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Protein

Calcium/calmodulin-dependent protein kinase kinase 2

Gene

Camkk2

Organism
Rattus norvegicus (Rat)
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 and CAMK4. Phosphorylates CAMK1D (By similarity). Seems to be involved in hippocampal activation of CREB1 (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. May play a role in neurite growth. Isoform 2 may promote neurite elongation, while isoform 1 may promoter neurite branching.By similarity4 Publications

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei193ATPPROSITE-ProRule annotation1
Active sitei311Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi170 – 178ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • calcium ion binding Source: UniProtKB
  • calmodulin binding Source: RGD
  • calmodulin-dependent protein kinase activity Source: RGD
  • protein kinase activator activity Source: RGD
  • protein kinase activity Source: RGD

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620092 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

Chemistry databases

ChEMBLiCHEMBL1795115

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000861462 – 587Calcium/calmodulin-dependent protein kinase kinase 2Add BLAST586

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei99PhosphoserineBy similarity1
Modified residuei113PhosphoserineBy similarity1
Modified residuei128PhosphoserineBy similarity1
Modified residuei132PhosphoserineBy similarity1
Modified residuei136PhosphoserineBy similarity1
Modified residuei494PhosphoserineCombined sources1
Modified residuei510PhosphoserineCombined sources1
Modified residuei571PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated by PKA (By similarity). Each isoform may show a different pattern of phosphorylation (By similarity). Autophosphorylated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiO88831
PRIDEiO88831

PTM databases

iPTMnetiO88831
PhosphoSitePlusiO88831
SwissPalmiO88831

Expressioni

Tissue specificityi

Mainly expressed in brain, but detected in all tissues tested (at protein level). In the brain, isoform 1 may be predominant. with high levels in the cerebellum and hippocampus, although isoform 3 is detectable. Isoform 3 is also expressed in lung.1 Publication

Interactioni

Subunit structurei

Interacts with calmodulin.1 Publication

GO - Molecular functioni

  • calmodulin binding Source: RGD

Protein-protein interaction databases

BioGridi249725, 7 interactors
STRINGi10116.ENSRNOP00000001774

Structurei

3D structure databases

ProteinModelPortaliO88831
SMRiO88831
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini164 – 445Protein kinasePROSITE-ProRule annotationAdd BLAST282

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni203 – 225RP domainAdd BLAST23
Regioni471 – 476Autoinhibitory domainBy similarity6
Regioni474 – 499Calmodulin-bindingBy similarityAdd BLAST26

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi110 – 113Poly-Ser4
Compositional biasi548 – 551Poly-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
HOGENOMiHOG000007846
HOVERGENiHBG052262
InParanoidiO88831
KOiK07359
PhylomeDBiO88831

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 (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O88831-1) [UniParc]FASTAAdd to basket
Also known as: CAMKK2+E16

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 SDRAAPQDEL GSGGVSRESQ KPCEALRGLS SLSIHLGMES
60 70 80 90 100
FIVVTECEPG RGVDLSLARD QPLEADGQEL PLDASEPESR SLLSGGKMSL
110 120 130 140 150
QERSQGGPAS SSSLDMNGRC ICPSLSYSPA SSPQSSPRMP RRPTVESHHV
160 170 180 190 200
SITGLQDCVQ LNQYTLKDEI GKGSYGVVKL AYNENDNTYY AMKVLSKKKL
210 220 230 240 250
IRQAGFPRRP PPRGTRPAPG GCIQPRGPIE QVYQEIAILK KLDHPNVVKL
260 270 280 290 300
VEVLDDPNED HLYMVFELVN QGPVMEVPTL KPLSEDQARF YFQDLIKGIE
310 320 330 340 350
YLHYQKIIHR DIKPSNLLVG EDGHIKIADF GVSNEFKGSD ALLSNTVGTP
360 370 380 390 400
AFMAPESLSE TRKIFSGKAL DVWAMGVTLY CFVFGQCPFM DERIMCLHSK
410 420 430 440 450
IKSQALEFPD QPDIAEDLKD LITRMLDKNP ESRIVVPEIK LHPWVTRHGA
460 470 480 490 500
EPLPSEDENC TLVEVTEEEV ENSVKHIPSL ATVILVKTMI RKRSFGNPFE
510 520 530 540 550
GSRREERSLS APGNLLTKKP TREWEPLSEP KEARQRRQPP GPRASPCGGG
560 570 580
GSALVKGGPC VESCGAPAPG SPPRTPPQQP EEAMEPE
Length:587
Mass (Da):64,446
Last modified:November 1, 1998 - v1
Checksum:iC9E49B72578F3971
GO
Isoform 2 (identifier: O88831-2) [UniParc]FASTAAdd to basket
Also known as: CAMKK2-E16

The sequence of this isoform differs from the canonical sequence as follows:
     519-587: KPTREWEPLS...QQPEEAMEPE → QGSEDSLRGPEPAPVGEEEVLL

Show »
Length:540
Mass (Da):59,558
Checksum:i8E4D167BB8D8888C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti180L → S AA sequence (PubMed:8631893).Curated1
Sequence conflicti245P → V AA sequence (PubMed:8631893).Curated1
Sequence conflicti300Missing AA sequence (PubMed:8631893).Curated1
Sequence conflicti465V → S AA sequence (PubMed:8631893).Curated1
Sequence conflicti468E → T AA sequence (PubMed:8631893).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_046047519 – 587KPTRE…AMEPE → QGSEDSLRGPEPAPVGEEEV LL in isoform 2. CuratedAdd BLAST69

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB018081 mRNA Translation: BAA33524.1
PIRiJC5669
RefSeqiNP_112628.1, NM_031338.1 [O88831-1]
UniGeneiRn.229208

Genome annotation databases

GeneIDi83506
KEGGirno:83506
UCSCiRGD:620092 rat [O88831-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKKCC2_RAT
AccessioniPrimary (citable) accession number: O88831
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: November 1, 1998
Last modified: May 23, 2018
This is version 134 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health