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Q8IU85 (KCC1D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | 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 kinase ID
Short name=CaM-KI delta
Short name=CaMKI delta
Short name=CaMKID
CaMKI-like protein kinase
Short name=CKLiK
Gene names
Name:CAMK1D
Synonyms:CAMKID
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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 Ref.1 Ref.7 Ref.8 Ref.9

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.2

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. Ref.1 Ref.2

Subcellular location

Cytoplasm Probable. Nucleus Probable. Note: Predominantly cytoplasmic. Nuclear localization increases upon activation by KCl treatment in hippocampal neurons. Ref.1 Ref.8

Tissue specificity

Widely expressed. Highly and mostly expressed in polymorphonuclear leukocytes (neutrophilic and eosinophilic granulocytes) while little or no expression is observed in monocytes and lymphocytes. Ref.1 Ref.2 Ref.7

Developmental stage

Expressed during hippocampal formation with high expression in the pyramidal cell layers. Ref.8 Ref.9

Induction

Expression increases upon treatment of EC cells with DMSO and retinoic acid. Induced by KCL in PC12 cells. Ref.1 Ref.2 Ref.8

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
Polymorphism
   LigandATP-binding
Calcium
Calmodulin-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Allosteric 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 electronic annotation. Source: Ensembl

positive regulation of CREB transcription factor activity

Inferred from direct assay Ref.8. Source: UniProtKB

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neutrophil chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phagocytosis

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of respiratory burst

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of dendrite development

Inferred from mutant phenotype Ref.9. Source: UniProtKB

regulation of granulocyte chemotaxis

Inferred from mutant phenotype Ref.7. Source: UniProtKB

   Cellular_componentcalcium- and calmodulin-dependent protein kinase complex

Traceable author statement PubMed 11264466. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.8. Source: UniProtKB

nucleus

Inferred from direct assay Ref.8. 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 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IU85-1)

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: Q8IU85-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 385385Calcium/calmodulin-dependent protein kinase type 1D
PRO_0000086082

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
Compositional bias326 – 36439Ser-rich

Sites

Active site1441Proton acceptor By similarity
Binding site521ATP By similarity

Amino acid modifications

Modified residue1221Phosphoserine Ref.11
Modified residue1801Phosphothreonine; by CaMKK1 and CaMKK2 Ref.2 Ref.11

Natural variations

Alternative sequence348 – 38538LAPST…HSGSK → AYVAKPESLS in isoform 2.
VSP_012135
Natural variant661I → M. Ref.13
Corresponds to variant rs34194224 [ dbSNP | Ensembl ].
VAR_040599

Experimental info

Mutagenesis521K → A: Catalytically inactive form. Ref.8
Mutagenesis1801T → A: Loss of ionomycin-induced activation. Ref.2 Ref.8

Secondary structure

.............................................. 385
Helix Strand Turn

Details...

Sequences

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

Last modified March 1, 2003. Version 1.
Checksum: 717467D019E30FC9

FASTA38542,914
        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 GDTALNKNIH ESVSAQIRKN 

       310        320        330        340        350        360 
FAKSKWRQAF NATAVVRHMR KLHLGSSLDS SNASVSSSLS LASQKDCLAP STLCSFISSS 

       370        380 
SGVSGVGAER RPRPTTVTAV HSGSK 

« Hide

Isoform 2 [UniParc].

Checksum: 1FA184EEFA976FB4
Show »

