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UniProtKB - Q16566 (KCC4_HUMAN)

Entry version 197 (25 May 2022)
Sequence version 1 (01 Nov 1996)
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Protein

Calcium/calmodulin-dependent protein kinase type IV

Gene

CAMK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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.

8 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activated by Ca2+/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 Ca2+/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.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei75ATPPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei164Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi52 – 60ATPPROSITE-ProRule annotation9

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>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

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		2.7.11.17, 2681

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		Q16566

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-111932, CaMK IV-mediated phosphorylation of CREB
R-HSA-2151201, Transcriptional activation of mitochondrial biogenesis
R-HSA-442729, CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde
R-HSA-9022535, Loss of phosphorylation of MECP2 at T308
R-HSA-9022692, Regulation of MECP2 expression and activity
R-HSA-9617324, Negative regulation of NMDA receptor-mediated neuronal transmission

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		Q16566

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q16566

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:CAMK4
Synonyms:CAMK, CAMK-GR, CAMKIV
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 5

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:1464, CAMK4

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		114080, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q16566

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000152495

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi12S → A: Loss of activity. 1 Publication1
Mutagenesisi13S → A: Loss of activity. 1 Publication1
Mutagenesisi57 – 58TS → AA: Loss of phosphorylation of CREB1. 1 Publication2
Mutagenesisi75K → E: Loss of activity; dominant negative form. 1 Publication1
Mutagenesisi189S → A: Increases phosphorylation of CREB1 2-fold. Decreases total O-linked glycosylation 2-fold. Increases ATP-binding affinity. 1 Publication1
Mutagenesisi200T → A: Loss of activation by CaMKK1 or CaMKK2. 1 Publication1
Mutagenesisi309 – 312HMDT → DEDD: Fully active Ca2+/CaM-independent kinase; when associated with 320-A-A-321. 1 Publication4
Mutagenesisi320 – 321FN → DD: Fully active Ca2+/CaM-independent kinase; when associated with 309-A--A-312. Loss of interaction with PPP2CA/PPP2CB. 2 Publications2

Organism-specific databases

DisGeNET

More...DisGeNETi		814

Open Targets

More...OpenTargetsi		ENSG00000152495

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA26050

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q16566, Tbio

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL2494

Drug and drug target database

More...DrugBanki		DB07676, 3-({[(3S)-3,4-dihydroxybutyl]oxy}amino)-1H,2'H-2,3'-biindol-2'-one
DB07664, K-00546

DrugCentral

More...DrugCentrali		Q16566

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		CAMK4

Domain mapping of disease mutations (DMDM)

More...DMDMi		2499586

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000861061 – 473Calcium/calmodulin-dependent protein kinase type IVAdd BLAST473

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei12Phosphoserine; by autocatalysis1 Publication1
Modified residuei13Phosphoserine; by autocatalysis1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi57O-linked (GlcNAc) threonine1 Publication1
Glycosylationi58O-linked (GlcNAc) serine1 Publication1
Glycosylationi137O-linked (GlcNAc) serine1 Publication1
Glycosylationi189O-linked (GlcNAc) serine1 Publication1
Modified residuei200Phosphothreonine; by CaMKK1 and CaMKK23 Publications1
Modified residuei336Phosphoserine; by autocatalysisBy similarity1
Modified residuei341PhosphoserineBy similarity1
Glycosylationi344O-linked (GlcNAc) serine1 Publication1
Glycosylationi345O-linked (GlcNAc) serine1 Publication1
Glycosylationi356O-linked (GlcNAc) serine1 Publication1
Modified residuei360PhosphoserineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylated by CaMKK1 and CaMKK2 on Thr-200. Dephosphorylated by protein phosphatase 2A. Autophosphorylated on Ser-12 and Ser-13.3 Publications
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.3 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		Q16566

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q16566

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q16566

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q16566

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q16566

PeptideAtlas

More...PeptideAtlasi		Q16566

PRoteomics IDEntifications database

More...PRIDEi		Q16566

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		60921

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		Q16566, 7 sites, 1 O-linked glycan (3 sites)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q16566

MetOSite database of methionine sulfoxide sites

More...MetOSitei		Q16566

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q16566

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in brain, thymus, CD4 T-cells, testis and epithelial ovarian cancer tissue.3 Publications

<p>This subsection of the 'Expression' section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified 'at the protein level'.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stagei

Expressed during differentiation of monocyte-derived dendritic cells (at protein level).1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000152495, Expressed in caudate nucleus and 164 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q16566, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q16566, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000152495, Group enriched (brain, lymphoid tissue)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer (By similarity).

