KCC2D_CAEEL
ID KCC2D_CAEEL Reviewed; 720 AA.
AC O62305; A5JYT0; A7LPH2; B3GWC8; O62304; Q21431; Q7JLT8; Q9NG91; Q9NH55;
AC Q9NH56; Q9NH57; Q9NH58; Q9NH59; Q9NH60; Q9U6Q0;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type II {ECO:0000303|PubMed:10647014};
DE Short=CaM kinase II {ECO:0000303|PubMed:10647014};
DE EC=2.7.11.17;
DE AltName: Full=Uncoordinated protein 43;
GN Name=unc-43; ORFNames=K11E8.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAD53949.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D), TISSUE SPECIFICITY, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF GLU-108.
RX PubMed=10647014; DOI=10.1038/46072;
RA Reiner D.J., Newton E.M., Tian H., Thomas J.H.;
RT "Diverse behavioural defects caused by mutations in Caenorhabditis elegans
RT unc-43 CaM kinase II.";
RL Nature 402:199-203(1999).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAF63321.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS E; F; G; H; I; K AND L).
RA Guarin E., Hernandez M.C., Gomez M., Schulman H., Nef P.;
RT "Biochemical properties of calcium/calmodulin-pependent protein kinase II
RT (UNC-43) Isoforms in Caernohabditis elegans.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:CAO82047.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:CAO82047.1};
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 [4]
RP FUNCTION.
RX PubMed=10571181; DOI=10.1016/s0092-8674(00)81525-1;
RA Troemel E.R., Sagasti A., Bargmann C.I.;
RT "Lateral signaling mediated by axon contact and calcium entry regulates
RT asymmetric odorant receptor expression in C. elegans.";
RL Cell 99:387-398(1999).
RN [5]
RP INTERACTION WITH NSY-1.
RX PubMed=11336672; DOI=10.1016/s0092-8674(01)00313-0;
RA Sagasti A., Hisamoto N., Hyodo J., Tanaka-Hino M., Matsumoto K.,
RA Bargmann C.I.;
RT "The CaMKII UNC-43 activates the MAPKKK NSY-1 to execute a lateral
RT signaling decision required for asymmetric olfactory neuron fates.";
RL Cell 105:221-232(2001).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12221132; DOI=10.1091/mbc.e02-01-0005;
RA Bandyopadhyay J., Lee J., Lee J., Lee J.I., Yu J.-R., Jee C., Cho J.-H.,
RA Jung S., Lee M.H., Zannoni S., Singson A., Kim D., Koo H.-S., Ahnn J.;
RT "Calcineurin, a calcium/calmodulin-dependent protein phosphatase, is
RT involved in movement, fertility, egg laying, and growth in Caenorhabditis
RT elegans.";
RL Mol. Biol. Cell 13:3281-3293(2002).
RN [7]
RP FUNCTION.
RX PubMed=15166144; DOI=10.1534/genetics.167.1.161;
RA Solomon A., Bandhakavi S., Jabbar S., Shah R., Beitel G.J., Morimoto R.I.;
RT "Caenorhabditis elegans OSR-1 regulates behavioral and physiological
RT responses to hyperosmotic environments.";
RL Genetics 167:161-170(2004).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16267094; DOI=10.1242/dev.02083;
RA Corrigan C., Subramanian R., Miller M.A.;
RT "Eph and NMDA receptors control Ca2+/calmodulin-dependent protein kinase II
RT activation during C. elegans oocyte meiotic maturation.";
RL Development 132:5225-5237(2005).
RN [9]
RP INTERACTION WITH TIR-1, AND SUBCELLULAR LOCATION.
RX PubMed=15625192; DOI=10.1101/gad.1276505;
RA Chuang C.-F., Bargmann C.I.;
RT "A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric
RT odorant receptor expression via ASK1 MAPKKK signaling.";
RL Genes Dev. 19:270-281(2005).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP PHE-97; GLU-108; LYS-147; ASP-236; HIS-280; ARG-281 AND THR-284.
RX PubMed=16079277; DOI=10.1242/jcs.02457;
RA Umemura T., Rapp P., Rongo C.;
RT "The role of regulatory domain interactions in UNC-43 CaMKII localization
RT and trafficking.";
RL J. Cell Sci. 118:3327-3338(2005).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17898212; DOI=10.1523/jneurosci.5634-06.2007;
RA Liu Q., Chen B., Ge Q., Wang Z.W.;
RT "Presynaptic Ca2+/calmodulin-dependent protein kinase II modulates
RT neurotransmitter release by activating BK channels at Caenorhabditis
RT elegans neuromuscular junction.";
RL J. Neurosci. 27:10404-10413(2007).
RN [12]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-170; SER-179 AND
RP ALA-665.
RX PubMed=17941711; DOI=10.1371/journal.pgen.0030156;
RA LeBoeuf B., Gruninger T.R., Garcia L.R.;
RT "Food deprivation attenuates seizures through CaMKII and EAG K+ channels.";
RL PLoS Genet. 3:1622-1632(2007).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17942636; DOI=10.1152/ajpcell.00303.2007;
RA Nehrke K., Denton J., Mowrey W.;
RT "Intestinal Ca2+ wave dynamics in freely moving C. elegans coordinate
RT execution of a rhythmic motor program.";
RL Am. J. Physiol. 294:C333-344(2008).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21771813; DOI=10.1242/dev.069740;
RA Chang C., Hsieh Y.W., Lesch B.J., Bargmann C.I., Chuang C.F.;
RT "Microtubule-based localization of a synaptic calcium-signaling complex is
RT required for left-right neuronal asymmetry in C. elegans.";
RL Development 138:3509-3518(2011).
RN [15]
RP FUNCTION, AND INTERACTION WITH EGL-2.
RX PubMed=21145946; DOI=10.1016/j.neuroscience.2010.12.002;
RA LeBoeuf B., Guo X., Garcia L.R.;
RT "The effects of transient starvation persist through direct interactions
RT between CaMKII and ether-a-go-go K+ channels in C. elegans males.";
RL Neuroscience 175:1-17(2011).
RN [16]
RP FUNCTION.
RX PubMed=22629462; DOI=10.1371/journal.pone.0037831;
RA Wani K.A., Catanese M., Normantowicz R., Herd M., Maher K.N., Chase D.L.;
RT "D1 dopamine receptor signaling is modulated by the R7 RGS protein EAT-16
RT and the R7 binding protein RSBP-1 in Caenoerhabditis elegans motor
RT neurons.";
RL PLoS ONE 7:E37831-E37831(2012).
RN [17]
RP FUNCTION, AND MUTAGENESIS OF GLU-108.
RX PubMed=23805378; DOI=10.7554/elife.00518;
RA Tao L., Xie Q., Ding Y.H., Li S.T., Peng S., Zhang Y.P., Tan D., Yuan Z.,
RA Dong M.Q.;
RT "CAMKII and Calcineurin regulate the lifespan of Caenorhabditis elegans
RT through the FOXO transcription factor DAF-16.";
RL Elife 2:E00518-E00518(2013).
RN [18]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=23325232; DOI=10.1523/jneurosci.2355-12.2013;
RA Qin Y., Zhang X., Zhang Y.;
RT "A neuronal signaling pathway of CaMKII and Gqalpha regulates experience-
RT dependent transcription of tph-1.";
RL J. Neurosci. 33:925-935(2013).
RN [19]
RP FUNCTION.
RX PubMed=23663262; DOI=10.1186/1749-8104-8-10;
RA Caylor R.C., Jin Y., Ackley B.D.;
RT "The Caenorhabditis elegans voltage-gated calcium channel subunits UNC-2
RT and UNC-36 and the calcium-dependent kinase UNC-43/CaMKII regulate
RT neuromuscular junction morphology.";
RL Neural Dev. 8:10-10(2013).
RN [20]
RP FUNCTION.
RX PubMed=23505381; DOI=10.1371/journal.pgen.1003324;
RA Xie Y., Moussaif M., Choi S., Xu L., Sze J.Y.;
RT "RFX transcription factor DAF-19 regulates 5-HT and innate immune responses
RT to pathogenic bacteria in Caenorhabditis elegans.";
RL PLoS Genet. 9:e1003324-e1003324(2013).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-343 OF ISOFORM I, ACTIVITY
RP REGULATION, PHOSPHORYLATION AT THR-284, AND MUTAGENESIS OF ASP-134.
RX PubMed=16325579; DOI=10.1016/j.cell.2005.10.029;
RA Rosenberg O.S., Deindl S., Sung R.J., Nairn A.C., Kuriyan J.;
RT "Structure of the autoinhibited kinase domain of CaMKII and SAXS analysis
RT of the holoenzyme.";
RL Cell 123:849-860(2005).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 340-482 OF ISOFORM D, AND SUBUNIT.
RX PubMed=16441656; DOI=10.1111/j.1742-4658.2005.05088.x;
RA Rosenberg O.S., Deindl S., Comolli L.R., Hoelz A., Downing K.H.,
RA Nairn A.C., Kuriyan J.;
RT "Oligomerization states of the association domain and the holoenyzme of
RT Ca2+/CaM kinase II.";
RL FEBS J. 273:682-694(2006).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 5-288 OF ISOFORM E, INTERACTION
RP WITH CALMODULIN, ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS OF LYS-41;
RP PHE-97; ILE-100; ASP-134; ILE-200 AND 278-ALA-ILE-279.
RX PubMed=20139983; DOI=10.1038/nsmb.1751;
RA Chao L.H., Pellicena P., Deindl S., Barclay L.A., Schulman H., Kuriyan J.;
RT "Intersubunit capture of regulatory segments is a component of cooperative
RT CaMKII activation.";
RL Nat. Struct. Mol. Biol. 17:264-272(2010).
CC -!- FUNCTION: Acts in the signaling of a variety of pathways and processes.
