Q8IU85 (KCC1D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	385 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Inflammatory response Neurogenesis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Calcium Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of CREB transcription factor activity Inferred from direct assay Ref.8. Source: UniProtKB 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 apoptotic process Inferred from electronic annotation. Source: Compara 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_component	calcium- 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_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin-dependent protein kinase activity Inferred from electronic annotation. Source: 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 385

385

Calcium/calmodulin-dependent protein kinase type 1D

PRO_0000086082

Regions

Domain

23 – 279

257

Protein kinase

Nucleotide binding

29 – 37

9

ATP By similarity

Region

279 – 319

41

Autoinhibitory domain By similarity

Region

299 – 320

22

Calmodulin-binding By similarity

Motif

318 – 324

7

Nuclear export signal By similarity

Compositional bias

326 – 364

39

Ser-rich

Sites

Active site

144

1

Proton acceptor By similarity

Binding site

52

1

ATP By similarity

Amino acid modifications

Modified residue

122

1

Phosphoserine Ref.11

Modified residue

180

1

Phosphothreonine; by CaMKK1 and CaMKK2 Ref.2 Ref.11

Natural variations

Alternative sequence

348 – 385

38

LAPST…HSGSK → AYVAKPESLS in isoform 2.

VSP_012135

Natural variant

66

1

I → M. Ref.13
Corresponds to variant rs34194224 [ dbSNP | Ensembl ].

VAR_040599

Experimental info

Mutagenesis

52

1

K → A: Catalytically inactive form. Ref.8

Mutagenesis

180

1

T → A: Loss of ionomycin-induced activation. Ref.2 Ref.8

Secondary structure

1

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385

Helix Strand Turn

Details...

Beta strand

13 – 15

3

Helix

19 – 22

4

Beta strand

23 – 31

9

Beta strand

36 – 42

7

Turn

43 – 45

3

Beta strand

48 – 55

8

Helix

66 – 75

10

Beta strand

84 – 89

6

Beta strand

91 – 99

9

Helix

106 – 112

7

Helix

118 – 137

20

Helix

147 – 149

3

Beta strand

150 – 156

7

Beta strand

161 – 163

3

Helix

190 – 193

4

Helix

201 – 216

16

Helix

226 – 235

10

Turn

242 – 247

6

Helix

250 – 259

10

Turn

264 – 266

3

Helix

270 – 273

4

Helix

277 – 280

4

Helix

290 – 300

11

Helix

305 – 311

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 717467D019E30FC9	FASTA	385	42,914
	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
	Isoform 2 [UniParc]. Checksum: 1FA184EEFA976FB4	FASTA	357	40,190
	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 FAKSKWRQAF NATAVVRHMR KLHLGSSLDS SNASVSSSLS LASQKDCAYV AKPESLS

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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. , 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 , AL512284, AL512783, AL731559 Genomic DNA. Translation: CAI14410.1.
AL512284 , AL391314, AL512783, AL731559 Genomic DNA. Translation: CAH71693.1.
AL512284 , AL391314, AL512783, AL731559 Genomic DNA. Translation: CAH71694.1.
AL512783 , AL391314, AL512284, AL731559 Genomic DNA. Translation: CAH74035.1.
AL512783 , AL391314, AL512284, AL731559 Genomic DNA. Translation: CAH74036.1.
AL731559 , AL391314, AL512284, AL512783 Genomic DNA. Translation: CAI14675.1.
CH471072 Genomic DNA. Translation: EAW86314.1.
BC035745 mRNA. Translation: AAH35745.1.

IPI

IPI00170508.
IPI00170675.

RefSeq

NP_065130.1. NM_020397.2.
NP_705718.1. NM_153498.2.

UniGene

Hs.659517.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JC6	X-ray	2.30	A/C	1-333	[»]

ProteinModelPortal

Q8IU85.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8IU85. 6 interactions.

STRING

9606.ENSP00000368124.

PTM databases

PhosphoSite

Q8IU85.

Polymorphism databases

DMDM

56404610.

Proteomic databases

PaxDb

Q8IU85.

PRIDE

Q8IU85.

Protocols and materials databases

DNASU

57118.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000378845; ENSP00000368122; ENSG00000183049.
ENST00000378847; ENSP00000368124; ENSG00000183049.

GeneID

57118.

KEGG

hsa:57118.

UCSC

uc001ilo.3. human.

Organism-specific databases

CTD

57118.

GeneCards

GC10P012391.

HGNC

HGNC:19341. CAMK1D.

HPA

HPA007266.

MIM

607957. gene.

neXtProt

NX_Q8IU85.

PharmGKB

PA134992438.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233016.

HOVERGEN

HBG108055.

InParanoid

Q8IU85.

KO

K08794.

OMA

ETFEDKS.

OrthoDB

EOG46Q6SS.

PhylomeDB

Q8IU85.

Enzyme and pathway databases

BRENDA

2.7.11.17. 2681.

SignaLink

Q8IU85.

Gene expression databases

ArrayExpress

Q8IU85.

Bgee

Q8IU85.

CleanEx

HS_CAMK1D.

Genevestigator

Q8IU85.

GermOnline

ENSG00000183049. Homo sapiens.

Family and domain databases

InterPro

IPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

PANTHER

PTHR24347. PTHR24347. 1 hit.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q8IU85.

ChEMBL

CHEMBL5073.

ChiTaRS

CAMK1D. human.

EvolutionaryTrace

Q8IU85.

GenomeRNAi

57118.

NextBio

62987.

SOURCE

Search...

Entry information

Entry name

KCC1D_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.