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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei52 – 521ATPPROSITE-ProRule annotation
Active sitei144 – 1441Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi29 – 379ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. calmodulin-dependent protein kinase activity Source: MGI

GO - Biological processi

  1. inflammatory response Source: UniProtKB-KW
  2. negative regulation of apoptotic process Source: MGI
  3. positive regulation of apoptotic process Source: MGI
  4. positive regulation of CREB transcription factor activity Source: UniProtKB
  5. positive regulation of neuron projection development Source: UniProtKB
  6. positive regulation of neutrophil chemotaxis Source: UniProtKB
  7. positive regulation of phagocytosis Source: UniProtKB
  8. positive regulation of respiratory burst Source: UniProtKB
  9. regulation of dendrite development Source: UniProtKB
  10. regulation of granulocyte chemotaxis Source: UniProtKB
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
ProteomesiUP000000589: 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

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi52 – 521K → D: Catalytically inactive form.
Mutagenesisi289 – 2924IHES → DEDD: Constitutively active form; when associated with A-301. 1 Publication
Mutagenesisi301 – 3011F → A: Constitutively active form; when associated with 289-A--A-292. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 385385Calcium/calmodulin-dependent protein kinase type 1DPRO_0000086083Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei122 – 1221PhosphoserineBy similarity
Modified residuei180 – 1801Phosphothreonine; by CaMKK1 and CaMKK2By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8BW96.
PaxDbiQ8BW96.
PRIDEiQ8BW96.

PTM databases

PhosphoSiteiQ8BW96.

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

BgeeiQ8BW96.
CleanExiMM_CAMK1D.
ExpressionAtlasiQ8BW96. baseline and differential.
GenevestigatoriQ8BW96.

Interactioni

Protein-protein interaction databases

BioGridi230634. 1 interaction.
IntActiQ8BW96. 2 interactions.
MINTiMINT-4099544.

Structurei

3D structure databases

ProteinModelPortaliQ8BW96.
SMRiQ8BW96. Positions 11-334.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini23 – 279257Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni279 – 31941Autoinhibitory domainBy similarityAdd
BLAST
Regioni299 – 32022Calmodulin-bindingBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi318 – 3247Nuclear export signalBy similarity

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

eggNOGiCOG0515.
GeneTreeiENSGT00760000118944.
HOGENOMiHOG000233016.
HOVERGENiHBG108055.
InParanoidiQ8BW96.
KOiK08794.
OMAiTGHTGSK.
OrthoDBiEOG7WHH9K.
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.
IPR002290. Ser/Thr_dual-sp_kinase.
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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti30 – 301G → Q in BAC35295. (PubMed:16141072)Curated
Sequence conflicti327 – 3271S → N in BAC35295. (PubMed:16141072)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3131MAREN…ETLGT → MAEFVSWSCLNFRWSWIKGS RNS in isoform 3. 1 PublicationVSP_012136Add
BLAST
Alternative sequencei333 – 38553ASVSS…HTGSK → VWHLPRSVVSFLLRRGSQES ELRGDPQPPL in isoform 2. 1 PublicationVSP_012137Add
BLAST

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.1. mouse. [Q8BW96-1]

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. Positions 11-334.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi230634. 1 interaction.
IntActiQ8BW96. 2 interactions.
MINTiMINT-4099544.

PTM databases

PhosphoSiteiQ8BW96.

Proteomic databases

MaxQBiQ8BW96.
PaxDbiQ8BW96.
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.1. mouse. [Q8BW96-1]

Organism-specific databases

CTDi57118.
MGIiMGI:2442190. Camk1d.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118944.
HOGENOMiHOG000233016.
HOVERGENiHBG108055.
InParanoidiQ8BW96.
KOiK08794.
OMAiTGHTGSK.
OrthoDBiEOG7WHH9K.
PhylomeDBiQ8BW96.
TreeFamiTF314166.

Miscellaneous databases

ChiTaRSiCamk1d. mouse.
NextBioi378629.
PROiQ8BW96.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BW96.
CleanExiMM_CAMK1D.
ExpressionAtlasiQ8BW96. baseline and differential.
GenevestigatoriQ8BW96.

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.
IPR002290. Ser/Thr_dual-sp_kinase.
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...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

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: February 4, 2015
This is version 114 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

External Data

Dasty 3

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 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.