KKCC_CAEEL
ID KKCC_CAEEL Reviewed; 541 AA.
AC Q3Y416; G4RS26; G5EDZ4;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase kinase {ECO:0000303|PubMed:10336483};
DE Short=CaM-KK {ECO:0000303|PubMed:10336483};
DE Short=CaM-kinase kinase {ECO:0000250|UniProtKB:P97756};
DE EC=2.7.11.17 {ECO:0000269|PubMed:10336483, ECO:0000269|PubMed:10428833, ECO:0000269|PubMed:12231504};
GN Name=ckk-1 {ECO:0000312|WormBase:C05H8.1b};
GN ORFNames=C05H8.1 {ECO:0000312|WormBase:C05H8.1b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:BAA77824.4}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, AND ACTIVITY REGULATION.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:BAA77824.4};
RX PubMed=10336483; DOI=10.1074/jbc.274.22.15803;
RA Tokumitsu H., Takahashi N., Eto K., Yano S., Soderling T.R.,
RA Muramatsu M.-A.;
RT "Substrate recognition by Ca2+/Calmodulin-dependent protein kinase kinase.
RT Role of the arg-pro-rich insert domain.";
RL J. Biol. Chem. 274:15803-15810(1999).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000312|EMBL:BAA77824.4}
RP IDENTIFICATION.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:BAA77824.4};
RX PubMed=8631893; DOI=10.1074/jbc.271.18.10806;
RA Edelman A.M., Mitchelhill K.I., Selbert M.A., Anderson K.A., Hook S.S.,
RA Stapleton D., Goldstein E.G., Means A.R., Kemp B.E.;
RT "Multiple Ca(2+)-calmodulin-dependent protein kinase kinases from rat
RT brain. Purification, regulation by Ca(2+)-calmodulin, and partial amino
RT acid sequence.";
RL J. Biol. Chem. 271:10806-10810(1996).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=10428833; DOI=10.1074/jbc.274.32.22556;
RA Eto K., Takahashi N., Kimura Y., Masuho Y., Arai K., Muramatsu M.A.,
RA Tokumitsu H.;
RT "Ca(2+)/Calmodulin-dependent protein kinase cascade in Caenorhabditis
RT elegans. Implication in transcriptional activation.";
RL J. Biol. Chem. 274:22556-22562(1999).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND TISSUE SPECIFICITY.
RX PubMed=12231504; DOI=10.1093/embo-reports/kvf191;
RA Kimura Y., Corcoran E.E., Eto K., Gengyo-Ando K., Muramatsu M.A.,
RA Kobayashi R., Freedman J.H., Mitani S., Hagiwara M., Means A.R.,
RA Tokumitsu H.;
RT "A CaMK cascade activates CRE-mediated transcription in neurons of
RT Caenorhabditis elegans.";
RL EMBO Rep. 3:962-966(2002).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase which
CC phosphorylates cmk-1 (PubMed:10336483, PubMed:10428833,
CC PubMed:12231504). Component of a calcium-triggered signaling cascade
CC involved in CRE-mediated transcriptional activation, probably through
CC cmk-1-mediated crh-1/CREB phosphorylation (PubMed:12231504).
CC {ECO:0000269|PubMed:10336483, ECO:0000269|PubMed:10428833,
CC ECO:0000269|PubMed:12231504}.
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=2.7.11.17;
CC Evidence={ECO:0000269|PubMed:10336483, ECO:0000269|PubMed:10428833,
CC ECO:0000269|PubMed:12231504};
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=2.7.11.17; Evidence={ECO:0000269|PubMed:10336483,
CC ECO:0000269|PubMed:10428833, ECO:0000269|PubMed:12231504};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10336483, ECO:0000269|PubMed:10428833,
CC ECO:0000269|PubMed:12231504};
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin (PubMed:10336483,
CC PubMed:10428833). Binding of calmodulin may relieve intrasteric
CC autoinhibition (By similarity). {ECO:0000250|UniProtKB:P97756,
CC ECO:0000269|PubMed:10336483, ECO:0000269|PubMed:10428833}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:C05H8.1b};
CC IsoId=Q3Y416-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:C05H8.1a};
CC IsoId=Q3Y416-2; Sequence=VSP_058065;
CC -!- TISSUE SPECIFICITY: Expressed in head and tail neurons and vulval
CC muscles. {ECO:0000269|PubMed:12231504}.
CC -!- DOMAIN: The autoinhibitory domain overlaps with the calmodulin binding
CC region and may be involved in intrasteric autoinhibition.
CC {ECO:0000250|UniProtKB:P97756}.
CC -!- DOMAIN: The RP domain (arginine/proline-rich) is involved in the
CC recognition of substrates such as cmk-1.
CC {ECO:0000250|UniProtKB:P97756}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AB016838; BAA77824.4; -; mRNA.
DR EMBL; BX284603; CCD63131.1; -; Genomic_DNA.