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

By similarity2 Publications

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		107264, 26 interactors

Database of interacting proteins

More...DIPi		DIP-41997N

Protein interaction database and analysis system

More...IntActi		Q16566, 30 interactors

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000282356

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		Q16566

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q16566, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1473
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

AlphaFold Protein Structure Database

More...AlphaFoldDBi		Q16566

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q16566

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		Q16566

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini46 – 300Protein kinasePROSITE-ProRule annotationAdd BLAST255

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni305 – 321Autoinhibitory domainAdd BLAST17
Regioni306 – 323PP2A-bindingAdd BLAST18
Regioni322 – 341Calmodulin-bindingSequence analysisAdd BLAST20
Regioni341 – 368DisorderedSequence analysisAdd BLAST28
Regioni445 – 473DisorderedSequence analysisAdd BLAST29

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular type of amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi351 – 368Basic and acidic residuesSequence analysisAdd BLAST18

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate.1 Publication

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG0032, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000160006

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_000288_63_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q16566

Identification of Orthologs from Complete Genome Data

More...OMAi		TKMVPEA

Database of Orthologous Groups

More...OrthoDBi		330091at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q16566

TreeFam database of animal gene trees

More...TreeFami		TF351230

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR011009, Kinase-like_dom_sf
IPR000719, Prot_kinase_dom
IPR017441, Protein_kinase_ATP_BS
IPR008271, Ser/Thr_kinase_AS

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00069, Pkinase, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00220, S_TKc, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF56112, SSF56112, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS00107, PROTEIN_KINASE_ATP, 1 hit
PS50011, PROTEIN_KINASE_DOM, 1 hit
PS00108, PROTEIN_KINASE_ST, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

Q16566-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLKVTVPSCS ASSCSSVTAS AAPGTASLVP DYWIDGSNRD ALSDFFEVES 
        60         70         80         90        100
ELGRGATSIV YRCKQKGTQK PYALKVLKKT VDKKIVRTEI GVLLRLSHPN 
       110        120        130        140        150
IIKLKEIFET PTEISLVLEL VTGGELFDRI VEKGYYSERD AADAVKQILE 
       160        170        180        190        200
AVAYLHENGI VHRDLKPENL LYATPAPDAP LKIADFGLSK IVEHQVLMKT 
       210        220        230        240        250
VCGTPGYCAP EILRGCAYGP EVDMWSVGII TYILLCGFEP FYDERGDQFM 
       260        270        280        290        300
FRRILNCEYY FISPWWDEVS LNAKDLVRKL IVLDPKKRLT TFQALQHPWV 
       310        320        330        340        350
TGKAANFVHM DTAQKKLQEF NARRKLKAAV KAVVASSRLG SASSSHGSIQ 
       360        370        380        390        400
ESHKASRDPS PIQDGNEDMK AIPEGEKIQG DGAQAAVKGA QAELMKVQAL 
       410        420        430        440        450
EKVKGADINA EEAPKMVPKA VEDGIKVADL ELEEGLAEEK LKTVEEAAAP 
       460        470 
REGQGSSAVG FEVPQQDVIL PEY
Length:473
Mass (Da):51,926
Last modified:November 1, 1996 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iEFEE51E5612326DC
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RE65D6RE65_HUMAN
Calcium/calmodulin-dependent protei...
CAMK4
142Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
D6REY7D6REY7_HUMAN
Calcium/calmodulin-dependent protei...
CAMK4
109Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
D6RCD6D6RCD6_HUMAN
Calcium/calmodulin-dependent protei...
CAMK4
88Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAH16695 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_040604150E → G in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040605178D → N1 PublicationCorresponds to variant dbSNP:rs35548075EnsemblClinVar.1
Natural variantiVAR_040606465Q → R1 PublicationCorresponds to variant dbSNP:rs56360861EnsemblClinVar.1
Natural variantiVAR_040607469I → M in a lung large cell carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1239950009Ensembl.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
D30742 mRNA Translation: BAA06403.1
L17000 mRNA Translation: AAA35639.1
L24959 mRNA Translation: AAA18251.1
CH471086 Genomic DNA Translation: EAW49033.1
CH471086 Genomic DNA Translation: EAW49034.1
BC016695 mRNA Translation: AAH16695.2 Different initiation.
BC025687 mRNA Translation: AAH25687.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS4103.1

Protein sequence database of the Protein Information Resource

More...PIRi		A53036

NCBI Reference Sequences

More...RefSeqi		NP_001310303.1, NM_001323374.1
NP_001310304.1, NM_001323375.1
NP_001735.1, NM_001744.5

