UniProtKB - O62305 (KCC2D_CAEEL)
Protein
Calcium/calmodulin-dependent protein kinase type II
Gene
unc-43
Organism
Caenorhabditis elegans
Status
Functioni
Acts in the signaling of a variety of pathways and processes. Phosphorylates 'Ser-319' of daf-16 in response to stress signals, such as heat, starvation and oxidation, which plays a role in prolonging lifespan. Required for viability under chronic osmotic stress in which it acts downstream of osr-1. Has roles in locomotion, oocyte maturation, brood size, egg laying, defecation, meiotic maturation and neuronal cell fate specification. Required for the regulation of synaptic density and neuromuscular junction morphology. Regulates the synaptic trafficking of glr-1. Bidirectional modulator of neurotransmitter release with negative modulatory effects mainly mediated via slo-1 activation. Involved in activation of ADF neurons and increased tph-1 transcription following exposure to pathogenic bacteria which leads to learned olfactory aversion to the bacteria. Implicated in the muscle regulation of spicule protraction. In conjunction with egl-2 has a role in the suppression of mating behavior under food deprivation to encourage foraging. Involved in restricting str-2 expression to only one of the two AWC neurons. May suppress the functional response to an internal pacemaker, perhaps by modulating the activity of the IP3 receptor.14 Publications
Catalytic activityi
ATP + a protein = ADP + a phosphoprotein.1 Publication
Cofactori
Mg2+1 Publication
Activity regulationi
Ca2+/calmodulin binding removes an autoinhibitory regulatory segment located C-terminal to the kinase domain. This releases the catalytic activity of the enzyme and makes accessible a regulatory residue Thr-284. Phosphorylation of Thr-284 by another kinase domain within the oligomeric holoenzyme keeps CaMKII active in the absence of Ca2+/calmodulin by preventing the rebinding of the regulatory segment to the kinase domain and by increasing the affinity of calmodulin for the enzyme. Can respond to high-frequency Ca2+ pulses to become Ca2+ independent.2 Publications
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Binding sitei | 41 | ATPPROSITE-ProRule annotation1 Publication | 1 | |
| Active sitei | 134 | Proton acceptorCurated | 1 |
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Nucleotide bindingi | 18 – 26 | ATPPROSITE-ProRule annotationBy similarity | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- calmodulin binding Source: GO_Central
- calmodulin-dependent protein kinase activity Source: WormBase
- identical protein binding Source: IntAct
- ion channel binding Source: WormBase
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- cell differentiation Source: GO_Central
- MAPK cascade Source: WormBase
- medium-term memory Source: WormBase
- nervous system development Source: GO_Central
- peptidyl-serine phosphorylation Source: WormBase
- peptidyl-threonine phosphorylation Source: WormBase
- positive regulation of gene expression Source: UniProtKB
- protein phosphorylation Source: WormBase
Keywordsi
| Molecular function | Calmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase |
| Biological process | Stress response |
| Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
| BRENDAi | 2.7.11.17 1045 |
| SignaLinki | O62305 |
Names & Taxonomyi
| Protein namesi | Recommended name: Calcium/calmodulin-dependent protein kinase type II1 Publication (EC:2.7.11.17)Short name: CaM kinase II1 Publication Alternative name(s): Uncoordinated protein 43 |
| Gene namesi | Name:unc-43 ORF Names:K11E8.1 |
| Organismi | Caenorhabditis elegans |
| Taxonomic identifieri | 6239 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Nematoda › Chromadorea › Rhabditida › Rhabditoidea › Rhabditidae › Peloderinae › Caenorhabditis |
| Proteomesi |
|
Organism-specific databases
| WormBasei | K11E8.1a ; CE42693 ; WBGene00006779 ; unc-43 K11E8.1b ; CE28052 ; WBGene00006779 ; unc-43 K11E8.1d ; CE28054 ; WBGene00006779 ; unc-43 K11E8.1e ; CE28055 ; WBGene00006779 ; unc-43 K11E8.1f ; CE28056 ; WBGene00006779 ; unc-43 K11E8.1g ; CE28057 ; WBGene00006779 ; unc-43 K11E8.1h ; CE28058 ; WBGene00006779 ; unc-43 K11E8.1i ; CE28059 ; WBGene00006779 ; unc-43 K11E8.1k ; CE28060 ; WBGene00006779 ; unc-43 K11E8.1l ; CE28061 ; WBGene00006779 ; unc-43 K11E8.1m ; CE35590 ; WBGene00006779 ; unc-43 K11E8.1n ; CE40979 ; WBGene00006779 ; unc-43 K11E8.1o ; CE41430 ; WBGene00006779 ; unc-43 K11E8.1p ; CE42670 ; WBGene00006779 ; unc-43 |
Pathology & Biotechi
Disruption phenotypei
Increased frequency of defecation, typified by a weaker repetition of the defecation motor program, an echo, 10 s after the primary motor program. Abnormal spicule protraction. Lack of tph-1 transcriptional up-regulation during learned olfactory aversion to bacteria. Reduced brood size, body length and width. Lethargic movement. A gain-of function mutation reduces locomotory activity, alters excitation of three muscle types and lengthens the period of the motor output of a behavioral clock. Both classes of mutation inhibit neurotransmitter release.6 Publications
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 41 | K → M: Loss of kinase activity. 1 Publication | 1 | |
| Mutagenesisi | 97 | F → E: Loss of cooperative activation of adjacent holoenzyme subunits. 2 Publications | 1 | |
| Mutagenesisi | 97 | F → K: Increase in calcium independent kinase activity, no effect on translocation to the neurite. 2 Publications | 1 | |
| Mutagenesisi | 100 | I → K: Loss of cooperative activation of adjacent holoenzyme subunits. 1 Publication | 1 | |
| Mutagenesisi | 108 | E → K in n498gf; slight increase in calcium independent kinase activity, no effect on translocation to the neurite. Nuclear translocation of daf-16 resulting in lifespan extension. 3 Publications | 1 | |
| Mutagenesisi | 134 | D → N: Loss of autoinhibition and increase in binding of Ca2+/calmodulin. 2 Publications | 1 | |
| Mutagenesisi | 147 | K → E: Slight increase in calcium independent kinase activity, no effect on translocation to the neurite. 1 Publication | 1 | |
| Mutagenesisi | 170 | G → E in sy574; abnormal spicule protraction; when associated with V-665. 1 Publication | 1 | |
| Mutagenesisi | 179 | S → L in e408; males display locomotor and muscle seizure defects and egg laying defects. 1 Publication | 1 | |
| Mutagenesisi | 200 | I → K: Loss of cooperative activation of adjacent holoenzyme subunits. 1 Publication | 1 | |
| Mutagenesisi | 236 | D → R: Increase in calcium independent kinase activity, loss of translocation to neurites and glr-1 trafficking. 1 Publication | 1 | |
| Mutagenesisi | 278 – 279 | AI → DD: Decrease in binding of Ca2+/calmodulin. 1 Publication | 2 | |
| Mutagenesisi | 280 | H → K: Increase in calcium independent kinase activity, no effect on translocation to the neurite. 1 Publication | 1 | |
| Mutagenesisi | 281 | R → E: Increase in calcium independent kinase activity and translocation to an unlocalized pool in the neurite. Small decrease in glr-1 trafficking. 1 Publication | 1 | |
| Mutagenesisi | 284 | T → D: Constitutively activate kinase activity, increase in translocation to the neurites. 1 Publication | 1 | |
| Mutagenesisi | 665 | A → V in sy574; abnormal spicule protraction; when associated with E-170. 1 Publication | 1 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000396645 | 1 – 720 | Calcium/calmodulin-dependent protein kinase type IIAdd BLAST | 720 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 284 | Phosphothreonine; by autocatalysis1 Publication | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
| EPDi | O62305 |
| PeptideAtlasi | O62305 |
| PRIDEi | O62305 |
PTM databases
| iPTMneti | O62305 |
Expressioni
Tissue specificityi
Expressed in the nervous system. Observed in the ADF and AWC neurons. Position in AWC neurons is regulated by microtubules. Localized to clusters in ventral cord neurites which appear to be required for glr-1 trafficking. Also present in oocytes.4 Publications
Interactioni
Subunit structurei
Dodecamer. Subunits are tightly packed around a central ring-shaped scaffold with extensive contacts between the regulatory segment of one kinase and the catalytic domain of another enabling cooperative activation of a subunit by the adjacent molecule (PubMed:16441656, PubMed:20139983). Interacts with and phosphorylates daf-16; the interaction promotes daf-16 nuclear localization. Interacts with egl-2 and tir-1 (PubMed:15625192, PubMed:21145946). Interacts with nsy-1 (PubMed:11336672).5 Publications
Binary interactionsi
GO - Molecular functioni
- calmodulin binding Source: GO_Central
- identical protein binding Source: IntAct
- ion channel binding Source: WormBase
Protein-protein interaction databases
| BioGridi | 43023, 8 interactors |
| DIPi | DIP-25971N DIP-58986N |
| IntActi | O62305, 10 interactors |
| MINTi | O62305 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| ProteinModelPortali | O62305 |
| SMRi | O62305 |
| ModBasei | Search... |
| MobiDBi | Search... |
Miscellaneous databases
| EvolutionaryTracei | O62305 |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 12 – 269 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 258 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.Sequence analysis
Phylogenomic databases
| InParanoidi | O62305 |
| PhylomeDBi | O62305 |
Family and domain databases
| InterProi | View protein in InterPro IPR013543 Ca/CaM-dep_prot_kinase-assoc IPR039071 CAMK2 IPR011009 Kinase-like_dom_sf IPR032710 NTF2-like_dom_sf IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR008271 Ser/Thr_kinase_AS |
| PANTHERi | PTHR43940 PTHR43940, 1 hit |
| Pfami | View protein in Pfam PF08332 CaMKII_AD, 1 hit PF00069 Pkinase, 1 hit |
| SMARTi | View protein in SMART SM00220 S_TKc, 1 hit |
| SUPFAMi | SSF54427 SSF54427, 1 hit SSF56112 SSF56112, 1 hit |
| PROSITEi | View protein in PROSITE PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit |
Sequences (15+)i
Sequence statusi: Complete.
