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Q63450 (KCC1A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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-516', 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 By similarity. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-275' and 'Ser-294'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation By similarity. 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. Ref.6 Ref.9 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19

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. Ref.10 Ref.11

Subunit structure

Monomer. Interacts with XPO1. Ref.14

Subcellular location

Cytoplasm. Nucleus. Note: Predominantly cytoplasmic. Ref.8 Ref.12 Ref.13 Ref.14

Tissue specificity

Widely expressed. 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. Ref.21

Post-translational modification

Phosphorylated by CaMKK1 and CaMKK2 on Thr-177. Ref.10

Polybiquitinated by the E3 ubiquitin-protein ligase complex SCF(FBXL12), leading to proteasomal degradation By similarity.

Miscellaneous

Dendrite development is blocked in hippocampal neurons silencing CAKM1.

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.

Contains 1 protein kinase domain.

Sequence caution

The sequence AAA19670.1 differs from that shown. Reason: Frameshift at positions 321 and 363.

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 term3D-structure
Allosteric enzyme
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

nucleocytoplasmic transport

Inferred from electronic annotation. Source: Ensembl

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 electronic annotation. Source: Ensembl

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 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

regulation of protein localization

Inferred from sequence or structural similarity. Source: UniProtKB

signal transduction

Inferred from electronic annotation. Source: Ensembl

   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 direct assay PubMed 17939993. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 374374Calcium/calmodulin-dependent protein kinase type 1
PRO_0000086078

Regions

Domain20 – 276257Protein kinase
Nucleotide binding26 – 349ATP By similarity
Region276 – 31641Autoinhibitory domain
Region296 – 31722Calmodulin-binding
Motif263 – 2642Involved in nuclear import Probable
Motif315 – 3217Nuclear export signal

Sites

Active site1411Proton acceptor
Binding site491ATP By similarity

Amino acid modifications

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

Experimental info

Mutagenesis1771T → A: Loss of activation by CaMKK1 and CaMKK2. Ref.10
Mutagenesis263 – 2642KR → AA: Partially excluded from the nucleus; when associated with 319-AQA-321.
Mutagenesis319 – 3213LQL → AQA: Retention in the nucleus. Partially excluded from the nucleus; when associated with 263-AA-264. Ref.14
Sequence conflict371A → T AA sequence Ref.5
Sequence conflict1121F → G in AAA19670. Ref.1
Sequence conflict1181A → R in AAA19670. Ref.1
Sequence conflict2391S → V AA sequence Ref.5
Sequence conflict3091A → R in AAA19670. Ref.1

Secondary structure

............................................. 374
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q63450 [UniParc].

Last modified July 15, 1998. Version 2.
Checksum: 37889B3DEF033AB2

FASTA37441,638
        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 TASHGELLTP TAGGPAAGCC CRDCCVEPGS 

       370 
ELPPAPPPSS RAMD 

« Hide

References

« Hide 'large scale' references
[1]"Calcium/calmodulin-dependent protein kinase I. cDNA cloning and identification of autophosphorylation site."
Picciotto M.R., Czernik A.J., Nairn A.C.
J. Biol. Chem. 268:26512-26521(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]Erratum
Picciotto M.R., Czernik A.J., Nairn A.C.
J. Biol. Chem. 270:10358-10358(1995)
[3]"Characterization of a rat cDNA clone encoding calcium/calmodulin-dependent protein kinase I."
Cho F.S., Phillips K.S., Bogucki B., Weaver T.E.
Biochim. Biophys. Acta 1224:156-160(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Lung.
[4]"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].
Tissue: Lung.
[5]"Purification and characterization of Ca2+/calmodulin-dependent protein kinase V from rat cerebrum."
Mochizuki H., Ito T., Hidaka H.
J. Biol. Chem. 268:9143-9147(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 12-37; 158-167; 233-241 AND 285-295.
[6]"CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases."
Sheng M., Thompson M.A., Greenberg M.E.
Science 252:1427-1430(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CREB1.
[7]"Similar substrate recognition motifs for mammalian AMP-activated protein kinase, higher plant HMG-CoA reductase kinase-A, yeast SNF1, and mammalian calmodulin-dependent protein kinase I."
Dale S., Wilson W.A., Edelman A.M., Hardie D.G.
FEBS Lett. 361:191-195(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBSTRATE RECOGNITION MOTIF.
[8]"Immunochemical localization of calcium/calmodulin-dependent protein kinase I."
Picciotto M.R., Zoli M., Bertuzzi G., Nairn A.C.
Synapse 20:75-84(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[9]"Regulation of activating transcription factor-1 and the cAMP response element-binding protein by Ca2+/calmodulin-dependent protein kinases type I, II, and IV."
Sun P., Lou L., Maurer R.A.
J. Biol. Chem. 271:3066-3073(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF ATF1 AND CREB1.
[10]"Multiple Ca(2+)-calmodulin-dependent protein kinase kinases from rat brain. Purification, regulation by Ca(2+)-calmodulin, and partial amino acid sequence."
Edelman A.M., Mitchelhill K.I., Selbert M.A., Anderson K.A., Hook S.S., Stapleton D., Goldstein E.G., Means A.R., Kemp B.E.
J. Biol. Chem. 271:10806-10810(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, PHOSPHORYLATION BY CAMKK1 AND CAMKK2, MUTAGENESIS OF THR-177.
[11]"Activation of a calcium-calmodulin-dependent protein kinase I cascade in PC12 cells."
Aletta J.M., Selbert M.A., Nairn A.C., Edelman A.M.
J. Biol. Chem. 271:20930-20934(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[12]"Expression and subcellular localization of multifunctional calmodulin-dependent protein kinases-I, -II and -IV are altered in rat hippocampal CA1 neurons after induction of long-term potentiation."
Ahmed B.Y., Yamaguchi F., Tsumura T., Gotoh T., Sugimoto K., Tai Y., Konishi R., Kobayashi R., Tokuda M.
Neurosci. Lett. 290:149-153(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[13]"Characterization of Ca2+/calmodulin-dependent protein kinase I as a myosin II regulatory light chain kinase in vitro and in vivo."
Suizu F., Fukuta Y., Ueda K., Iwasaki T., Tokumitsu H., Hosoya H.
Biochem. J. 367:335-345(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, FUNCTION IN PHOSPHORYLATION OF MYL9.
[14]"Cytoplasmic localization of calcium/calmodulin-dependent protein kinase I-alpha depends on a nuclear export signal in its regulatory domain."
Stedman D.R., Uboha N.V., Stedman T.T., Nairn A.C., Picciotto M.R.
FEBS Lett. 566:275-280(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL, MUTAGENESIS OF 319-LEU--LEU-321 AND 263-LYS-ARG-264, INTERACTION WITH XPO1.
[15]"Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I."
Wayman G.A., Kaech S., Grant W.F., Davare M., Impey S., Tokumitsu H., Nozaki N., Banker G., Soderling T.R.
J. Neurosci. 24:3786-3794(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN AXONAL OUTGROWTH.
[16]"Calmodulin-dependent kinase kinase/calmodulin kinase I activity gates extracellular-regulated kinase-dependent long-term potentiation."
Schmitt J.M., Guire E.S., Saneyoshi T., Soderling T.R.
J. Neurosci. 25:1281-1290(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN LONG-TERM POTENTIATION.
[17]"Phosphorylation of Numb regulates its interaction with the clathrin-associated adaptor AP-2."
Tokumitsu H., Hatano N., Yokokura S., Sueyoshi Y., Nozaki N., Kobayashi R.
FEBS Lett. 580:5797-5801(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF NUMB.
[18]"Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2."
Wayman G.A., Impey S., Marks D., Saneyoshi T., Grant W.F., Derkach V., Soderling T.R.
Neuron 50:897-909(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DENDTRITIC GROWTH.
[19]"Calmodulin-kinases regulate basal and estrogen stimulated medulloblastoma migration via Rac1."
Davare M.A., Saneyoshi T., Soderling T.R.
J. Neurooncol. 104:65-82(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MEDULLOBLASTOMA CELLS MIGRATION.
[20]"Structural basis for the autoinhibition of calcium/calmodulin-dependent protein kinase I."
Goldberg J., Nairn A.C., Kuriyan J.
Cell 84:875-887(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Tissue: Brain.
[21]"Structure of the complex of calmodulin with the target sequence of calmodulin-dependent protein kinase I: studies of the kinase activation mechanism."
Clapperton J.A., Martin S.R., Smerdon S.J., Gamblin S.J., Bayley P.M.
Biochemistry 41:14669-14679(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 294-318 IN COMPLEX WITH CALMODULIN, DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L24907 mRNA. Translation: AAA19670.1. Frameshift.
L26288 mRNA. Translation: AAA66944.1.
BC071177 mRNA. Translation: AAH71177.1.
PIRS50193.
RefSeqNP_604463.1. NM_134468.1.
XP_006237065.1. XM_006237003.1.
UniGeneRn.11018.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A06X-ray2.50A1-322[»]
1MXEX-ray1.70E/F294-318[»]
2L7LNMR-B299-320[»]
ProteinModelPortalQ63450.
SMRQ63450. Positions 10-316.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid251279. 1 interaction.
IntActQ63450. 5 interactions.
MINTMINT-3375300.
STRING10116.ENSRNOP00000033456.

PTM databases

PhosphoSiteQ63450.

Proteomic databases

PRIDEQ63450.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000029728; ENSRNOP00000033456; ENSRNOG00000021781.
GeneID171503.
KEGGrno:171503.
UCSCRGD:629473. rat.

Organism-specific databases

CTD8536.
RGD629473. Camk1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115341.
HOVERGENHBG108055.
KOK08794.
OMAGKENNIE.
OrthoDBEOG7WHH9K.
PhylomeDBQ63450.

Enzyme and pathway databases

BRENDA2.7.11.17. 5301.

Gene expression databases

GenevestigatorQ63450.

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

EvolutionaryTraceQ63450.
NextBio622477.

Entry information

Entry nameKCC1A_RAT
AccessionPrimary (citable) accession number: Q63450
Secondary accession number(s): Q63084
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: April 16, 2014
This is version 126 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references