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   24-JAN-2024, entry version 145.
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.ENSP00000378476; -.
DR   BindingDB; Q5MAI5; -.
DR   ChEMBL; CHEMBL4523326; -.
DR   iPTMnet; Q5MAI5; -.
DR   PhosphoSitePlus; Q5MAI5; -.
DR   BioMuta; CDKL4; -.
DR   DMDM; 74762208; -.
DR   MassIVE; Q5MAI5; -.
DR   PaxDb; 9606-ENSP00000368080; -.
DR   PeptideAtlas; Q5MAI5; -.
DR   ProteomicsDB; 61426; -.
DR   ProteomicsDB; 63572; -. [Q5MAI5-1]
DR   Antibodypedia; 29610; 214 antibodies from 25 providers.
DR   DNASU; 344387; -.
DR   Ensembl; ENST00000378803.6; ENSP00000368080.1; ENSG00000205111.10. [Q5MAI5-2]
DR   Ensembl; ENST00000395035.4; ENSP00000378476.3; ENSG00000205111.10. [Q5MAI5-1]
DR   GeneID; 344387; -.
DR   KEGG; hsa:344387; -.
DR   UCSC; uc002rrm.3; human. [Q5MAI5-1]
DR   AGR; HGNC:19287; -.
DR   CTD; 344387; -.
DR   DisGeNET; 344387; -.
DR   GeneCards; CDKL4; -.
DR   HGNC; HGNC:19287; CDKL4.
DR   HPA; ENSG00000205111; Tissue enhanced (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; HNTPTPD; -.
DR   OrthoDB; 244018at2759; -.
DR   PhylomeDB; Q5MAI5; -.
DR   TreeFam; TF101031; -.
DR   PathwayCommons; Q5MAI5; -.
DR   SignaLink; Q5MAI5; -.
DR   BioGRID-ORCS; 344387; 7 hits in 1178 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 male germ line stem cell (sensu Vertebrata) in testis and 93 other cell types or 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; IEA:UniProtKB-EC.
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   CDD; cd07847; STKc_CDKL1_4; 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; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR24056; CELL DIVISION PROTEIN KINASE; 1.
DR   PANTHER; PTHR24056:SF120; CYCLIN-DEPENDENT KINASE-LIKE 4; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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
//