This entry describes 15 isoformsi produced by alternative splicing. AlignAdd to basketThis entry has 15 described isoforms and 4 potential isoforms that are computationally mapped.iShow all
Isoform c1 Publication (identifier: O62305-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MMNASTKFSD NYDVKEELGK GAFSVVRRCV HKTTGLEFAA KIINTKKLSA
60 70 80 90 100
RDFQKLEREA RICRKLQHPN IVRLHDSIQE ESFHYLVFDL VTGGELFEDI
110 120 130 140 150
VAREFYSEAD ASHCIQQILE SIAYCHSNGI VHRDLKPENL LLASKAKGAA
160 170 180 190 200
VKLADFGLAI EVNDSEAWHG FAGTPGYLSP EVLKKDPYSK PVDIWACGVI
210 220 230 240 250
LYILLVGYPP FWDEDQHRLY AQIKAGAYDY PSPEWDTVTP EAKSLIDSML
260 270 280 290 300
TVNPKKRITA DQALKVPWIC NRERVASAIH RQDTVDCLKK FNARRKLKAA
310 320 330 340 350
ISAVKMVTRM SGVLRTSDST GSVASNGSTT HDASQVAGTS SQPTSPAAEV
360 370 380 390 400
YPNVLLFNPQ KFPRNCVHPF TTHPYYSPKE SSKKKLFFTL LFEVCPHTSR
410 420 430 440 450
SHILLRDNTK NIYHPYHCFT NKMSNYERAA PSSHGSSTTK KIANAIADLV
460 470 480 490 500
IRRSSPSIRR KTEADVHNSN RNRKVSAPAN LQHALVPVID VVVATGALAS
510 520 530 540 550
SSVDNLSAST SSDLGRNLLN KKEQGPPSTI KESSESSQTI DDNDSEKGGG
560 570 580 590 600
QLKHENTVVR ADGATGIVSS SNSSTASKSS STNLSAQKQD IVRVTQTLLD
610 620 630 640 650
AISCKDFETY TRLCDTSMTC FEPEALGNLI EGIEFHRFYF DGNRKNQVHT
660 670 680 690 700
TMLNPNVHII GEDAACVAYV KLTQFLDRNG EAHTRQSQES RVWSKKQGRW
710 720
VCVHVHRSTQ PSTNTTVSEF
Note: No experimental confirmation available.Curated
Isoform o1 Publication (identifier: O62305-14) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
1-416: Missing.
417-514: HCFTNKMSNY...NLSASTSSDL → MDGLLARLKL...KPEKLEVEAD
548-585: Missing.
