Q91YS8 (KCC1A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcium/calmodulin-dependent protein kinase type 1
EC=2.7.11.17

Alternative name(s):
CaM kinase I
Short name=CaM-KI
CaM kinase I alpha
Short name=CaMKI-alpha

Gene names

Name:

Camk1

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	374 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, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca2+ elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-673', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation. Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K+ and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I By similarity. Ref.2
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-177 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-177 results in several fold increase in total activity. Unlike CaMK4, is unable to exhibit autonomous activity after Ca2+/calmodulin activation By similarity.
Subunit structure	Monomer. Interacts with XPO1 By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Predominantly cytoplasmic By similarity.
Tissue specificity	Ubiquitous.
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.
Post-translational modification	Phosphorylated by CaMKK1 and CaMKK2 on Thr-177.
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	Cell cycle Differentiation Neurogenesis
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW nucleocytoplasmic transport Inferred from direct assay PubMed 12130539PubMed 18332106. Source: MGI positive regulation of dendritic spine development Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of muscle cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of neuron projection development Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein export from nucleus Inferred from direct assay PubMed 11081517. Source: MGI positive regulation of protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of synapse structural plasticity Inferred from sequence or structural similarity. Source: UniProtKB regulation of muscle cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB regulation of protein binding Inferred from sequence or structural similarity. Source: UniProtKB signal transduction Inferred from direct assay PubMed 12130539. Source: MGI
Cellular_component	calcium- and calmodulin-dependent protein kinase complex Traceable author statement PubMed 11264466. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin-dependent protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 374	374	Calcium/calmodulin-dependent protein kinase type 1		PRO_0000086077
Regions
	Domain	20 – 276	257	Protein kinase
	Nucleotide binding	26 – 34	9	ATP By similarity
	Region	276 – 316	41	Autoinhibitory domain By similarity
	Region	296 – 317	22	Calmodulin-binding By similarity
	Motif	315 – 321	7	Nuclear export signal By similarity
Sites
	Active site	141	1	Proton acceptor By similarity
	Binding site	49	1	ATP By similarity
Amino acid modifications
	Modified residue	177	1	Phosphothreonine; by CaMKK1 and CaMKK2 By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q91YS8 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 37889CDA717D3AB2	FASTA	374	41,624
	10 20 30 40 50 60 MPGAVEGPRW KQAEDIRDIY DFRDVLGTGA FSEVILAEDK RTQKLVAIKC IAKKALEGKE 70 80 90 100 110 120 GSMENEIAVL HKIKHPNIVA LDDIYESGGH LYLIMQLVSG GELFDRIVEK GFYTERDASR 130 140 150 160 170 180 LIFQVLDAVK YLHDLGIVHR DLKPENLLYY SLDEDSKIMI SDFGLSKMED PGSVLSTACG 190 200 210 220 230 240 TPGYVAPEVL AQKPYSKAVD CWSIGVIAYI LLCGYPPFYD ENDAKLFEQI LKAEYEFDSP 250 260 270 280 290 300 YWDDISDSAK DFIRHLMEKD PEKRFTCEQA LQHPWIAGDT ALDKNIHQSV SEQIKKNFAK 310 320 330 340 350 360 SKWKQAFNAT AVVRHMRKLQ LGTSQEGQGQ TGSHGELLTP TAGGPAAGCC CRDCCVEPGS 370 ELPPAPPPSS RAMD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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].
[2]	"Calcium activation of ERK mediated by calmodulin kinase I." Schmitt J.M., Wayman G.A., Nozaki N., Soderling T.R. J. Biol. Chem. 279:24064-24072(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION OF MAPK1/ERK2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC014825 mRNA. Translation: AAH14825.1.
IPI	IPI00130439.
RefSeq	NP_598687.1. NM_133926.2.
UniGene	Mm.277373.
3D structure databases
ProteinModelPortal	Q91YS8.
SMR	Q91YS8. Positions 10-316.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q91YS8. 1 interaction.
STRING	10090.ENSMUSP00000032409.
PTM databases
PhosphoSite	Q91YS8.
Proteomic databases
PaxDb	Q91YS8.
PRIDE	Q91YS8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000032409; ENSMUSP00000032409; ENSMUSG00000030272.
GeneID	52163.
KEGG	mmu:52163.
Organism-specific databases
CTD	8536.
MGI	MGI:1098535. Camk1.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00670000097661.
HOGENOM	HOG000233016.
HOVERGEN	HBG108055.
InParanoid	Q91YS8.
KO	K08794.
OMA	QAMNIAD.
OrthoDB	EOG46Q6SS.
Gene expression databases
ArrayExpress	Q91YS8.
Bgee	Q91YS8.
CleanEx	MM_CAMK1.
Genevestigator	Q91YS8.
GermOnline	ENSMUSG00000030272. 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
NextBio	308578.
SOURCE	Search...

Entry information

Entry name

KCC1A_MOUSE

Accession

Primary (citable) accession number: Q91YS8

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2003
Last sequence update:	December 1, 2001
Last modified:	April 3, 2013
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program