UniProt Accession

 KCC4_HUMAN; Q16566; D3DSZ7 

Genbank Protein ID

 D30742; L17000; L24959; CH471086; CH471086; BC016695; BC025687 

Genbank Nucleotide ID

 BAA06403.1; AAA35639.1; AAA18251.1; EAW49033.1; EAW49034.1; AAH16695.2; AAH25687.1 

Protein Name

 Calcium/calmodulin-dependent protein kinase type IV 

Protein Synonyms/Alias

 CaMK IV; CaM kinase-GR 

Gene Name

 CAMK4 

Gene Synonyms/Alias

 CAMK; CAMK-GR; CAMKIV 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
133	LFDRIVEKGYYSERD	ubiquitination	[1]
182	PAPDAPLKIADFGLS	ubiquitination	[1]
190	IADFGLSKIVEHQVL	acetylation	[2]
190	IADFGLSKIVEHQVL	ubiquitination	[1, 3]
199	VEHQVLMKTVCGTPG	ubiquitination	[1]
279	NAKDLVRKLIVLDPK	ubiquitination	[1]
303	QHPWVTGKAANFVHM	ubiquitination	[1]
316	HMDTAQKKLQEFNAR	ubiquitination	[1]
331	RKLKAAVKAVVASSR	ubiquitination	[1]
404	VQALEKVKGADINAE	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 46 300 Protein kinase.
 NP_BIND 52 60 ATP (By similarity).
 REGION 305 321 Autoinhibitory domain.
 REGION 306 323 PP2A-binding.
 REGION 322 341 Calmodulin-binding (Potential).
 ACT_SITE 164 164 Proton acceptor (By similarity).
 BINDING 75 75 ATP (By similarity).
 MOD_RES 12 12 Phosphoserine; by autocatalysis.
 MOD_RES 13 13 Phosphoserine; by autocatalysis.
 MOD_RES 200 200 Phosphothreonine; by CaMKK1 and CaMKK2.
 MOD_RES 336 336 Phosphoserine; by autocatalysis.
 MOD_RES 360 360 Phosphoserine.
 CARBOHYD 57 57 O-linked (GlcNAc).
 CARBOHYD 58 58 O-linked (GlcNAc).
 CARBOHYD 137 137 O-linked (GlcNAc).
 CARBOHYD 189 189 O-linked (GlcNAc).
 CARBOHYD 344 344 O-linked (GlcNAc).
 CARBOHYD 345 345 O-linked (GlcNAc).
 CARBOHYD 356 356 O-linked (GlcNAc).  

Keyword

 3D-structure; Adaptive immunity; ATP-binding; Calcium; Calmodulin-binding; Complete proteome; Cytoplasm; Glycoprotein; Immunity; Inflammatory response; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 473 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005730; C:nucleolus; IDA:HPA.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004683; F:calmodulin-dependent protein kinase activity; IEA:EC.
 GO:0007202; P:activation of phospholipase C activity; TAS:Reactome.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0007616; P:long-term memory; IGI:UniProtKB.
 GO:0043011; P:myeloid dendritic cell differentiation; IMP:UniProtKB.
 GO:0007270; P:neuron-neuron synaptic transmission; IEA:Compara.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0006913; P:nucleocytoplasmic transport; IEA:Compara.
 GO:0046827; P:positive regulation of protein export from nucleus; IEA:Compara.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; IDA:UniProtKB.
 GO:0006468; P:protein phosphorylation; TAS:ProtInc.
 GO:0045670; P:regulation of osteoclast differentiation; TAS:UniProtKB.
 GO:0033081; P:regulation of T cell differentiation in thymus; TAS:UniProtKB.
 GO:0007268; P:synaptic transmission; TAS:Reactome. 

Interpro

 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00069; Pkinase 

SMART

 SM00220; S_TKc 

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS