CDKL4_HUMAN
ID CDKL4_HUMAN Reviewed; 379 AA.
AC Q5MAI5; Q2NME9;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 09-JUL-2014, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Cyclin-dependent kinase-like 4;
DE EC=2.7.11.22;
GN Name=CDKL4;
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] (ISOFORMS 1 AND 2).
RA Wang P.Z., Wang F., Wang X., Wu J.;
RT "Molecular cloning and characterization of human cyclin-dependent kinase-
RT like 4.";
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP VARIANTS [LARGE SCALE ANALYSIS] PRO-38; HIS-53; CYS-228; TYR-288 AND
RP CYS-307.
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:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5MAI5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5MAI5-2; Sequence=VSP_055220;
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; AY845084; AAW30008.1; -; mRNA.
DR EMBL; AY847283; AAW31760.1; -; mRNA.
DR EMBL; AC079615; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092672; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS33184.1; -. [Q5MAI5-2]
DR CCDS; CCDS86834.1; -. [Q5MAI5-1]
DR RefSeq; NP_001009565.1; NM_001009565.2. [Q5MAI5-2]
DR RefSeq; NP_001333840.1; NM_001346911.1. [Q5MAI5-1]
DR RefSeq; XP_011531117.1; XM_011532815.2. [Q5MAI5-1]
DR AlphaFoldDB; Q5MAI5; -.
DR SMR; Q5MAI5; -.
DR BioGRID; 131301; 14.
DR IntAct; Q5MAI5; 8.
DR STRING; 9606.ENSP00000368080; -.
DR BindingDB; Q5MAI5; -.
DR ChEMBL; CHEMBL4523326; -.
DR iPTMnet; Q5MAI5; -.
DR PhosphoSitePlus; Q5MAI5; -.
DR BioMuta; CDKL4; -.
DR DMDM; 74762208; -.
DR MassIVE; Q5MAI5; -.
DR PaxDb; Q5MAI5; -.
DR PeptideAtlas; Q5MAI5; -.
DR PRIDE; Q5MAI5; -.
DR ProteomicsDB; 61426; -.
DR ProteomicsDB; 63572; -. [Q5MAI5-1]
DR Antibodypedia; 29610; 194 antibodies from 25 providers.
DR DNASU; 344387; -.
DR Ensembl; ENST00000378803.6; ENSP00000368080.1; ENSG00000205111.9. [Q5MAI5-2]
DR Ensembl; ENST00000395035.4; ENSP00000378476.3; ENSG00000205111.9. [Q5MAI5-1]
DR GeneID; 344387; -.
DR KEGG; hsa:344387; -.
DR UCSC; uc002rrm.3; human. [Q5MAI5-1]
DR CTD; 344387; -.
DR DisGeNET; 344387; -.
DR GeneCards; CDKL4; -.
DR HGNC; HGNC:19287; CDKL4.
DR HPA; ENSG00000205111; Tissue enhanced (choroid plexus, testis).
DR neXtProt; NX_Q5MAI5; -.
DR PharmGKB; PA134892546; -.
DR VEuPathDB; HostDB:ENSG00000205111; -.
DR eggNOG; KOG0593; Eukaryota.
DR GeneTree; ENSGT00940000161857; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; Q5MAI5; -.
DR OMA; LNFCHTH; -.
DR OrthoDB; 398098at2759; -.
DR PhylomeDB; Q5MAI5; -.
DR TreeFam; TF101031; -.
DR PathwayCommons; Q5MAI5; -.
DR SignaLink; Q5MAI5; -.
DR BioGRID-ORCS; 344387; 7 hits in 1101 CRISPR screens.
DR ChiTaRS; CDKL4; human.
DR GenomeRNAi; 344387; -.
DR Pharos; Q5MAI5; Tdark.
DR PRO; PR:Q5MAI5; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q5MAI5; protein.
DR Bgee; ENSG00000205111; Expressed in adrenal tissue and 92 other tissues.
DR ExpressionAtlas; Q5MAI5; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
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; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..379
FT /note="Cyclin-dependent kinase-like 4"
FT /id="PRO_0000085824"
FT DOMAIN 4..286
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
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 VAR_SEQ 310..377
FT /note="QAPKSAFPRLFLKTKICQVQRNETQTSGNQILPNGPILQNSMVTVMTNINSA
FT VYQVTVLHLLSENFEV -> VLPL (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_055220"
FT VARIANT 38
FT /note="S -> P (in dbSNP:rs35947084)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041992"
FT VARIANT 53
FT /note="R -> H (in dbSNP:rs35454041)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041993"
FT VARIANT 118
FT /note="H -> Y (in dbSNP:rs6731369)"
FT /id="VAR_053930"
FT VARIANT 228
FT /note="F -> C (in dbSNP:rs56353587)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041994"
FT VARIANT 288
FT /note="S -> Y (in dbSNP:rs34819676)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041995"
FT VARIANT 307
FT /note="R -> C (in dbSNP:rs56330730)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041996"
SQ SEQUENCE 379 AA; 43384 MW; 95B4783DA12B0C4A CRC64;
MEKYEKLAKT GEGSYGVVFK CRNKTSGQVV AVKKFVESED DPVVKKIALR EIRMLKQLKH
PNLVNLIEVF RRKRKMHLVF EYCDHTLLNE LERNPNGVAD GVIKSVLWQT LQALNFCHIH
NCIHRDIKPE NILITKQGII KICDFGFAQI LIPGDAYTDY VATRWYRAPE LLVGDTQYGS
SVDIWAIGCV FAELLTGQPL WPGKSDVDQL YLIIRTLGKL IPRHQSIFKS NGFFHGISIP
EPEDMETLEE KFSDVHPVAL NFMKGCLKMN PDDRLTCSQL LESSYFDSFQ EAQIKRKARN
EGRNRRRQQQ APKSAFPRLF LKTKICQVQR NETQTSGNQI LPNGPILQNS MVTVMTNINS
AVYQVTVLHL LSENFEVKS