DR EMBL; BX284603; CCD63132.1; -; Genomic_DNA.
DR PIR; T37317; T37317.
DR RefSeq; NP_001021152.1; NM_001025981.2. [Q3Y416-2]
DR RefSeq; NP_001021153.1; NM_001025982.3. [Q3Y416-1]
DR PDB; 1IQ5; X-ray; 1.80 A; B=440-466.
DR PDBsum; 1IQ5; -.
DR AlphaFoldDB; Q3Y416; -.
DR SMR; Q3Y416; -.
DR STRING; 6239.C05H8.1b; -.
DR EPD; Q3Y416; -.
DR PaxDb; Q3Y416; -.
DR EnsemblMetazoa; C05H8.1a.1; C05H8.1a.1; WBGene00000518. [Q3Y416-2]
DR EnsemblMetazoa; C05H8.1b.1; C05H8.1b.1; WBGene00000518. [Q3Y416-1]
DR GeneID; 182278; -.
DR KEGG; cel:CELE_C05H8.1; -.
DR UCSC; C05H8.1b; c. elegans. [Q3Y416-1]
DR CTD; 182278; -.
DR WormBase; C05H8.1a; CE33594; WBGene00000518; ckk-1. [Q3Y416-2]
DR WormBase; C05H8.1b; CE37082; WBGene00000518; ckk-1. [Q3Y416-1]
DR eggNOG; KOG0585; Eukaryota.
DR GeneTree; ENSGT00940000154890; -.
DR InParanoid; Q3Y416; -.
DR OMA; YCFLFGH; -.
DR OrthoDB; 1044255at2759; -.
DR PhylomeDB; Q3Y416; -.
DR Reactome; R-CEL-111932; CaMK IV-mediated phosphorylation of CREB.
DR Reactome; R-CEL-442729; CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde.
DR Reactome; R-CEL-9619229; Activation of RAC1 downstream of NMDARs.
DR PRO; PR:Q3Y416; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00000518; Expressed in larva and 3 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IDA:WormBase.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IDA:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0032147; P:activation of protein kinase activity; IBA:GO_Central.
DR GO; GO:0019722; P:calcium-mediated signaling; TAS:WormBase.
DR GO; GO:0061762; P:CAMKK-AMPK signaling cascade; IBA:GO_Central.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; IDA:WormBase.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:WormBase.
DR GO; GO:0007165; P:signal transduction; 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; Calmodulin-binding;
KW Kinase; Magnesium; Metal-binding; Nucleotide-binding; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..541
FT /note="Calcium/calmodulin-dependent protein kinase kinase"
FT /evidence="ECO:0000305"
FT /id="PRO_0000435388"
FT DOMAIN 130..411
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 83..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 169..190
FT /note="RP domain"
FT /evidence="ECO:0000250|UniProtKB:P97756"
FT REGION 437..442
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250|UniProtKB:P97756"
FT REGION 440..465
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:P97756"
FT REGION 462..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..106
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 276
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 136..144
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 159
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..114
FT /note="MKNTFARYSLTIPSIPENVISHLRQWNEWMVGDTSDDSPGPSSTVSTMTTTG
FT TVDRRSLLSAASMVRQQSDTTGVRRLVRARAVQEDDEAGPHSSNNLAATMSPNLSRPTR
FT YVK -> MYTFQ (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_058065"
FT HELIX 446..458
FT /evidence="ECO:0007829|PDB:1IQ5"
FT STRAND 460..462
FT /evidence="ECO:0007829|PDB:1IQ5"
SQ SEQUENCE 541 AA; 60804 MW; 865ADD21AD2DD4B7 CRC64;
MKNTFARYSL TIPSIPENVI SHLRQWNEWM VGDTSDDSPG PSSTVSTMTT TGTVDRRSLL
SAASMVRQQS DTTGVRRLVR ARAVQEDDEA GPHSSNNLAA TMSPNLSRPT RYVKSVSQQR
SESYIQLNQY RLMEEIGQGS YGIVKLAYNE EDKNLYALKV LDKMKLLKNF ACFRQPPPRR
NKENAAPSVL RNPLQLVQKE IAILKKLSHP NVVKLVEVLD DPNDNYLYMV FEFVEKGSIL
EIPTDKPLDE DTAWSYFRDT LCGLEYLHYQ KIVHRDIKPS NLLLSDIGQV KIADFGVSCE
FEGIDAFLSG TAGTPAFMAP EALTEGANHF YSGRAQDIWS LGITLYAFVI GTVPFVDNYI
IALHKKIKND PIVFPEAPIL SEALQDIILG MLKKDPGHRL MLHEVKVHTW VTRDGTVPMS
SEQENCHLVT VTEEEIENCV RVIPRLDTLI LVKAMGHRKR FGNPFRNKLS AQSSIRDRRK
SSSVKDPTYV PPPNSPPATS NNNLNSTKVD RPEIKCIEMN LSGLTLKVDE AMQSKVESAR
Q
