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Protein

Calcium/calmodulin-dependent protein kinase type 1D

Gene

CAMK1D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

Enzyme 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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei52ATPPROSITE-ProRule annotation1
Active sitei144Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi29 – 37ATPPROSITE-ProRule annotation9

GO - Molecular functioni

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
  • 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 functionAllosteric enzyme, Calmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase
Biological processInflammatory response, Neurogenesis
LigandATP-binding, Calcium, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.17 2681
SignaLinkiQ8IU85
SIGNORiQ8IU85

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000183049.12
HGNCiHGNC:19341 CAMK1D
MIMi607957 gene
neXtProtiNX_Q8IU85

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi52K → A: Catalytically inactive form. 1 Publication1
Mutagenesisi180T → A: Loss of ionomycin-induced activation. 2 Publications1

Organism-specific databases

DisGeNETi57118
OpenTargetsiENSG00000183049
PharmGKBiPA134992438

Chemistry databases

ChEMBLiCHEMBL5073
DrugBankiDB08454 N-(5-METHYL-1H-PYRAZOL-3-YL)-2-PHENYLQUINAZOLIN-4-AMINE
GuidetoPHARMACOLOGYi1953

Polymorphism and mutation databases

BioMutaiCAMK1D
DMDMi56404610

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860821 – 385Calcium/calmodulin-dependent protein kinase type 1DAdd BLAST385

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki113Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei122PhosphoserineCombined sources1
Modified residuei180Phosphothreonine; by CaMKK1 and CaMKK2Combined sources1 Publication1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8IU85
MaxQBiQ8IU85
PaxDbiQ8IU85
PeptideAtlasiQ8IU85
PRIDEiQ8IU85
ProteomicsDBi70522
70523 [Q8IU85-2]

PTM databases

iPTMnetiQ8IU85
PhosphoSitePlusiQ8IU85

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

BgeeiENSG00000183049
CleanExiHS_CAMK1D
ExpressionAtlasiQ8IU85 baseline and differential
GenevisibleiQ8IU85 HS

Organism-specific databases

HPAiHPA007266

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121382, 37 interactors
IntActiQ8IU85, 8 interactors
STRINGi9606.ENSP00000368124

Chemistry databases

BindingDBiQ8IU85

Structurei

Secondary structure

1385
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi13 – 15Combined sources3
Helixi19 – 22Combined sources4
Beta strandi23 – 31Combined sources9
Beta strandi36 – 42Combined sources7
Turni43 – 45Combined sources3
Beta strandi48 – 55Combined sources8
Helixi66 – 75Combined sources10
Beta strandi84 – 89Combined sources6
Beta strandi91 – 99Combined sources9
Helixi106 – 112Combined sources7
Helixi118 – 137Combined sources20
Helixi147 – 149Combined sources3
Beta strandi150 – 156Combined sources7
Beta strandi161 – 163Combined sources3
Helixi190 – 193Combined sources4
Helixi201 – 216Combined sources16
Helixi226 – 235Combined sources10
Turni242 – 247Combined sources6
Helixi250 – 259Combined sources10
Turni264 – 266Combined sources3
Helixi270 – 273Combined sources4
Helixi277 – 280Combined sources4
Helixi290 – 300Combined sources11
Helixi305 – 311Combined sources7

3D structure databases

ProteinModelPortaliQ8IU85
SMRiQ8IU85
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8IU85

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 279Protein kinasePROSITE-ProRule annotationAdd BLAST257

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni279 – 319Autoinhibitory domainBy similarityAdd BLAST41
Regioni299 – 320Calmodulin-bindingBy similarityAdd BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi318 – 324Nuclear export signalBy similarity7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi326 – 364Ser-richAdd BLAST39

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

Phylogenomic databases

eggNOGiKOG0032 Eukaryota
ENOG410XRMJ LUCA
GeneTreeiENSGT00760000118944
HOGENOMiHOG000233016
HOVERGENiHBG108055
InParanoidiQ8IU85
KOiK08794
OMAiRMFAVKC
OrthoDBiEOG091G0HK9
PhylomeDBiQ8IU85
TreeFamiTF314166

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

Sequences (2)i

Sequence statusi: Complete.

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

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

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

Show »
Length:357
Mass (Da):40,190
Checksum:i1FA184EEFA976FB4
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04059966I → M1 PublicationCorresponds to variant dbSNP:rs34194224Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012135348 – 385LAPST…HSGSK → AYVAKPESLS in isoform 2. 1 PublicationAdd BLAST38

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
CCDSiCCDS7091.1 [Q8IU85-1]
CCDS7092.1 [Q8IU85-2]
RefSeqiNP_065130.1, NM_020397.3 [Q8IU85-2]
NP_705718.1, NM_153498.3 [Q8IU85-1]
UniGeneiHs.600547
Hs.659517

Genome annotation databases

EnsembliENST00000378845; ENSP00000368122; ENSG00000183049 [Q8IU85-2]
ENST00000619168; ENSP00000478874; ENSG00000183049 [Q8IU85-1]
GeneIDi57118
KEGGihsa:57118
UCSCiuc001iln.4 human [Q8IU85-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKCC1D_HUMAN
AccessioniPrimary (citable) accession number: Q8IU85
Secondary accession number(s): B0YIY0, Q9HD31
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: March 1, 2003
Last modified: June 20, 2018
This is version 153 of the entry and version 1 of the sequence. See complete history.
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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