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Protein

Calcium/calmodulin-dependent protein kinase kinase 2

Gene

Camkk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei194ATPPROSITE-ProRule annotation1
Active sitei312Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi171 – 179ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium/calmodulin-dependent protein kinase kinase 2 (EC:2.7.11.17)
Short name:
CaM-KK 2
Short name:
CaM-kinase kinase 2
Short name:
CaMKK 2
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 namesi
Name:Camkk2
Synonyms:Kiaa0787
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:2444812 Camkk2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice are unable to form spatial long-term memory.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000861452 – 588Calcium/calmodulin-dependent protein kinase kinase 2Add BLAST587

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei99PhosphoserineCombined sources1
Modified residuei114PhosphoserineBy similarity1
Modified residuei129PhosphoserineCombined sources1
Modified residuei133PhosphoserineCombined sources1
Modified residuei137PhosphoserineCombined sources1
Modified residuei495PhosphoserineCombined sources1
Modified residuei511PhosphoserineBy similarity1
Modified residuei572PhosphoserineCombined sources1
Isoform 2 (identifier: Q8C078-2)
Modified residuei522PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated and phosphorylated by PKA. Each isoform may show a different pattern of phosphorylation.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ8C078
PeptideAtlasiQ8C078
PRIDEiQ8C078

PTM databases

iPTMnetiQ8C078
PhosphoSitePlusiQ8C078

Expressioni

Tissue specificityi

Expressed in all tissues tested. A differential expression pattern compared to CAMKK1 is observed in the brain.1 Publication

Gene expression databases

BgeeiENSMUSG00000029471
ExpressionAtlasiQ8C078 baseline and differential
GenevisibleiQ8C078 MM

Interactioni

Subunit structurei

Interacts with calmodulin.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
PPM1FP495933EBI-937199,EBI-719945From Homo sapiens.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi228904, 1 interactor
IntActiQ8C078, 5 interactors
MINTiQ8C078
STRINGi10090.ENSMUSP00000107297

Structurei

3D structure databases

ProteinModelPortaliQ8C078
SMRiQ8C078
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini165 – 446Protein kinasePROSITE-ProRule annotationAdd BLAST282

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni204 – 226RP domainAdd BLAST23
Regioni472 – 477Autoinhibitory domainBy similarity6
Regioni475 – 500Calmodulin-bindingBy similarityAdd BLAST26

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi549 – 552Poly-Gly4

Domaini

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

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0585 Eukaryota
ENOG410YHHF LUCA
GeneTreeiENSGT00530000063214
HOGENOMiHOG000007846
HOVERGENiHBG052262
InParanoidiQ8C078
KOiK07359
OMAiITGMQDC
OrthoDBiEOG091G01DB
PhylomeDBiQ8C078
TreeFamiTF313013

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8C078-1) [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.

« Hide

        10         20         30         40         50
MSSCVSSQPT SDRVAPQDEL GSGGGSREGQ KPCEALRGLS SLSIHLGMES
60 70 80 90 100
FIVVTECEPG RGVDLNLARD QPPEADGQEL PLEASDPESR SPLSGRKMSL
110 120 130 140 150
QEPSQGGPAS SSNSLDMNGR CICPSLSYSP ASSPQSSPRM PRRPTVESHH
160 170 180 190 200
VSITGLQDCV QLNQYTLKDE IGKGSYGVVK LAYNENDNTY YAMKVLSKKK
210 220 230 240 250
LIRQAGFPRR PPPRGARPAP GGCIQPRGPI EQVYQEIAIL KKLDHPNVVK
260 270 280 290 300
LVEVLDDPNE DHLYMVFELV NQGPVMEVPT LKPLSEDQAR FYFQDLIKGI
310 320 330 340 350
EYLHYQKIIH RDIKPSNLLV GEDGHIKIAD FGVSNEFKGS DALLSNTVGT
360 370 380 390 400
PAFMAPESLS ETRKIFSGKA LDVWAMGVTL YCFVFGQCPF MDERIMCLHS
410 420 430 440 450
KIKSQALEFP DQPDIAEDLK DLITRMLDKN PESRIVVPEI KLHPWVTRHG
460 470 480 490 500
AEPLPSEDEN CTLVEVTEEE VENSVKHIPS LATVILVKTM IRKRSFGNPF
510 520 530 540 550
EGSRREERSL SAPGNLLTKK PTREWEPLSE PKEARQRRQP PGPRAGPCGG
560 570 580
GGSALVKGGP CVESWGAPAP GSPPRMPPLQ PEEVMEPE
Length:588
Mass (Da):64,618
Last modified:December 7, 2004 - v2
Checksum:iAED7433ADB3477A5
GO
Isoform 2 (identifier: Q8C078-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     520-588: KPTREWEPLS...LQPEEVMEPE → QGSEDSPRGPEPAPVGEEEVLL