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000282356.9; ENSP00000282356.4; ENSG00000152495.11
ENST00000512453.5; ENSP00000422634.1; ENSG00000152495.11

Database of genes from NCBI RefSeq genomes

More...GeneIDi		814

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:814

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000282356.9; ENSP00000282356.4; NM_001744.6; NP_001735.1

UCSC genome browser

More...UCSCi		uc003kpf.4, human

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D30742 mRNA Translation: BAA06403.1
L17000 mRNA Translation: AAA35639.1
L24959 mRNA Translation: AAA18251.1
CH471086 Genomic DNA Translation: EAW49033.1
CH471086 Genomic DNA Translation: EAW49034.1
BC016695 mRNA Translation: AAH16695.2 Different initiation.
BC025687 mRNA Translation: AAH25687.1
CCDSiCCDS4103.1
PIRiA53036
RefSeqiNP_001310303.1, NM_001323374.1
NP_001310304.1, NM_001323375.1
NP_001735.1, NM_001744.5

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2W4OX-ray2.17A15-340[»]
AlphaFoldDBiQ16566
SMRiQ16566
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi107264, 26 interactors
DIPiDIP-41997N
IntActiQ16566, 30 interactors
STRINGi9606.ENSP00000282356

Chemistry databases

BindingDBiQ16566
ChEMBLiCHEMBL2494
DrugBankiDB07676, 3-({[(3S)-3,4-dihydroxybutyl]oxy}amino)-1H,2'H-2,3'-biindol-2'-one
DB07664, K-00546
DrugCentraliQ16566

PTM databases

GlyGeniQ16566, 7 sites, 1 O-linked glycan (3 sites)
iPTMnetiQ16566
MetOSiteiQ16566
PhosphoSitePlusiQ16566

Genetic variation databases

BioMutaiCAMK4
DMDMi2499586

Proteomic databases

EPDiQ16566
jPOSTiQ16566
MassIVEiQ16566
MaxQBiQ16566
PaxDbiQ16566
PeptideAtlasiQ16566
PRIDEiQ16566
ProteomicsDBi60921

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		2084, 626 antibodies from 42 providers

The DNASU plasmid repository

More...DNASUi		814

Genome annotation databases

EnsembliENST00000282356.9; ENSP00000282356.4; ENSG00000152495.11
ENST00000512453.5; ENSP00000422634.1; ENSG00000152495.11
GeneIDi814
KEGGihsa:814
MANE-SelectiENST00000282356.9; ENSP00000282356.4; NM_001744.6; NP_001735.1
UCSCiuc003kpf.4, human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		814
DisGeNETi814

GeneCards: human genes, protein and diseases

More...GeneCardsi		CAMK4
HGNCiHGNC:1464, CAMK4
HPAiENSG00000152495, Group enriched (brain, lymphoid tissue)
MIMi114080, gene
neXtProtiNX_Q16566
OpenTargetsiENSG00000152495
PharmGKBiPA26050
VEuPathDBiHostDB:ENSG00000152495

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG0032, Eukaryota
GeneTreeiENSGT00940000160006
HOGENOMiCLU_000288_63_0_1
InParanoidiQ16566
OMAiTKMVPEA
OrthoDBi330091at2759
PhylomeDBiQ16566
TreeFamiTF351230

Enzyme and pathway databases

BRENDAi2.7.11.17, 2681
PathwayCommonsiQ16566
ReactomeiR-HSA-111932, CaMK IV-mediated phosphorylation of CREB
R-HSA-2151201, Transcriptional activation of mitochondrial biogenesis
R-HSA-442729, CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde
R-HSA-9022535, Loss of phosphorylation of MECP2 at T308
R-HSA-9022692, Regulation of MECP2 expression and activity
R-HSA-9617324, Negative regulation of NMDA receptor-mediated neuronal transmission
SignaLinkiQ16566
SIGNORiQ16566

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		814, 5 hits in 1104 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		CAMK4, human
EvolutionaryTraceiQ16566

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		CAMK4

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		814
PharosiQ16566, Tbio

Protein Ontology

More...PROi		PR:Q16566
RNActiQ16566, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000152495, Expressed in caudate nucleus and 164 other tissues
ExpressionAtlasiQ16566, baseline and differential
GenevisibleiQ16566, HS

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

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiKCC4_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q16566
Secondary accession number(s): D3DSZ7
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: May 25, 2022
This is version 197 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with genetic variants
    List of human entries with genetic variants
  4. Human variants curated from literature reports
    Index of human variants curated from literature reports
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families
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