UniProtKB - Q96RR4 (KKCC2_HUMAN)
Calcium/calmodulin-dependent protein kinase kinase 2
CAMKK2
Functioni
Catalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 194 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 312 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 171 – 179 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- calcium ion binding Source: UniProtKB
- calmodulin binding Source: UniProtKB
- calmodulin-dependent protein kinase activity Source: UniProtKB-EC
- protein tyrosine kinase activity Source: UniProtKB
GO - Biological processi
- calcium-mediated signaling Source: UniProtKB
- CAMKK-AMPK signaling cascade Source: ParkinsonsUK-UCL
- cellular response to reactive oxygen species Source: ParkinsonsUK-UCL
- MAPK cascade Source: UniProtKB
- positive regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
- positive regulation of protein phosphorylation Source: ParkinsonsUK-UCL
- positive regulation of transcription, DNA-templated Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: UniProtKB
- regulation of protein kinase activity Source: UniProtKB
Keywordsi
Molecular function | Calmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.17, 2681 |
PathwayCommonsi | Q96RR4 |
Reactomei | R-HSA-111932, CaMK IV-mediated phosphorylation of CREB R-HSA-442729, CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde R-HSA-9619229, Activation of RAC1 downstream of NMDARs R-HSA-9619483, Activation of AMPK downstream of NMDARs |
SignaLinki | Q96RR4 |
SIGNORi | Q96RR4 |
Names & Taxonomyi
Protein namesi | Recommended name: Calcium/calmodulin-dependent protein kinase kinase 2 (EC:2.7.11.17)Short name: CaM-KK 2 Short name: CaM-kinase kinase 2 Short name: CaMKK 2 Alternative name(s): Calcium/calmodulin-dependent protein kinase kinase beta Short name: CaM-KK beta Short name: CaM-kinase kinase beta Short name: CaMKK beta |
Gene namesi | Name:CAMKK2 Synonyms:CAMKKB, KIAA0787 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1470, CAMKK2 |
MIMi | 615002, gene |
neXtProti | NX_Q96RR4 |
VEuPathDBi | HostDB:ENSG00000110931.18 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Other locations
- Cytoplasm 1 Publication
- neuron projection 1 Publication
Note: Predominantly nuclear in unstimulated cells, relocalizes into cytoplasm and neurites after forskolin induction.1 Publication
Cytosol
- cytosol Source: HPA
Nucleus
- nucleoplasm Source: Reactome
Other locations
- neuron projection Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell projection, Cytoplasm, NucleusPathology & Biotechi
Organism-specific databases
DisGeNETi | 10645 |
OpenTargetsi | ENSG00000110931 |
PharmGKBi | PA26052 |
Miscellaneous databases
Pharosi | Q96RR4, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5284 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q96RR4 |
GuidetoPHARMACOLOGYi | 1957 |
Genetic variation databases
BioMutai | CAMKK2 |
DMDMi | 317373374 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000086144 | 2 – 588 | Calcium/calmodulin-dependent protein kinase kinase 2Add BLAST | 587 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Modified residuei | 2 | N-acetylserineCombined sources | 1 | ||
Modified residuei | 100 | PhosphoserineBy similarity | 1 | ||
Modified residuei | 114 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 129 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 133 | PhosphoserineBy similarity | 1 | ||
Modified residuei | 137 | PhosphoserineBy similarity | 1 | ||
Modified residuei | 495 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 511 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 572 | PhosphoserineBy similarity | 1 | ||
Isoform 5 (identifier: Q96RR4-5) | |||||
Modified residuei | 479 | PhosphoserineCombined sources | 1 | ||
Isoform 3 (identifier: Q96RR4-3) | |||||
Modified residuei | 522 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q96RR4 |
jPOSTi | Q96RR4 |
MassIVEi | Q96RR4 |
MaxQBi | Q96RR4 |
PaxDbi | Q96RR4 |
PeptideAtlasi | Q96RR4 |
PRIDEi | Q96RR4 |
ProteomicsDBi | 78009 [Q96RR4-1] 78010 [Q96RR4-2] 78011 [Q96RR4-3] 78012 [Q96RR4-4] 78013 [Q96RR4-5] 78014 [Q96RR4-6] 78015 [Q96RR4-7] |
PTM databases
iPTMneti | Q96RR4 |
PhosphoSitePlusi | Q96RR4 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000110931, Expressed in cerebellum and 245 other tissues |
ExpressionAtlasi | Q96RR4, baseline and differential |
Genevisiblei | Q96RR4, HS |
Organism-specific databases
HPAi | ENSG00000110931, Tissue enriched (brain) |
Interactioni
Subunit structurei
Interacts with calmodulin.
By similarityGO - Molecular functioni
- calmodulin binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 115889, 34 interactors |
IntActi | Q96RR4, 24 interactors |
STRINGi | 9606.ENSP00000312741 |
Chemistry databases
BindingDBi | Q96RR4 |
Miscellaneous databases
RNActi | Q96RR4, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q96RR4 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q96RR4 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 165 – 446 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 282 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 204 – 226 | RP domainAdd BLAST | 23 | |
Regioni | 472 – 477 | Autoinhibitory domainBy similarity | 6 | |
Regioni | 475 – 500 | Calmodulin-bindingBy similarityAdd BLAST | 26 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0585, Eukaryota |
GeneTreei | ENSGT00940000161828 |
HOGENOMi | CLU_000288_63_0_1 |
InParanoidi | Q96RR4 |
OMAi | CCLLIEV |
OrthoDBi | 856506at2759 |
PhylomeDBi | Q96RR4 |
TreeFami | TF313013 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (7+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 7 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 7 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSSCVSSQPS SNRAAPQDEL GGRGSSSSES QKPCEALRGL SSLSIHLGME
60 70 80 90 100
SFIVVTECEP GCAVDLGLAR DRPLEADGQE VPLDTSGSQA RPHLSGRKLS
110 120 130 140 150
LQERSQGGLA AGGSLDMNGR CICPSLPYSP VSSPQSSPRL PRRPTVESHH
160 170 180 190 200
VSITGMQDCV QLNQYTLKDE IGKGSYGVVK LAYNENDNTY YAMKVLSKKK
210 220 230 240 250
LIRQAGFPRR PPPRGTRPAP GGCIQPRGPI EQVYQEIAIL KKLDHPNVVK
260 270 280 290 300
LVEVLDDPNE DHLYMVFELV NQGPVMEVPT LKPLSEDQAR FYFQDLIKGI
310 320 330 340 350
EYLHYQKIIH RDIKPSNLLV GEDGHIKIAD FGVSNEFKGS DALLSNTVGT
360 370 380 390 400
PAFMAPESLS ETRKIFSGKA LDVWAMGVTL YCFVFGQCPF MDERIMCLHS
410 420 430 440 450
KIKSQALEFP DQPDIAEDLK DLITRMLDKN PESRIVVPEI KLHPWVTRHG
460 470 480 490 500
AEPLPSEDEN CTLVEVTEEE VENSVKHIPS LATVILVKTM IRKRSFGNPF
510 520 530 540 550
EGSRREERSL SAPGNLLTKK PTRECESLSE LKEARQRRQP PGHRPAPRGG
560 570 580
GGSALVRGSP CVESCWAPAP GSPARMHPLR PEEAMEPE
The sequence of this isoform differs from the canonical sequence as follows:
442-484: Missing.
520-532: KPTRECESLSELK → QGSEDNLQGTDPP
533-541: EARQRRQPP → PVGEEEVLL
542-554: Missing.
555-588: Missing.
