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Q8BW96 (KCC1D_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Camk1d
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length385 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.4

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

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.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Note: Predominantly cytoplasmic By similarity. Nuclear upon activation By similarity.

Tissue specificity

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. Ref.1

Developmental stage

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. Ref.4

Induction

Down-regulated upon cholesterol-rich diet. Ref.2

Domain

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 similarities

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

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processInflammatory response
Neurogenesis
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Calcium
Calmodulin-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termAllosteric enzyme
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processinflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of apoptotic process

Inferred from direct assay Ref.1. Source: MGI

positive regulation of CREB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of apoptotic process

Inferred from direct assay Ref.1. Source: MGI

positive regulation of neuron projection development

Inferred from mutant phenotype Ref.4. Source: UniProtKB

positive regulation of neutrophil chemotaxis

Inferred from mutant phenotype Ref.4. Source: UniProtKB

positive regulation of phagocytosis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of respiratory burst

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of dendrite development

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of granulocyte chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calmodulin-dependent protein kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8BW96-1)

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.
Isoform 2 (identifier: Q8BW96-2)

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.
Isoform 3 (identifier: Q8BW96-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 385385Calcium/calmodulin-dependent protein kinase type 1D
PRO_0000086083

Regions

Domain23 – 279257Protein kinase
Nucleotide binding29 – 379ATP By similarity
Region279 – 31941Autoinhibitory domain By similarity
Region299 – 32022Calmodulin-binding By similarity
Motif318 – 3247Nuclear export signal By similarity

Sites

Active site1441Proton acceptor By similarity
Binding site521ATP By similarity

Amino acid modifications

Modified residue1221Phosphoserine By similarity
Modified residue1801Phosphothreonine; by CaMKK1 and CaMKK2 By similarity

Natural variations

Alternative sequence1 – 3131MAREN…ETLGT → MAEFVSWSCLNFRWSWIKGS RNS in isoform 3.
VSP_012136
Alternative sequence333 – 38553ASVSS…HTGSK → VWHLPRSVVSFLLRRGSQES ELRGDPQPPL in isoform 2.
VSP_012137

Experimental info

Mutagenesis521K → D: Catalytically inactive form.
Mutagenesis289 – 2924IHES → DEDD: Constitutively active form; when associated with A-301. Ref.4
Mutagenesis3011F → A: Constitutively active form; when associated with 289-A--A-292. Ref.4
Sequence conflict301G → Q in BAC35295. Ref.3
Sequence conflict3271S → N in BAC35295. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) [UniParc].

Last modified December 7, 2004. Version 2.
Checksum: 320EB0D3D5670055

FASTA38542,919
        10         20         30         40         50         60 
MARENGESSS SWKKQAEDIK KIFEFKETLG TGAFSEVVLA EEKATGKLFA VKCIPKKALK 

        70         80         90        100        110        120 
GKESSIENEI AVLRKIKHEN IVALEDIYES PNHLYLVMQL VSGGELFDRI VEKGFYTEKD 

       130        140        150        160        170        180 
ASTLIRQVLD AVYYLHRMGI VHRDLKPENL LYYSQDEESK IMISDFGLSK MEGKGDVMST 

       190        200        210        220        230        240 
ACGTPGYVAP EVLAQKPYSK AVDCWSIGVI AYILLCGYPP FYDENDSKLF EQILKAEYEF 

       250        260        270        280        290        300 
DSPYWDDISD SAKDFIRNLM EKDPNKRYTC EQAARHPWIA GDTALSKNIH ESVSAQIRKN 

       310        320        330        340        350        360 
FAKSKWRQAF NATAVVRHMR RLQLGSSLDS SNASVSSNLS LASQKDCLAP STLCSFLSSS 

       370        380 
SGVAGVGAER RPRPTTVTTG HTGSK 

« Hide

Isoform 2 (Beta) [UniParc].

Checksum: F3D0573864293BF5
Show »

FASTA36241,110
Isoform 3 [UniParc].

Checksum: BAC17016D8CF9F91
Show »

FASTA37742,135

References

« Hide 'large scale' references
[1]"Effects of PU.1-induced mouse calcium-calmodulin-dependent kinase I-like kinase (CKLiK) on apoptosis of murine erythroleukemia cells."
Yamada T., Suzuki M., Satoh H., Kihara-Negishi F., Nakano H., Oikawa T.
Exp. Cell Res. 294:39-50(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY.
[2]"Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice."
Maxwell K.N., Soccio R.E., Duncan E.M., Sehayek E., Breslow J.L.
J. Lipid Res. 44:2109-2119(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INDUCTION.
Strain: C57BL/6.
Tissue: Liver.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6J and NOD.
Tissue: Brain and Lung.
[4]"A cascade of Ca(2+)/calmodulin-dependent protein kinases regulates the differentiation and functional activation of murine neutrophils."
Gaines P., Lamoureux J., Marisetty A., Chi J., Berliner N.
Exp. Hematol. 36:832-844(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE, MUTAGENESIS OF 289-ILE--SER-292 AND PHE-301.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_796317.2. NM_177343.3.
XP_006497530.1. XM_006497467.1.
UniGeneMm.191949.

3D structure databases

ProteinModelPortalQ8BW96.
SMRQ8BW96. Positions 11-334.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid230634. 1 interaction.
IntActQ8BW96. 2 interactions.
MINTMINT-4099544.

PTM databases

PhosphoSiteQ8BW96.

Proteomic databases

PaxDbQ8BW96.
PRIDEQ8BW96.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000044009; ENSMUSP00000037028; ENSMUSG00000039145. [Q8BW96-1]
ENSMUST00000114987; ENSMUSP00000110638; ENSMUSG00000039145. [Q8BW96-3]
GeneID227541.
KEGGmmu:227541.
UCSCuc008ifp.1. mouse. [Q8BW96-1]

Organism-specific databases

CTD57118.
MGIMGI:2442190. Camk1d.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115341.
HOGENOMHOG000233016.
HOVERGENHBG108055.
InParanoidQ8BW96.
KOK08794.
OMAPYWDQIS.
OrthoDBEOG7WHH9K.
PhylomeDBQ8BW96.
TreeFamTF314166.

Gene expression databases

ArrayExpressQ8BW96.
BgeeQ8BW96.
CleanExMM_CAMK1D.
GenevestigatorQ8BW96.

Family and domain databases

InterProIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24347. PTHR24347. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCAMK1D. mouse.
NextBio378629.
PROQ8BW96.
SOURCESearch...

Entry information

Entry nameKCC1D_MOUSE
AccessionPrimary (citable) accession number: Q8BW96
Secondary accession number(s): Q3U450, Q80W64, Q8BWI7
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 7, 2004
Last modified: April 16, 2014
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot