Q8BW96 (KCC1D_MOUSE) 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-KI delta
Short name=CaMKI delta
CaM kinase ID
CaMKI-like protein kinase
Short name=CKLiK
Short name=mCKLiK

Gene names

Name:

Camk1d

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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 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 process	Inflammatory response Neurogenesis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Calcium Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	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 sequence or structural similarity. Source: UniProtKB 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 apoptotic process Inferred from direct assay Ref.1. Source: MGI 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_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. 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 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 385	385	Calcium/calmodulin-dependent protein kinase type 1D		PRO_0000086083
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
Sites
	Active site	144	1	Proton acceptor By similarity
	Binding site	52	1	ATP By similarity
Amino acid modifications
	Modified residue	122	1	Phosphoserine By similarity
	Modified residue	180	1	Phosphothreonine; by CaMKK1 and CaMKK2 By similarity
Natural variations
	Alternative sequence	1 – 31	31	MAREN…ETLGT → MAEFVSWSCLNFRWSWIKGS RNS in isoform 3.		VSP_012136
	Alternative sequence	333 – 385	53	ASVSS…HTGSK → VWHLPRSVVSFLLRRGSQES ELRGDPQPPL in isoform 2.		VSP_012137
Experimental info
	Mutagenesis	52	1	K → D: Catalytically inactive form.
	Mutagenesis	289 – 292	4	IHES → DEDD: Constitutively active form; when associated with A-301. Ref.4
	Mutagenesis	301	1	F → A: Constitutively active form; when associated with 289-A--A-292. Ref.4
	Sequence conflict	30	1	G → Q in BAC35295. Ref.3
	Sequence conflict	327	1	S → N in BAC35295. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified December 7, 2004. Version 2. Checksum: 320EB0D3D5670055	FASTA	385	42,919
	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
	Isoform 2 (Beta) [UniParc]. Checksum: F3D0573864293BF5	FASTA	362	41,110
	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 SNVWHLPRSV VSFLLRRGSQ ESELRGDPQP PL
	Isoform 3 [UniParc]. Checksum: BAC17016D8CF9F91	FASTA	377	42,135
	10 20 30 40 50 60 MAEFVSWSCL NFRWSWIKGS RNSGAFSEVV LAEEKATGKL FAVKCIPKKA LKGKESSIEN 70 80 90 100 110 120 EIAVLRKIKH ENIVALEDIY ESPNHLYLVM QLVSGGELFD RIVEKGFYTE KDASTLIRQV 130 140 150 160 170 180 LDAVYYLHRM GIVHRDLKPE NLLYYSQDEE SKIMISDFGL SKMEGKGDVM STACGTPGYV 190 200 210 220 230 240 APEVLAQKPY SKAVDCWSIG VIAYILLCGY PPFYDENDSK LFEQILKAEY EFDSPYWDDI 250 260 270 280 290 300 SDSAKDFIRN LMEKDPNKRY TCEQAARHPW IAGDTALSKN IHESVSAQIR KNFAKSKWRQ 310 320 330 340 350 360 AFNATAVVRH MRRLQLGSSL DSSNASVSSN LSLASQKDCL APSTLCSFLS SSSGVAGVGA 370 ERRPRPTTVT TGHTGSK

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00226188. IPI00403595. IPI00480395.
RefSeq	NP_796317.2. NM_177343.3.
UniGene	Mm.191949.
3D structure databases
ProteinModelPortal	Q8BW96.
SMR	Q8BW96. Positions 11-334.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8BW96. 1 interaction.
PTM databases
PhosphoSite	Q8BW96.
Proteomic databases
PaxDb	Q8BW96.
PRIDE	Q8BW96.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000044009; ENSMUSP00000037028; ENSMUSG00000039145. ENSMUST00000114987; ENSMUSP00000110638; ENSMUSG00000039145.
GeneID	227541.
KEGG	mmu:227541.
Organism-specific databases
CTD	57118.
MGI	MGI:2442190. Camk1d.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00670000097661.
HOGENOM	HOG000233016.
HOVERGEN	HBG108055.
InParanoid	Q8BW96.
KO	K08794.
OMA	ETFEDKS.
Gene expression databases
ArrayExpress	Q8BW96.
Bgee	Q8BW96.
CleanEx	MM_CAMK1D.
Genevestigator	Q8BW96.
GermOnline	ENSMUSG00000039145. Mus musculus.
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
ChiTaRS	CAMK1D. mouse.
NextBio	378629.
SOURCE	Search...

Entry information

Entry name

KCC1D_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program