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Protein

Cyclin-dependent kinase-like 5

Gene

CDKL5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Mediates phosphorylation of MECP2.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei42ATPPROSITE-ProRule annotation1
Active sitei135Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi19 – 27ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: HGNC
  • kinase activity Source: MGI
  • protein kinase activity Source: HGNC
  • protein serine/threonine kinase activity Source: ProtInc
  • Rac GTPase binding Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.22. 2681.
SignaLinkiO76039.
SIGNORiO76039.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase-like 5 (EC:2.7.11.22)
Alternative name(s):
Serine/threonine-protein kinase 9
Gene namesi
Name:CDKL5
Synonyms:STK9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:11411. CDKL5.

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

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)18 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:300672
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05802240A → V in EIEE2; causes mislocalization of the protein in the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs122460159Ensembl.1
Natural variantiVAR_05802372I → N in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs62641235Ensembl.1
Natural variantiVAR_05802472I → T in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs62641235Ensembl.1
Natural variantiVAR_058025127H → R in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs267608468Ensembl.1
Natural variantiVAR_078625145H → Y in EIEE2; unknown pathological significance. 1 Publication1
Natural variantiVAR_023560152C → F in EIEE2; affect activity; causes mislocalization of the protein in the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs122460157Ensembl.1
Natural variantiVAR_023561175R → S in EIEE2; affect activity; does not affect the cellular distribution of the protein. 2 PublicationsCorresponds to variant dbSNP:rs61749700Ensembl.1
Natural variantiVAR_058026178R → P in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs267606715Ensembl.1
Natural variantiVAR_071103178R → Q in EIEE2. 3 PublicationsCorresponds to variant dbSNP:rs267606715Ensembl.1
Natural variantiVAR_078712178R → W in EIEE2. 1 Publication1
Natural variantiVAR_037635180P → L in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs61749704Ensembl.1
Natural variantiVAR_078626182L → P in EIEE2. 1 Publication1
Natural variantiVAR_078219196S → L in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs267608501Ensembl.1
Natural variantiVAR_078627207G → E in EIEE2. 1 Publication1
Natural variantiVAR_058027220L → P in EIEE2; causes mislocalization of the protein in the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs267608511Ensembl.1
Natural variantiVAR_058028288T → I in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs267606713Ensembl.1
Natural variantiVAR_058029291C → Y in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs267606714Ensembl.1
Natural variantiVAR_058030399N → T in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs267608611Ensembl.1
Natural variantiVAR_078628581H → Y in EIEE2; unknown pathological significance. 1 Publication1
Natural variantiVAR_058032718V → M in EIEE2. 2 PublicationsCorresponds to variant dbSNP:rs267608653Ensembl.1
Natural variantiVAR_078714726 – 1030Missing in EIEE2. 1 PublicationAdd BLAST305
Natural variantiVAR_037636793V → A in EIEE2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs62643617Ensembl.1
Natural variantiVAR_078630858R → C in EIEE2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs773760466Ensembl.1
Natural variantiVAR_078220994G → R in EIEE2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs866859766Ensembl.1

Keywords - Diseasei

Disease mutation, Epilepsy, Mental retardation

Organism-specific databases

DisGeNETi6792.
MalaCardsiCDKL5.
MIMi300672. phenotype.
OpenTargetsiENSG00000008086.
PharmGKBiPA36218.

Chemistry databases

ChEMBLiCHEMBL1163112.

Polymorphism and mutation databases

BioMutaiCDKL5.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000858261 – 1030Cyclin-dependent kinase-like 5Add BLAST1030

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei407PhosphoserineCombined sources1
Modified residuei479PhosphoserineCombined sources1
Modified residuei720PhosphoserineCombined sources1
Modified residuei761PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylated.

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO76039.
MaxQBiO76039.
PaxDbiO76039.
PeptideAtlasiO76039.
PRIDEiO76039.

PTM databases

iPTMnetiO76039.
PhosphoSitePlusiO76039.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000008086.
CleanExiHS_CDKL5.
ExpressionAtlasiO76039. baseline and differential.
GenevisibleiO76039. HS.

Organism-specific databases

HPAiCAB011577.
HPA002847.

Interactioni

Subunit structurei

Interacts with MECP2.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112668. 17 interactors.
IntActiO76039. 7 interactors.
MINTiMINT-7241055.
STRINGi9606.ENSP00000369325.

Chemistry databases

BindingDBiO76039.

