CDKL3_HUMAN
ID CDKL3_HUMAN Reviewed; 592 AA.
AC Q8IVW4; D3DQA0; D3DQA1; Q9P114;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Cyclin-dependent kinase-like 3 {ECO:0000305};
DE EC=2.7.11.22;
DE AltName: Full=Serine/threonine-protein kinase NKIAMRE;
GN Name=CDKL3 {ECO:0000312|HGNC:HGNC:15483};
GN Synonyms=NKIAMRE {ECO:0000303|Ref.1};
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] (ISOFORM 2).
RC TISSUE=Fetal heart;
RA Midmer M., Haq R., Zanke B.W.;
RT "NKIAMRE a novel kinase deleted in human leukemia.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [4] {ECO:0007744|PDB:3ZDU}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1-324 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 [5]
RP VARIANT [LARGE SCALE ANALYSIS] THR-394.
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 -!- INTERACTION:
CC Q8IVW4; Q8WYN0: ATG4A; NbExp=3; IntAct=EBI-3919850, EBI-3044060;
CC Q8IVW4; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-3919850, EBI-3867333;
CC Q8IVW4; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-3919850, EBI-11988027;
CC Q8IVW4; Q9NQM4: DNAAF6; NbExp=3; IntAct=EBI-3919850, EBI-10239299;
CC Q8IVW4; P51114-2: FXR1; NbExp=3; IntAct=EBI-3919850, EBI-11022345;
CC Q8IVW4; P51116: FXR2; NbExp=7; IntAct=EBI-3919850, EBI-740459;
CC Q8IVW4; Q08379: GOLGA2; NbExp=3; IntAct=EBI-3919850, EBI-618309;
CC Q8IVW4; Q13422-7: IKZF1; NbExp=3; IntAct=EBI-3919850, EBI-11522367;
CC Q8IVW4; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-3919850, EBI-2556193;
CC Q8IVW4; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-3919850, EBI-749265;
CC Q8IVW4; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-3919850, EBI-10172052;
CC Q8IVW4; Q9P2M1: LRP2BP; NbExp=3; IntAct=EBI-3919850, EBI-18273118;
CC Q8IVW4; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-3919850, EBI-741037;
CC Q8IVW4; P23508: MCC; NbExp=3; IntAct=EBI-3919850, EBI-307531;
CC Q8IVW4; Q99750: MDFI; NbExp=3; IntAct=EBI-3919850, EBI-724076;
CC Q8IVW4; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-3919850, EBI-742948;
CC Q8IVW4; Q5JR59-3: MTUS2; NbExp=4; IntAct=EBI-3919850, EBI-11522433;
CC Q8IVW4; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-3919850, EBI-79165;
CC Q8IVW4; Q8WWB5: PIH1D2; NbExp=3; IntAct=EBI-3919850, EBI-10232538;
CC Q8IVW4; Q15276: RABEP1; NbExp=3; IntAct=EBI-3919850, EBI-447043;
CC Q8IVW4; P14373: TRIM27; NbExp=6; IntAct=EBI-3919850, EBI-719493;
CC Q8IVW4; O94972: TRIM37; NbExp=3; IntAct=EBI-3919850, EBI-741602;
CC Q8IVW4; O43829: ZBTB14; NbExp=3; IntAct=EBI-3919850, EBI-10176632;
CC Q8IVW4; O43298: ZBTB43; NbExp=3; IntAct=EBI-3919850, EBI-740718;
CC Q8IVW4; Q96BR9: ZBTB8A; NbExp=6; IntAct=EBI-3919850, EBI-742740;
CC Q8IVW4; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-3919850, EBI-527853;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IVW4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IVW4-2; Sequence=VSP_016148;
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; AF130372; AAF36509.1; -; mRNA.
DR EMBL; CH471062; EAW62263.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62264.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62265.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62266.1; -; Genomic_DNA.
DR EMBL; BC041799; AAH41799.1; -; mRNA.
DR CCDS; CCDS47264.1; -. [Q8IVW4-1]
DR CCDS; CCDS47265.1; -. [Q8IVW4-2]
DR RefSeq; NP_001107047.1; NM_001113575.1. [Q8IVW4-1]
DR RefSeq; NP_001287782.1; NM_001300853.1.
DR RefSeq; NP_057592.2; NM_016508.3. [Q8IVW4-2]
DR RefSeq; XP_016865024.1; XM_017009535.1.
DR PDB; 3ZDU; X-ray; 2.20 A; A=1-324.
DR PDBsum; 3ZDU; -.
DR AlphaFoldDB; Q8IVW4; -.
DR SMR; Q8IVW4; -.
DR BioGRID; 119419; 56.
DR IntAct; Q8IVW4; 61.
DR STRING; 9606.ENSP00000265334; -.
DR BindingDB; Q8IVW4; -.
DR ChEMBL; CHEMBL1163117; -.
DR DrugCentral; Q8IVW4; -.
DR iPTMnet; Q8IVW4; -.
DR PhosphoSitePlus; Q8IVW4; -.
DR BioMuta; CDKL3; -.
DR DMDM; 74762479; -.
DR jPOST; Q8IVW4; -.
DR MassIVE; Q8IVW4; -.
DR MaxQB; Q8IVW4; -.
DR PaxDb; Q8IVW4; -.
DR PeptideAtlas; Q8IVW4; -.
DR PRIDE; Q8IVW4; -.
DR ProteomicsDB; 70783; -. [Q8IVW4-1]
DR ProteomicsDB; 70784; -. [Q8IVW4-2]
DR Antibodypedia; 2061; 204 antibodies from 29 providers.
DR DNASU; 51265; -.
DR Ensembl; ENST00000265334.9; ENSP00000265334.4; ENSG00000006837.12. [Q8IVW4-1]
DR Ensembl; ENST00000523832.1; ENSP00000430496.1; ENSG00000006837.12. [Q8IVW4-2]
DR GeneID; 51265; -.
DR KEGG; hsa:51265; -.
DR MANE-Select; ENST00000265334.9; ENSP00000265334.4; NM_001113575.2; NP_001107047.1.
DR UCSC; uc003kzf.5; human. [Q8IVW4-1]
DR CTD; 51265; -.
DR DisGeNET; 51265; -.
DR GeneCards; CDKL3; -.
DR HGNC; HGNC:15483; CDKL3.
DR HPA; ENSG00000006837; Tissue enhanced (testis).
DR MIM; 608459; gene.
DR neXtProt; NX_Q8IVW4; -.
DR OpenTargets; ENSG00000006837; -.
DR PharmGKB; PA26319; -.
DR VEuPathDB; HostDB:ENSG00000006837; -.
DR eggNOG; KOG0593; Eukaryota.
DR GeneTree; ENSGT00940000161317; -.
DR HOGENOM; CLU_000288_136_1_1; -.
DR InParanoid; Q8IVW4; -.
DR OMA; GMEVKQV; -.
DR OrthoDB; 398098at2759; -.
DR PhylomeDB; Q8IVW4; -.
DR TreeFam; TF101031; -.
DR PathwayCommons; Q8IVW4; -.
DR SignaLink; Q8IVW4; -.
DR BioGRID-ORCS; 51265; 14 hits in 1102 CRISPR screens.
DR ChiTaRS; CDKL3; human.
DR GenomeRNAi; 51265; -.
DR Pharos; Q8IVW4; Tchem.
DR PRO; PR:Q8IVW4; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q8IVW4; protein.
DR Bgee; ENSG00000006837; Expressed in sperm and 114 other tissues.
DR ExpressionAtlas; Q8IVW4; baseline and differential.
DR Genevisible; Q8IVW4; HS.
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:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0097484; P:dendrite extension; IBA:GO_Central.
DR GO; GO:0030517; P:negative regulation of axon extension; IBA:GO_Central.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IBA:GO_Central.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
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; 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; Alternative splicing; ATP-binding; Cytoplasm; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..592
FT /note="Cyclin-dependent kinase-like 3"
FT /id="PRO_0000085820"
FT DOMAIN 4..286
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 368..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 459..485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 44..50
FT /note="[NKR]KIAxRE"
FT COMPBIAS 368..382
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 466..484
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 125
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 MOD_RES 158
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9JM01"
FT MOD_RES 160
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9JM01"
FT VAR_SEQ 456..592
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_016148"
FT VARIANT 394
FT /note="M -> T (in dbSNP:rs35687772)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041991"
FT CONFLICT 345
FT /note="K -> E (in Ref. 1; AAF36509)"
FT /evidence="ECO:0000305"
FT STRAND 4..13
FT /evidence="ECO:0007829|PDB:3ZDU"
FT STRAND 16..23
FT /evidence="ECO:0007829|PDB:3ZDU"
FT TURN 24..26
FT /evidence="ECO:0007829|PDB:3ZDU"
FT STRAND 29..34
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 45..56
FT /evidence="ECO:0007829|PDB:3ZDU"
FT STRAND 65..69
FT /evidence="ECO:0007829|PDB:3ZDU"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:3ZDU"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:3ZDU"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 86..92
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 99..118
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:3ZDU"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:3ZDU"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 161..164
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 169..172
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 181..196
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 206..216
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 222..230
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 257..266
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 277..281
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 284..287
FT /evidence="ECO:0007829|PDB:3ZDU"
FT HELIX 291..308
FT /evidence="ECO:0007829|PDB:3ZDU"
SQ SEQUENCE 592 AA; 67514 MW; 2B1AF08906EB7697 CRC64;
MEMYETLGKV GEGSYGTVMK CKHKNTGQIV AIKIFYERPE QSVNKIAMRE IKFLKQFHHE
NLVNLIEVFR QKKKIHLVFE FIDHTVLDEL QHYCHGLESK RLRKYLFQIL RAIDYLHSNN
IIHRDIKPEN ILVSQSGITK LCDFGFARTL AAPGDIYTDY VATRWYRAPE LVLKDTSYGK
PVDIWALGCM IIEMATGNPY LPSSSDLDLL HKIVLKVGNL SPHLQNIFSK SPIFAGVVLP
QVQHPKNARK KYPKLNGLLA DIVHACLQID PADRISSSDL LHHEYFTRDG FIEKFMPELK
AKLLQEAKVN SLIKPKESSK ENELRKDERK TVYTNTLLSS SVLGKEIEKE KKPKEIKVRV
IKVKGGRGDI SEPKKKEYEG GLGQQDANEN VHPMSPDTKL VTIEPPNPIN PSTNCNGLKE
NPHCGGSVTM PPINLTNSNL MAANLSSNLF HPSVRLTERA KKRRTSSQSI GQVMPNSRQE
DPGPIQSQME KGIFNERTGH SDQMANENKR KLNFSRSDRK EFHFPELPVT IQSKDTKGME
VKQIKMLKRE SKKTESSKIP TLLNVDQNQE KQEGGDGHCE GKNLKRNRFF FW
