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 24-JAN-2024, entry version 175. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 70. DR IntAct; Q92772; 66. DR STRING; 9606.ENSP00000306340; -. 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 CPTAC; non-CPTAC-3026; -. DR CPTAC; non-CPTAC-3027; -. DR EPD; Q92772; -. DR MassIVE; Q92772; -. DR MaxQB; Q92772; -. DR PaxDb; 9606-ENSP00000412365; -. DR PeptideAtlas; Q92772; -. DR Antibodypedia; 24675; 286 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 AGR; HGNC:1782; -. DR CTD; 8999; -. DR DisGeNET; 8999; -. DR GeneCards; CDKL2; -. DR HGNC; HGNC:1782; CDKL2. DR HPA; ENSG00000138769; Tissue enhanced (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 OrthoDB; 244018at2759; -. DR PhylomeDB; Q92772; -. DR TreeFam; TF101031; -. DR PathwayCommons; Q92772; -. DR SignaLink; Q92772; -. DR BioGRID-ORCS; 8999; 18 hits in 1177 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 147 other cell types or tissues. DR ExpressionAtlas; Q92772; baseline and differential. 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; IEA:UniProtKB-EC. DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0007548; P:sex differentiation; TAS:ProtInc. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd07846; STKc_CDKL2_3; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24056; CELL DIVISION PROTEIN KINASE; 1. DR PANTHER; PTHR24056:SF241; CYCLIN-DEPENDENT KINASE-LIKE 2; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q92772; HS. 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 //