UniProtKB - Q8IU85 (KCC1D_HUMAN)
Protein
Calcium/calmodulin-dependent protein kinase type 1D
Gene
CAMK1D
Organism
Homo sapiens (Human)
Status
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
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: MGI
- protein serine kinase activity Source: RHEA
- protein threonine kinase activity Source: RHEA
GO - Biological processi
- inflammatory response Source: UniProtKB-KW
- negative regulation of apoptotic process Source: Ensembl
- nervous system development Source: UniProtKB-KW
- peptidyl-serine phosphorylation Source: GO_Central
- positive regulation of apoptotic process Source: Ensembl
- positive regulation of CREB transcription factor activity Source: UniProtKB
- positive regulation of neuron projection development Source: UniProtKB
- positive regulation of neutrophil chemotaxis Source: UniProtKB
- positive regulation of phagocytosis Source: UniProtKB
- positive regulation of respiratory burst Source: UniProtKB
- regulation of dendrite development Source: UniProtKB
- regulation of granulocyte chemotaxis Source: UniProtKB
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 |
PathwayCommonsi | Q8IU85 |
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 | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:19341, CAMK1D |
MIMi | 607957, gene |
neXtProti | NX_Q8IU85 |
VEuPathDBi | HostDB:ENSG00000183049.12 |
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
DisGeNETi | 57118 |
OpenTargetsi | ENSG00000183049 |
PharmGKBi | PA134992438 |
Miscellaneous databases
Pharosi | Q8IU85, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5073 |
DrugBanki | DB12010, Fostamatinib DB08454, N-(5-METHYL-1H-PYRAZOL-3-YL)-2-PHENYLQUINAZOLIN-4-AMINE |
DrugCentrali | Q8IU85 |
GuidetoPHARMACOLOGYi | 1953 |
Genetic variation 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 | Graphical view | 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 conjugationProteomic databases
EPDi | Q8IU85 |
jPOSTi | Q8IU85 |
MassIVEi | Q8IU85 |
MaxQBi | Q8IU85 |
PaxDbi | Q8IU85 |
PeptideAtlasi | Q8IU85 |
PRIDEi | Q8IU85 |
ProteomicsDBi | 70522 [Q8IU85-1] 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 putamen and 222 other tissues |
ExpressionAtlasi | Q8IU85, baseline and differential |
Genevisiblei | Q8IU85, HS |
Organism-specific databases
HPAi | ENSG00000183049, Low tissue specificity |
Interactioni
GO - Molecular functioni
- calmodulin binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 121382, 44 interactors |
IntActi | Q8IU85, 20 interactors |
STRINGi | 9606.ENSP00000478874 |
Chemistry databases
BindingDBi | Q8IU85 |
Miscellaneous databases
RNActi | Q8IU85, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q8IU85 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
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 |
GeneTreei | ENSGT00940000156776 |
InParanoidi | Q8IU85 |
OMAi | RDKFYIV |
OrthoDBi | 25795at2759 |
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 |
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 |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8IU85-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A087WUR6 | A0A087WUR6_HUMAN | Calcium/calmodulin-dependent protei... | CAMK1D | 291 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040599 | 66 | I → M1 PublicationCorresponds to variant dbSNP:rs34194224EnsemblClinVar. | 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 |
