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O76039 (CDKL5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1030 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mediates phosphorylation of MECP2. Ref.7 Ref.8

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

Interacts with MECP2. Ref.7

Subcellular location

Nucleus Ref.8.

Tissue specificity

Expressed in brain, lung, kidney, prostate, ovary, placenta, pancreas and testis.

Post-translational modification

Autophosphorylated. Ref.7 Ref.8

Involvement in disease

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).

Epileptic encephalopathy, early infantile, 2 (EIEE2) [MIM:300672]: A severe form of epilepsy characterized by seizures or spasms beginning in infancy. Patients with epileptic encephalopathy early infantile type 2 manifest features resembling Rett syndrome such as microcephaly, lack of speech development, stereotypic hand movements. However, EIEE2 and Rett syndrome are considered two distinct entities.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.6 Ref.7 Ref.8 Ref.13 Ref.14 Ref.15 Ref.16 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23

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 componentNucleus
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DiseaseDisease mutation
Epilepsy
Mental retardation
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processneuron 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.8. Source: HGNC

protein phosphorylation

Traceable author statement Ref.1. Source: ProtInc

regulation of dendrite development

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

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.8. Source: HGNC

ruffle membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from direct assay Ref.8. Source: HGNC

Rac GTPase binding

Inferred from sequence or structural similarity. Source: BHF-UCL

cyclin-dependent protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

kinase activity

Inferred from direct assay Ref.7. Source: MGI

protein kinase activity

Inferred from direct assay Ref.8. Source: HGNC

protein serine/threonine kinase activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O76039-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O76039-2)

The sequence of this isoform differs from the canonical sequence as follows:
     905-1030: DGGCDGRRQR...YHENAALTGK → GQMDPGWHVS...NLNDLKETAL
Note: Predominant transcript in brain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10301030Cyclin-dependent kinase-like 5
PRO_0000085826

Regions

Domain13 – 297285Protein kinase
Nucleotide binding19 – 279ATP By similarity
Compositional bias784 – 7896Poly-Lys

Sites

Active site1351Proton acceptor By similarity
Binding site421ATP By similarity

Amino acid modifications

Modified residue4071Phosphoserine Ref.9 Ref.10 Ref.11 Ref.12
Modified residue7201Phosphoserine Ref.11
Modified residue7611Phosphoserine Ref.9

Natural variations

Alternative sequence905 – 1030126DGGCD…ALTGK → GQMDPGWHVSSVTRSATEGP SYSEQLGAKSGPNGHPYNRT NRSRMPNLNDLKETAL in isoform 2.
VSP_044082
Natural variant401A → V in EIEE2; causes mislocalization of the protein in the cytoplasm. Ref.19 Ref.20
VAR_058022
Natural variant721I → N in EIEE2. Ref.15
VAR_058023
Natural variant721I → T in EIEE2. Ref.23
VAR_058024
Natural variant1271H → R in EIEE2. Ref.23
VAR_058025
Natural variant1521C → F in EIEE2; affect activity; causes mislocalization of the protein in the cytoplasm. Ref.8 Ref.13
VAR_023560
Natural variant1751R → S in EIEE2; affect activity; does not affect the cellular distribution of the protein. Ref.8 Ref.13
VAR_023561
Natural variant1781R → P in EIEE2. Ref.21
VAR_058026
Natural variant1801P → L in EIEE2. Ref.16
VAR_037635
Natural variant2201L → P in EIEE2; causes mislocalization of the protein in the cytoplasm. Ref.19 Ref.20
VAR_058027
Natural variant2881T → I in EIEE2. Ref.21
VAR_058028
Natural variant2911C → Y in EIEE2. Ref.21
VAR_058029
Natural variant3681N → H in a colorectal cancer sample; somatic mutation. Ref.17
VAR_036578
Natural variant3741A → T in a metastatic melanoma sample; somatic mutation. Ref.18
VAR_041997
Natural variant3991N → T in EIEE2. Ref.22
VAR_058030
Natural variant4441R → C. Ref.15
VAR_058031
Natural variant5741P → Q in an ovarian serous carcinoma sample; somatic mutation. Ref.18
VAR_041998
Natural variant7181V → M in EIEE2. Ref.19
VAR_058032
Natural variant7341T → A. Ref.18
Corresponds to variant rs55803460 [ dbSNP | Ensembl ].
VAR_041999
Natural variant7911Q → P. Ref.2 Ref.13 Ref.18 Ref.23
Corresponds to variant rs35478150 [ dbSNP | Ensembl ].
VAR_023562
Natural variant7931V → A in EIEE2; unknown pathological significance. Ref.16
VAR_037636
Natural variant9231R → C. Ref.23
VAR_058033
Natural variant9991V → M.
Corresponds to variant rs35693326 [ dbSNP | Ensembl ].
VAR_037637
Natural variant10231E → G. Ref.18
Corresponds to variant rs34166184 [ dbSNP | Ensembl ].
VAR_042000