CC Phosphorylates 'Ser-319' of daf-16 in response to stress signals, such
CC as heat, starvation and oxidation, which plays a role in prolonging
CC lifespan. Required for viability under chronic osmotic stress in which
CC it acts downstream of osr-1. Has roles in locomotion, oocyte
CC maturation, brood size, egg laying, defecation, meiotic maturation and
CC neuronal cell fate specification. Required for the regulation of
CC synaptic density and neuromuscular junction morphology. Regulates the
CC synaptic trafficking of glr-1. Bidirectional modulator of
CC neurotransmitter release with negative modulatory effects mainly
CC mediated via slo-1 activation. Involved in activation of ADF neurons
CC and increased tph-1 transcription following exposure to pathogenic
CC bacteria which leads to learned olfactory aversion to the bacteria
CC (PubMed:23325232, PubMed:23505381). Implicated in the muscle regulation
CC of spicule protraction. In conjunction with egl-2 has a role in the
CC suppression of mating behavior under food deprivation to encourage
CC foraging. Involved in restricting str-2 expression to only one of the
CC two AWC neurons. May suppress the functional response to an internal
CC pacemaker, perhaps by modulating the activity of the IP3 receptor.
CC {ECO:0000269|PubMed:10571181, ECO:0000269|PubMed:12221132,
CC ECO:0000269|PubMed:15166144, ECO:0000269|PubMed:16079277,
CC ECO:0000269|PubMed:16267094, ECO:0000269|PubMed:17898212,
CC ECO:0000269|PubMed:17941711, ECO:0000269|PubMed:17942636,
CC ECO:0000269|PubMed:21145946, ECO:0000269|PubMed:21771813,
CC ECO:0000269|PubMed:22629462, ECO:0000269|PubMed:23325232,
CC ECO:0000269|PubMed:23505381, ECO:0000269|PubMed:23663262,
CC ECO:0000269|PubMed:23805378}.
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:16079277};
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:16079277};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:16079277};
CC -!- ACTIVITY REGULATION: Ca2(+)/calmodulin binding removes an
CC autoinhibitory regulatory segment located C-terminal to the kinase
CC domain. This releases the catalytic activity of the enzyme and makes
CC accessible a regulatory residue Thr-284. Phosphorylation of Thr-284 by
CC another kinase domain within the oligomeric holoenzyme keeps CaMKII
CC active in the absence of Ca(2+)/calmodulin by preventing the rebinding
CC of the regulatory segment to the kinase domain and by increasing the
CC affinity of calmodulin for the enzyme. Can respond to high-frequency
CC Ca(2+) pulses to become Ca(2+) independent.
CC {ECO:0000269|PubMed:16325579, ECO:0000269|PubMed:20139983}.
CC -!- SUBUNIT: Dodecamer. Subunits are tightly packed around a central ring-
CC shaped scaffold with extensive contacts between the regulatory segment
CC of one kinase and the catalytic domain of another enabling cooperative
CC activation of a subunit by the adjacent molecule (PubMed:16441656,
CC PubMed:20139983). Interacts with and phosphorylates daf-16; the
CC interaction promotes daf-16 nuclear localization. Interacts with egl-2
CC and tir-1 (PubMed:15625192, PubMed:21145946). Interacts with nsy-1
CC (PubMed:11336672). {ECO:0000269|PubMed:11336672,
CC ECO:0000269|PubMed:15625192, ECO:0000269|PubMed:16441656,
CC ECO:0000269|PubMed:20139983, ECO:0000269|PubMed:21145946}.
CC -!- INTERACTION:
CC O62305; P91409: syx-4; NbExp=3; IntAct=EBI-313095, EBI-326499;
CC O62305; O62305: unc-43; NbExp=5; IntAct=EBI-313095, EBI-313095;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16079277}. Cell
CC projection, axon {ECO:0000269|PubMed:15625192}. Perikaryon
CC {ECO:0000269|PubMed:15625192, ECO:0000269|PubMed:16079277}.
CC Note=Localizes at or near the Golgi apparatus (PubMed:16079277).
CC Localizes to post-synaptic regions and is enriched in punctate
CC structures in axons of AWC neurons where it co-localizes with tir-1.
CC Localization is regulated by tir-1 (PubMed:15625192).
CC {ECO:0000269|PubMed:15625192, ECO:0000269|PubMed:16079277}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=15;
CC Name=c {ECO:0000269|PubMed:9851916};
CC IsoId=O62305-1; Sequence=Displayed;
CC Name=a {ECO:0000269|PubMed:9851916};
CC IsoId=O62305-2; Sequence=VSP_039592, VSP_039608;
CC Name=b {ECO:0000269|PubMed:9851916};
CC IsoId=O62305-3; Sequence=VSP_039595, VSP_039596;
CC Name=d {ECO:0000269|PubMed:10647014, ECO:0000269|PubMed:9851916};
CC IsoId=O62305-4; Sequence=VSP_039597, VSP_039603, VSP_039611;
CC Name=e {ECO:0000269|PubMed:9851916, ECO:0000269|Ref.2}; Synonyms=C
CC {ECO:0000269|Ref.2};
CC IsoId=O62305-5; Sequence=VSP_039604, VSP_039605, VSP_039611;
CC Name=f {ECO:0000269|PubMed:9851916, ECO:0000269|Ref.2}; Synonyms=E
CC {ECO:0000269|Ref.2};
CC IsoId=O62305-6; Sequence=VSP_039598, VSP_039602;
CC Name=g {ECO:0000269|PubMed:9851916, ECO:0000269|Ref.2}; Synonyms=B
CC {ECO:0000269|Ref.2};
CC IsoId=O62305-7; Sequence=VSP_039597, VSP_039603;
CC Name=h {ECO:0000269|PubMed:9851916, ECO:0000269|Ref.2}; Synonyms=D
CC {ECO:0000269|Ref.2};
CC IsoId=O62305-8; Sequence=VSP_039604, VSP_039605;
CC Name=i {ECO:0000269|PubMed:9851916, ECO:0000269|Ref.2}; Synonyms=H
CC {ECO:0000269|Ref.2};
CC IsoId=O62305-9; Sequence=VSP_039597, VSP_039603, VSP_039612,
CC VSP_039613;
CC Name=k {ECO:0000269|PubMed:9851916, ECO:0000269|Ref.2}; Synonyms=F
CC {ECO:0000269|Ref.2};
CC IsoId=O62305-10; Sequence=VSP_039599, VSP_039601;
CC Name=l {ECO:0000269|PubMed:9851916, ECO:0000269|Ref.2}; Synonyms=G
CC {ECO:0000269|Ref.2};
CC IsoId=O62305-11; Sequence=VSP_039600, VSP_039601;
CC Name=m {ECO:0000269|PubMed:9851916};
CC IsoId=O62305-12; Sequence=VSP_039594, VSP_039606;
CC Name=n {ECO:0000269|PubMed:9851916};
CC IsoId=O62305-13; Sequence=VSP_039590, VSP_039610;
CC Name=o {ECO:0000269|PubMed:9851916};
CC IsoId=O62305-14; Sequence=VSP_039593, VSP_039607, VSP_039611;
CC Name=p {ECO:0000269|PubMed:9851916};
CC IsoId=O62305-15; Sequence=VSP_039591, VSP_039609;
CC -!- TISSUE SPECIFICITY: Expressed in the nervous system. Observed in the
CC ADF and AWC neurons. Position in AWC neurons is regulated by
CC microtubules. Localized to clusters in ventral cord neurites which
CC appear to be required for glr-1 trafficking. Also present in oocytes.
CC {ECO:0000269|PubMed:10647014, ECO:0000269|PubMed:16079277,
CC ECO:0000269|PubMed:16267094, ECO:0000269|PubMed:23325232}.
CC -!- DISRUPTION PHENOTYPE: Increased frequency of defecation, typified by a
CC weaker repetition of the defecation motor program, an echo, 10 s after
CC the primary motor program. Abnormal spicule protraction. Lack of tph-1
CC transcriptional up-regulation during learned olfactory aversion to
CC bacteria. Reduced brood size, body length and width. Lethargic
CC movement. A gain-of function mutation reduces locomotory activity,
CC alters excitation of three muscle types and lengthens the period of the
CC motor output of a behavioral clock. Both classes of mutation inhibit
CC neurotransmitter release. {ECO:0000269|PubMed:10647014,
CC ECO:0000269|PubMed:12221132, ECO:0000269|PubMed:17898212,
CC ECO:0000269|PubMed:17941711, ECO:0000269|PubMed:17942636,
CC ECO:0000269|PubMed:23325232}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000255}.
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DR EMBL; AF180735; AAD53949.1; -; mRNA.
DR EMBL; AF233262; AAF63320.1; -; mRNA.
DR EMBL; AF233263; AAF63321.1; -; mRNA.
DR EMBL; AF233264; AAF63322.1; -; mRNA.
DR EMBL; AF233265; AAF63323.1; -; mRNA.
DR EMBL; AF233266; AAF63324.1; -; mRNA.
DR EMBL; AF233267; AAF63325.1; -; mRNA.
DR EMBL; AF255956; AAF71543.1; -; mRNA.
DR EMBL; Z70279; CAA94242.3; -; Genomic_DNA.
DR EMBL; Z70279; CAA94243.3; -; Genomic_DNA.
DR EMBL; AL023841; CAA94243.3; JOINED; Genomic_DNA.
DR EMBL; Z70279; CAC42322.1; -; Genomic_DNA.
DR EMBL; AL023841; CAC42322.1; JOINED; Genomic_DNA.
DR EMBL; Z70279; CAC42323.1; -; Genomic_DNA.
DR EMBL; AL023841; CAC42323.1; JOINED; Genomic_DNA.
DR EMBL; Z70279; CAC42324.1; -; Genomic_DNA.
DR EMBL; AL023841; CAC42324.1; JOINED; Genomic_DNA.
DR EMBL; Z70279; CAC42325.1; -; Genomic_DNA.
DR EMBL; AL023841; CAC42325.1; JOINED; Genomic_DNA.
DR EMBL; Z70279; CAC42326.1; -; Genomic_DNA.
DR EMBL; AL023841; CAC42326.1; JOINED; Genomic_DNA.
DR EMBL; Z70279; CAC42327.1; -; Genomic_DNA.
DR EMBL; AL023841; CAC42327.1; JOINED; Genomic_DNA.
DR EMBL; Z70279; CAC42328.1; -; Genomic_DNA.
DR EMBL; AL023841; CAC42328.1; JOINED; Genomic_DNA.
DR EMBL; Z70279; CAC42329.1; -; Genomic_DNA.
DR EMBL; AL023841; CAC42329.1; JOINED; Genomic_DNA.
DR EMBL; Z70279; CAE46679.1; -; Genomic_DNA.
DR EMBL; Z70279; CAN86910.1; -; Genomic_DNA.
DR EMBL; Z70279; CAO82047.1; -; Genomic_DNA.
DR EMBL; Z70279; CAQ58116.1; -; Genomic_DNA.
DR PIR; B88809; B88809.
DR PIR; T23616; T23616.
DR RefSeq; NP_001023293.2; NM_001028122.4. [O62305-2]
DR RefSeq; NP_001023294.1; NM_001028123.3.
DR RefSeq; NP_001023296.1; NM_001028125.3.
DR RefSeq; NP_001023297.1; NM_001028126.3.
DR RefSeq; NP_001023298.1; NM_001028127.3. [O62305-6]
DR RefSeq; NP_001023299.1; NM_001028128.3.
DR RefSeq; NP_001023300.1; NM_001028129.3.
DR RefSeq; NP_001023301.1; NM_001028130.3.
DR RefSeq; NP_001023302.1; NM_001028131.3.
DR RefSeq; NP_001023303.1; NM_001028132.3.
DR RefSeq; NP_001023304.1; NM_001028133.4. [O62305-12]
DR RefSeq; NP_001122788.1; NM_001129316.2. [O62305-13]
DR RefSeq; NP_001122789.1; NM_001129317.2. [O62305-14]
DR RefSeq; NP_001129863.1; NM_001136391.2. [O62305-15]
DR PDB; 2BDW; X-ray; 1.80 A; A/B=1-298, A/B=514-543.
DR PDB; 2F86; X-ray; 2.64 A; B/D/F/H/J/L/N=585-720.
DR PDB; 3KK8; X-ray; 1.72 A; A=5-288.
DR PDB; 3KK9; X-ray; 3.21 A; A=6-287.
DR PDB; 3KL8; X-ray; 3.37 A; A/C/E/G/I=5-273.
DR PDBsum; 2BDW; -.
DR PDBsum; 2F86; -.
DR PDBsum; 3KK8; -.
DR PDBsum; 3KK9; -.
DR PDBsum; 3KL8; -.
DR AlphaFoldDB; O62305; -.
DR SMR; O62305; -.
DR BioGRID; 43023; 21.
DR DIP; DIP-25971N; -.
DR DIP; DIP-58986N; -.
DR IntAct; O62305; 10.
DR MINT; O62305; -.
DR iPTMnet; O62305; -.
DR EPD; O62305; -.
DR PeptideAtlas; O62305; -.
DR EnsemblMetazoa; K11E8.1a.1; K11E8.1a.1; WBGene00006779. [O62305-2]
DR EnsemblMetazoa; K11E8.1b.1; K11E8.1b.1; WBGene00006779. [O62305-3]
DR EnsemblMetazoa; K11E8.1b.2; K11E8.1b.2; WBGene00006779. [O62305-3]
DR EnsemblMetazoa; K11E8.1b.3; K11E8.1b.3; WBGene00006779. [O62305-3]
DR EnsemblMetazoa; K11E8.1d.1; K11E8.1d.1; WBGene00006779. [O62305-4]
DR EnsemblMetazoa; K11E8.1d.2; K11E8.1d.2; WBGene00006779. [O62305-4]
DR EnsemblMetazoa; K11E8.1e.1; K11E8.1e.1; WBGene00006779. [O62305-5]
DR EnsemblMetazoa; K11E8.1e.2; K11E8.1e.2; WBGene00006779. [O62305-5]
DR EnsemblMetazoa; K11E8.1f.1; K11E8.1f.1; WBGene00006779. [O62305-6]
DR EnsemblMetazoa; K11E8.1f.2; K11E8.1f.2; WBGene00006779. [O62305-6]
DR EnsemblMetazoa; K11E8.1g.1; K11E8.1g.1; WBGene00006779. [O62305-7]
DR EnsemblMetazoa; K11E8.1g.2; K11E8.1g.2; WBGene00006779. [O62305-7]
DR EnsemblMetazoa; K11E8.1h.1; K11E8.1h.1; WBGene00006779. [O62305-8]
DR EnsemblMetazoa; K11E8.1h.2; K11E8.1h.2; WBGene00006779. [O62305-8]
DR EnsemblMetazoa; K11E8.1i.1; K11E8.1i.1; WBGene00006779. [O62305-9]
DR EnsemblMetazoa; K11E8.1k.1; K11E8.1k.1; WBGene00006779. [O62305-10]
DR EnsemblMetazoa; K11E8.1l.1; K11E8.1l.1; WBGene00006779. [O62305-11]
DR EnsemblMetazoa; K11E8.1m.1; K11E8.1m.1; WBGene00006779. [O62305-12]
DR EnsemblMetazoa; K11E8.1n.1; K11E8.1n.1; WBGene00006779. [O62305-13]
DR EnsemblMetazoa; K11E8.1o.1; K11E8.1o.1; WBGene00006779. [O62305-14]
DR EnsemblMetazoa; K11E8.1p.1; K11E8.1p.1; WBGene00006779. [O62305-15]
DR GeneID; 177921; -.
DR UCSC; K11E8.1a.1; c. elegans.
DR CTD; 177921; -.
