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Protein

Calcium/calmodulin-dependent protein kinase type 1D

Gene

Camk1d

Organism
Mus musculus (Mouse)
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 (By similarity). Isoform 1 but not isoform 2 activates CREB1.By similarity2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

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 (By similarity).By similarity

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

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

GO - Biological processi

Keywordsi

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

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-KI delta
Short name:
CaMKI delta
CaM kinase ID
CaMKI-like protein kinase
Short name:
CKLiK
Short name:
mCKLiK
Gene namesi
Name:Camk1d
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2442190 Camk1d

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 → D: Catalytically inactive form. 1
Mutagenesisi289 – 292IHES → DEDD: Constitutively active form; when associated with A-301. 1 Publication4
Mutagenesisi301F → A: Constitutively active form; when associated with 289-A--A-292. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860831 – 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)By similarity
Modified residuei122PhosphoserineBy similarity1
Modified residuei180Phosphothreonine; by CaMKK1 and CaMKK2By similarity1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8BW96
PeptideAtlasiQ8BW96
PRIDEiQ8BW96

PTM databases

iPTMnetiQ8BW96
PhosphoSitePlusiQ8BW96

Expressioni

Tissue specificityi

Expressed ubiquitously with high levels in brain and low levels in kidney. Isoform 2 is highly expressed in brain compared to other tissues. In hematopoietic cell lines predominant expression was detected in T and EC cells.1 Publication

Developmental stagei

In EML cell line differentiation, expression increases 4 to 8 hours after treatment with all-trans retinoic acid (ATRA) and then declines after 24 hours of ATRA induction.1 Publication

Inductioni

Down-regulated upon cholesterol-rich diet.1 Publication

Gene expression databases

BgeeiENSMUSG00000039145 Expressed in 226 organ(s), highest expression level in dorsal pancreas
CleanExiMM_CAMK1D
ExpressionAtlasiQ8BW96 baseline and differential
GenevisibleiQ8BW96 MM

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi230634, 1 interactor
IntActiQ8BW96, 2 interactors
MINTiQ8BW96
STRINGi10090.ENSMUSP00000037028

Structurei

3D structure databases

ProteinModelPortaliQ8BW96
SMRiQ8BW96
ModBaseiSearch...
MobiDBiSearch...

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

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
InParanoidiQ8BW96
KOiK08794
OMAiNKLHGQP
OrthoDBiEOG091G0HK9
PhylomeDBiQ8BW96
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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q8BW96-1) [UniParc]FASTAAdd to basket
Also known as: Alpha

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 GDTALSKNIH ESVSAQIRKN
310 320 330 340 350
FAKSKWRQAF NATAVVRHMR RLQLGSSLDS SNASVSSNLS LASQKDCLAP
360 370 380
STLCSFLSSS SGVAGVGAER RPRPTTVTTG HTGSK
Length:385
Mass (Da):42,919
Last modified:December 7, 2004 - v2
Checksum:i320EB0D3D5670055
GO
Isoform 2 (identifier: Q8BW96-2) [UniParc]FASTAAdd to basket
Also known as: Beta

The sequence of this isoform differs from the canonical sequence as follows:
     333-385: ASVSSNLSLA...TVTTGHTGSK → VWHLPRSVVSFLLRRGSQESELRGDPQPPL

Note: Inactive. Does not activate CREB1.
Show »
Length:362
Mass (Da):41,110
Checksum:iF3D0573864293BF5
GO
Isoform 3 (identifier: Q8BW96-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-31: MARENGESSSSWKKQAEDIKKIFEFKETLGT → MAEFVSWSCLNFRWSWIKGSRNS

Show »
Length:377
Mass (Da):42,135
Checksum:iBAC17016D8CF9F91
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti30G → Q in BAC35295 (PubMed:16141072).Curated1
Sequence conflicti327S → N in BAC35295 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0121361 – 31MAREN…ETLGT → MAEFVSWSCLNFRWSWIKGS RNS in isoform 3. 1 PublicationAdd BLAST31
Alternative sequenceiVSP_012137333 – 385ASVSS…HTGSK → VWHLPRSVVSFLLRRGSQES ELRGDPQPPL in isoform 2. 1 PublicationAdd BLAST53

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY273822 mRNA Translation: AAP31673.1
AK052401 mRNA Translation: BAC34975.1
AK053173 mRNA Translation: BAC35295.1
AK147616 mRNA Translation: BAE28027.1
AK154434 mRNA Translation: BAE32584.1
AK170777 mRNA Translation: BAE42022.1
CCDSiCCDS15665.1 [Q8BW96-1]
CCDS70975.1 [Q8BW96-3]
RefSeqiNP_001277303.1, NM_001290374.1
NP_001277304.1, NM_001290375.1
NP_001277305.1, NM_001290376.1 [Q8BW96-3]
NP_796317.2, NM_177343.4 [Q8BW96-1]
UniGeneiMm.191949

Genome annotation databases

EnsembliENSMUST00000044009; ENSMUSP00000037028; ENSMUSG00000039145 [Q8BW96-1]
ENSMUST00000114987; ENSMUSP00000110638; ENSMUSG00000039145 [Q8BW96-3]
GeneIDi227541
KEGGimmu:227541
UCSCiuc008ifp.2 mouse [Q8BW96-1]
uc056zje.1 mouse [Q8BW96-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY273822 mRNA Translation: AAP31673.1
AK052401 mRNA Translation: BAC34975.1
AK053173 mRNA Translation: BAC35295.1
AK147616 mRNA Translation: BAE28027.1
AK154434 mRNA Translation: BAE32584.1
AK170777 mRNA Translation: BAE42022.1
CCDSiCCDS15665.1 [Q8BW96-1]
CCDS70975.1 [Q8BW96-3]
RefSeqiNP_001277303.1, NM_001290374.1
NP_001277304.1, NM_001290375.1
NP_001277305.1, NM_001290376.1 [Q8BW96-3]
NP_796317.2, NM_177343.4 [Q8BW96-1]
UniGeneiMm.191949

3D structure databases

ProteinModelPortaliQ8BW96
SMRiQ8BW96
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi230634, 1 interactor
IntActiQ8BW96, 2 interactors
MINTiQ8BW96
STRINGi10090.ENSMUSP00000037028

PTM databases

iPTMnetiQ8BW96
PhosphoSitePlusiQ8BW96

Proteomic databases

PaxDbiQ8BW96
PeptideAtlasiQ8BW96
PRIDEiQ8BW96

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000044009; ENSMUSP00000037028; ENSMUSG00000039145 [Q8BW96-1]
ENSMUST00000114987; ENSMUSP00000110638; ENSMUSG00000039145 [Q8BW96-3]
GeneIDi227541
KEGGimmu:227541
UCSCiuc008ifp.2 mouse [Q8BW96-1]
uc056zje.1 mouse [Q8BW96-3]

Organism-specific databases

CTDi57118
MGIiMGI:2442190 Camk1d

Phylogenomic databases

eggNOGiKOG0032 Eukaryota
ENOG410XRMJ LUCA
GeneTreeiENSGT00760000118944
HOGENOMiHOG000233016
HOVERGENiHBG108055
InParanoidiQ8BW96
KOiK08794
OMAiNKLHGQP
OrthoDBiEOG091G0HK9
PhylomeDBiQ8BW96
TreeFamiTF314166

Miscellaneous databases

ChiTaRSiCamk1d mouse
PROiPR:Q8BW96
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000039145 Expressed in 226 organ(s), highest expression level in dorsal pancreas
CleanExiMM_CAMK1D
ExpressionAtlasiQ8BW96 baseline and differential
GenevisibleiQ8BW96 MM

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
ProtoNetiSearch...

Entry informationi

Entry nameiKCC1D_MOUSE
AccessioniPrimary (citable) accession number: Q8BW96
Secondary accession number(s): Q3U450, Q80W64, Q8BWI7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 7, 2004
Last modified: November 7, 2018
This is version 139 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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