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Reviewed, UniProtKB/Swiss-Prot O76039 (CDKL5_HUMAN)

Last modified November 25, 2008. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1030 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Tissue specificity

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

Involvement in disease

Chromosomal aberrations involving CDKL5 are a cause of X-linked infantile spasm syndrome (ISSX) [MIM:308350]; also known as X-linked West syndrome. Translocation t(X;6)(p22.3;q14); translocation t(X;7)(p22.3;p15). ISSX is characterized by infantile spasms, hypsarrhythmia on EEG, and developmental arrest leading to severe to profound mental retardation.

Defects in CDKL5 are a cause of X-linked infantile spasm syndrome (ISSX) [MIM:308350].

Defects in CDKL5 are a cause of atypical CDKL5-related Rett syndrome [MIM:300672]. Rett syndrome is an X-linked dominant disease. It is a progressive neurologic developmental disorder and one of the most common causes of mental retardation in females. Patients appear to develop normally until 6 to 18 months of age, then gradually lose speech and purposeful hand movements and develop microcephaly, seizures, autism, ataxia, intermittent hyperventilation, and stereotypic hand movements. After initial regression, the condition stabilizes and patients usually survive into adulthood. Atypical, CDKL5-related Rett syndrome is characterized by a severe early-onset phenotype and atypical features such as infantile spasms.

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.

Binary interactions

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

Natural variations

Natural variant1521C → F in atypical CDKL5-related Rett syndrome.
VAR_023560
Natural variant1751R → S in atypical CDKL5-related Rett syndrome.
VAR_023561
Natural variant1801P → L in ISSX.
VAR_037635
Natural variant3681N → H in a colorectal cancer sample; somatic mutation.
VAR_036578
Natural variant3741A → T in a metastatic melanoma sample; somatic mutation.
VAR_041997
Natural variant5741P → Q in an ovarian serous carcinoma sample; somatic mutation.
VAR_041998
Natural variant7341T → A
VAR_041999
Natural variant7911Q → P: dbSNP rs35478150.
VAR_023562
Natural variant7931V → A in ISSX; uncertain pathogenicity.
VAR_037636
Natural variant9991V → M: dbSNP rs35693326.
VAR_037637
Natural variant10231E → G
VAR_042000

Experimental info

Sequence conflict339 – 3402HR → GT in CAA61445. Ref.4
Sequence conflict5411L → W in CAA61445. Ref.4
Sequence conflict731 – 76434Missing in CAA61445. Ref.4

Sequences

Sequence LengthMass (Da)Tools
O76039-1 [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

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: 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 X-LINKED INFANTILE SPASM SYNDROME, 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. 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: 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 ATYPICAL CDKL5-RELATED RETT SYNDROME.
[6]"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 ATYPICAL CDKL5-RELATED RETT SYNDROME PHE-152 AND SER-175, VARIANT PRO-791.
[7]"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 ATYPICAL RETT SYNDROME.
[8]"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 ISSX LEU-180 AND ALA-793.
[9]"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: 16959974] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-368.
[10]"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: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-374; GLN-574; ALA-734; PRO-791 AND GLY-1023.
+Additional computationally mapped references.

Web resources

Cross-references

<

Sequence databases

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.
PIRS58296.
RefSeqNP_001032420.1.
NP_003150.1.
UniGeneHs.659851

3D structure databases

HSSPHSSP built from PDB template 1H00 based on UniProtKB P24941.
ModBaseSearch...

Protein-protein interaction databases

IntActO76039.

PTM databases

PhosphoSiteO76039.

Genome annotation databases

EnsemblENSG00000008086. Homo sapiens. [Contig view]
GeneID6792.
KEGGhsa:6792.

Organism-specific databases

H-InvDBHIX0021511.
HGNCHGNC:11411. CDKL5.
HPACAB011577.
HPA002847.
MIM300203. gene.
300672. phenotype.
308350. phenotype.
Orphanet778. Rett syndrome.
3451. West syndrome.
PharmGKBPA36218.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOVERGENO76039.

Gene expression databases

ArrayExpressO76039.
CleanExHS_CDKL5.
GermOnlineENSG00000008086. Homo sapiens.

Family and domain databases

InterProIPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio26529.
SOURCESearch...