Experimental info

Sequence conflict339 – 3402HR → GT in CAA61445. Ref.5
Sequence conflict5411L → W in CAA61445. Ref.5
Sequence conflict731 – 76434Missing in CAA61445. Ref.5

Secondary structure

.............................................. 1030
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: 8A1C9C438610EF08

FASTA1,030115,538
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 6E955E0B40DBC1B8
Show »

FASTA960107,519

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN EIEE2, CHROMOSOMAL TRANSLOCATION, VARIANT PRO-791.
[3]"A novel transcript of cyclin-dependent kinase-like 5 (CDKL5) has an alternative C-terminus and is the predominant transcript in brain."
Williamson S.L., Giudici L., Kilstrup-Nielsen C., Gold W., Pelka G.J., Tam P.P., Grimm A., Prodi D., Landsberger N., Christodoulou J.
Hum. Genet. 131:187-200(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
[4]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 339-789.
[6]"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] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN EIEE2.
[7]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MECP2, FUNCTION, AUTOPHOSPHORYLATION, INVOLVEMENT IN EIEE2.
[8]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EIEE2 PHE-152 AND SER-175.
[9]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-761, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-720, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS EIEE2 PHE-152 AND SER-175, VARIANT PRO-791.
[14]"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] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN EIEE2.
[15]"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] [Europe PMC] [Abstract]
Cited for: VARIANT EIEE2 ASN-72, VARIANT CYS-444.
[16]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS EIEE2 LEU-180 AND ALA-793.
[17]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-368.
[18]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-374; GLN-574; ALA-734; PRO-791 AND GLY-1023.
[19]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS EIEE2 VAL-40; PRO-220 AND MET-718.
[20]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS EIEE2 VAL-40 AND PRO-220, CHARACTERIZATION OF VARIANTS EIEE2 VAL-40 AND PRO-220.
[21]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS EIEE2 PRO-178; ILE-288 AND TYR-291.
[22]"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] [Europe PMC] [Abstract]
Cited for: VARIANT EIEE2 THR-399.
[23]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS EIEE2 THR-72 AND ARG-127, VARIANTS PRO-791 AND CYS-923.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y15057 mRNA. Translation: CAA75342.1.
AY217744 mRNA. Translation: AAO64440.1.
HQ171445 mRNA. Translation: ADN38258.1.
Z92542, AL109798 Genomic DNA. Translation: CAI42485.1.
AL109798, Z92542 Genomic DNA. Translation: CAI41159.1.
X89059 mRNA. Translation: CAA61445.1. Frameshift.
PIRS58296.
RefSeqNP_001032420.1. NM_001037343.1.
NP_003150.1. NM_003159.2.
UniGeneHs.659851.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4BGQX-ray2.00A1-303[»]
ProteinModelPortalO76039.
SMRO76039. Positions 9-343.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112668. 6 interactions.
IntActO76039. 6 interactions.
MINTMINT-7241055.
STRING9606.ENSP00000369325.

Chemistry

BindingDBO76039.
ChEMBLCHEMBL1163112.

PTM databases

PhosphoSiteO76039.

Proteomic databases

PaxDbO76039.
PRIDEO76039.

Protocols and materials databases

DNASU6792.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379989; ENSP00000369325; ENSG00000008086. [O76039-1]
ENST00000379996; ENSP00000369332; ENSG00000008086. [O76039-1]
GeneID6792.
KEGGhsa:6792.
UCSCuc004cym.3. human. [O76039-1]
uc022btn.1. human. [O76039-2]

Organism-specific databases

CTD6792.
GeneCardsGC0XP018443.
HGNCHGNC:11411. CDKL5.
HPACAB011577.
HPA002847.
MIM300203. gene.
300672. phenotype.
neXtProtNX_O76039.
PharmGKBPA36218.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000049181.
HOVERGENHBG050863.
InParanoidO76039.
KOK08824.
OMAQPGSTSK.
OrthoDBEOG7992PS.
PhylomeDBO76039.
TreeFamTF101032.

Enzyme and pathway databases

BRENDA2.7.11.22. 2681.
SignaLinkO76039.

Gene expression databases

BgeeO76039.
CleanExHS_CDKL5.
GenevestigatorO76039.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCDKL5. human.
GeneWikiCDKL5.
GenomeRNAi6792.
NextBio26529.
PROO76039.
SOURCESearch...

Entry information

Entry nameCDKL5_HUMAN
AccessionPrimary (citable) accession number: O76039
Secondary accession number(s): G9B9X4 expand/collapse secondary AC list , Q14198, Q5H985, Q8IYC7, Q9UJL6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1998
Last modified: April 16, 2014
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM