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Q8C078 (KKCC2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcium/calmodulin-dependent protein kinase kinase 2

Short name=CaM-KK 2
Short name=CaM-kinase kinase 2
Short name=CaMKK 2
EC=2.7.11.17
Alternative name(s):
Calcium/calmodulin-dependent protein kinase kinase beta
Short name=CaM-KK beta
Short name=CaM-kinase kinase beta
Short name=CaMKK beta
Gene names
Name:Camkk2
Synonyms:Kiaa0787
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length588 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca2+ signals By similarity. May play a role in neurite growth. Isoform 2 may promote neurite elongation, while isoform 1 may promoter neurite branching By similarity. May 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 relieve 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

Nucleus By similarity. Cytoplasm By similarity. Cell projection By similarity. Note: Predominantly nuclear in unstimulated cells By similarity. Found in the cytoplasm and neurites after forskolin induction 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 and phosphorylated by PKA By similarity. Each isoform mayshow a different pattern of phosphorylation 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PPM1FP495933EBI-937199,EBI-719945From a different organism.

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:
     520-588: KPTREWEPLS...LQPEEVMEPE → QGSEDSPRGPEPAPVGEEEVLL
Note: Contains a phosphoserine at position 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 588587Calcium/calmodulin-dependent protein kinase kinase 2
PRO_0000086145

Regions

Domain165 – 446282Protein kinase
Nucleotide binding171 – 1799ATP By similarity
Region204 – 22623RP domain
Region472 – 4776Autoinhibitory domain By similarity
Region475 – 50026Calmodulin-binding By similarity
Compositional bias549 – 5524Poly-Gly

Sites

Active site3121Proton acceptor By similarity
Binding site1941ATP By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue1291Phosphoserine Ref.7
Modified residue1331Phosphoserine Ref.7
Modified residue4951Phosphoserine By similarity

Natural variations

Alternative sequence485 – 50319ILVKT…PFEGS → VRRAGPLTKNKNRESPRQG in isoform 4.
VSP_012150
Alternative sequence4981N → T in isoform 3.
VSP_012151
Alternative sequence499 – 5079Missing in isoform 3.
VSP_012152
Alternative sequence504 – 58885Missing in isoform 4.
VSP_012153
Alternative sequence508 – 58881RSLSA…VMEPE → RSKVAAGRNVPCQRLETCSR SKAAKTAPGAQSRPLWGRRK CSCERWSLRGKLGGSGPWLP TTHASTAARGGDGAGVAAWT T in isoform 3.
VSP_012154
Alternative sequence520 – 58869KPTRE…VMEPE → QGSEDSPRGPEPAPVGEEEV LL in isoform 2.
VSP_012155
Alternative sequence533 – 58856EARQR…VMEPE → VNACLPACAIASPPLGPGGG QLQSKHVGISSRQDVPSAGA AVPGSLRASGFPARGIQGLG SHGVSCMRAGLRCMALHPEC LRTYPGSSGPLDG in isoform 5.
VSP_012156

Experimental info

Sequence conflict1761Y → F in BAC32023. Ref.2
Sequence conflict2901R → H in BAC27681. Ref.2
Sequence conflict396 – 3983MCL → IWR Ref.1
Sequence conflict4011K → R Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 7, 2004. Version 2.
Checksum: AED7433ADB3477A5

FASTA58864,618
        10         20         30         40         50         60 
MSSCVSSQPT SDRVAPQDEL GSGGGSREGQ KPCEALRGLS SLSIHLGMES FIVVTECEPG 

        70         80         90        100        110        120 
RGVDLNLARD QPPEADGQEL PLEASDPESR SPLSGRKMSL QEPSQGGPAS SSNSLDMNGR 

       130        140        150        160        170        180 
CICPSLSYSP ASSPQSSPRM PRRPTVESHH VSITGLQDCV QLNQYTLKDE IGKGSYGVVK 

       190        200        210        220        230        240 
LAYNENDNTY YAMKVLSKKK LIRQAGFPRR PPPRGARPAP GGCIQPRGPI EQVYQEIAIL 

       250        260        270        280        290        300 
KKLDHPNVVK LVEVLDDPNE DHLYMVFELV NQGPVMEVPT LKPLSEDQAR FYFQDLIKGI 

       310        320        330        340        350        360 
EYLHYQKIIH RDIKPSNLLV GEDGHIKIAD FGVSNEFKGS DALLSNTVGT PAFMAPESLS 

       370        380        390        400        410        420 
ETRKIFSGKA LDVWAMGVTL YCFVFGQCPF MDERIMCLHS KIKSQALEFP DQPDIAEDLK 

       430        440        450        460        470        480 
DLITRMLDKN PESRIVVPEI KLHPWVTRHG AEPLPSEDEN CTLVEVTEEE VENSVKHIPS 

       490        500        510        520        530        540 
LATVILVKTM IRKRSFGNPF EGSRREERSL SAPGNLLTKK PTREWEPLSE PKEARQRRQP 

       550        560        570        580 
PGPRAGPCGG GGSALVKGGP CVESWGAPAP GSPPRMPPLQ PEEVMEPE 

« Hide

Isoform 2 [UniParc].

Checksum: FEB2385A4D793FF2
Show »

FASTA54159,617
Isoform 3 [UniParc].

Checksum: A79C6F3E1CE6DDCA
Show »

FASTA57963,477
Isoform 4 [UniParc].

Checksum: 0ADB843145944187
Show »

FASTA50355,517
Isoform 5 [UniParc].

Checksum: 83E6E29CA297E2B5
Show »

FASTA62568,051

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] [Europe PMC] [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. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129 AND SER-133, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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.
RefSeqNP_001186605.1. NM_001199676.1.
NP_663333.1. NM_145358.2.
XP_006530293.1. XM_006530230.1.
XP_006530294.1. XM_006530231.1.
UniGeneMm.289237.

3D structure databases

ProteinModelPortalQ8C078.
SMRQ8C078. Positions 160-507.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ8C078. 3 interactions.
MINTMINT-4099835.

PTM databases

PhosphoSiteQ8C078.

Proteomic databases

PaxDbQ8C078.
PRIDEQ8C078.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000111668; ENSMUSP00000107297; ENSMUSG00000029471. [Q8C078-2]
GeneID207565.
KEGGmmu:207565.
UCSCuc008zlz.3. mouse. [Q8C078-1]
uc008zma.3. mouse. [Q8C078-2]
uc008zmb.1. mouse. [Q8C078-5]
uc008zmc.2. mouse. [Q8C078-4]

Organism-specific databases

CTD10645.
MGIMGI:2444812. Camkk2.
RougeSearch...

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00530000063214.
HOGENOMHOG000007846.
HOVERGENHBG052262.
InParanoidQ8C078.
KOK07359.
OMAMNGRCIC.
OrthoDBEOG7F5114.
PhylomeDBQ8C078.
TreeFamTF313013.

Gene expression databases

GenevestigatorQ8C078.

Family and domain databases

InterProIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24347. PTHR24347. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio371961.
PROQ8C078.
SOURCESearch...

Entry information

Entry nameKKCC2_MOUSE
AccessionPrimary (citable) accession number: Q8C078
Secondary accession number(s): Q80TS0 expand/collapse secondary AC list , Q8BXM8, Q8C0G3, Q8CH42, Q8QZT7
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 7, 2004
Last modified: April 16, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot