KCC4_RAT
ID KCC4_RAT Reviewed; 474 AA.
AC P13234; A1A5L5; Q63892;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 3.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type IV;
DE Short=CaMK IV;
DE EC=2.7.11.17;
DE AltName: Full=CaM kinase-GR;
DE AltName: Full=Calspermin;
GN Name=Camk4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA]
RP OF 437-474, PARTIAL PROTEIN SEQUENCE, AND ALTERNATIVE SPLICING.
RX PubMed=1648230; DOI=10.1073/pnas.88.13.5784;
RA Ohmstede C.-A., Bland M.M., Merrill B.M., Sahyoun N.;
RT "Relationship of genes encoding Ca2+/calmodulin-dependent protein kinase Gr
RT and calspermin: a gene within a gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:5784-5788(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=1649385; DOI=10.1128/mcb.11.8.3960-3971.1991;
RA Means A.R., Cruzalegui F., Lemagueresse B., Needleman D.S., Slaughter G.R.,
RA Ono T.;
RT "A novel Ca2+/calmodulin-dependent protein kinase and a male germ cell-
RT specific calmodulin-binding protein are derived from the same gene.";
RL Mol. Cell. Biol. 11:3960-3971(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8412563; DOI=10.1016/0169-328x(93)90029-o;
RA Sakagami H., Kondo H.;
RT "Cloning and sequencing of a gene encoding the beta polypeptide of
RT Ca2+/calmodulin-dependent protein kinase IV and its expression confined to
RT the mature cerebellar granule cells.";
RL Brain Res. Mol. Brain Res. 19:215-218(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7493991; DOI=10.1074/jbc.270.49.29507;
RA Sun Z., Means R.L., LeMagueresse B., Means A.R.;
RT "Organization and analysis of the complete rat calmodulin-dependent protein
RT kinase IV gene.";
RL J. Biol. Chem. 270:29507-29514(1995).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 250-474 (ISOFORM 1).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=2538431; DOI=10.1016/s0021-9258(18)83630-4;
RA Ohmstede C.-A., Jenson K.F., Sahyoun N.;
RT "Ca2+/calmodulin-dependent protein kinase enriched in cerebellar granule
RT cells. Identification of a novel neuronal calmodulin-dependent protein
RT kinase.";
RL J. Biol. Chem. 264:5866-5875(1989).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 306-474 (ISOFORM 2), AND PROTEIN SEQUENCE OF
RP 335-361.
RC STRAIN=Sprague-Dawley;
RX PubMed=2914893; DOI=10.1016/s0021-9258(18)94144-x;
RA Ono T., Slaughter G.R., Cook R.G., Means A.R.;
RT "Molecular cloning sequence and distribution of rat calspermin, a high
RT affinity calmodulin-binding protein.";
RL J. Biol. Chem. 264:2081-2087(1989).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF CREB1.
RX PubMed=1646483; DOI=10.1126/science.1646483;
RA Sheng M., Thompson M.A., Greenberg M.E.;
RT "CREB: a Ca(2+)-regulated transcription factor phosphorylated by
RT calmodulin-dependent kinases.";
RL Science 252:1427-1430(1991).
RN [9]
RP ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS OF 305-HIS--THR-308 AND
RP 316-PHE-ASN-317.
RX PubMed=7961813; DOI=10.1016/s0021-9258(19)61953-8;
RA Tokumitsu H., Brickey D.A., Glod J., Hidaka H., Sikela J., Soderling T.R.;
RT "Activation mechanisms for Ca2+/calmodulin-dependent protein kinase IV.
RT Identification of a brain CaM-kinase IV kinase.";
RL J. Biol. Chem. 269:28640-28647(1994).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF CREB1, AND SUBCELLULAR LOCATION.
RX PubMed=8065343; DOI=10.1128/mcb.14.9.6107-6116.1994;
RA Matthews R.P., Guthrie C.R., Wailes L.M., Zhao X., Means A.R.,
RA McKnight G.S.;
RT "Calcium/calmodulin-dependent protein kinase types II and IV differentially
RT regulate CREB-dependent gene expression.";
RL Mol. Cell. Biol. 14:6107-6116(1994).
RN [11]
RP ACTIVITY REGULATION, AND PHOSPHORYLATION.
RX PubMed=7592527; DOI=10.1093/oxfordjournals.jbchem.a124764;
RA Okuno S., Kitani T., Fujisawa H.;
RT "Full activation of brain calmodulin-dependent protein kinase IV requires
RT phosphorylation of the amino-terminal serine-rich region by calmodulin-
RT dependent protein kinase IV kinase.";
RL J. Biochem. 117:686-690(1995).
RN [12]
RP ACTIVITY REGULATION, PHOSPHORYLATION AT THR-196, AND MUTAGENESIS OF
RP THR-196.
RX PubMed=7615569; DOI=10.1074/jbc.270.29.17616;
RA Selbert M.A., Anderson K.A., Huang Q.H., Goldstein E.G., Means A.R.,
RA Edelman A.M.;
RT "Phosphorylation and activation of Ca(2+)-calmodulin-dependent protein
RT kinase IV by Ca(2+)-calmodulin-dependent protein kinase Ia kinase.
RT Phosphorylation of threonine 196 is essential for activation.";
RL J. Biol. Chem. 270:17616-17621(1995).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF ATF1 AND CREB1.
RX PubMed=8621702; DOI=10.1074/jbc.271.6.3066;
RA Sun P., Lou L., Maurer R.A.;
RT "Regulation of activating transcription factor-1 and the cAMP response
RT element-binding protein by Ca2+/calmodulin-dependent protein kinases type
RT I, II, and IV.";
RL J. Biol. Chem. 271:3066-3073(1996).
RN [14]
RP ACTIVITY REGULATION, PHOSPHORYLATION AT SER-332, AND MUTAGENESIS OF
RP SER-332.
RX PubMed=8636117; DOI=10.1074/jbc.271.12.6903;
RA Watanabe S., Okuno S., Kitani T., Fujisawa H.;
RT "Inactivation of calmodulin-dependent protein kinase IV by
RT autophosphorylation of serine 332 within the putative calmodulin-binding
RT domain.";
RL J. Biol. Chem. 271:6903-6910(1996).
RN [15]
RP PHOSPHORYLATION BY CAMKK1 AND CAMKK2.
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 [16]
RP PHOSPHORYLATION BY CAMKK2.
RX PubMed=9822657; DOI=10.1074/jbc.273.48.31880;
RA Anderson K.A., Means R.L., Huang Q.-H., Kemp B.E., Goldstein E.G.,
RA Selbert M.A., Edelman A.M., Fremeau R.T., Means A.R.;
RT "Components of a calmodulin-dependent protein kinase cascade. Molecular
RT cloning, functional characterization and cellular localization of
RT Ca2+/calmodulin-dependent protein kinase kinase beta.";
RL J. Biol. Chem. 273:31880-31889(1998).
RN [17]
RP INTERACTION WITH SERINE/THREONINE PROTEIN PHOSPHATASE 2A, AND
RP DEPHOSPHORYLATION.
RX PubMed=9596578; DOI=10.1126/science.280.5367.1258;
RA Westphal R.S., Anderson K.A., Means A.R., Wadzinski B.E.;
RT "A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and
RT protein phosphatase 2A.";
RL Science 280:1258-1261(1998).
RN [18]
RP INTERACTION WITH CAMKK1.
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 [19]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-71; THR-196 AND GLU-207.
RX PubMed=14701808; DOI=10.1074/jbc.m312613200;
RA Lemrow S.M., Anderson K.A., Joseph J.D., Ribar T.J., Noeldner P.K.,
RA Means A.R.;
RT "Catalytic activity is required for calcium/calmodulin-dependent protein
RT kinase IV to enter the nucleus.";
RL J. Biol. Chem. 279:11664-11671(2004).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-337; SER-437 AND SER-443, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: [Isoform 1]: Calcium/calmodulin-dependent protein kinase that
CC operates in the calcium-triggered CaMKK-CaMK4 signaling cascade and
CC regulates, mainly by phosphorylation, the activity of several
CC transcription activators, such as CREB1, MEF2D, JUN and RORA, which
CC play pivotal roles in immune response, inflammation, and memory
CC consolidation. In the thymus, regulates the CD4(+)/CD8(+) double
CC positive thymocytes selection threshold during T-cell ontogeny. In CD4
CC memory T-cells, is required to link T-cell antigen receptor (TCR)
CC signaling to the production of IL2, IFNG and IL4 (through the
CC regulation of CREB and MEF2). Regulates the differentiation and
CC survival phases of osteoclasts and dendritic cells (DCs). Mediates DCs
CC survival by linking TLR4 and the regulation of temporal expression of
CC BCL2. Phosphorylates the transcription activator CREB1 on 'Ser-133' in
CC hippocampal neuron nuclei and contribute to memory consolidation and
CC long term potentiation (LTP) in the hippocampus. Can activate the MAP
CC kinases MAPK1/ERK2, MAPK8/JNK1 and MAPK14/p38 and stimulate
CC transcription through the phosphorylation of ELK1 and ATF2. Can also
CC phosphorylate in vitro CREBBP, PRM2, MEF2A and STMN1/OP18 (By
CC similarity). {ECO:0000250}.