Show »
Length:541
Mass (Da):59,617
Checksum:iFEB2385A4D793FF2
GO
Isoform 3 (identifier: Q8C078-3) [UniParc]FASTAAdd to basket

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

Show »
Length:579
Mass (Da):63,477
Checksum:iA79C6F3E1CE6DDCA
GO
Isoform 4 (identifier: Q8C078-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     485-503: ILVKTMIRKRSFGNPFEGS → VRRAGPLTKNKNRESPRQG
     504-588: Missing.

Show »
Length:503
Mass (Da):55,517
Checksum:i0ADB843145944187
GO
Isoform 5 (identifier: Q8C078-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     533-588: EARQRRQPPG...LQPEEVMEPE → VNACLPACAI...YPGSSGPLDG

Note: No experimental confirmation available.
Show »
Length:625
Mass (Da):68,051
Checksum:i83E6E29CA297E2B5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti176Y → F in BAC32023 (PubMed:16141072).Curated1
Sequence conflicti290R → H in BAC27681 (PubMed:16141072).Curated1
Sequence conflicti396 – 398MCL → IWR (PubMed:12654522).Curated3
Sequence conflicti401K → R (PubMed:12654522).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012150485 – 503ILVKT…PFEGS → VRRAGPLTKNKNRESPRQG in isoform 4. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_012151498N → T in isoform 3. 1 Publication1
Alternative sequenceiVSP_012152499 – 507Missing in isoform 3. 1 Publication9
Alternative sequenceiVSP_012153504 – 588Missing in isoform 4. 1 PublicationAdd BLAST85
Alternative sequenceiVSP_012154508 – 588RSLSA…VMEPE → RSKVAAGRNVPCQRLETCSR SKAAKTAPGAQSRPLWGRRK CSCERWSLRGKLGGSGPWLP TTHASTAARGGDGAGVAAWT T in isoform 3. 1 PublicationAdd BLAST81
Alternative sequenceiVSP_012155520 – 588KPTRE…VMEPE → QGSEDSPRGPEPAPVGEEEV LL in isoform 2. 1 PublicationAdd BLAST69
Alternative sequenceiVSP_012156533 – 588EARQR…VMEPE → VNACLPACAIASPPLGPGGG QLQSKHVGISSRQDVPSAGA AVPGSLRASGFPARGIQGLG SHGVSCMRAGLRCMALHPEC LRTYPGSSGPLDG in isoform 5. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS19655.1 [Q8C078-2]
CCDS80395.1 [Q8C078-1]
RefSeqiNP_001186605.1, NM_001199676.1 [Q8C078-1]
NP_663333.1, NM_145358.2 [Q8C078-2]
XP_006530293.1, XM_006530230.3 [Q8C078-5]
XP_006530294.1, XM_006530231.3 [Q8C078-5]
XP_017176252.1, XM_017320763.1 [Q8C078-1]
UniGeneiMm.289237

Genome annotation databases

EnsembliENSMUST00000111668; ENSMUSP00000107297; ENSMUSG00000029471 [Q8C078-1]
ENSMUST00000200109; ENSMUSP00000143732; ENSMUSG00000029471 [Q8C078-2]
GeneIDi207565
KEGGimmu:207565
UCSCiuc008zlz.3 mouse [Q8C078-1]
uc008zma.3 mouse [Q8C078-2]
uc008zmb.1 mouse [Q8C078-5]
uc008zmc.2 mouse [Q8C078-4]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKKCC2_MOUSE
AccessioniPrimary (citable) accession number: Q8C078
Secondary accession number(s): Q80TS0
, Q8BXM8, Q8C0G3, Q8CH42, Q8QZT7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 7, 2004
Last modified: May 23, 2018
This is version 144 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

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