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Protein

Calcium/calmodulin-dependent protein kinase kinase 1

Gene

Camkk1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death.3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Activated by Ca2+/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Partially inhibited upon phosphorylation by PRCAKA/PKA. May be regulated through phosphorylation by CAMK1 and CAMK4.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei157 – 1571ATPPROSITE-ProRule annotation
Active sitei275 – 2751Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi134 – 1429ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • calmodulin binding Source: RGD
  • calmodulin-dependent protein kinase activity Source: RGD

GO - Biological processi

  • activation of protein kinase activity Source: RGD
  • positive regulation of protein kinase activity Source: RGD
  • protein phosphorylation Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Calmodulin-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.17. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium/calmodulin-dependent protein kinase kinase 1 (EC:2.7.11.17)
Short name:
CaM-KK 1
Short name:
CaM-kinase kinase 1
Short name:
CaMKK 1
Alternative name(s):
CaM-kinase IV kinase
Calcium/calmodulin-dependent protein kinase kinase alpha
Short name:
CaM-KK alpha
Short name:
CaM-kinase kinase alpha
Short name:
CaMKK alpha
Gene namesi
Name:Camkk1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi62023. Camkk1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi74 – 741S → A: Decrease in phosphorylation by PKA. 1 Publication
Mutagenesisi108 – 1081T → A: Decrease in phosphorylation and partial inhibition by PKA. Almost loss of inhibition by PKA; when associated with A-458. 2 Publications
Mutagenesisi172 – 1721R → E: Loss of substrate recognition and interaction with CAMK4. 1 Publication
Mutagenesisi177 – 1771R → E: Loss of substrate recognition and interaction with CAMK4. 1 Publication
Mutagenesisi458 – 4581S → A: Decrease in phosphorylation and partial inhibition by PKA. Almost loss of inhibition by PKA; when associated with A-108. 1 Publication
Mutagenesisi459 – 4591F → D: Loss of binding to Ca(2+)/calmodulin. 1 Publication
Mutagenesisi463 – 4631F → D: Loss of binding to Ca(2+)/calmodulin. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 505505Calcium/calmodulin-dependent protein kinase kinase 1PRO_0000086143Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei74 – 741Phosphoserine1 Publication
Modified residuei92 – 921PhosphoserineBy similarity
Modified residuei100 – 1001PhosphoserineBy similarity
Modified residuei108 – 1081Phosphothreonine2 Publications
Modified residuei458 – 4581PhosphoserineCombined sources1 Publication
Modified residuei475 – 4751PhosphoserineCombined sources
Modified residuei492 – 4921PhosphoserineBy similarity

Post-translational modificationi

Appears to be autophosphorylated. Phosphorylated at multiple sites by PRCAKA/PKA. Phosphorylation of Ser-458 is blocked upon binding to Ca2+/calmodulin. May be phosphorylated by CAMK1 and CAMK4.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP97756.
PRIDEiP97756.

PTM databases

iPTMnetiP97756.
PhosphoSiteiP97756.

Expressioni

Tissue specificityi

Mostly expressed in the brain with higher levels in cortex and hippocampus. Lower expression levels were detected in striatum, nucleus accumbens and cerebellum (at protein level). Abundant in forebrain, weaker in cerebellum and also detected in thymus and spleen.2 Publications

Interactioni

Subunit structurei

Interacts with CAMK4 and calmodulin.3 Publications

GO - Molecular functioni

  • calmodulin binding Source: RGD

Protein-protein interaction databases

BioGridi248789. 1 interaction.
IntActiP97756. 4 interactions.
MINTiMINT-1203156.
STRINGi10116.ENSRNOP00000025009.

Structurei

Secondary structure

1
505
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi444 – 45310Combined sources
Beta strandi455 – 4573Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CKKNMR-B438-463[»]
ProteinModelPortaliP97756.
SMRiP97756. Positions 438-463.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP97756.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini128 – 409282Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni167 – 18923RP domain1 PublicationAdd
BLAST
Regioni435 – 4406Autoinhibitory domain2 Publications
Regioni438 – 46326Calmodulin-binding2 PublicationsAdd
BLAST

Domaini

The autoinhibitory domain overlaps with the calmodulin binding region and may be involved in intrasteric autoinhibition.1 Publication
The RP domain (arginine/proline-rich) is involved in the recognition of CAMKI and CAMK4 as substrates.1 Publication

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0585. Eukaryota.
ENOG410YHHF. LUCA.
HOGENOMiHOG000007846.
HOVERGENiHBG052262.
InParanoidiP97756.
KOiK07359.
PhylomeDBiP97756.

Family and domain databases

InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P97756-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MERSPAVCCQ DPRAELVERV AAISVAHLEE AEEGPEPASN GVDPPPRARA
60 70 80 90 100
ASVIPGSASR PTPVRPSLSA RKFSLQERPA GSCLEAQVGP YSTGPASHMS
110 120 130 140 150
PRAWRRPTIE SHHVAISDTE DCVQLNQYKL QSEIGKGAYG VVRLAYNERE
160 170 180 190 200
DRHYAMKVLS KKKLLKQYGF PRRPPPRGSQ APQGGPAKQL LPLERVYQEI
210 220 230 240 250
AILKKLDHVN VVKLIEVLDD PAEDNLYLVF DLLRKGPVME VPCDKPFPEE
260 270 280 290 300
QARLYLRDII LGLEYLHCQK IVHRDIKPSN LLLGDDGHVK IADFGVSNQF
310 320 330 340 350
EGNDAQLSST AGTPAFMAPE AISDTGQSFS GKALDVWATG VTLYCFVYGK
360 370 380 390 400
CPFIDEYILA LHRKIKNEAV VFPEEPEVSE ELKDLILKML DKNPETRIGV
410 420 430 440 450
SDIKLHPWVT KHGEEPLPSE EEHCSVVEVT EEEVKNSVKL IPSWTTVILV
460 470 480 490 500
KSMLRKRSFG NPFEPQARRE ERSMSAPGNL LLKEGCGEGG KSPELPGVQE

DEAAS
Length:505
Mass (Da):55,908
Last modified:May 1, 1997 - v1
Checksum:i6B268780AC9B67E1
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti45 – 451P → S in AAC42070 (PubMed:7642608).Curated
Sequence conflicti81 – 811G → E in AAC42070 (PubMed:7642608).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L42810 mRNA. Translation: AAC42070.1.
AB023658 mRNA. Translation: BAA75246.1.
S83194 mRNA. Translation: AAB46910.1.
PIRiA57156.
RefSeqiNP_113850.1. NM_031662.1.
UniGeneiRn.4851.

Genome annotation databases

GeneIDi60341.
KEGGirno:60341.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L42810 mRNA. Translation: AAC42070.1.
AB023658 mRNA. Translation: BAA75246.1.
S83194 mRNA. Translation: AAB46910.1.
PIRiA57156.
RefSeqiNP_113850.1. NM_031662.1.
UniGeneiRn.4851.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CKKNMR-B438-463[»]
ProteinModelPortaliP97756.
SMRiP97756. Positions 438-463.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248789. 1 interaction.
IntActiP97756. 4 interactions.
MINTiMINT-1203156.
STRINGi10116.ENSRNOP00000025009.

PTM databases

iPTMnetiP97756.
PhosphoSiteiP97756.

Proteomic databases

PaxDbiP97756.
PRIDEiP97756.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi60341.
KEGGirno:60341.

Organism-specific databases

CTDi84254.
RGDi62023. Camkk1.

Phylogenomic databases

eggNOGiKOG0585. Eukaryota.
ENOG410YHHF. LUCA.
HOGENOMiHOG000007846.
HOVERGENiHBG052262.
InParanoidiP97756.
KOiK07359.
PhylomeDBiP97756.

Enzyme and pathway databases

BRENDAi2.7.11.17. 5301.

Miscellaneous databases

EvolutionaryTraceiP97756.
PROiP97756.

Family and domain databases

InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of a Ca2+/calmodulin-dependent protein kinase cascade. Molecular cloning and expression of calcium/calmodulin-dependent protein kinase kinase."
    Tokumitsu H., Enslen H., Soderling T.R.
    J. Biol. Chem. 270:19320-19324(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 214-230 AND 291-310, FUNCTION, ENZYME REGULATION, INTERACTION WITH CALMODULIN, TISSUE SPECIFICITY.
    Tissue: Brain.
  2. "Evidence for the existence of Ca2+/calmodulin-dependent protein kinase IV kinase isoforms in rat brain."
    Okuno S., Kitani T., Fujisawa H.
    J. Biochem. 119:1176-1181(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  3. "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: PROTEIN SEQUENCE OF 4-13; 20-38; 50-60; 137-148; 196-210; 275-288; 291-311; 333-340; 351-360; 365-382; 389-397; 405-408; 440-444; 458-468 AND 473-478, FUNCTION IN PHOSPHORYLATION OF CAMK1 AND CAMK4, AUTOPHOSPHORYLATION.
  4. "Distribution of Ca2+/calmodulin-dependent protein kinase kinase alpha in the rat central nervous system: an immunohistochemical study."
    Nakamura Y., Okuno S., Kitani T., Otake K., Sato F., Fujisawa H.
    Neurosci. Lett. 204:61-64(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  5. "Calcium/calmodulin-dependent protein kinase kinase: identification of regulatory domains."
    Tokumitsu H., Wayman G.A., Muramatsu M.-A., Soderling T.R.
    Biochemistry 36:12823-12827(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION, REGION.
  6. "Inhibitory cross-talk by cAMP kinase on the calmodulin-dependent protein kinase cascade."
    Wayman G.A., Tokumitsu H., Soderling T.R.
    J. Biol. Chem. 272:16073-16076(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-108 AND SER-458, MUTAGENESIS OF THR-108 AND SER-458, PHOSPHORYLATION BY PRCAKA.
  7. "Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway."
    Yano S., Tokumitsu H., Soderling T.R.
    Nature 396:584-587(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF AKT1.
  8. "Inhibition of the Ca2+/calmodulin-dependent protein kinase I cascade by cAMP-dependent protein kinase."
    Matsushita M., Nairn A.C.
    J. Biol. Chem. 274:10086-10093(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-74 AND THR-108, MUTAGENESIS OF SER-74 AND THR-108, PHOSPHORYLATION BY PRCAKA, TISSUE SPECIFICITY.
  9. "Substrate recognition by Ca2+/Calmodulin-dependent protein kinase kinase. Role of the arg-pro-rich insert domain."
    Tokumitsu H., Takahashi N., Eto K., Yano S., Soderling T.R., Muramatsu M.-A.
    J. Biol. Chem. 274:15803-15810(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ARG-172 AND ARG-177, DOMAIN RP, INTERACTION WITH CAMK4.
  10. "Distinct immunohistochemical localization of two isoforms of Ca2+/calmodulin-dependent protein kinase kinases in the adult rat brain."
    Sakagami H., Umemiya M., Saito S., Kondo H.
    Eur. J. Neurosci. 12:89-99(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  11. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458 AND SER-475, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. "A novel target recognition revealed by calmodulin in complex with Ca2+-calmodulin-dependent kinase kinase."
    Osawa M., Tokumitsu H., Swindells M.B., Kurihara H., Orita M., Shibanuma T., Furuya T., Ikura M.
    Nat. Struct. Biol. 6:819-824(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 438-463 IN COMPLEX WITH CA(2+)/CALMODULIN, MUTAGENESIS OF PHE-459 AND PHE-463, REGION.

Entry informationi

Entry nameiKKCC1_RAT
AccessioniPrimary (citable) accession number: P97756
Secondary accession number(s): Q64572, Q794E3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: May 1, 1997
Last modified: June 8, 2016
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.