CC -!- FUNCTION: [Isoform 2]: Heat-stable, acidic, calmodulin-binding protein.
CC {ECO:0000269|PubMed:1646483, ECO:0000269|PubMed:8065343,
CC ECO:0000269|PubMed:8621702}.
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 -!- 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;
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin. Binding of
CC calmodulin results in conformational change that relieves intrasteric
CC autoinhibition and allows phosphorylation of Thr-196 within the
CC activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-196 results
CC in a 10-20-fold increase in total activity to generate
CC Ca(2+)/calmodulin-independent activity. Autophosphorylation of the N-
CC terminus Ser-11 and Ser-12 is required for full activation. Inactivated
CC by protein phosphatase 2A (PPP2CA/PPP2CB) which dephosphorylates Thr-
CC 196, thereby terminating autonomous activity and helping to maintain
CC the enzyme in its autoinhibited state (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Interacts with protein phosphatase 2A
CC (PPP2CA/PPP2CB); the interaction is mutually exclusive with binding to
CC Ca(2+)/calmodulin. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Localized in hippocampal
CC neuron nuclei. In spermatids, associated with chromatin and nuclear
CC matrix. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Calcium-calmodulin-dependent protein kinase type IV,
CC Beta;
CC IsoId=P13234-1; Sequence=Displayed;
CC Name=2; Synonyms=Calspermin, Testis-specific;
CC IsoId=P13234-2; Sequence=VSP_004789;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in brain and isoform 2 is
CC testis specific.
CC -!- DOMAIN: The autoinhibitory domain overlaps with the calmodulin binding
CC region and interacts in the inactive folded state with the catalytic
CC domain as a pseudosubstrate. {ECO:0000250}.
CC -!- PTM: Phosphorylated by CaMKK1 and CaMKK2 on Thr-196. Dephosphorylated
CC by protein phosphatase 2A. Autophosphorylated on Ser-11 and Ser-12 (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Glycosylation at Ser-185 modulates the phosphorylation of CaMK4 at
CC Thr-196 and negatively regulates its activity toward CREB1 in basal
CC conditions and during early inomycin stimulation. {ECO:0000250}.
CC -!- PTM: The N-terminus of calspermin is blocked.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB28372.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M63334; AAA40865.1; -; mRNA.
DR EMBL; M74488; AAA40845.1; -; Genomic_DNA.
DR EMBL; M64757; AAA40856.1; -; mRNA.
DR EMBL; M64757; AAA40857.1; -; mRNA.
DR EMBL; S65840; AAB28372.1; ALT_INIT; mRNA.
DR EMBL; BC128706; AAI28707.1; -; mRNA.
DR EMBL; J04600; AAA41867.1; -; mRNA.
DR EMBL; J04446; AAA40990.1; -; mRNA.
DR PIR; A41103; TVRTC4.
DR PIR; I52637; I52637.
DR RefSeq; NP_036859.2; NM_012727.3. [P13234-1]
DR RefSeq; XP_006254585.1; XM_006254523.3. [P13234-1]
DR RefSeq; XP_017456340.1; XM_017600851.1. [P13234-1]
DR AlphaFoldDB; P13234; -.
DR SMR; P13234; -.
DR BioGRID; 247127; 2.
DR STRING; 10116.ENSRNOP00000027771; -.
DR GlyGen; P13234; 7 sites.
DR iPTMnet; P13234; -.
DR PhosphoSitePlus; P13234; -.
DR PaxDb; P13234; -.
DR PRIDE; P13234; -.
DR Ensembl; ENSRNOT00000027771; ENSRNOP00000027771; ENSRNOG00000020478. [P13234-1]
DR GeneID; 25050; -.
DR KEGG; rno:25050; -.
DR UCSC; RGD:2264; rat. [P13234-1]
DR CTD; 814; -.
DR RGD; 2264; Camk4.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000160006; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; P13234; -.
DR OMA; TKMVPEA; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; P13234; -.
DR TreeFam; TF351230; -.
