CDKL2_HUMAN
ID CDKL2_HUMAN Reviewed; 493 AA.
AC Q92772; B2R695;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Cyclin-dependent kinase-like 2 {ECO:0000305};
DE EC=2.7.11.22;
DE AltName: Full=Protein kinase p56 KKIAMRE {ECO:0000303|PubMed:9000130};
DE AltName: Full=Serine/threonine-protein kinase KKIAMRE;
GN Name=CDKL2 {ECO:0000312|HGNC:HGNC:1782};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Fetal brain;
RX PubMed=9000130;
RA Taglienti C.A., Wysk M., Davis R.J.;
RT "Molecular cloning of the epidermal growth factor-stimulated protein kinase
RT p56 KKIAMRE.";
RL Oncogene 13:2563-2574(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5] {ECO:0007744|PDB:4AAA, ECO:0007744|PDB:4BBM}
RP X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 1-308 IN COMPLEX WITH SYNTHETIC
RP INHIBITOR.
RX PubMed=29420175; DOI=10.1016/j.celrep.2017.12.083;
RA Canning P., Park K., Goncalves J., Li C., Howard C.J., Sharpe T.D.,
RA Holt L.J., Pelletier L., Bullock A.N., Leroux M.R.;
RT "CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary
RT Function.";
RL Cell Rep. 22:885-894(2018).
RN [6]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-98; GLN-149; THR-197 AND VAL-411.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.22;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9000130}. Nucleus
CC {ECO:0000269|PubMed:9000130}.
CC -!- TISSUE SPECIFICITY: Expressed in testis and kidney, and at lower level
CC in brain and lung. {ECO:0000269|PubMed:9000130}.
CC -!- DOMAIN: The [NKR]KIAxRE motif seems to be a cyclin-binding region.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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DR EMBL; U35146; AAC50918.1; -; mRNA.
DR EMBL; AK312490; BAG35392.1; -; mRNA.
DR EMBL; CH471057; EAX05740.1; -; Genomic_DNA.
DR EMBL; BC093646; AAH93646.1; -; mRNA.
DR EMBL; BC093981; AAH93981.1; -; mRNA.
DR CCDS; CCDS3570.1; -.
DR RefSeq; NP_001317653.1; NM_001330724.1.
DR RefSeq; NP_003939.1; NM_003948.4.
DR RefSeq; XP_016864299.1; XM_017008810.1.
DR PDB; 4AAA; X-ray; 1.53 A; A=1-308.
DR PDB; 4BBM; X-ray; 2.00 A; A/B=1-308.
DR PDBsum; 4AAA; -.
DR PDBsum; 4BBM; -.
DR AlphaFoldDB; Q92772; -.
DR SMR; Q92772; -.
DR BioGRID; 114479; 11.
DR IntAct; Q92772; 66.
DR STRING; 9606.ENSP00000412365; -.
DR BindingDB; Q92772; -.
DR ChEMBL; CHEMBL5728; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q92772; -.
DR iPTMnet; Q92772; -.
DR PhosphoSitePlus; Q92772; -.
DR BioMuta; CDKL2; -.
DR DMDM; 74762639; -.
DR EPD; Q92772; -.
DR MassIVE; Q92772; -.
DR MaxQB; Q92772; -.
DR PaxDb; Q92772; -.
DR PeptideAtlas; Q92772; -.
DR PRIDE; Q92772; -.
DR Antibodypedia; 24675; 250 antibodies from 28 providers.
DR DNASU; 8999; -.
DR Ensembl; ENST00000429927.6; ENSP00000412365.2; ENSG00000138769.11.
DR GeneID; 8999; -.
DR KEGG; hsa:8999; -.
DR UCSC; uc003hiq.4; human.
DR CTD; 8999; -.
DR DisGeNET; 8999; -.
DR GeneCards; CDKL2; -.
DR HGNC; HGNC:1782; CDKL2.
DR HPA; ENSG00000138769; Tissue enhanced (brain, choroid plexus, retina, testis).
DR MIM; 603442; gene.
DR neXtProt; NX_Q92772; -.
DR OpenTargets; ENSG00000138769; -.
DR PharmGKB; PA26318; -.
DR VEuPathDB; HostDB:ENSG00000138769; -.