DR WormBase; K11E8.1a; CE42693; WBGene00006779; unc-43. [O62305-2]
DR WormBase; K11E8.1b; CE28052; WBGene00006779; unc-43. [O62305-3]
DR WormBase; K11E8.1d; CE28054; WBGene00006779; unc-43. [O62305-4]
DR WormBase; K11E8.1e; CE28055; WBGene00006779; unc-43. [O62305-5]
DR WormBase; K11E8.1f; CE28056; WBGene00006779; unc-43. [O62305-6]
DR WormBase; K11E8.1g; CE28057; WBGene00006779; unc-43. [O62305-7]
DR WormBase; K11E8.1h; CE28058; WBGene00006779; unc-43. [O62305-8]
DR WormBase; K11E8.1i; CE28059; WBGene00006779; unc-43. [O62305-9]
DR WormBase; K11E8.1k; CE28060; WBGene00006779; unc-43. [O62305-10]
DR WormBase; K11E8.1l; CE28061; WBGene00006779; unc-43. [O62305-11]
DR WormBase; K11E8.1m; CE35590; WBGene00006779; unc-43. [O62305-12]
DR WormBase; K11E8.1n; CE40979; WBGene00006779; unc-43. [O62305-13]
DR WormBase; K11E8.1o; CE41430; WBGene00006779; unc-43. [O62305-14]
DR WormBase; K11E8.1p; CE42670; WBGene00006779; unc-43. [O62305-15]
DR eggNOG; KOG0033; Eukaryota.
DR GeneTree; ENSGT00940000159769; -.
DR InParanoid; O62305; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; O62305; -.
DR BRENDA; 2.7.11.17; 1045.
DR Reactome; R-CEL-3371571; HSF1-dependent transactivation.
DR Reactome; R-CEL-4086398; Ca2+ pathway.
DR Reactome; R-CEL-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-CEL-5578775; Ion homeostasis.
DR Reactome; R-CEL-936837; Ion transport by P-type ATPases.
DR SignaLink; O62305; -.
DR EvolutionaryTrace; O62305; -.
DR PRO; PR:O62305; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00006779; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR ExpressionAtlas; O62305; baseline and differential.
DR GO; GO:1904115; C:axon cytoplasm; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IDA:WormBase.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IDA:WormBase.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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:0044325; F:transmembrane transporter binding; IPI:WormBase.
DR GO; GO:0000165; P:MAPK cascade; IMP:WormBase.
DR GO; GO:0072375; P:medium-term memory; IMP:WormBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:WormBase.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:WormBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:WormBase.
DR GO; GO:0042427; P:serotonin biosynthetic process; IMP:UniProtKB.
DR InterPro; IPR013543; Ca/CaM-dep_prot_kinase-assoc.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR032710; NTF2-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; PF08332; CaMKII_AD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54427; SSF54427; 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 Cell projection; Cytoplasm; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Stress response; Transferase.
FT CHAIN 1..720
FT /note="Calcium/calmodulin-dependent protein kinase type II"
FT /id="PRO_0000396645"
FT DOMAIN 12..269
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 317..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 504..586
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..536
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 537..553
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 563..586
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 134
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT BINDING 18..26
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:20139983"
FT MOD_RES 284
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16325579"
FT VAR_SEQ 1..505
FT /note="Missing (in isoform n)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_039590"
FT VAR_SEQ 1..504
FT /note="Missing (in isoform p)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_039591"
FT VAR_SEQ 1..490
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_039592"
FT VAR_SEQ 1..416
FT /note="Missing (in isoform o)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_039593"
FT VAR_SEQ 1..414
FT /note="Missing (in isoform m)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_039594"
FT VAR_SEQ 113..138
FT /note="HCIQQILESIAYCHSNGIVHRDLKPE -> CCIMQILDGVNYCHQRGIVHRD
FT MKV (in isoform b)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_039595"
FT VAR_SEQ 139..720
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_039596"
FT VAR_SEQ 299..314
FT /note="AAISAVKMVTRMSGVL -> GAILTTMIATRNLSNL (in isoform d,
FT isoform g and isoform i)"
FT /evidence="ECO:0000303|PubMed:10647014,
FT ECO:0000303|PubMed:9851916, ECO:0000303|Ref.2"
