Q00532 (CDKL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase-like 1
EC=2.7.11.22

Alternative name(s):
Protein kinase p42 KKIALRE
Serine/threonine-protein kinase KKIALRE

Gene names

Name:

CDKL1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	357 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subcellular location	Cytoplasm. Nucleus Ref.6.
Tissue specificity	Highly expressed in kidney, and to a lower extent in ovary. Ref.6
Domain	The [NKR]KIAxRE motif seems to be a cyclin-binding region.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence AAI04978.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAS00095.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAA47002.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	heart development Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cyclin-dependent 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: Q00532-1)

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: Q00532-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MELSTDTGWN...HFKKIYSSMM
     56-56: K → KAPSPYAAEP...RGGSAAQEPT
     98-121: VPEHLVKSITWQTLQAVNFCHKHN → ICNIFVCTGR...ELTSSDSPQR
     247-357: EPLELKFPNI...KKLNYRFPNI → SLCLSVTLTE...EQEKYLSYGA

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 357

357

Cyclin-dependent kinase-like 1

PRO_0000085810

Regions

Domain

4 – 287

284

Protein kinase

Nucleotide binding

10 – 18

9

ATP By similarity

Motif

45 – 51

7

[NKR]KIAxRE

Sites

Active site

126

1

Proton acceptor By similarity

Binding site

33

1

ATP By similarity

Natural variations

Alternative sequence

1

1

M → MELSTDTGWNQKSNFPPCDS RVSKEEAQLPFPTPSSYGAD SSNQTYAHKSQSEREQHKEV RAVLNHCSGLDGGEESGLCG TSTRIDAGTGNGTDDKVTDQ HRHRRCLQGTKGNNRGSEVW GLLLQGNVDRSGGAPSAGVL LRRRGYSCALHGLRKFANLA GLLSRQQDSARGVSHHSRLK IHFKKIYSSMM in isoform 2.

VSP_041239

Alternative sequence

56

1

K → KAPSPYAAEPSLCGMKMVRR GKKEFLPAVAEKVDAPSGVG GQGQDSVTVGSLGRRSTYGR KQEKQVRQREGIIYCYVAVL LRIYYFDQGCVAREEEQFQE LVFGPFCHIGSYFTGHRTNV RPYILLLSRPSPFKTAAGTY EAGLVILECSYFLAEQEPYC PTQALQQPHPIIGPWALEGG GVESKEDRHPPPKEAPASCE GFLRSAVPKQAYTPFKTSPD KRLSDCVATPPWAPPTPLII SSGVLVAICSMIDPVPEFHS EGLLAKATSGSAGILVWIFL CNDAFIYGKYILRSGVLWVR GLPGFKSEAAALCHKCYSSA DPKREQQQDLLQRVKEQSFH SVNGAQARHKGSPSPHQTQE PSWPHPVDPTPGHRWSCLPV PCRAPALLSPWVVDGTGCCG AGGGSDRGGSAAQEPT in isoform 2.

VSP_041240

Alternative sequence

98 – 121

24

VPEHL…CHKHN → ICNIFVCTGRRLGEHTEALS KKKKKGGGGPFLKLRAASCR ITLFKNVGCGLETTGDLSLN SGGGAASRGVAAALRALVCG TELTSSDSPQR in isoform 2.

VSP_041241

Alternative sequence

247 – 357

111

EPLEL…RFPNI → SLCLSVTLTEGGLLASGAVK RSQMGSSVSQATSWPHPDIV AETAELDDIAMARQTPVMLR FNRQKEQEKYLSYGA in isoform 2.

VSP_041242

Natural variant

66

1

L → P. Ref.3
Corresponds to variant rs11570814 [ dbSNP | Ensembl ].

VAR_020576

Natural variant

274

1

Q → E. Ref.1 Ref.3 Ref.7
Corresponds to variant rs7161563 [ dbSNP | Ensembl ].

VAR_020577

Natural variant

329

1

L → V. Ref.3 Ref.7
Corresponds to variant rs9323183 [ dbSNP | Ensembl ].

VAR_020578

Natural variant

341

1

K → N. Ref.3
Corresponds to variant rs11570886 [ dbSNP | Ensembl ].

VAR_020579

Experimental info

Sequence conflict

152

1

A → T in CAA47002. Ref.1

Sequence conflict

152

1

A → T in AAL58838. Ref.2

Sequence conflict

152

1

A → T in AAS00095. Ref.3

Sequence conflict

152

1

A → T in AAI04978. Ref.5

Sequence conflict

301

1

N → D in CAA47002. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

357

Helix Strand Turn

Details...

Beta strand

4 – 12

9

Beta strand

14 – 23

10

Turn

24 – 26

3

Beta strand

29 – 35

7

Helix

42 – 57

16

Beta strand

66 – 72

7

Beta strand

75 – 81

7

Beta strand

84 – 86

3

Helix

87 – 93

7

Helix

100 – 119

20

Helix

129 – 131

3

Beta strand

132 – 134

3

Beta strand

140 – 142

3

Helix

165 – 167

3

Helix

170 – 174

5

Helix

182 – 197

16

Helix

207 – 218

12

Helix

223 – 230

8

Helix

233 – 235

3

Helix

249 – 252

4

Helix

258 – 267

10

Turn

272 – 274

3

Helix

278 – 282

5

Helix

285 – 287

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 5. Checksum: 3EA30F059885F846	FASTA	357	41,671
	10 20 30 40 50 60 MEKYEKIGKI GEGSYGVVFK CRNRDTGQIV AIKKFLESED DPVIKKIALR EIRMLKQLKH 70 80 90 100 110 120 PNLVNLLEVF RRKRRLHLVF EYCDHTVLHE LDRYQRGVPE HLVKSITWQT LQAVNFCHKH 130 140 150 160 170 180 NCIHRDVKPE NILITKHSVI KLCDFGFARL LAGPSDYYTD YVATRWYRSP ELLVGDTQYG 190 200 210 220 230 240 PPVDVWAIGC VFAELLSGVP LWPGKSDVDQ LYLIRKTLGD LIPRHQQVFS TNQYFSGVKI 250 260 270 280 290 300 PDPEDMEPLE LKFPNISYPA LGLLKGCLHM DPTQRLTCEQ LLHHPYFENI REIEDLAKEH 310 320 330 340 350 NKPTRKTLRK SRKHHCFTET SKLQYLPQLT GSSILPALDN KKYYCDTKKL NYRFPNI
	Isoform 2 [UniParc]. Checksum: 1D0D58391FEB4D76	FASTA	993	108,931
	10 20 30 40 50 60 MELSTDTGWN QKSNFPPCDS RVSKEEAQLP FPTPSSYGAD SSNQTYAHKS QSEREQHKEV 70 80 90 100 110 120 RAVLNHCSGL DGGEESGLCG TSTRIDAGTG NGTDDKVTDQ HRHRRCLQGT KGNNRGSEVW 130 140 150 160 170 180 GLLLQGNVDR SGGAPSAGVL LRRRGYSCAL HGLRKFANLA GLLSRQQDSA RGVSHHSRLK 190 200 210 220 230 240 IHFKKIYSSM MEKYEKIGKI GEGSYGVVFK CRNRDTGQIV AIKKFLESED DPVIKKIALR 250 260 270 280 290 300 EIRMLKAPSP YAAEPSLCGM KMVRRGKKEF LPAVAEKVDA PSGVGGQGQD SVTVGSLGRR 310 320 330 340 350 360 STYGRKQEKQ VRQREGIIYC YVAVLLRIYY FDQGCVAREE EQFQELVFGP FCHIGSYFTG 370 380 390 400 410 420 HRTNVRPYIL LLSRPSPFKT AAGTYEAGLV ILECSYFLAE QEPYCPTQAL QQPHPIIGPW 430 440 450 460 470 480 ALEGGGVESK EDRHPPPKEA PASCEGFLRS AVPKQAYTPF KTSPDKRLSD CVATPPWAPP 490 500 510 520 530 540 TPLIISSGVL VAICSMIDPV PEFHSEGLLA KATSGSAGIL VWIFLCNDAF IYGKYILRSG 550 560 570 580 590 600 VLWVRGLPGF KSEAAALCHK CYSSADPKRE QQQDLLQRVK EQSFHSVNGA QARHKGSPSP 610 620 630 640 650 660 HQTQEPSWPH PVDPTPGHRW SCLPVPCRAP ALLSPWVVDG TGCCGAGGGS DRGGSAAQEP 670 680 690 700 710 720 TQLKHPNLVN LLEVFRRKRR LHLVFEYCDH TVLHELDRYQ RGICNIFVCT GRRLGEHTEA 730 740 750 760 770 780 LSKKKKKGGG GPFLKLRAAS CRITLFKNVG CGLETTGDLS LNSGGGAASR GVAAALRALV 790 800 810 820 830 840 CGTELTSSDS PQRCIHRDVK PENILITKHS VIKLCDFGFA RLLAGPSDYY TDYVATRWYR 850 860 870 880 890 900 SPELLVGDTQ YGPPVDVWAI GCVFAELLSG VPLWPGKSDV DQLYLIRKTL GDLIPRHQQV 910 920 930 940 950 960 FSTNQYFSGV KIPDPEDMSL CLSVTLTEGG LLASGAVKRS QMGSSVSQAT SWPHPDIVAE 970 980 990 TAELDDIAMA RQTPVMLRFN RQKEQEKYLS YGA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A family of human cdc2-related protein kinases." Meyerson M., Enders G.H., Wu C.-L., Su L.-K., Gorka C., Nelson C., Harlow E., Tsai L.-H. EMBO J. 11:2909-2917(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLU-274.
[2]	"The cloning of 2nd splicing version of human serine/threonine-protein kinase KKIALRE (cyclin-dependent kinase like-1)." Hu W.-X., Tang L.-J., Shi Y.-W. Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	NIEHS SNPs program Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANTS PRO-66; GLU-274; VAL-329 AND ASN-341.
[4]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Cerebellum.
[6]	"Molecular cloning of the epidermal growth factor-stimulated protein kinase p56 KKIAMRE." Taglienti C.A., Wysk M., Davis R.J. Oncogene 13:2563-2574(1996) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[7]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLU-274 AND VAL-329.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X66358, X66359 mRNA. Translation: CAA47002.1. Different initiation.
AF390028 mRNA. Translation: AAL58838.1.
AY525548 Genomic DNA. Translation: AAS00095.1. Different initiation.
AL359397 Genomic DNA. No translation available.
BC104977 mRNA. Translation: AAI04978.1. Different initiation.