Structurei

Secondary structure

11030
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni10 – 12Combined sources3
Beta strandi13 – 24Combined sources12
Beta strandi26 – 32Combined sources7
Turni33 – 35Combined sources3
Beta strandi38 – 43Combined sources6
Helixi55 – 66Combined sources12
Beta strandi75 – 81Combined sources7
Beta strandi84 – 90Combined sources7
Beta strandi93 – 95Combined sources3
Helixi96 – 102Combined sources7
Helixi109 – 128Combined sources20
Helixi138 – 140Combined sources3
Beta strandi141 – 143Combined sources3
Beta strandi149 – 151Combined sources3
Helixi180 – 183Combined sources4
Helixi191 – 206Combined sources16
Helixi216 – 227Combined sources12
Helixi232 – 240Combined sources9
Helixi242 – 244Combined sources3
Helixi258 – 262Combined sources5
Turni263 – 265Combined sources3
Helixi268 – 277Combined sources10
Helixi282 – 284Combined sources3
Helixi288 – 292Combined sources5
Helixi295 – 298Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BGQX-ray2.00A1-303[»]
ProteinModelPortaliO76039.
SMRiO76039.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 297Protein kinasePROSITE-ProRule annotationAdd BLAST285

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi784 – 789Poly-Lys6

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0593. Eukaryota.
ENOG410XNSW. LUCA.
GeneTreeiENSGT00830000128262.
HOGENOMiHOG000049181.
HOVERGENiHBG050863.
InParanoidiO76039.
KOiK08824.
OMAiHSFVEGK.
OrthoDBiEOG091G01A9.
PhylomeDBiO76039.
TreeFamiTF101032.

Family and domain databases

InterProiView protein in InterPro
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O76039-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MKIPNIGNVM NKFEILGVVG EGAYGVVLKC RHKETHEIVA IKKFKDSEEN
60 70 80 90 100
EEVKETTLRE LKMLRTLKQE NIVELKEAFR RRGKLYLVFE YVEKNMLELL
110 120 130 140 150
EEMPNGVPPE KVKSYIYQLI KAIHWCHKND IVHRDIKPEN LLISHNDVLK
160 170 180 190 200
LCDFGFARNL SEGNNANYTE YVATRWYRSP ELLLGAPYGK SVDMWSVGCI
210 220 230 240 250
LGELSDGQPL FPGESEIDQL FTIQKVLGPL PSEQMKLFYS NPRFHGLRFP
260 270 280 290 300
AVNHPQSLER RYLGILNSVL LDLMKNLLKL DPADRYLTEQ CLNHPTFQTQ
310 320 330 340 350
RLLDRSPSRS AKRKPYHVES STLSNRNQAG KSTALQSHHR SNSKDIQNLS
360 370 380 390 400
VGLPRADEGL PANESFLNGN LAGASLSPLH TKTYQASSQP GSTSKDLTNN
410 420 430 440 450
NIPHLLSPKE AKSKTEFDFN IDPKPSEGPG TKYLKSNSRS QQNRHSFMES
460 470 480 490 500
SQSKAGTLQP NEKQSRHSYI DTIPQSSRSP SYRTKAKSHG ALSDSKSVSN
510 520 530 540 550
LSEARAQIAE PSTSRYFPSS CLDLNSPTSP TPTRHSDTRT LLSPSGRNNR
560 570 580 590 600
NEGTLDSRRT TTRHSKTMEE LKLPEHMDSS HSHSLSAPHE SFSYGLGYTS
610 620 630 640 650
PFSSQQRPHR HSMYVTRDKV RAKGLDGSLS IGQGMAARAN SLQLLSPQPG
660 670 680 690 700
EQLPPEMTVA RSSVKETSRE GTSSFHTRQK SEGGVYHDPH SDDGTAPKEN
710 720 730 740 750
RHLYNDPVPR RVGSFYRVPS PRPDNSFHEN NVSTRVSSLP SESSSGTNHS
760 770 780 790 800
KRQPAFDPWK SPENISHSEQ LKEKEKQGFF RSMKKKKKKS QTVPNSDSPD
810 820 830 840 850
LLTLQKSIHS ASTPSSRPKE WRPEKISDLQ TQSQPLKSLR KLLHLSSASN
860 870 880 890 900
HPASSDPRFQ PLTAQQTKNS FSEIRIHPLS QASGGSSNIR QEPAPKGRPA
910 920 930 940 950
LQLPDGGCDG RRQRHHSGPQ DRRFMLRTTE QQGEYFCCGD PKKPHTPCVP
960 970 980 990 1000
NRALHRPISS PAPYPVLQVR GTSMCPTLQV RGTDAFSCPT QQSGFSFFVR
1010 1020 1030
HVMREALIHR AQVNQAALLT YHENAALTGK
Length:1,030
Mass (Da):115,538
Last modified:November 1, 1998 - v1
Checksum:i8A1C9C438610EF08
GO
Isoform 2 (identifier: O76039-2) [UniParc]FASTAAdd to basket

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

Note: Predominant transcript in brain.
Show »
Length:960
Mass (Da):107,519
Checksum:i6E955E0B40DBC1B8
GO

Sequence cautioni

The sequence CAA61445 differs from that shown. Reason: Frameshift at position 415.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti339 – 340HR → GT in CAA61445 (PubMed:8864140).Curated2
Sequence conflicti541L → W in CAA61445 (PubMed:8864140).Curated1
Sequence conflicti731 – 764Missing in CAA61445 (PubMed:8864140).CuratedAdd BLAST34