CCDSi | CCDS7091.1 [Q8IU85-1] CCDS7092.1 [Q8IU85-2] |
RefSeqi | NP_065130.1, NM_020397.3 [Q8IU85-2] NP_705718.1, NM_153498.3 [Q8IU85-1] |
Genome annotation databases
Ensembli | ENST00000378845; ENSP00000368122; ENSG00000183049 [Q8IU85-2] ENST00000619168; ENSP00000478874; ENSG00000183049 [Q8IU85-1] |
GeneIDi | 57118 |
KEGGi | hsa:57118 |
UCSCi | uc001iln.4, human [Q8IU85-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS7091.1 [Q8IU85-1] CCDS7092.1 [Q8IU85-2] |
RefSeqi | NP_065130.1, NM_020397.3 [Q8IU85-2] NP_705718.1, NM_153498.3 [Q8IU85-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2JC6 | X-ray | 2.30 | A/C | 1-333 | [»] | |
6QP5 | X-ray | 1.90 | A | 10-329 | [»] | |
6T28 | X-ray | 1.55 | AAA | 1-385 | [»] | |
6T29 | X-ray | 1.48 | AAA | 1-385 | [»] | |
6T6F | X-ray | 1.97 | A/B | 10-329 | [»] | |
SMRi | Q8IU85 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 121382, 44 interactors |
IntActi | Q8IU85, 20 interactors |
STRINGi | 9606.ENSP00000478874 |
Chemistry databases
BindingDBi | Q8IU85 |
ChEMBLi | CHEMBL5073 |
DrugBanki | DB12010, Fostamatinib DB08454, N-(5-METHYL-1H-PYRAZOL-3-YL)-2-PHENYLQUINAZOLIN-4-AMINE |
DrugCentrali | Q8IU85 |
GuidetoPHARMACOLOGYi | 1953 |
PTM databases
iPTMneti | Q8IU85 |
PhosphoSitePlusi | Q8IU85 |
Genetic variation databases
BioMutai | CAMK1D |
DMDMi | 56404610 |
Proteomic databases
EPDi | Q8IU85 |
jPOSTi | Q8IU85 |
MassIVEi | Q8IU85 |
MaxQBi | Q8IU85 |
PaxDbi | Q8IU85 |
PeptideAtlasi | Q8IU85 |
PRIDEi | Q8IU85 |
ProteomicsDBi | 70522 [Q8IU85-1] 70523 [Q8IU85-2] |
Protocols and materials databases
Antibodypediai | 1550, 432 antibodies |
DNASUi | 57118 |
Genome annotation databases
Ensembli | ENST00000378845; ENSP00000368122; ENSG00000183049 [Q8IU85-2] ENST00000619168; ENSP00000478874; ENSG00000183049 [Q8IU85-1] |
GeneIDi | 57118 |
KEGGi | hsa:57118 |
UCSCi | uc001iln.4, human [Q8IU85-1] |
Organism-specific databases
CTDi | 57118 |
DisGeNETi | 57118 |
GeneCardsi | CAMK1D |
HGNCi | HGNC:19341, CAMK1D |
HPAi | ENSG00000183049, Low tissue specificity |
MIMi | 607957, gene |
neXtProti | NX_Q8IU85 |
OpenTargetsi | ENSG00000183049 |
PharmGKBi | PA134992438 |
VEuPathDBi | HostDB:ENSG00000183049.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0032, Eukaryota |
GeneTreei | ENSGT00940000156776 |
InParanoidi | Q8IU85 |
OMAi | RDKFYIV |
OrthoDBi | 25795at2759 |
PhylomeDBi | Q8IU85 |
TreeFami | TF314166 |
Enzyme and pathway databases
BRENDAi | 2.7.11.17, 2681 |
PathwayCommonsi | Q8IU85 |
SignaLinki | Q8IU85 |
SIGNORi | Q8IU85 |
Miscellaneous databases
BioGRID-ORCSi | 57118, 3 hits in 1021 CRISPR screens |
ChiTaRSi | CAMK1D, human |
EvolutionaryTracei | Q8IU85 |
GenomeRNAii | 57118 |
Pharosi | Q8IU85, Tchem |
PROi | PR:Q8IU85 |
RNActi | Q8IU85, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000183049, Expressed in putamen and 222 other tissues |
ExpressionAtlasi | Q8IU85, baseline and differential |
Genevisiblei | Q8IU85, HS |
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 |
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 |
ProtoNeti | Search... |
MobiDBi | Search... |
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: | April 7, 2021 | |
This is version 172 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, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families