Reactome | UniProt:Q16566 CAMK4

Schema > ReferenceGeneProduct > Entries

UniProt:Q16566 CAMK4 Show undefined attributes

chain	chain:1-473
checksum	EFEE51E5612326DC
comment	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.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)ACTIVITY REGULATION Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-200 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-200 results in a 10-20-fold increase in total activity to generate Ca(2+)/calmodulin-independent activity. Autophosphorylation of the N-terminus Ser-12 and Ser-13 is required for full activation. Inactivated by protein phosphatase 2A (PPP2CA/PPP2CB) which dephosphorylates Thr-200, thereby terminating autonomous activity and helping to maintain the enzyme in its autoinhibited state.SUBUNIT Monomer (By similarity). Interacts with protein phosphatase 2A (PPP2CA/PPP2CB); the interaction is mutually exclusive with binding to Ca(2+)/calmodulin.SUBCELLULAR LOCATION Localized in hippocampal neuron nuclei. In spermatids, associated with chromatin and nuclear matrix (By similarity).TISSUE SPECIFICITY Expressed in brain, thymus, CD4 T-cells, testis and epithelial ovarian cancer tissue.DEVELOPMENTAL STAGE Expressed during differentiation of monocyte-derived dendritic cells (at protein level).DOMAIN The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate.PTM Phosphorylated by CaMKK1 and CaMKK2 on Thr-200. Dephosphorylated by protein phosphatase 2A. Autophosphorylated on Ser-12 and Ser-13.PTM Glycosylation at Ser-189 modulates the phosphorylation of CaMK4 at Thr-200 and negatively regulates its activity toward CREB1 in basal conditions and during early inomycin stimulation.SIMILARITY Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.SEQUENCE CAUTION Extended N-terminus.
crossReference	[DatabaseIdentifier:12818649] ZINC - World Drugs:KCC4_HUMAN [DatabaseIdentifier:11482075] ENSEMBL:ENSG00000152495 [DatabaseIdentifier:11583491] ENSEMBL:ENSP00000422634 [DatabaseIdentifier:11583490] ENSEMBL:ENSP00000282356 [DatabaseIdentifier:11706189] ENSEMBL:ENST00000512453 [DatabaseIdentifier:11706190] ENSEMBL:ENST00000282356 [DatabaseIdentifier:11781065] Guide to Pharmacology - Targets:1955 [DatabaseIdentifier:11794464] GeneCards:CAMK4 [DatabaseIdentifier:11810410] GlyGen:Q16566 [DatabaseIdentifier:11831520] HMDB Protein:HMDBP01381 [DatabaseIdentifier:11847437] HPA:ENSG00000152495-CAMK4 [DatabaseIdentifier:12132113] OpenTargets:ENSG00000152495 [DatabaseIdentifier:12222475] PDB:2W4O [DatabaseIdentifier:12275287] PRO:Q16566 [DatabaseIdentifier:12292297] Pharos - Targets:Q16566 [DatabaseIdentifier:12389249] RefSeq:NP_001310303.1 [DatabaseIdentifier:12389248] RefSeq:NP_001310304.1 [DatabaseIdentifier:12389250] RefSeq:NP_001735.1 [DatabaseIdentifier:12804928] ZINC - Biogenic:KCC4_HUMAN [DatabaseIdentifier:12805996] ZINC - FDA approved:KCC4_HUMAN [DatabaseIdentifier:12807082] ZINC - Investigational:KCC4_HUMAN [DatabaseIdentifier:12810625] ZINC - Predictions - Purchasable:KCC4_HUMAN [DatabaseIdentifier:12812374] ZINC - Substances:KCC4_HUMAN [DatabaseIdentifier:12815741] ZINC target:Q16566
databaseName	UniProt
dbId	57901
description	recommendedName: Calcium/calmodulin-dependent protein kinase type IV shortName: CaMK IV ecNumber: 2.7.11.17 alternativeName: CaM kinase-GR
displayName	UniProt:Q16566 CAMK4
geneName	CAMK4 CAMK CAMK-GR CAMKIV
identifier	Q16566
isSequenceChanged	false
keyword	3D-structure Adaptive immunity ATP-binding Calcium Calmodulin-binding Cytoplasm Glycoprotein Immunity Inflammatory response Kinase Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Serine/threonine-protein kinase Transferase
modified	[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType	Protein
name	CAMK4
otherIdentifier	11739304_a_at 1421_at 1422_g_at 16987945 210349_PM_at 210349_at 229029_PM_at 229029_at 241871_PM_at 241871_at 2823881 2823882 2823883 2823884 2823885 2823886 2823904 2823908 2823910 2823911 2823912 2823916 2823917 2823922 2823923 2823924 2823932 2823933 2823934 2823935 2823936 2823937 2823938 2823939 2823940 2823941 2823942 2823943 2823944 2823945 2823946 2823947 2823959 2823961 2823963 2823964 2823965 2823966 2823967 2823969 2823971 2823973 2823975 2823977 2823978 2823979 33514_at 46191_at 53694_at 68195_at 8107307 814 A_14_P104648 A_23_P250347 D30742_at GE57160 GO:0000166 GO:0001650 GO:0002250 GO:0002376 GO:0003824 GO:0004672 GO:0004674 GO:0004683 GO:0005516 GO:0005524 GO:0005634 GO:0005654 GO:0005737 GO:0005783 GO:0006355 GO:0006468 GO:0006954 GO:0007165 GO:0007616 GO:0009931 GO:0016301 GO:0016740 GO:0030154 GO:0033081 GO:0035556 GO:0043011 GO:0045670 GO:0045893 GO:0050877 GO:0070062 GO:0106310 GO:0140096 HMNXSV003009172 Hs.190146.0.A1_3p_at Hs.6187.0.A1_3p_at ILMN_1767168 ILMN_2166582 PH_hs_0020794 PH_hs_0025799 TC05000521.hg g407005_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-111902] p-S12,S13,T200-CAMK4 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9619155] p-T200-CAMK4 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-112280] CAMK4 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-57900] CAMK4 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000152495] ENSEMBL:ENSG00000152495 CAMK4 [ReferenceDNASequence:11347526] BioGPS Gene:814 CAMK4 [ReferenceDNASequence:11393247] COSMIC - genes:CAMK4 CAMK4 [ReferenceDNASequence:11423223] CTD Gene:814 CAMK4 [ReferenceDNASequence:11429183] dbSNP Gene:814 CAMK4 [ReferenceDNASequence:11826161] HGNC:1464 CAMK4 [ReferenceDNASequence:11887547] KEGG:hsa:814 CAMK4 [ReferenceDNASequence:11977315] Monarch:814 CAMK4 [ReferenceDNASequence:12061408] NCBI Gene:814 CAMK4 [ReferenceDNASequence:12116506] OMIM:114080 CAMK4 [ReferenceDNASequence:12693932] UCSC:Q16566 CAMK4
referenceTranscript	[ReferenceRNASequence:12571020] RefSeq:NM_001323374.2 CAMK4 [ReferenceRNASequence:12571018] RefSeq:NM_001744.6 CAMK4 [ReferenceRNASequence:12571019] RefSeq:NM_001323375.2 CAMK4
schemaClass	ReferenceGeneProduct
secondaryIdentifier	KCC4_HUMAN D3DSZ7
sequenceLength	473
species	[Species:48887] Homo sapiens
stId	uniprot:Q16566
url	http://purl.uniprot.org/uniprot/Q16566

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-111902] p-S12,S13,T200-CAMK4 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-9619155] p-T200-CAMK4 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-112280] CAMK4 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-57900] CAMK4 [cytosol]
(referenceSequence)	[ModifiedResidue:9619153] O-phospho-L-threonine at 200 [ModifiedResidue:111901] O-phospho-L-serine at 12 [ModifiedResidue:379819] O-phospho-L-serine at 13
(interactor)	[UndirectedInteraction:11220075] UniProt:Q9Y2X7 <-> UniProt:Q16566 (IntAct) [UndirectedInteraction:11299569] UniProt:Q16566 <-> UniProt:P02724 (IntAct) [UndirectedInteraction:11299571] UniProt:Q16566 <-> UniProt:Q14161 (IntAct)

Cite Us!