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Protein

Calcium/calmodulin-dependent protein kinase type IV

Gene

Camk4

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

Functioni

Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK4 signaling cascade and regulates, mainly by phosphorylation, the activity of several transcription activators, such as CREB1, MEF2D, JUN and RORA, which play pivotal roles in immune response, inflammation, and memory consolidation. In the thymus, regulates the CD4+/CD8+ double positive thymocytes selection threshold during T-cell ontogeny. In CD4 memory T-cells, is required to link T-cell antigen receptor (TCR) signaling to the production of IL2, IFNG and IL4 (through the regulation of CREB and MEF2). Regulates the differentiation and survival phases of osteoclasts and dendritic cells (DCs). Mediates DCs survival by linking TLR4 and the regulation of temporal expression of BCL2. Phosphorylates the transcription activator CREB1 on 'Ser-133' in hippocampal neuron nuclei and contribute to memory consolidation and long term potentiation (LTP) in the hippocampus. Can activate the MAP kinases MAPK1/ERK2, MAPK8/JNK1 and MAPK14/p38 and stimulate transcription through the phosphorylation of ELK1 and ATF2. Can also phosphorylate in vitro CREBBP, PRM2, MEF2A and STMN1/OP18 (By similarity). May be involved in spermatogenesis.By similarity5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Activity regulationi

Activated by Ca2+/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-196 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-196 results in a 10-20-fold increase in total activity to generate Ca2+/calmodulin-independent activity. Autophosphorylation of the N-terminus Ser-11 and Ser-12 is required for full activation. Inactivated by protein phosphatase 2A (PPP2CA/PPP2CB) which dephosphorylates Thr-196, thereby terminating autonomous activity and helping to maintain the enzyme in its autoinhibited state.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei71ATPPROSITE-ProRule annotation1
Active sitei160Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi48 – 56ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase
Biological processAdaptive immunity, Immunity, Inflammatory response
LigandATP-binding, Calcium, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.17 3474

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium/calmodulin-dependent protein kinase type IV (EC:2.7.11.17)
Short name:
CaMK IV
Alternative name(s):
CaM kinase-GR
Gene namesi
Name:Camk4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:88258 Camk4

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

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Male mice are infertile with impairment of spermiogenesis in late elongating spermatids. The sequential deposition of sperm basic nuclear proteins on chromatin is disrupted, with a specific loss of protamine-2 and prolonged retention of Tnp2 in step-15 spermatids.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000861071 – 469Calcium/calmodulin-dependent protein kinase type IVAdd BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei11Phosphoserine; by autocatalysisBy similarity1
Modified residuei12Phosphoserine; by autocatalysisBy similarity1
Glycosylationi53O-linked (GlcNAc) threonineBy similarity1
Glycosylationi54O-linked (GlcNAc) serineBy similarity1
Glycosylationi133O-linked (GlcNAc) serineBy similarity1
Glycosylationi185O-linked (GlcNAc) serineBy similarity1
Modified residuei196PhosphothreonineCombined sources1
Modified residuei332Phosphoserine; by autocatalysisBy similarity1
Modified residuei337PhosphoserineBy similarity1
Glycosylationi340O-linked (GlcNAc) serineBy similarity1
Glycosylationi341O-linked (GlcNAc) serineBy similarity1
Glycosylationi352O-linked (GlcNAc) serineBy similarity1
Modified residuei433PhosphoserineBy similarity1
Modified residuei439PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by CaMKK1 and CaMKK2 on Thr-196. Dephosphorylated by protein phosphatase 2A. Autophosphorylated on Ser-11 and Ser-12 (By similarity).By similarity
Glycosylation at Ser-185 modulates the phosphorylation of CaMK4 at Thr-196 and negatively regulates its activity toward CREB1 in basal conditions and during early inomycin stimulation.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP08414
MaxQBiP08414
PaxDbiP08414
PeptideAtlasiP08414
PRIDEiP08414

PTM databases

iPTMnetiP08414
PhosphoSitePlusiP08414

Expressioni

Tissue specificityi

Expressed in brain and testis.2 Publications

Gene expression databases

CleanExiMM_CAMK4

Interactioni

Subunit structurei

Monomer. Interacts with protein phosphatase 2A (PPP2CA/PPP2CB); the interaction is mutually exclusive with binding to Ca2+/calmodulin.By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiP08414, 2 interactors
MINTiP08414
STRINGi10090.ENSMUSP00000046539

Structurei

3D structure databases

ProteinModelPortaliP08414
SMRiP08414
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini42 – 296Protein kinasePROSITE-ProRule annotationAdd BLAST255

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni297 – 336Autoinhibitory domainBy similarityAdd BLAST40
Regioni302 – 319PP2A-bindingBy similarityAdd BLAST18
Regioni318 – 337Calmodulin-bindingSequence analysisAdd BLAST20

Domaini

The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate.By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0032 Eukaryota
ENOG410XRMJ LUCA
HOGENOMiHOG000233016
HOVERGENiHBG108055
InParanoidiP08414
PhylomeDBiP08414

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, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P08414-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLKVTVPSCP SSPCSSVTAS TENLVPDYWI DGSNRDPLGD FFEVESELGR
60 70 80 90 100
GATSIVYRCK QKGTQKPYAL KVLKKTVDKK IVRTEIGVLL RLSHPNIIKL
110 120 130 140 150
KEIFETPTEI SLVLELVTGG ELFDRIVEKG YYSERDARDA VKQILEAVAY
160 170 180 190 200
LHENGIVHRD LKPENLLYAT PAPDAPLKIA DFGLSKIVEH QVLMKTVCGT
210 220 230 240 250
PGYCAPEILR GCAYGPEVDM WSVGIITYIL LCGFEPFYDE RGDQFMFRRI
260 270 280 290 300
LNCEYYFISP WWDEVSLNAK DLVKKLIVLD PKKRLTTFQA LQHPWVTGKA
310 320 330 340 350
ANFVHMDTAQ KKLQEFNARR KLKAAVKAVV ASSRLGSASS SHTSIQENHK
360 370 380 390 400
ASSDPPSTQD AKDSTDLLGK KMQEEDQEED QVEAEASADE MRKLQSEEVE
410 420 430 440 450
KDAGVKEEET SSMVPQDPED ELETDDPEMK RDSEEKLKSV EEEMDPMTEE
460
EAPDAGLGVP QQDAIQPEY
Length:469
Mass (Da):52,628
Last modified:April 1, 1993 - v2
Checksum:iCE1F98670822F975
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q8BGR3Q8BGR3_MOUSE
Calcium/calmodulin-dependent protei...
Camk4 mCG_140514
469Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti278 – 280VLD → CFGI in AAA37366 (PubMed:2536634).Curated3
Sequence conflicti302N → T in AAA37366 (PubMed:2536634).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M16206 mRNA Translation: AAA39933.1
M64266 mRNA Translation: AAA37364.1
J03057 mRNA Translation: AAA37366.1
X58995 mRNA Translation: CAA41741.1
CCDSiCCDS29122.1
PIRiS17656
UniGeneiMm.222329
Mm.410854

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M16206 mRNA Translation: AAA39933.1
M64266 mRNA Translation: AAA37364.1
J03057 mRNA Translation: AAA37366.1
X58995 mRNA Translation: CAA41741.1
CCDSiCCDS29122.1
PIRiS17656
UniGeneiMm.222329
Mm.410854

3D structure databases

ProteinModelPortaliP08414
SMRiP08414
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP08414, 2 interactors
MINTiP08414
STRINGi10090.ENSMUSP00000046539

PTM databases

iPTMnetiP08414
PhosphoSitePlusiP08414

Proteomic databases

EPDiP08414
MaxQBiP08414
PaxDbiP08414
PeptideAtlasiP08414
PRIDEiP08414

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:88258 Camk4

Phylogenomic databases

eggNOGiKOG0032 Eukaryota
ENOG410XRMJ LUCA
HOGENOMiHOG000233016
HOVERGENiHBG108055
InParanoidiP08414
PhylomeDBiP08414

Enzyme and pathway databases

BRENDAi2.7.11.17 3474

Miscellaneous databases

PROiPR:P08414
SOURCEiSearch...

Gene expression databases

CleanExiMM_CAMK4

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, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKCC4_MOUSE
AccessioniPrimary (citable) accession number: P08414
Secondary accession number(s): Q61381
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: April 1, 1993
Last modified: November 7, 2018
This is version 169 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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Main funding by: National Institutes of Health

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