Note: No experimental confirmation available.Curated
Show »Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| G5EDZ5 | G5EDZ5_CAEEL | Calcium/calmodulin-dependent protei... | unc-43 CELE_K11E8.1, K11E8.1 | 681 | Annotation score: | ||
| E7EM33 | E7EM33_CAEEL | Calcium/calmodulin-dependent protei... | unc-43 CELE_K11E8.1, K11E8.1 | 103 | Annotation score: | ||
| F5GUA8 | F5GUA8_CAEEL | Calcium/calmodulin-dependent protei... | unc-43 CELE_K11E8.1, K11E8.1 | 266 | Annotation score: | ||
| F5GUA9 | F5GUA9_CAEEL | Calcium/calmodulin-dependent protei... | unc-43 CELE_K11E8.1, K11E8.1 | 298 | Annotation score: |
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_039590 | 1 – 505 | Missing in isoform n. 1 PublicationAdd BLAST | 505 | |
| Alternative sequenceiVSP_039591 | 1 – 504 | Missing in isoform p. 1 PublicationAdd BLAST | 504 | |
| Alternative sequenceiVSP_039592 | 1 – 490 | Missing in isoform a. 1 PublicationAdd BLAST | 490 | |
| Alternative sequenceiVSP_039593 | 1 – 416 | Missing in isoform o. 1 PublicationAdd BLAST | 416 | |
| Alternative sequenceiVSP_039594 | 1 – 414 | Missing in isoform m. 1 PublicationAdd BLAST | 414 | |
| Alternative sequenceiVSP_039595 | 113 – 138 | HCIQQ…DLKPE → CCIMQILDGVNYCHQRGIVH RDMKV in isoform b. 1 PublicationAdd BLAST | 26 | |
| Alternative sequenceiVSP_039596 | 139 – 720 | Missing in isoform b. 1 PublicationAdd BLAST | 582 | |
| Alternative sequenceiVSP_039597 | 299 – 314 | AAISA…MSGVL → GAILTTMIATRNLSNL in isoform d, isoform g and isoform i. 3 PublicationsAdd BLAST | 16 | |
| Alternative sequenceiVSP_039598 | 299 – 313 | AAISA…RMSGV → GAILTTMIATRNLSS in isoform f. 2 PublicationsAdd BLAST | 15 | |
| Alternative sequenceiVSP_039599 | 299 – 302 | AAIS → VVDS in isoform k. 2 Publications | 4 | |
| Alternative sequenceiVSP_039600 | 299 – 302 | AAIS → VAIC in isoform l. 2 Publications | 4 | |
| Alternative sequenceiVSP_039601 | 303 – 720 | Missing in isoform k and isoform l. 2 PublicationsAdd BLAST | 418 | |
| Alternative sequenceiVSP_039602 | 314 – 515 | Missing in isoform f. 2 PublicationsAdd BLAST | 202 | |
| Alternative sequenceiVSP_039603 | 315 – 514 | Missing in isoform d, isoform g and isoform i. 3 PublicationsAdd BLAST | 200 | |
| Alternative sequenceiVSP_039604 | 350 – 364 | VYPNV…QKFPR → GAILTTMIATRNLSN in isoform e and isoform h. 3 PublicationsAdd BLAST | 15 | |
| Alternative sequenceiVSP_039605 | 365 – 513 | Missing in isoform e and isoform h. 3 PublicationsAdd BLAST | 149 | |
| Alternative sequenceiVSP_039606 | 415 – 512 | PYHCF…ASTSS → MDGLLARLKLGSKRKKKTSS SVKRSSRPESARQAPRDTTG SLYSNLTASSSTVSACSAPE IVVLKKEQVVLAVDHKDQVD EQKKKNEQVVKKPEKLEVEA D in isoform m. 1 PublicationAdd BLAST | 98 | |
| Alternative sequenceiVSP_039607 | 417 – 514 | HCFTN…TSSDL → MDGLLARLKLGSKRKKKTSS SVKRSSRPESARQAPRDTTG SLYSNLTASSSTVSACSAPE IVVLKKEQVVLAVDHKDQVD EQKKKNEQVVKKPEKLEVEA D in isoform o. 1 PublicationAdd BLAST | 98 | |
| Alternative sequenceiVSP_039608 | 491 – 515 | VVVAT…SSDLG → MKNIEYWQVLLNKIFATYKI KMKQC in isoform a. 1 PublicationAdd BLAST | 25 | |
| Alternative sequenceiVSP_039609 | 505 – 513 | NLSASTSSD → MIATRNLSN in isoform p. 1 Publication | 9 | |
| Alternative sequenceiVSP_039610 | 506 – 515 | LSASTSSDLG → MNFLRFSGKC in isoform n. 1 Publication | 10 | |
| Alternative sequenceiVSP_039611 | 548 – 585 | Missing in isoform d, isoform e and isoform o. 3 PublicationsAdd BLAST | 38 | |
| Alternative sequenceiVSP_039612 | 549 – 550 | GG → NE in isoform i. 2 Publications | 2 | |
| Alternative sequenceiVSP_039613 | 551 – 720 | Missing in isoform i. 2 PublicationsAdd BLAST | 170 |
Sequence databases
Genome annotation databases
| GeneIDi | 177921 |
| UCSCi | K11E8.1a.1 c. elegans |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Entry informationi
| Entry namei | KCC2D_CAEEL | |
| Accessioni | O62305Primary (citable) accession number: O62305 Secondary accession number(s): A5JYT0 Q9U6Q0 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 10, 2010 |
| Last sequence update: | October 1, 2001 | |
| Last modified: | September 12, 2018 | |
| This is version 158 of the entry and version 2 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Caenorhabditis annotation project | |