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05802240A → V in EIEE2; causes mislocalization of the protein in the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs122460159Ensembl.1
Natural variantiVAR_05802372I → N in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs62641235Ensembl.1
Natural variantiVAR_05802472I → T in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs62641235Ensembl.1
Natural variantiVAR_058025127H → R in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs267608468Ensembl.1
Natural variantiVAR_078625145H → Y in EIEE2; unknown pathological significance. 1 Publication1
Natural variantiVAR_023560152C → F in EIEE2; affect activity; causes mislocalization of the protein in the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs122460157Ensembl.1
Natural variantiVAR_023561175R → S in EIEE2; affect activity; does not affect the cellular distribution of the protein. 2 PublicationsCorresponds to variant dbSNP:rs61749700Ensembl.1
Natural variantiVAR_058026178R → P in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs267606715Ensembl.1
Natural variantiVAR_071103178R → Q in EIEE2. 3 PublicationsCorresponds to variant dbSNP:rs267606715Ensembl.1
Natural variantiVAR_078712178R → W in EIEE2. 1 Publication1
Natural variantiVAR_037635180P → L in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs61749704Ensembl.1
Natural variantiVAR_078626182L → P in EIEE2. 1 Publication1
Natural variantiVAR_078219196S → L in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs267608501Ensembl.1
Natural variantiVAR_078627207G → E in EIEE2. 1 Publication1
Natural variantiVAR_058027220L → P in EIEE2; causes mislocalization of the protein in the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs267608511Ensembl.1
Natural variantiVAR_058028288T → I in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs267606713Ensembl.1
Natural variantiVAR_058029291C → Y in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs267606714Ensembl.1
Natural variantiVAR_036578368N → H in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_041997374A → T in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_058030399N → T in EIEE2. 1 PublicationCorresponds to variant dbSNP:rs267608611Ensembl.1
Natural variantiVAR_058031444R → C1 PublicationCorresponds to variant dbSNP:rs61753977Ensembl.1
Natural variantiVAR_041998574P → Q in an ovarian serous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_078628581H → Y in EIEE2; unknown pathological significance. 1 Publication1
Natural variantiVAR_078713647P → L Probable disease-associated mutation found in a patient with autism spectrum disorder. 1 Publication1
Natural variantiVAR_058032718V → M in EIEE2. 2 PublicationsCorresponds to variant dbSNP:rs267608653Ensembl.1
Natural variantiVAR_078714726 – 1030Missing in EIEE2. 1 PublicationAdd BLAST305
Natural variantiVAR_041999734T → A1 PublicationCorresponds to variant dbSNP:rs55803460Ensembl.1
Natural variantiVAR_023562791Q → P4 PublicationsCorresponds to variant dbSNP:rs35478150Ensembl.1
Natural variantiVAR_037636793V → A in EIEE2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs62643617Ensembl.1
Natural variantiVAR_078629855 – 1030Missing Probable disease-associated mutation found in a patient with infatile spasms. 1 PublicationAdd BLAST176
Natural variantiVAR_078630858R → C in EIEE2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs773760466Ensembl.1
Natural variantiVAR_058033923R → C1 PublicationCorresponds to variant dbSNP:rs267608664Ensembl.1
Natural variantiVAR_078220994G → R in EIEE2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs866859766Ensembl.1
Natural variantiVAR_037637999V → M. Corresponds to variant dbSNP:rs35693326Ensembl.1
Natural variantiVAR_0420001023E → G1 PublicationCorresponds to variant dbSNP:rs34166184Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044082905 – 1030DGGCD…ALTGK → GQMDPGWHVSSVTRSATEGP SYSEQLGAKSGPNGHPYNRT NRSRMPNLNDLKETAL in isoform 2. 1 PublicationAdd BLAST126

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS14186.1. [O76039-1]
CCDS83458.1. [O76039-2]
PIRiS58296.
RefSeqiNP_001032420.1. NM_001037343.1. [O76039-1]
NP_001310218.1. NM_001323289.1. [O76039-2]
NP_003150.1. NM_003159.2. [O76039-1]
UniGeneiHs.659851.
Hs.696079.

Genome annotation databases

EnsembliENST00000379989; ENSP00000369325; ENSG00000008086. [O76039-1]
ENST00000379996; ENSP00000369332; ENSG00000008086. [O76039-1]
ENST00000623535; ENSP00000485244; ENSG00000008086. [O76039-2]
GeneIDi6792.
KEGGihsa:6792.
UCSCiuc004cym.4. human. [O76039-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiCDKL5_HUMAN
AccessioniPrimary (citable) accession number: O76039
Secondary accession number(s): G9B9X4
, Q14198, Q5H985, Q8IYC7, Q9UJL6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1998
Last modified: July 5, 2017
This is version 175 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Caution

It is uncertain whether Met-1 or Met-10 is the initiator.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families