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF5H4I7 | F5H4I7_HUMAN | Calcium/calmodulin-dependent protei... | CAMKK2 | 125 | Annotation score: | ||
F5GZ00 | F5GZ00_HUMAN | Calcium/calmodulin-dependent protei... | CAMKK2 | 343 | Annotation score: | ||
F5H360 | F5H360_HUMAN | Calcium/calmodulin-dependent protei... | CAMKK2 | 87 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 206 | G → A in AAD31507 (PubMed:9822657).Curated | 1 | |
Sequence conflicti | 331 | F → I in BAF84761 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 347 | T → Y in AAD31507 (PubMed:9822657).Curated | 1 | |
Sequence conflicti | 371 | L → K in AAD31507 (PubMed:9822657).Curated | 1 | |
Sequence conflicti | 554 | A → H in AAK91829 (PubMed:11395482).Curated | 1 | |
Sequence conflicti | 557 | R → N in AAK91829 (PubMed:11395482).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_032788 | 10 | S → N1 PublicationCorresponds to variant dbSNP:rs28360477Ensembl. | 1 | |
Natural variantiVAR_020532 | 85 | T → S4 PublicationsCorresponds to variant dbSNP:rs3817190Ensembl. | 1 | |
Natural variantiVAR_040610 | 123 | C → Y1 PublicationCorresponds to variant dbSNP:rs35403710Ensembl. | 1 | |
Natural variantiVAR_040611 | 127 | P → L in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_040612 | 182 | A → T in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1207121718Ensembl. | 1 | |
Natural variantiVAR_020533 | 363 | R → C. Corresponds to variant dbSNP:rs1132780Ensembl. | 1 | |
Natural variantiVAR_040613 | 492 | R → H1 PublicationCorresponds to variant dbSNP:rs34129994Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_012142 | 442 – 484 | Missing in isoform 4, isoform 5 and isoform 6. 2 PublicationsAdd BLAST | 43 | |
Alternative sequenceiVSP_012143 | 520 – 532 | KPTRE…LSELK → QGSEDNLQGTDPP in isoform 3 and isoform 5. 4 PublicationsAdd BLAST | 13 | |
Alternative sequenceiVSP_012148 | 533 – 554 | EARQR…GGGSA → GTKKKKGLDSMTSTVAAGWL DRRV in isoform 7. 2 PublicationsAdd BLAST | 22 | |
Alternative sequenceiVSP_012144 | 533 – 541 | EARQRRQPP → PVGEEEVLL in isoform 3 and isoform 5. 4 Publications | 9 | |
Alternative sequenceiVSP_012146 | 533 | E → T in isoform 2 and isoform 6. 3 Publications | 1 | |
Alternative sequenceiVSP_012147 | 534 – 554 | Missing in isoform 2 and isoform 6. 3 PublicationsAdd BLAST | 21 | |
Alternative sequenceiVSP_012145 | 542 – 554 | Missing in isoform 3 and isoform 5. 4 PublicationsAdd BLAST | 13 | |
Alternative sequenceiVSP_012149 | 555 – 588 | Missing in isoform 2, isoform 3, isoform 5, isoform 6 and isoform 7. 8 PublicationsAdd BLAST | 34 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2ZV2 | X-ray | 2.40 | A | 158-448 | [»] | |
5UY6 | X-ray | 1.70 | A | 161-449 | [»] | |
5UYJ | X-ray | 1.60 | A | 161-449 | [»] | |
5VT1 | X-ray | 1.90 | A | 161-449 | [»] | |
5YV8 | X-ray | 1.93 | A | 158-448 | [»] | |
5YV9 | X-ray | 2.53 | A | 158-448 | [»] | |
5YVA | X-ray | 2.57 | A | 158-448 | [»] | |
5YVB | X-ray | 2.02 | A | 158-448 | [»] | |
5YVC | X-ray | 2.02 | A | 158-448 | [»] | |
6BKU | X-ray | 2.00 | A | 162-449 | [»] | |
6BLE | X-ray | 1.90 | A | 161-449 | [»] | |
6BQL | X-ray | 2.00 | A | 161-449 | [»] | |
6BQP | X-ray | 1.95 | A | 161-449 | [»] | |
6BQQ | X-ray | 1.80 | A | 161-449 | [»] | |
6BRC | X-ray | 2.20 | A/B | 161-449 | [»] | |
6CMJ | X-ray | 2.40 | A/B | 149-465 | [»] | |
6EF5 | X-ray | 2.44 | Q/S | 508-514 | [»] | |
6EWW | X-ray | 2.68 | E/F/G/H | 97-104 | [»] | |
6FEL | X-ray | 2.84 | E/F/G/H | 508-515 | [»] | |
6Y8A | X-ray | 1.50 | P | 508-515 | [»] | |
SMRi | Q96RR4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 115889, 34 interactors |
IntActi | Q96RR4, 24 interactors |
STRINGi | 9606.ENSP00000312741 |
Chemistry databases
BindingDBi | Q96RR4 |
ChEMBLi | CHEMBL5284 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q96RR4 |
GuidetoPHARMACOLOGYi | 1957 |
PTM databases
iPTMneti | Q96RR4 |
PhosphoSitePlusi | Q96RR4 |
Genetic variation databases
BioMutai | CAMKK2 |
DMDMi | 317373374 |
Proteomic databases
EPDi | Q96RR4 |
jPOSTi | Q96RR4 |
MassIVEi | Q96RR4 |
MaxQBi | Q96RR4 |
PaxDbi | Q96RR4 |
PeptideAtlasi | Q96RR4 |
PRIDEi | Q96RR4 |
ProteomicsDBi | 78009 [Q96RR4-1] 78010 [Q96RR4-2] 78011 [Q96RR4-3] 78012 [Q96RR4-4] 78013 [Q96RR4-5] 78014 [Q96RR4-6] 78015 [Q96RR4-7] |
Protocols and materials databases
Antibodypediai | 19059, 369 antibodies |
DNASUi | 10645 |
Genome annotation databases
Organism-specific databases
CTDi | 10645 |
DisGeNETi | 10645 |
GeneCardsi | CAMKK2 |
HGNCi | HGNC:1470, CAMKK2 |
HPAi | ENSG00000110931, Tissue enriched (brain) |
MIMi | 615002, gene |
neXtProti | NX_Q96RR4 |
OpenTargetsi | ENSG00000110931 |
PharmGKBi | PA26052 |
VEuPathDBi | HostDB:ENSG00000110931.18 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0585, Eukaryota |
GeneTreei | ENSGT00940000161828 |
HOGENOMi | CLU_000288_63_0_1 |
InParanoidi | Q96RR4 |
OMAi | CCLLIEV |
OrthoDBi | 856506at2759 |
PhylomeDBi | Q96RR4 |
TreeFami | TF313013 |
Enzyme and pathway databases
BRENDAi | 2.7.11.17, 2681 |
PathwayCommonsi | Q96RR4 |
Reactomei | R-HSA-111932, CaMK IV-mediated phosphorylation of CREB R-HSA-442729, CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde R-HSA-9619229, Activation of RAC1 downstream of NMDARs R-HSA-9619483, Activation of AMPK downstream of NMDARs |
SignaLinki | Q96RR4 |
SIGNORi | Q96RR4 |
Miscellaneous databases
BioGRID-ORCSi | 10645, 10 hits in 903 CRISPR screens |
ChiTaRSi | CAMKK2, human |
EvolutionaryTracei | Q96RR4 |
GeneWikii | CAMKK2 |
GenomeRNAii | 10645 |
Pharosi | Q96RR4, Tchem |
PROi | PR:Q96RR4 |
RNActi | Q96RR4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000110931, Expressed in cerebellum and 245 other tissues |
ExpressionAtlasi | Q96RR4, baseline and differential |
Genevisiblei | Q96RR4, HS |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KKCC2_HUMAN | |
Accessioni | Q96RR4Primary (citable) accession number: Q96RR4 Secondary accession number(s): A8K7Q7 Q9Y5N2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 7, 2004 |
Last sequence update: | January 11, 2011 | |
Last modified: | February 10, 2021 | |
This is version 178 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human and mouse protein kinases
Human and mouse protein kinases: classification and index