IPI

IPI00973840.
IPI01017912.

PIR

S22745.
S23383.

RefSeq

NP_004187.2. NM_004196.3.

UniGene

Hs.679430.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4AGU	X-ray	2.40	A/B/C	1-303	[»]

ProteinModelPortal

Q00532.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q00532. 1 interaction.

STRING

9606.ENSP00000216378.

Polymorphism databases

DMDM

229463050.

Proteomic databases

PaxDb

Q00532.

PRIDE

Q00532.

Protocols and materials databases

DNASU

8814.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000395834; ENSP00000379176; ENSG00000100490.

GeneID

8814.

KEGG

hsa:8814.

UCSC

uc001wxz.3. human.
uc010anu.2. human.

Organism-specific databases

CTD

8814.

GeneCards

GC14M050796.

HGNC

HGNC:1781. CDKL1.

MIM

603441. gene.

neXtProt

NX_Q00532.

PharmGKB

PA26317.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233024.

HOVERGEN

HBG014652.

KO

K08824.

OrthoDB

EOG40GCQ2.

Enzyme and pathway databases

BRENDA

2.7.11.22. 2681.

Gene expression databases

Bgee

Q00532.

CleanEx

HS_CDKL1.

Genevestigator

Q00532.

GermOnline

ENSG00000100490. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

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

BindingDB

Q00532.

ChEMBL

CHEMBL5789.

GenomeRNAi

8814.

NextBio

33062.

SOURCE

Search...

Entry information

Entry name

CDKL1_HUMAN

Accession

Primary (citable) accession number: Q00532
Secondary accession number(s): Q2M3A4, Q6QUA0, Q8WXQ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	May 5, 2009
Last modified:	May 1, 2013
This is version 128 of the entry and version 5 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.