DR eggNOG; KOG0593; Eukaryota.
DR GeneTree; ENSGT00940000160368; -.
DR HOGENOM; CLU_000288_136_0_1; -.
DR InParanoid; Q92772; -.
DR PhylomeDB; Q92772; -.
DR TreeFam; TF101031; -.
DR PathwayCommons; Q92772; -.
DR SignaLink; Q92772; -.
DR BioGRID-ORCS; 8999; 18 hits in 1101 CRISPR screens.
DR ChiTaRS; CDKL2; human.
DR GeneWiki; CDKL2; -.
DR GenomeRNAi; 8999; -.
DR Pharos; Q92772; Tchem.
DR PRO; PR:Q92772; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q92772; protein.
DR Bgee; ENSG00000138769; Expressed in endothelial cell and 145 other tissues.
DR ExpressionAtlas; Q92772; baseline and differential.
DR Genevisible; Q92772; HS.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0007548; P:sex differentiation; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Nucleus;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..493
FT /note="Cyclin-dependent kinase-like 2"
FT /id="PRO_0000085814"
FT DOMAIN 4..287
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 363..384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 45..51
FT /note="[NKR]KIAxRE"
FT ACT_SITE 126
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 10..18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 33
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VARIANT 77
FT /note="Y -> S (in dbSNP:rs35921414)"
FT /id="VAR_053928"
FT VARIANT 98
FT /note="L -> I (in an ovarian papillary serous
FT adenocarcinoma sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041987"
FT VARIANT 132
FT /note="I -> T (in dbSNP:rs17000707)"
FT /id="VAR_053929"
FT VARIANT 149
FT /note="R -> Q (in an ovarian mucinous carcinoma sample;
FT somatic mutation; dbSNP:rs755711267)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041988"
FT VARIANT 197
FT /note="M -> T (in dbSNP:rs56343717)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041989"
FT VARIANT 411
FT /note="A -> V (in dbSNP:rs56231363)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041990"
FT HELIX 1..3
FT /evidence="ECO:0007829|PDB:4AAA"
FT STRAND 4..9
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 10..13
FT /evidence="ECO:0007829|PDB:4AAA"
FT STRAND 16..23
FT /evidence="ECO:0007829|PDB:4AAA"
FT TURN 24..26
FT /evidence="ECO:0007829|PDB:4AAA"
FT STRAND 29..37
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 42..57
FT /evidence="ECO:0007829|PDB:4AAA"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:4AAA"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:4AAA"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 87..93
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 100..119
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:4AAA"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:4AAA"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 147..150
FT /evidence="ECO:0007829|PDB:4BBM"
FT HELIX 154..163
FT /evidence="ECO:0007829|PDB:4BBM"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:4BBM"
FT HELIX 170..173
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 182..197
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 207..218
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 223..231
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 249..252
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 258..267
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 278..283
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 285..288
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:4AAA"
FT HELIX 292..301
FT /evidence="ECO:0007829|PDB:4AAA"
SQ SEQUENCE 493 AA; 56019 MW; 5CC20A91CBF89EFE CRC64;
MEKYENLGLV GEGSYGMVMK CRNKDTGRIV AIKKFLESDD DKMVKKIAMR EIKLLKQLRH
ENLVNLLEVC KKKKRWYLVF EFVDHTILDD LELFPNGLDY QVVQKYLFQI INGIGFCHSH
NIIHRDIKPE NILVSQSGVV KLCDFGFART LAAPGEVYTD YVATRWYRAP ELLVGDVKYG
KAVDVWAIGC LVTEMFMGEP LFPGDSDIDQ LYHIMMCLGN LIPRHQELFN KNPVFAGVRL
PEIKEREPLE RRYPKLSEVV IDLAKKCLHI DPDKRPFCAE LLHHDFFQMD GFAERFSQEL
QLKVQKDARN VSLSKKSQNR KKEKEKDDSL VEERKTLVVQ DTNADPKIKD YKLFKIKGSK
IDGEKAEKGN RASNASCLHD SRTSHNKIVP STSLKDCSNV SVDHTRNPSV AIPPLTHNLS
AVAPSINSGM GTETIPIQGY RVDEKTKKCS IPFVKPNRHS PSGIYNINVT TLVSGPPLSD
DSGADLPQME HQH