DR BRENDA; 2.7.11.17; 5301.
DR Reactome; R-RNO-111932; CaMK IV-mediated phosphorylation of CREB.
DR Reactome; R-RNO-442729; CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde.
DR PRO; PR:P13234; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000020478; Expressed in testis and 13 other tissues.
DR Genevisible; P13234; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0001650; C:fibrillar center; IEA:Ensembl.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IDA:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007616; P:long-term memory; ISS:UniProtKB.
DR GO; GO:0043011; P:myeloid dendritic cell differentiation; ISS:UniProtKB.
DR GO; GO:0007270; P:neuron-neuron synaptic transmission; ISO:RGD.
DR GO; GO:0006913; P:nucleocytoplasmic transport; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0099527; P:postsynapse to nucleus signaling pathway; ISO:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
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 Adaptive immunity; Alternative promoter usage; Alternative splicing;
KW ATP-binding; Calcium; Calmodulin-binding; Cytoplasm;
KW Direct protein sequencing; Glycoprotein; Immunity; Inflammatory response;
KW Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..474
FT /note="Calcium/calmodulin-dependent protein kinase type IV"
FT /id="PRO_0000086108"
FT DOMAIN 42..296
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 297..336
FT /note="Autoinhibitory domain"
FT REGION 302..319
FT /note="PP2A-binding"
FT /evidence="ECO:0000250"
FT REGION 318..337
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
FT REGION 336..474
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..356
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 357..396
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 397..417
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 418..449
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 160
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 48..56
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 71
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 11
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 12
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q16566"
FT MOD_RES 196
FT /note="Phosphothreonine; by CaMKK1 and CaMKK2"
FT /evidence="ECO:0000250|UniProtKB:Q16566"
FT MOD_RES 332
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8636117"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 437
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 443
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 53
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250"
FT CARBOHYD 54
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 133
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 185
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 340
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 341
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 352
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..305
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1649385,
FT ECO:0000303|PubMed:2914893"
FT /id="VSP_004789"
FT MUTAGEN 71
FT /note="K->M: Loss of kinase activity; confers cytoplasmic
FT localization."
FT /evidence="ECO:0000269|PubMed:14701808"
FT MUTAGEN 196
FT /note="T->A: Loss of kinase activity; confers nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:14701808,
FT ECO:0000269|PubMed:7615569"
FT MUTAGEN 207
FT /note="E->K: Loss of kinase activity; confers nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:14701808"
FT MUTAGEN 305..308
FT /note="HMDT->DEDD: Increases Ca(2+)/calmodulin-independent
FT activity."
FT /evidence="ECO:0000269|PubMed:7961813"
FT MUTAGEN 316..317
FT /note="FN->DD: Increases Ca(2+)/calmodulin-independent
FT activity."
FT /evidence="ECO:0000269|PubMed:7961813"
FT MUTAGEN 332
FT /note="S->A: No decrease in Ca(2+)/calmodulin-dependent
FT activity after activation by CaMKKs."
FT /evidence="ECO:0000269|PubMed:8636117"
FT CONFLICT 142..143
FT /note="KQ -> NE (in Ref. 1; AAA40845)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="M -> I (in Ref. 1; AAA40845/AAA40865 and 6;
FT AAA41867)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 474 AA; 53151 MW; E7B20E942419EB89 CRC64;
MLKVTVPSCP SSPCSSVTSS TENLVPDYWI DGSKRDPLSD FFEVESELGR GATSIVYRCK
QKGTQKPYAL KVLKKTVDKK IVRTEIGVLL RLSHPNIIKL KEIFETPTEI SLVLELVTGG
ELFDRIVEKG YYSERDAADA VKQILEAVAY LHENGIVHRD LKPENLLYAT PAPDAPLKIA
DFGLSKIVEH QVLMKTVCGT PGYCAPEILR GCAYGPEVDM WSVGIITYIL LCGFEPFYDE
RGDQFMFRRI LNCEYYFISP WWDEVSLNAK DLVKKLIVLD PKKRLTTFQA LQHPWVTGKA
ANFVHMDTAQ KKLQEFNARR KLKAAVKAVV ASSRLGSASS SHTNIQESNK ASSEAQPAQD
GKDKTDPLEN KMQAGDHEAA KAAADETMKL QSEEVEEEEG VKEEEEEEEE EEETSRMVPQ
EPEDRLETDD QEMKRNSEET LKSVEEEMDP KAEEEAAAVG LGVPPQQDAI LPEY
