CAMK1D

Functionⁱ

Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, activates CREB-dependent gene transcription, regulates calcium-mediated granulocyte function and respiratory burst and promotes basal dendritic growth of hippocampal neurons. In neutrophil cells, required for cytokine-induced proliferative responses and activation of the respiratory burst. Activates the transcription factor CREB1 in hippocampal neuron nuclei. May play a role in apoptosis of erythroleukemia cells. In vitro, phosphorylates transcription factor CREM isoform Beta.4 Publications

Catalytic activityⁱ

ATP + a protein = ADP + a phosphoprotein.1 Publication

Activity regulationⁱ

Activated by Ca²⁺/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-180 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-180 results in several fold increase in total activity. Unlike CaMK4, may be unable to exhibit autonomous activity after Ca²⁺/calmodulin activation.2 Publications

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	52	ATPPROSITE-ProRule annotation		1
Active siteⁱ	144	Proton acceptorPROSITE-ProRule annotation		1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	29 – 37	ATPPROSITE-ProRule annotation		9

GO - Molecular functionⁱ

ATP binding Source: UniProtKB-KW
calmodulin binding Source: GO_Central
calmodulin-dependent protein kinase activity Source: GO_Central

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

inflammatory response Source: UniProtKB-KW
intracellular signal transduction Source: GO_Central
negative regulation of apoptotic process Source: Ensembl
peptidyl-serine phosphorylation Source: GO_Central
peptidyl-threonine phosphorylation Source: GO_Central
positive regulation of apoptotic process Source: Ensembl
positive regulation of CREB transcription factor activity
Source: UniProtKB
Inferred from direct assayⁱ
- 16324104
positive regulation of neuron projection development Source: UniProtKB
positive regulation of neutrophil chemotaxis Source: UniProtKB
positive regulation of phagocytosis
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 15840691
positive regulation of respiratory burst
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 15840691
regulation of dendrite development
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 17056143
regulation of granulocyte chemotaxis
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 15840691

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Allosteric enzyme, Calmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase
Biological process	Inflammatory response, Neurogenesis
Ligand	ATP-binding, Calcium, Nucleotide-binding

Enzyme and pathway databases

BRENDAⁱ	2.7.11.17 2681
SignaLinkⁱ	Q8IU85
SIGNORⁱ	Q8IU85

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Calcium/calmodulin-dependent protein kinase type 1D (EC:2.7.11.17) Alternative name(s): CaM kinase I delta Short name: CaM kinase ID Short name: CaM-KI delta Short name: CaMKI delta Short name: CaMKID CaMKI-like protein kinase Short name: CKLiK
Gene namesⁱ	Name:CAMK1D Synonyms:CAMKID
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 10

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000183049.12
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:19341 CAMK1D
MIMⁱ	607957 gene
neXtProtⁱ	NX_Q8IU85

Keywords - Cellular componentⁱ

Cytoplasm, Nucleus

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	52	K → A: Catalytically inactive form. 1 Publication		1
Mutagenesisⁱ	180	T → A: Loss of ionomycin-induced activation. 2 Publications		1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	57118
Open Targets More...OpenTargetsⁱ	ENSG00000183049
PharmGKBⁱ	PA134992438

Chemistry databases

ChEMBLⁱ	CHEMBL5073
Drug and drug target database More...DrugBankⁱ	DB08454 N-(5-METHYL-1H-PYRAZOL-3-YL)-2-PHENYLQUINAZOLIN-4-AMINE
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	1953

Polymorphism and mutation databases

BioMutaⁱ	CAMK1D
DMDMⁱ	56404610

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000086082	1 – 385	Calcium/calmodulin-dependent protein kinase type 1DAdd BLAST		385

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Cross-linkⁱ	113	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residueⁱ	122	PhosphoserineCombined sources	1
Modified residueⁱ	180	Phosphothreonine; by CaMKK1 and CaMKK2Combined sources1 Publication	1

Keywords - PTMⁱ

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDⁱ	Q8IU85
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q8IU85
PaxDbⁱ	Q8IU85
PeptideAtlas More...PeptideAtlasⁱ	Q8IU85
PRIDEⁱ	Q8IU85
ProteomicsDBⁱ	70522 70523 [Q8IU85-2]

PTM databases

iPTMnetⁱ	Q8IU85
PhosphoSitePlusⁱ	Q8IU85

Expressionⁱ

Tissue specificityⁱ

Widely expressed. Highly and mostly expressed in polymorphonuclear leukocytes (neutrophilic and eosinophilic granulocytes) while little or no expression is observed in monocytes and lymphocytes.3 Publications

Developmental stageⁱ

Expressed during hippocampal formation with high expression in the pyramidal cell layers.2 Publications

Inductionⁱ

Expression increases upon treatment of EC cells with DMSO and retinoic acid. Induced by KCL in PC12 cells.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000183049 Expressed in 207 organ(s), highest expression level in putamen
CleanExⁱ	HS_CAMK1D
ExpressionAtlasⁱ	Q8IU85 baseline and differential
Genevisibleⁱ	Q8IU85 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA007266

HPAⁱ

HPA007266

Interactionⁱ

GO - Molecular functionⁱ

calmodulin binding Source: GO_Central

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	121382, 37 interactors
IntActⁱ	Q8IU85, 8 interactors
STRINGⁱ	9606.ENSP00000368124

Chemistry databases

BindingDBⁱ	Q8IU85

BindingDBⁱ

Q8IU85

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	13 – 15	Combined sources	3
Helixⁱ	19 – 22	Combined sources	4
Beta strandⁱ	23 – 31	Combined sources	9
Beta strandⁱ	36 – 42	Combined sources	7
Turnⁱ	43 – 45	Combined sources	3
Beta strandⁱ	48 – 55	Combined sources	8
Helixⁱ	66 – 75	Combined sources	10
Beta strandⁱ	84 – 89	Combined sources	6
Beta strandⁱ	91 – 99	Combined sources	9
Helixⁱ	106 – 112	Combined sources	7
Helixⁱ	118 – 137	Combined sources	20
Helixⁱ	147 – 149	Combined sources	3
Beta strandⁱ	150 – 156	Combined sources	7
Beta strandⁱ	161 – 163	Combined sources	3
Helixⁱ	190 – 193	Combined sources	4
Helixⁱ	201 – 216	Combined sources	16
Helixⁱ	226 – 235	Combined sources	10
Turnⁱ	242 – 247	Combined sources	6
Helixⁱ	250 – 259	Combined sources	10
Turnⁱ	264 – 266	Combined sources	3
Helixⁱ	270 – 273	Combined sources	4
Helixⁱ	277 – 280	Combined sources	4
Helixⁱ	290 – 300	Combined sources	11
Helixⁱ	305 – 311	Combined sources	7

Show more details

3D structure databases

ProteinModelPortalⁱ	Q8IU85
SMRⁱ	Q8IU85
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q8IU85

EvolutionaryTraceⁱ

Q8IU85

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	23 – 279	Protein kinasePROSITE-ProRule annotationAdd BLAST		257

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	279 – 319	Autoinhibitory domainBy similarityAdd BLAST		41
Regionⁱ	299 – 320	Calmodulin-bindingBy similarityAdd BLAST		22

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	318 – 324	Nuclear export signalBy similarity		7

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	326 – 364	Ser-richAdd BLAST		39

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

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

Phylogenomic databases

eggNOGⁱ	KOG0032 Eukaryota ENOG410XRMJ LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000118944
HOGENOMⁱ	HOG000233016
HOVERGENⁱ	HBG108055
InParanoidⁱ	Q8IU85
KEGG Orthology (KO) More...KOⁱ	K08794
OMAⁱ	RMFAVKC
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0HK9
PhylomeDBⁱ	Q8IU85
TreeFamⁱ	TF314166

Family and domain databases

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
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2+)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.ⁱShow all

Isoform 1 (identifier: Q8IU85-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MARENGESSS SWKKQAEDIK KIFEFKETLG TGAFSEVVLA EEKATGKLFA 
        60         70         80         90        100
VKCIPKKALK GKESSIENEI AVLRKIKHEN IVALEDIYES PNHLYLVMQL 
       110        120        130        140        150
VSGGELFDRI VEKGFYTEKD ASTLIRQVLD AVYYLHRMGI VHRDLKPENL 
       160        170        180        190        200
LYYSQDEESK IMISDFGLSK MEGKGDVMST ACGTPGYVAP EVLAQKPYSK 
       210        220        230        240        250
AVDCWSIGVI AYILLCGYPP FYDENDSKLF EQILKAEYEF DSPYWDDISD 
       260        270        280        290        300
SAKDFIRNLM EKDPNKRYTC EQAARHPWIA GDTALNKNIH ESVSAQIRKN 
       310        320        330        340        350
FAKSKWRQAF NATAVVRHMR KLHLGSSLDS SNASVSSSLS LASQKDCLAP 
       360        370        380 
STLCSFISSS SGVSGVGAER RPRPTTVTAV HSGSK

Length:385

Mass (Da):42,914

Last modified:March 1, 2003 - v1

Checksum:ⁱ717467D019E30FC9

GO

Isoform 2 (identifier: Q8IU85-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
348-385: LAPSTLCSFISSSSGVSGVGAERRPRPTTVTAVHSGSK → AYVAKPESLS

« Hide

        10         20         30         40         50
MARENGESSS SWKKQAEDIK KIFEFKETLG TGAFSEVVLA EEKATGKLFA 
        60         70         80         90        100
VKCIPKKALK GKESSIENEI AVLRKIKHEN IVALEDIYES PNHLYLVMQL 
       110        120        130        140        150
VSGGELFDRI VEKGFYTEKD ASTLIRQVLD AVYYLHRMGI VHRDLKPENL 
       160        170        180        190        200
LYYSQDEESK IMISDFGLSK MEGKGDVMST ACGTPGYVAP EVLAQKPYSK 
       210        220        230        240        250
AVDCWSIGVI AYILLCGYPP FYDENDSKLF EQILKAEYEF DSPYWDDISD 
       260        270        280        290        300
SAKDFIRNLM EKDPNKRYTC EQAARHPWIA GDTALNKNIH ESVSAQIRKN 
       310        320        330        340        350
FAKSKWRQAF NATAVVRHMR KLHLGSSLDS SNASVSSSLS LASQKDCAYV 