FT /id="VSP_039597"
FT VAR_SEQ 299..313
FT /note="AAISAVKMVTRMSGV -> GAILTTMIATRNLSS (in isoform f)"
FT /evidence="ECO:0000303|PubMed:9851916, ECO:0000303|Ref.2"
FT /id="VSP_039598"
FT VAR_SEQ 299..302
FT /note="AAIS -> VVDS (in isoform k)"
FT /evidence="ECO:0000303|PubMed:9851916, ECO:0000303|Ref.2"
FT /id="VSP_039599"
FT VAR_SEQ 299..302
FT /note="AAIS -> VAIC (in isoform l)"
FT /evidence="ECO:0000303|PubMed:9851916, ECO:0000303|Ref.2"
FT /id="VSP_039600"
FT VAR_SEQ 303..720
FT /note="Missing (in isoform k and isoform l)"
FT /evidence="ECO:0000303|PubMed:9851916, ECO:0000303|Ref.2"
FT /id="VSP_039601"
FT VAR_SEQ 314..515
FT /note="Missing (in isoform f)"
FT /evidence="ECO:0000303|PubMed:9851916, ECO:0000303|Ref.2"
FT /id="VSP_039602"
FT VAR_SEQ 315..514
FT /note="Missing (in isoform d, isoform g and isoform i)"
FT /evidence="ECO:0000303|PubMed:10647014,
FT ECO:0000303|PubMed:9851916, ECO:0000303|Ref.2"
FT /id="VSP_039603"
FT VAR_SEQ 350..364
FT /note="VYPNVLLFNPQKFPR -> GAILTTMIATRNLSN (in isoform e and
FT isoform h)"
FT /evidence="ECO:0000303|PubMed:10647014,
FT ECO:0000303|PubMed:9851916, ECO:0000303|Ref.2"
FT /id="VSP_039604"
FT VAR_SEQ 365..513
FT /note="Missing (in isoform e and isoform h)"
FT /evidence="ECO:0000303|PubMed:10647014,
FT ECO:0000303|PubMed:9851916, ECO:0000303|Ref.2"
FT /id="VSP_039605"
FT VAR_SEQ 415..512
FT /note="PYHCFTNKMSNYERAAPSSHGSSTTKKIANAIADLVIRRSSPSIRRKTEADV
FT HNSNRNRKVSAPANLQHALVPVIDVVVATGALASSSVDNLSASTSS -> MDGLLARLK
FT LGSKRKKKTSSSVKRSSRPESARQAPRDTTGSLYSNLTASSSTVSACSAPEIVVLKKEQ
FT VVLAVDHKDQVDEQKKKNEQVVKKPEKLEVEAD (in isoform m)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_039606"
FT VAR_SEQ 417..514
FT /note="HCFTNKMSNYERAAPSSHGSSTTKKIANAIADLVIRRSSPSIRRKTEADVHN
FT SNRNRKVSAPANLQHALVPVIDVVVATGALASSSVDNLSASTSSDL -> MDGLLARLK
FT LGSKRKKKTSSSVKRSSRPESARQAPRDTTGSLYSNLTASSSTVSACSAPEIVVLKKEQ
FT VVLAVDHKDQVDEQKKKNEQVVKKPEKLEVEAD (in isoform o)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_039607"
FT VAR_SEQ 491..515
FT /note="VVVATGALASSSVDNLSASTSSDLG -> MKNIEYWQVLLNKIFATYKIKMK
FT QC (in isoform a)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_039608"
FT VAR_SEQ 505..513
FT /note="NLSASTSSD -> MIATRNLSN (in isoform p)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_039609"
FT VAR_SEQ 506..515
FT /note="LSASTSSDLG -> MNFLRFSGKC (in isoform n)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_039610"
FT VAR_SEQ 548..585
FT /note="Missing (in isoform d, isoform e and isoform o)"
FT /evidence="ECO:0000303|PubMed:10647014,
FT ECO:0000303|PubMed:9851916, ECO:0000303|Ref.2"
FT /id="VSP_039611"
FT VAR_SEQ 549..550
FT /note="GG -> NE (in isoform i)"
FT /evidence="ECO:0000303|PubMed:9851916, ECO:0000303|Ref.2"
FT /id="VSP_039612"
FT VAR_SEQ 551..720
FT /note="Missing (in isoform i)"
FT /evidence="ECO:0000303|PubMed:9851916, ECO:0000303|Ref.2"
FT /id="VSP_039613"
FT MUTAGEN 41
FT /note="K->M: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:20139983"
FT MUTAGEN 97
FT /note="F->E: Loss of cooperative activation of adjacent
FT holoenzyme subunits."
FT /evidence="ECO:0000269|PubMed:16079277,
FT ECO:0000269|PubMed:20139983"
FT MUTAGEN 97
FT /note="F->K: Increase in calcium independent kinase
FT activity, no effect on translocation to the neurite."
FT /evidence="ECO:0000269|PubMed:16079277,
FT ECO:0000269|PubMed:20139983"
FT MUTAGEN 100
FT /note="I->K: Loss of cooperative activation of adjacent
FT holoenzyme subunits."
FT /evidence="ECO:0000269|PubMed:20139983"
FT MUTAGEN 108
FT /note="E->K: In n498gf; slight increase in calcium
FT independent kinase activity, no effect on translocation to
FT the neurite. Nuclear translocation of daf-16 resulting in
FT lifespan extension."
FT /evidence="ECO:0000269|PubMed:10647014,
FT ECO:0000269|PubMed:16079277, ECO:0000269|PubMed:23805378"
FT MUTAGEN 134
FT /note="D->N: Loss of autoinhibition and increase in binding
FT of Ca2+/calmodulin."
FT /evidence="ECO:0000269|PubMed:16325579,
FT ECO:0000269|PubMed:20139983"
FT MUTAGEN 147
FT /note="K->E: Slight increase in calcium independent kinase
FT activity, no effect on translocation to the neurite."
FT /evidence="ECO:0000269|PubMed:16079277"
FT MUTAGEN 170
FT /note="G->E: In sy574; abnormal spicule protraction; when
FT associated with V-665."
FT /evidence="ECO:0000269|PubMed:17941711"
FT MUTAGEN 179
FT /note="S->L: In e408; males display locomotor and muscle
FT seizure defects and egg laying defects."
FT /evidence="ECO:0000269|PubMed:17941711"
FT MUTAGEN 200
FT /note="I->K: Loss of cooperative activation of adjacent
FT holoenzyme subunits."
FT /evidence="ECO:0000269|PubMed:20139983"
FT MUTAGEN 236
FT /note="D->R: Increase in calcium independent kinase
FT activity, loss of translocation to neurites and glr-1
FT trafficking."
FT /evidence="ECO:0000269|PubMed:16079277"
FT MUTAGEN 278..279
FT /note="AI->DD: Decrease in binding of Ca2+/calmodulin."
FT /evidence="ECO:0000269|PubMed:20139983"
FT MUTAGEN 280
FT /note="H->K: Increase in calcium independent kinase
FT activity, no effect on translocation to the neurite."
FT /evidence="ECO:0000269|PubMed:16079277"
FT MUTAGEN 281
FT /note="R->E: Increase in calcium independent kinase
FT activity and translocation to an unlocalized pool in the
FT neurite. Small decrease in glr-1 trafficking."
FT /evidence="ECO:0000269|PubMed:16079277"
FT MUTAGEN 284
FT /note="T->D: Constitutively activate kinase activity,
FT increase in translocation to the neurites."
FT /evidence="ECO:0000269|PubMed:16079277"
FT MUTAGEN 665
FT /note="A->V: In sy574; abnormal spicule protraction; when
FT associated with E-170."
FT /evidence="ECO:0000269|PubMed:17941711"
FT TURN 7..11
FT /evidence="ECO:0007829|PDB:3KK8"
FT STRAND 12..21
FT /evidence="ECO:0007829|PDB:3KK8"
FT STRAND 24..31
FT /evidence="ECO:0007829|PDB:3KK8"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:3KK8"
FT STRAND 37..44
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 50..65
FT /evidence="ECO:0007829|PDB:3KK8"
FT STRAND 74..79
FT /evidence="ECO:0007829|PDB:3KK8"
FT STRAND 81..88
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 96..103
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 108..127
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:3KK8"
FT STRAND 140..146
FT /evidence="ECO:0007829|PDB:3KK8"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 180..183
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 191..206
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 216..225
FT /evidence="ECO:0007829|PDB:3KK8"
FT TURN 232..237
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 240..249
FT /evidence="ECO:0007829|PDB:3KK8"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 260..263
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 267..270
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:3KK8"
FT HELIX 282..309
FT /evidence="ECO:0007829|PDB:2BDW"
FT HELIX 585..604
FT /evidence="ECO:0007829|PDB:2F86"
FT HELIX 607..613
FT /evidence="ECO:0007829|PDB:2F86"
FT STRAND 614..621
FT /evidence="ECO:0007829|PDB:2F86"
FT HELIX 623..625
FT /evidence="ECO:0007829|PDB:2F86"
FT HELIX 634..637
FT /evidence="ECO:0007829|PDB:2F86"
FT STRAND 640..642
FT /evidence="ECO:0007829|PDB:2F86"
FT STRAND 649..660
FT /evidence="ECO:0007829|PDB:2F86"
FT TURN 661..663
FT /evidence="ECO:0007829|PDB:2F86"
FT STRAND 664..676
FT /evidence="ECO:0007829|PDB:2F86"
FT STRAND 682..696
FT /evidence="ECO:0007829|PDB:2F86"
FT STRAND 699..708
FT /evidence="ECO:0007829|PDB:2F86"
SQ SEQUENCE 720 AA; 79927 MW; 3231366FFF81A695 CRC64;
MMNASTKFSD NYDVKEELGK GAFSVVRRCV HKTTGLEFAA KIINTKKLSA RDFQKLEREA
RICRKLQHPN IVRLHDSIQE ESFHYLVFDL VTGGELFEDI VAREFYSEAD ASHCIQQILE
SIAYCHSNGI VHRDLKPENL LLASKAKGAA VKLADFGLAI EVNDSEAWHG FAGTPGYLSP
EVLKKDPYSK PVDIWACGVI LYILLVGYPP FWDEDQHRLY AQIKAGAYDY PSPEWDTVTP
EAKSLIDSML TVNPKKRITA DQALKVPWIC NRERVASAIH RQDTVDCLKK FNARRKLKAA
ISAVKMVTRM SGVLRTSDST GSVASNGSTT HDASQVAGTS SQPTSPAAEV YPNVLLFNPQ
KFPRNCVHPF TTHPYYSPKE SSKKKLFFTL LFEVCPHTSR SHILLRDNTK NIYHPYHCFT
NKMSNYERAA PSSHGSSTTK KIANAIADLV IRRSSPSIRR KTEADVHNSN RNRKVSAPAN
LQHALVPVID VVVATGALAS SSVDNLSAST SSDLGRNLLN KKEQGPPSTI KESSESSQTI
DDNDSEKGGG QLKHENTVVR ADGATGIVSS SNSSTASKSS STNLSAQKQD IVRVTQTLLD
AISCKDFETY TRLCDTSMTC FEPEALGNLI EGIEFHRFYF DGNRKNQVHT TMLNPNVHII
GEDAACVAYV KLTQFLDRNG EAHTRQSQES RVWSKKQGRW VCVHVHRSTQ PSTNTTVSEF
