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Protein

Calcium/calmodulin-dependent protein kinase kinase 1

Gene

CAMKK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.1 Publication

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 (By similarity). May be regulated through phosphorylation by CAMK1 and CAMK4.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei157ATPPROSITE-ProRule annotation1
Active sitei275Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi134 – 142ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-442717 CREB phosphorylation through the activation of CaMKK
SignaLinkiQ8N5S9
SIGNORiQ8N5S9

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
Synonyms:CAMKKA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000004660.14
HGNCiHGNC:1469 CAMKK1
MIMi611411 gene
neXtProtiNX_Q8N5S9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi84254
OpenTargetsiENSG00000004660
PharmGKBiPA26051

Chemistry databases

ChEMBLiCHEMBL5256
GuidetoPHARMACOLOGYi1956

Polymorphism and mutation databases

BioMutaiCAMKK1
DMDMi56404620

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000861411 – 505Calcium/calmodulin-dependent protein kinase kinase 1Add BLAST505

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei67PhosphoserineCombined sources1
Modified residuei74PhosphoserineBy similarity1
Modified residuei78Asymmetric dimethylarginineBy similarity1
Modified residuei100PhosphoserineBy similarity1
Modified residuei108PhosphothreonineBy similarity1
Modified residuei458PhosphoserineCombined sources1
Modified residuei475PhosphoserineBy similarity1
Modified residuei492PhosphoserineCombined sources1

Post-translational modificationi

Appears to be autophosphorylated in a Ca2+/calmodulin-dependent manner. Phosphorylated at multiple sites by PRCAKA/PKA. Phosphorylation of Ser-458 is blocked upon binding to Ca2+/calmodulin. In vitro, phosphorylated by CAMK1 and CAMK4 (By similarity).By similarity

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

MaxQBiQ8N5S9
PeptideAtlasiQ8N5S9
PRIDEiQ8N5S9
ProteomicsDBi72092
72093 [Q8N5S9-2]
TopDownProteomicsiQ8N5S9-2 [Q8N5S9-2]

PTM databases

iPTMnetiQ8N5S9
PhosphoSitePlusiQ8N5S9

Miscellaneous databases

PMAP-CutDBiQ8N5S9

Expressioni

Gene expression databases

BgeeiENSG00000004660
CleanExiHS_CAMKK1
ExpressionAtlasiQ8N5S9 baseline and differential
GenevisibleiQ8N5S9 HS

Organism-specific databases

HPAiCAB009111
HPA028062

Interactioni

Subunit structurei

Interacts with CAMK4 and calmodulin.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
YWHAHQ049175EBI-6424030,EBI-306940

GO - Molecular functioni

Protein-protein interaction databases

BioGridi123981, 25 interactors
IntActiQ8N5S9, 16 interactors
MINTiQ8N5S9

Chemistry databases

BindingDBiQ8N5S9

Structurei

Secondary structure

1505
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi128 – 136Combined sources9
Beta strandi138 – 147Combined sources10
Turni148 – 151Combined sources4
Beta strandi152 – 160Combined sources9
Turni161 – 163Combined sources3
Helixi195 – 205Combined sources11
Beta strandi214 – 219Combined sources6
Beta strandi223 – 231Combined sources9
Helixi249 – 268Combined sources20
Helixi278 – 280Combined sources3
Beta strandi281 – 283Combined sources3
Beta strandi289 – 291Combined sources3
Helixi314 – 316Combined sources3
Helixi319 – 322Combined sources4
Helixi331 – 348Combined sources18
Helixi358 – 367Combined sources10
Beta strandi374 – 376Combined sources3
Helixi380 – 389Combined sources10
Turni394 – 396Combined sources3
Helixi400 – 405Combined sources6
Helixi407 – 410Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6CCFX-ray2.10A/B124-411[»]
6CD6X-ray2.20A/B/C/D124-411[»]
ProteinModelPortaliQ8N5S9
SMRiQ8N5S9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini128 – 409Protein kinasePROSITE-ProRule annotationAdd BLAST282

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni167 – 189RP domainAdd BLAST23
Regioni435 – 440Autoinhibitory domainBy similarity6
Regioni438 – 463Calmodulin-bindingBy similarityAdd BLAST26

Domaini

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

Sequence similaritiesi

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

Phylogenomic databases

GeneTreeiENSGT00530000063214
HOGENOMiHOG000007846
HOVERGENiHBG052262
InParanoidiQ8N5S9
KOiK00908
PhylomeDBiQ8N5S9
TreeFamiTF313013

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N5S9-1) [UniParc]FASTAAdd to basket
Also known as: A, Variant 3

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEGGPAVCCQ DPRAELVERV AAIDVTHLEE ADGGPEPTRN GVDPPPRARA
60 70 80 90 100
ASVIPGSTSR LLPARPSLSA RKLSLQERPA GSYLEAQAGP YATGPASHIS
110 120 130 140 150
PRAWRRPTIE SHHVAISDAE DCVQLNQYKL QSEIGKGAYG VVRLAYNESE
160 170 180 190 200
DRHYAMKVLS KKKLLKQYGF PRRPPPRGSQ AAQGGPAKQL LPLERVYQEI
210 220 230 240 250
AILKKLDHVN VVKLIEVLDD PAEDNLYLVF DLLRKGPVME VPCDKPFSEE
260 270 280 290 300
QARLYLRDVI LGLEYLHCQK IVHRDIKPSN LLLGDDGHVK IADFGVSNQF
310 320 330 340 350
EGNDAQLSST AGTPAFMAPE AISDSGQSFS GKALDVWATG VTLYCFVYGK
360 370 380 390 400
CPFIDDFILA LHRKIKNEPV VFPEEPEISE ELKDLILKML DKNPETRIGV
410 420 430 440 450
PDIKLHPWVT KNGEEPLPSE EEHCSVVEVT EEEVKNSVRL IPSWTTVILV
460 470 480 490 500
KSMLRKRSFG NPFEPQARRE ERSMSAPGNL LVKEGFGEGG KSPELPGVQE

DEAAS
Length:505
Mass (Da):55,735
Last modified:December 7, 2004 - v2
Checksum:i92A055D20E487C86
GO
Isoform 2 (identifier: Q8N5S9-2) [UniParc]FASTAAdd to basket
Also known as: B, Variant 1

The sequence of this isoform differs from the canonical sequence as follows:
     228-228: L → LALQNQAQNIQLDSTNIAKPHSLLPSEQQDSGSTWAARS
     483-505: Missing.

Show »
Length:520
Mass (Da):57,523
Checksum:i7FDC2623527C827E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020531375E → G2 PublicationsCorresponds to variant dbSNP:rs7214723Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012140228L → LALQNQAQNIQLDSTNIAKP HSLLPSEQQDSGSTWAARS in isoform 2. 3 Publications1
Alternative sequenceiVSP_012141483 – 505Missing in isoform 2. 3 PublicationsAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF425232 mRNA Translation: AAN37386.1
AF425301 mRNA Translation: AAN37387.1
AL136576 mRNA Translation: CAB66511.1
BC031647 mRNA Translation: AAH31647.1
BC043487 mRNA Translation: AAH43487.1
CCDSiCCDS11038.1 [Q8N5S9-1]
CCDS11039.1 [Q8N5S9-2]
RefSeqiNP_115670.1, NM_032294.2 [Q8N5S9-1]
NP_757343.2, NM_172206.1
NP_757344.2, NM_172207.2 [Q8N5S9-2]
XP_016880709.1, XM_017025220.1 [Q8N5S9-1]
UniGeneiHs.8417

Genome annotation databases

EnsembliENST00000158166; ENSP00000158166; ENSG00000004660 [Q8N5S9-2]
ENST00000348335; ENSP00000323118; ENSG00000004660 [Q8N5S9-1]
GeneIDi84254
KEGGihsa:84254
UCSCiuc002fwu.4 human [Q8N5S9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKKCC1_HUMAN
AccessioniPrimary (citable) accession number: Q8N5S9
Secondary accession number(s): Q9BQH3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 7, 2004
Last modified: June 20, 2018
This is version 150 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

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