FASTA35740,190

References

« Hide 'large scale' references
[1]"Identification and characterization of CKLiK, a novel granulocyte Ca++/calmodulin-dependent protein kinase."
Verploegen S., Lammers J.-W.L., Koenderman L., Coffer P.J.
Blood 96:3215-3223(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION IN PHOSPHORYLATION OF CREM AND ACTIVATION OF CREB1, ENZYME REGULATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[2]"Identification and characterization of novel components of a Ca2+/calmodulin-dependent protein kinase cascade in HeLa cells."
Ishikawa Y., Tokumitsu H., Inuzuka H., Murata-Hori M., Hosoya H., Kobayashi R.
FEBS Lett. 550:57-63(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, ENZYME REGULATION, PHOSPHORYLATION AT THR-180, PHOSPHORYLATION BY CAMKK1 AND CAMKK2, MUTAGENESIS OF THR-180, TISSUE SPECIFICITY.
[3]NHLBI resequencing and genotyping service (RS&G)
Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Pancreas.
[7]"Characterization of the role of CaMKI-like kinase (CKLiK) in human granulocyte function."
Verploegen S., Ulfman L., van Deutekom H.W., van Aalst C., Honing H., Lammers J.W., Koenderman L., Coffer P.J.
Blood 106:1076-1083(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[8]"Prominent expression and activity-dependent nuclear translocation of Ca2+/calmodulin-dependent protein kinase Idelta in hippocampal neurons."
Sakagami H., Kamata A., Nishimura H., Kasahara J., Owada Y., Takeuchi Y., Watanabe M., Fukunaga K., Kondo H.
Eur. J. Neurosci. 22:2697-2707(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CREB1 ACTIVATION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, INDUCTION BY KCL, MUTAGENESIS OF LYS-52 AND THR-180.
[9]"Spatiotemporal expression of four isoforms of Ca2+/calmodulin-dependent protein kinase I in brain and its possible roles in hippocampal dendritic growth."
Kamata A., Sakagami H., Tokumitsu H., Owada Y., Fukunaga K., Kondo H.
Neurosci. Res. 57:86-97(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DENDTRITIC GROWTH, DEVELOPMENTAL STAGE.
[10]"Calmodulin-kinases: modulators of neuronal development and plasticity."
Wayman G.A., Lee Y.S., Tokumitsu H., Silva A.J., Silva A., Soderling T.R.
Neuron 59:914-931(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION IN NEURONAL PLASTICITY.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122 AND THR-180, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Crystal structure of human calmodulin-dependent protein kinase 1D."
Debreczeni J.E., Rellos P., Fedorov O., Niesen F.H., Bhatia C., Shrestha L., Salah E., Smee C., Colebrook S., Berridge G., Gileadi O., Bunkoczi G., Ugochukwu E., Pike A.C.W., Von Delft F., Knapp S., Sundstrom M., Weigelt J., Arrowsmith C.H., Edwards A.
Submitted (DEC-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-333 IN COMPLEX WITH INHIBITOR.
[13]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] MET-66.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF286366 mRNA. Translation: AAG00534.1.
AB081726 mRNA. Translation: BAC19846.1.
EF444962 Genomic DNA. Translation: ACA05959.1.
AL391314 expand/collapse EMBL AC list , AL512284, AL512783, AL731559 Genomic DNA. Translation: CAI14410.1.
AL512284 expand/collapse EMBL AC list , AL391314, AL512783, AL731559 Genomic DNA. Translation: CAH71693.1.
AL512284 expand/collapse EMBL AC list , AL391314, AL512783, AL731559 Genomic DNA. Translation: CAH71694.1.
AL512783 expand/collapse EMBL AC list , AL391314, AL512284, AL731559 Genomic DNA. Translation: CAH74035.1.
AL512783 expand/collapse EMBL AC list , AL391314, AL512284, AL731559 Genomic DNA. Translation: CAH74036.1.
AL731559 expand/collapse EMBL AC list , AL391314, AL512284, AL512783 Genomic DNA. Translation: CAI14675.1.
CH471072 Genomic DNA. Translation: EAW86314.1.
BC035745 mRNA. Translation: AAH35745.1.
CCDSCCDS7091.1. [Q8IU85-1]
CCDS7092.1. [Q8IU85-2]
RefSeqNP_065130.1. NM_020397.2. [Q8IU85-2]
NP_705718.1. NM_153498.2. [Q8IU85-1]
UniGeneHs.659517.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JC6X-ray2.30A/C1-333[»]
ProteinModelPortalQ8IU85.
SMRQ8IU85. Positions 11-334.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121382. 21 interactions.
IntActQ8IU85. 6 interactions.
STRING9606.ENSP00000368124.

Chemistry

BindingDBQ8IU85.
ChEMBLCHEMBL5073.
GuidetoPHARMACOLOGY1953.

PTM databases

PhosphoSiteQ8IU85.

Polymorphism databases

DMDM56404610.

Proteomic databases

MaxQBQ8IU85.
PaxDbQ8IU85.
PRIDEQ8IU85.

Protocols and materials databases

DNASU57118.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000378845; ENSP00000368122; ENSG00000183049. [Q8IU85-2]
ENST00000378847; ENSP00000368124; ENSG00000183049. [Q8IU85-1]
GeneID57118.
KEGGhsa:57118.
UCSCuc001ilo.3. human. [Q8IU85-1]

Organism-specific databases

CTD57118.
GeneCardsGC10P012391.
HGNCHGNC:19341. CAMK1D.
HPAHPA007266.
MIM607957. gene.
neXtProtNX_Q8IU85.
PharmGKBPA134992438.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233016.
HOVERGENHBG108055.
InParanoidQ8IU85.
KOK08794.
OMAPYWDQIS.
OrthoDBEOG7WHH9K.
PhylomeDBQ8IU85.
TreeFamTF314166.

Enzyme and pathway databases

BRENDA2.7.11.17. 2681.
SignaLinkQ8IU85.

Gene expression databases

ArrayExpressQ8IU85.
BgeeQ8IU85.
CleanExHS_CAMK1D.
GenevestigatorQ8IU85.

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. human.
EvolutionaryTraceQ8IU85.
GenomeRNAi57118.
NextBio62987.
PROQ8IU85.
SOURCESearch...

Entry information

Entry nameKCC1D_HUMAN
AccessionPrimary (citable) accession number: Q8IU85
Secondary accession number(s): B0YIY0, Q9HD31
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: March 1, 2003
Last modified: July 9, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM