InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CAMK4

Summary

InnateDB Protein

IDBP-485303.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CAMK4

Protein Name

calcium/calmodulin-dependent protein kinase IV

Synonyms

caMK; CaMK IV; CaMK-GR; IV;

Species

Homo sapiens

Ensembl Protein

ENSP00000422634

InnateDB Gene

IDBG-36661 (CAMK4)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:10617605, ECO:0000269PubMed:17909078, ECO:0000269PubMed:18829949, ECO:0000269PubMed:7961813, ECO:0000269PubMed:8065343, ECO:0000269PubMed:8855261, ECO:0000269PubMed:8980227, ECO:0000269PubMed:9154845}.

Subcellular Localization

Cytoplasm. Nucleus. Note=Localized in hippocampal neuron nuclei. In spermatids, associated with chromatin and nuclear matrix (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Expressed in brain, thymus, CD4 T-cells, testis and epithelial ovarian cancer tissue. {ECO:0000269PubMed:12065094, ECO:0000269PubMed:7961813, ECO:0000269PubMed:8397199}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 9 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	9 [view]
Protein-Protein	9 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004683	calmodulin-dependent protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005516	calmodulin binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0006468	protein phosphorylation
GO:0006954	inflammatory response
GO:0007165	signal transduction
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007202	activation of phospholipase C activity
GO:0007268	synaptic transmission
GO:0007616	long-term memory
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0033081	regulation of T cell differentiation in thymus
GO:0043011	myeloid dendritic cell differentiation
GO:0045087	innate immune response
GO:0045670	regulation of osteoclast differentiation
GO:0045893	positive regulation of transcription, DNA-templated
GO:0048011	neurotrophin TRK receptor signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005730	nucleolus
GO:0005829	cytosol
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt