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Q91YS8 (KCC1A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length374 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, 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.

Polybiquitinated by the E3 ubiquitin-protein ligase complex SCF(FBXL12), leading to proteasomal degradation 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 processCell cycle
Differentiation
Neurogenesis
   Cellular componentCytoplasm
Nucleus
   LigandATP-binding
Calmodulin-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Serine/threonine-protein kinase
Transferase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termAllosteric enzyme
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell 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: Ensembl

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

protein phosphorylation

Inferred from direct assay PubMed 18332106. Source: MGI

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

regulation of protein localization

Inferred from sequence or structural similarity. Source: UniProtKB

signal transduction

Inferred from direct assay PubMed 12130539. Source: MGI

   Cellular_componentcalcium- 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_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calmodulin-dependent protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 15284227. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 374374Calcium/calmodulin-dependent protein kinase type 1
PRO_0000086077

Regions

Domain20 – 276257Protein kinase
Nucleotide binding26 – 349ATP By similarity
Region276 – 31641Autoinhibitory domain By similarity
Region296 – 31722Calmodulin-binding By similarity
Motif315 – 3217Nuclear export signal By similarity

Sites

Active site1411Proton acceptor By similarity
Binding site491ATP By similarity

Amino acid modifications

Modified residue1771Phosphothreonine; by CaMKK1 and CaMKK2 By similarity
Cross-link59Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

Sequence LengthMass (Da)Tools
Q91YS8 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 37889CDA717D3AB2

FASTA37441,624
        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 

« Hide

References

« Hide '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.
CCDSCCDS20415.1.
RefSeqNP_598687.1. NM_133926.2.
UniGeneMm.277373.

3D structure databases

ProteinModelPortalQ91YS8.
SMRQ91YS8. Positions 10-299.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid206419. 4 interactions.
IntActQ91YS8. 2 interactions.
MINTMINT-4099529.
STRING10090.ENSMUSP00000032409.

PTM databases

PhosphoSiteQ91YS8.

Proteomic databases

MaxQBQ91YS8.
PaxDbQ91YS8.
PRIDEQ91YS8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000032409; ENSMUSP00000032409; ENSMUSG00000030272.
GeneID52163.
KEGGmmu:52163.
UCSCuc009dfk.1. mouse.

Organism-specific databases

CTD8536.
MGIMGI:1098535. Camk1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115341.
HOGENOMHOG000233016.
HOVERGENHBG108055.
InParanoidQ91YS8.
KOK08794.
OMAGKENNIE.
OrthoDBEOG7WHH9K.
PhylomeDBQ91YS8.
TreeFamTF314166.

Gene expression databases

ArrayExpressQ91YS8.
BgeeQ91YS8.
CleanExMM_CAMK1.
GenevestigatorQ91YS8.

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

NextBio308578.
PROQ91YS8.
SOURCESearch...

Entry information

Entry nameKCC1A_MOUSE
AccessionPrimary (citable) accession number: Q91YS8
Entry history
Integrated into UniProtKB/Swiss-Prot: January 10, 2003
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot