Reviewed,
UniProtKB/Swiss-Prot Q8C078 (KKCC2_MOUSE)
Last modified
February 9, 2010.
Version 78.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Calcium/calmodulin-dependent protein kinase kinase 2 Short name=CaM-kinase kinase 2 Short name=CaM-KK 2 Short name=CaMKK 2 EC=2.7.11.17 Alternative name(s): Calcium/calmodulin-dependent protein kinase kinase beta Short name=CaM-kinase kinase beta Short name=CaM-KK beta Short name=CaMKK beta | ||||
| Gene names |
| ||||
| Organism | Mus musculus (Mouse) | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus |
Protein attributes
| Sequence length | 588 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK4 and CAMK1D By similarity. Seems to be involved in hippocampal activation of CREB1. Ref.5 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Enzyme regulation | Activated by Ca2+/calmodulin. Binding of calmodulin may releave intrasteric autoinhibition. Autophosphorylation does not alter activity or regulation by Ca2+/calmodulin. In part, activity is independent on Ca2+/calmodulin By similarity. |
| Subunit structure | Interacts with calmodulin By similarity. |
| Subcellular location | Cytoplasm By similarity. |
| Tissue specificity | Expressed in all tissues tested. A differential expression pattern compared to CAMKK1 is observed in the brain. Ref.1 |
| Domain | The autoinhibitory domain overlaps with the calmodulin binding region and may be involved in intrasteric autoinhibition. The RP domain (arginine/proline-rich) is involved in the recognition of CAMKI and CAMK4 as substrates By similarity. |
| Post-translational modification | Autophosphorylated By similarity. |
| Disruption phenotype | Mice are unable to form spatial long-term memory. Ref.5 |
| Sequence similarities | Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Contains 1 protein kinase domain. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Cytoplasm |
| Coding sequence diversity | Alternative splicing |
| Ligand | ATP-binding Calmodulin-binding Nucleotide-binding |
| Molecular function | Kinase Serine/threonine-protein kinase Transferase |
| PTM | Phosphoprotein |
| Gene Ontology (GO) | |
| Biological process | protein amino acid autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB |
| Cellular component | cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion bindingInferred from sequence or structural similarity. Source: UniProtKB calmodulin bindingInferred from electronic annotation. Source: UniProtKB-KW calmodulin-dependent protein kinase activityInferred from electronic annotation. Source: EC |
| Complete GO annotation... | |
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q8C078-1) 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. | ||||||
| Isoform 2 (identifier: Q8C078-2) The sequence of this isoform differs from the canonical sequence as follows: 520-541: KPTREWEPLSEPKEARQRRQPP → QGSEDSPRGPEPAPVGEEEVLL | ||||||
| Note: Phosphorylated on Ser-522 (By similarity). | ||||||
| Isoform 3 (identifier: Q8C078-3) The sequence of this isoform differs from the canonical sequence as follows: 498-498: N → T 499-507: Missing. 508-588: RSLSAPGNLL...LQPEEVMEPE → RSKVAAGRNV...DGAGVAAWTT | ||||||
| Isoform 4 (identifier: Q8C078-4) The sequence of this isoform differs from the canonical sequence as follows: 485-503: ILVKTMIRKRSFGNPFEGS → VRRAGPLTKNKNRESPRQG 504-588: Missing. | ||||||
| Isoform 5 (identifier: Q8C078-5) The sequence of this isoform differs from the canonical sequence as follows: 533-588: EARQRRQPPG...LQPEEVMEPE → VNACLPACAI...YPGSSGPLDG | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 588 | 588 | Calcium/calmodulin-dependent protein kinase kinase 2 | PRO_0000086145 | |||||
Regions | |||||||||
| Domain | 165 – 446 | 282 | Protein kinase | ||||||
| Nucleotide binding | 171 – 179 | 9 | ATP By similarity | ||||||
| Region | 204 – 226 | 23 | RP domain | ||||||
| Region | 472 – 477 | 6 | Autoinhibitory domain By similarity | ||||||
| Region | 475 – 500 | 26 | Calmodulin-binding By similarity | ||||||
| Compositional bias | 549 – 552 | 4 | Poly-Gly | ||||||
Sites | |||||||||
| Active site | 312 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 194 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 99 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 129 | 1 | Phosphoserine Ref.7 | ||||||
| Modified residue | 133 | 1 | Phosphoserine Ref.7 | ||||||
| Modified residue | 495 | 1 | Phosphoserine Ref.6 | ||||||
| Modified residue | 511 | 1 | Phosphoserine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 485 – 503 | 19 | ILVKT…PFEGS → VRRAGPLTKNKNRESPRQG in isoform 4. | VSP_012150 | |||||
| Alternative sequence | 498 | 1 | N → T in isoform 3. | VSP_012151 | |||||