AKPESLS

Show »

Length:357

Mass (Da):40,190

Checksum:ⁱ1FA184EEFA976FB4

GO

Computationally mapped potential isoform sequencesⁱ

There is 1 potential isoform mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation
	A0A087WUR6	A0A087WUR6_HUMAN		Calcium/calmodulin-dependent protei... Calcium/calmodulin-dependent protein kinase type 1D	CAMK1D	291	Annotation score:

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_040599	66	I → M1 PublicationCorresponds to variant dbSNP:rs34194224Ensembl.		1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_012135	348 – 385	LAPST…HSGSK → AYVAKPESLS in isoform 2. 1 PublicationAdd BLAST		38

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF286366 mRNA Translation: AAG00534.1 AB081726 mRNA Translation: BAC19846.1 EF444962 Genomic DNA Translation: ACA05959.1 AL391314 Genomic DNA No translation available. AL512284 Genomic DNA No translation available. AL512783 Genomic DNA No translation available. AL731559 Genomic DNA No translation available. CH471072 Genomic DNA Translation: EAW86314.1 BC035745 mRNA Translation: AAH35745.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS7091.1 [Q8IU85-1] CCDS7092.1 [Q8IU85-2]
NCBI Reference Sequences More...RefSeqⁱ	NP_065130.1, NM_020397.3 [Q8IU85-2] NP_705718.1, NM_153498.3 [Q8IU85-1]
UniGeneⁱ	Hs.600547 Hs.659517

Genome annotation databases

Ensemblⁱ	ENST00000378845; ENSP00000368122; ENSG00000183049 [Q8IU85-2] ENST00000619168; ENSP00000478874; ENSG00000183049 [Q8IU85-1]
GeneIDⁱ	57118
KEGGⁱ	hsa:57118
UCSC genome browser More...UCSCⁱ	uc001iln.4 human [Q8IU85-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q8IU85	Calcium/calmodulin dependent protein kinase ID		MACMU		385	UniRef100_Q8IU85
CAMK1D isoform 1		PANTR		385
CAMK1D isoform 1		PONAB		385
Calcium/calmodulin dependent protein kinase ID		CERAT		385
Calcium/calmodulin dependent protein kinase ID		RHIRO		385
+6
Q8IU85-2	Calcium/calmodulin-dependent protein kinase ID, isoform CRA_b		HUMAN		357	UniRef100_Q5SQQ7
CAMK1D isoform 3		PANTR		357
Calcium/calmodulin-dependent protein kinase type 1D isoform 1		MACMU		357
CAMK1D isoform 3		PONAB		357
Calcium/calmodulin dependent protein kinase ID		PAPAN		357
+1

Protein	Similar proteins		Species	Score	Length	Source
Q8IU85	Calcium/calmodulin-dependent protein kinase type 1D		MOUSE		385	UniRef90_Q8IU85
Calcium/calmodulin dependent protein kinase ID		MACMU		385
CAMK1D isoform 1		PANTR		385
CAMK1D isoform 1		PONAB		385
Calcium/calmodulin dependent protein kinase ID		CERAT		385
+110

Protein	Similar proteins		Species	Score	Length	Source
Q8IU85	Calcium/calmodulin-dependent protein kinase type 1D		MOUSE		385	UniRef50_Q8IU85
Calcium/calmodulin dependent protein kinase ID		MACMU		385
CAMK1D isoform 1		PANTR		385
CAMK1D isoform 1		PONAB		385
Calcium/calmodulin dependent protein kinase ID		CERAT		385
+249

Entry informationⁱ

Entry nameⁱ	KCC1D_HUMAN
Accessionⁱ	Q8IU85Primary (citable) accession number: Q8IU85 Secondary accession number(s): B0YIY0, Q9HD31
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	December 7, 2004
	Last sequence update:	March 1, 2003
	Last modified:	September 12, 2018
	This is version 154 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q8IU85 (KCC1D_HUMAN)

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Calcium/calmodulin-dependent protein kinase type 1D

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<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

Sites

Regions

<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

GO - Biological processi

Enzyme and pathway databases

<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

Organism-specific databases

<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

Nucleus

Other locations

Nucleus

Other locations

Keywords - Cellular componenti

<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

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<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

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<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

Gene expression databases

Organism-specific databases

<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

GO - Molecular functioni

Protein-protein interaction databases

Chemistry databases

<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

3D structure databases

Miscellaneous databases

<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

Region

Motif

Compositional bias

<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

Phylogenomic databases

Family and domain databases

Computationally mapped potential isoform sequencesi

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<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 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

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Computationally mapped potential isoform sequencesⁱ

Keywords - Coding sequence diversityⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