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Protein

Calcium/calmodulin-dependent protein kinase type 1D

Gene

Camk1d

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

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 (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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Inflammatory response, Neurogenesis

Keywords - Ligandi

ATP-binding, Calcium, Calmodulin-binding, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2442190. Camk1d.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Predominantly cytoplasmic. Nuclear upon activation.By similarity

GO - Cellular componenti

Complete GO annotation...

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.
CleanExiMM_CAMK1D.
ExpressionAtlasiQ8BW96. baseline and differential.
GenevisibleiQ8BW96. MM.

Interactioni

Protein-protein interaction databases

BioGridi230634. 1 interactor.
IntActiQ8BW96. 2 interactors.
MINTiMINT-4099544.
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

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

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

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.
MINTiMINT-4099544.
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.
OMAiTGHTGSK.
OrthoDBiEOG091G0HK9.
PhylomeDBiQ8BW96.
TreeFamiTF314166.

Miscellaneous databases

ChiTaRSiCamk1d. mouse.
PROiQ8BW96.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000039145.
CleanExiMM_CAMK1D.
ExpressionAtlasiQ8BW96. baseline and differential.
GenevisibleiQ8BW96. MM.

Family and domain databases

InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKCC1D_MOUSE
AccessioniPrimary (citable) accession number: Q8BW96
Secondary accession number(s): Q3U450, Q80W64, Q8BWI7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 7, 2004
Last modified: November 2, 2016
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.