| Alternative sequence | 499 – 507 | 9 | Missing in isoform 3. | VSP_012152 | |||||
| Alternative sequence | 504 – 588 | 85 | Missing in isoform 4. | VSP_012153 | |||||
| Alternative sequence | 508 – 588 | 81 | RSLSA…VMEPE → RSKVAAGRNVPCQRLETCSR SKAAKTAPGAQSRPLWGRRK CSCERWSLRGKLGGSGPWLP TTHASTAARGGDGAGVAAWT T in isoform 3. | VSP_012154 | |||||
| Alternative sequence | 520 – 541 | 22 | KPTRE…RRQPP → QGSEDSPRGPEPAPVGEEEV LL in isoform 2. | VSP_012155 | |||||
| Alternative sequence | 533 – 588 | 56 | EARQR…VMEPE → VNACLPACAIASPPLGPGGG QLQSKHVGISSRQDVPSAGA AVPGSLRASGFPARGIQGLG SHGVSCMRAGLRCMALHPEC LRTYPGSSGPLDG in isoform 5. | VSP_012156 | |||||
Experimental info | |||||||||
| Sequence conflict | 176 | 1 | Y → F in BAC32023. Ref.2 | ||||||
| Sequence conflict | 290 | 1 | R → H in BAC27681. Ref.2 | ||||||
| Sequence conflict | 396 – 398 | 3 | MCL → IWR Ref.1 | ||||||
| Sequence conflict | 401 | 1 | K → R Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning of mouse Ca2+/calmodulin-dependent protein kinase kinase beta (CaMKKbeta) and characterization of CaMKKbeta and CaMKKalpha distribution in the adult mouse brain." Vinet J., Carra S., Blom J.M.C., Harvey M., Brunello N., Barden N., Tascedda F. Brain Res. Mol. Brain Res. 111:216-221(2003) [PubMed: 12654522] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. |
| [2] | "The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4). Strain: C57BL/6J. Tissue: Medulla oblongata, Retina and Testis. |
| [3] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: FVB/N. Tissue: Mammary tumor. |
| [4] | "Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H. DNA Res. 10:167-180(2003) [PubMed: 14621295] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 207-588 (ISOFORM 5). Tissue: Brain. |
| [5] | "Loss of Ca2+/calmodulin kinase kinase beta affects the formation of some, but not all, types of hippocampus-dependent long-term memory." Peters M., Mizuno K., Ris L., Angelo M., Godaux E., Giese K.P. J. Neurosci. 23:9752-9760(2003) [PubMed: 14586002] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE. |
| [6] | "Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed: 17114649] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, MASS SPECTROMETRY. Tissue: Brain cortex. |
| [7] | "Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129 AND SER-133, MASS SPECTROMETRY. Tissue: Liver. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF453383 mRNA. Translation: AAN75696.1. AK031399 mRNA. Translation: BAC27387.1. AK032070 mRNA. Translation: BAC27681.1. AK044660 mRNA. Translation: BAC32023.1. BC023103 mRNA. Translation: AAH23103.1. AK122370 mRNA. Translation: BAC65652.1. |
| IPI | IPI00404152. IPI00404236. IPI00457626. IPI00480226. IPI00480493. |
| RefSeq | NP_663333.1. |
| UniGene | Mm.289237 Mm.394637 Mm.474852 |
3D structure databases | |
| SMR | Q8C078. Positions 158-448, 475-500. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q8C078. |
PTM databases | |
| PhosphoSite | Q8C078. |
Proteomic databases | |
| PRIDE | Q8C078. |
Genome annotation databases | |
| Ensembl | ENSMUST00000047365; ENSMUSP00000048135; ENSMUSG00000029471; Mus musculus. [Genome view] ENSMUST00000086224; ENSMUSP00000083401; ENSMUSG00000029471; Mus musculus. [Genome view] ENSMUST00000111667; ENSMUSP00000107296; ENSMUSG00000029471; Mus musculus. [Genome view] ENSMUST00000111668; ENSMUSP00000107297; ENSMUSG00000029471; Mus musculus. [Genome view] |
| GeneID | 207565. |
| KEGG | mmu:207565. |
| NMPDR | fig|10090.3.peg.12398. |
| UCSC | uc008zly.1. mouse. uc008zlz.1. mouse. uc008zmc.1. mouse. |
Organism-specific databases | |
| CTD | 207565. |
| MGI | MGI:2444812. Camkk2. |
| Rouge | Search... |
Phylogenomic databases | |
| HOGENOM | HBG755340. |
| HOVERGEN | Q8C078. |
| InParanoid | Q8C078. |
| OMA | LPYSPVS. |
| PhylomeDB | Q8C078. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.17. 244. |
Gene expression databases | |
| ArrayExpress | Q8C078. |
| Bgee | Q8C078. |
| Genevestigator | Q8C078. |
| GermOnline | ENSMUSG00000029471. Mus musculus. |
Family and domain databases | |
| InterPro | IPR020657. Ca/CaM-dep_prot_kin_kinase. IPR020636. Ca/CaM-dep_prot_kinase-like. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. [Graphical view] |
| PANTHER | PTHR22982:SF40. Ca/CaM-dep_prot_kin_kinase. 1 hit. PTHR22982. Ca/CaM-dep_prot_kinase-like. 1 hit. |
| Pfam | PF00069. Pkinase. 1 hit. [Graphical view] |
| SMART | SM00220. S_TKc. 1 hit. [Graphical view] |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 371961. |
| SOURCE | Search... |
Entry information
| Entry name | KKCC2_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q8C078 Secondary accession number(s): Q80TS0 Q8QZT7 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


