol. 60:540-545(1996) [PubMed: 8864140] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 339-789.
[5]	"Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation." Weaving L.S., Christodoulou J., Williamson S.L., Friend K.L., McKenzie O.L.D., Archer H., Evans J., Clarke A., Pelka G.J., Tam P.P.L., Watson C., Lahooti H., Ellaway C.J., Bennetts B., Leonard H., Gecz J. Am. J. Hum. Genet. 75:1079-1093(2004) [PubMed: 15492925] [Abstract] Cited for: INVOLVEMENT IN EIEE2.
[6]	"CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome." 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. Hum. Mol. Genet. 14:1935-1946(2005) [PubMed: 15917271] [Abstract] Cited for: INTERACTION WITH MECP2, FUNCTION, AUTOPHOSPHORYLATION, INVOLVEMENT IN EIEE2.
[7]	"Functional consequences of mutations in CDKL5, an X-linked gene involved in infantile spasms and mental retardation." Bertani I., Rusconi L., Bolognese F., Forlani G., Conca B., De Monte L., Badaracco G., Landsberger N., Kilstrup-Nielsen C. J. Biol. Chem. 281:32048-32056(2006) [PubMed: 16935860] [Abstract] Cited for: FUNCTION, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EIEE2 PHE-152 AND SER-175.
[8]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-171; SER-306; SER-407; SER-646; SER-720; SER-726 AND SER-761, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-171; SER-306; SER-375; SER-377; SER-407; SER-476; SER-488; SER-529; SER-681; SER-720 AND SER-726, MASS SPECTROMETRY.
[11]	"Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are associated with severe neurodevelopmental retardation." Tao J., Van Esch H., Hagedorn-Greiwe M., Hoffmann K., Moser B., Raynaud M., Sperner J., Fryns J.-P., Schwinger E., Gecz J., Ropers H.-H., Kalscheuer V.M. Am. J. Hum. Genet. 75:1149-1154(2004) [PubMed: 15499549] [Abstract] Cited for: VARIANTS EIEE2 PHE-152 AND SER-175, VARIANT PRO-791.
[12]	"CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms." Scala E., Ariani F., Mari F., Caselli R., Pescucci C., Longo I., Meloni I., Giachino D., Bruttini M., Hayek G., Zappella M., Renieri A. J. Med. Genet. 42:103-107(2005) [PubMed: 15689447] [Abstract] Cited for: INVOLVEMENT IN EIEE2.
[13]	"Early onset seizures and Rett-like features associated with mutations in CDKL5." Evans J.C., Archer H.L., Colley J.P., Ravn K., Nielsen J.B., Kerr A., Williams E., Christodoulou J., Gecz J., Jardine P.E., Wright M.J., Pilz D.T., Lazarou L., Cooper D.N., Sampson J.R., Butler R., Whatley S.D., Clarke A.J. Eur. J. Hum. Genet. 13:1113-1120(2005) [PubMed: 16015284] [Abstract] Cited for: VARIANT EIEE2 ASN-72, VARIANT CYS-444.
[14]	"CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients." Archer H.L., 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. J. Med. Genet. 43:729-734(2006) [PubMed: 16611748] [Abstract] Cited for: VARIANTS EIEE2 LEU-180 AND ALA-793.
[15]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-368.
[16]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., 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 D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-374; GLN-574; ALA-734; PRO-791 AND GLY-1023.
[17]	"Key clinical features to identify girls with CDKL5 mutations." 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 M.A., Arzimanoglou A., Philippe C., Jonveaux P., Chelly J., Bienvenu T. Brain 131:2647-2661(2008) [PubMed: 18790821] [Abstract] Cited for: VARIANTS EIEE2 VAL-40; PRO-220 AND MET-718.
[18]	"Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy." Rosas-Vargas H., Bahi-Buisson N., Philippe C., Nectoux J., Girard B., N'Guyen Morel M.A., Gitiaux C., Lazaro L., Odent S., Jonveaux P., Chelly J., Bienvenu T. J. Med. Genet. 45:172-178(2008) [PubMed: 17993579] [Abstract] Cited for: VARIANTS EIEE2 VAL-40 AND PRO-220, CHARACTERIZATION OF VARIANTS EIEE2 VAL-40 AND PRO-220.
[19]	"CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy." Elia M., Falco M., Ferri R., Spalletta A., Bottitta M., Calabrese G., Carotenuto M., Musumeci S.A., Lo Giudice M., Fichera M. Neurology 71:997-999(2008) [PubMed: 18809835] [Abstract] Cited for: VARIANTS EIEE2 PRO-178; ILE-288 AND TYR-291.
[20]	"A novel mutation in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene associated with a severe Rett phenotype." Sprovieri T., Conforti F.L., Fiumara A., Mazzei R., Ungaro C., Citrigno L., Muglia M., Arena A., Quattrone A. Am. J. Med. Genet. A 149:722-725(2009) [PubMed: 19253388] [Abstract] Cited for: VARIANT EIEE2 THR-399.
[21]	"Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes." Russo S., Marchi M., Cogliati F., Bonati M.T., Pintaudi M., Veneselli E., Saletti V., Balestrini M., Ben-Zeev B., Larizza L. Neurogenetics 10:241-250(2009) [PubMed: 19241098] [Abstract] Cited for: VARIANTS EIEE2 THR-72 AND ARG-127, VARIANTS PRO-791 AND CYS-923.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y15057 mRNA. Translation: CAA75342.1. AY217744 mRNA. Translation: AAO64440.1. Z92542, AL109798 Genomic DNA. Translation: CAI42485.1. AL109798, Z92542 Genomic DNA. Translation: CAI41159.1. X89059 mRNA. Translation: CAA61445.1. Frameshift.
IPI	IPI00746301.
PIR	S58296.
RefSeq	NP_001032420.1. NM_001037343.1. NP_003150.1. NM_003159.2.
UniGene	Hs.659851.
3D structure databases
ProteinModelPortal	O76039.
SMR	O76039. Positions 10-302.
ModBase	Search...
Protein-protein interaction databases
IntAct	O76039. 4 interactions.
MINT	MINT-7241055.
STRING	O76039.
PTM databases
PhosphoSite	O76039.
Proteomic databases
PRIDE	O76039.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000379989; ENSP00000369325; ENSG00000008086. ENST00000379996; ENSP00000369332; ENSG00000008086.
GeneID	6792.
KEGG	hsa:6792.
UCSC	uc004cym.1. human.
Organism-specific databases
CTD	6792.
GeneCards	GC0XP018443.
H-InvDB	HIX0021511.
HGNC	HGNC:11411. CDKL5.
HPA	CAB011577. HPA002847.
MIM	300203. gene. 300672. phenotype.
neXtProt	NX_O76039.
Orphanet	3095. Atypical Rett syndrome. 3451. West syndrome.
PharmGKB	PA36218.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG10368.
GeneTree	ENSGT00600000084046.
HOGENOM	HBG443739.
HOVERGEN	HBG050863.
InParanoid	O76039.
OMA	PQPGEQL.
OrthoDB	EOG43R3M2.
PhylomeDB	O76039.
Enzyme and pathway databases
BRENDA	2.7.11.22. 2681.
Gene expression databases
ArrayExpress	O76039.
Bgee	O76039.
CleanEx	HS_CDKL5.
Genevestigator	O76039.
GermOnline	ENSG00000008086. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K08824.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	26529.
SOURCE	Search...

Entry information

Entry name

CDKL5_HUMAN

Accession

Primary (citable) accession number: O76039
Secondary accession number(s): Q14198 , Q5H985, Q8IYC7, Q9UJL6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.