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Protein

Calcium/calmodulin-dependent protein kinase kinase 1

Gene

CAMKK1

Organism
Homo sapiens (Human)
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.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)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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Calmodulin-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

HGNCiHGNC:1469. CAMKK1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA26051.

Chemistry

ChEMBLiCHEMBL5256.
GuidetoPHARMACOLOGYi1956.

Polymorphism and mutation databases

BioMutaiCAMKK1.
DMDMi56404620.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 505505Calcium/calmodulin-dependent protein kinase kinase 1PRO_0000086141Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei67 – 671PhosphoserineCombined sources
Modified residuei74 – 741PhosphoserineBy similarity
Modified residuei100 – 1001PhosphoserineBy similarity
Modified residuei108 – 1081PhosphothreonineBy similarity
Modified residuei458 – 4581PhosphoserineCombined sources
Modified residuei475 – 4751PhosphoserineBy similarity
Modified residuei492 – 4921PhosphoserineCombined sources

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

Phosphoprotein

Proteomic databases

EPDiQ8N5S9.
MaxQBiQ8N5S9.
PeptideAtlasiQ8N5S9.
PRIDEiQ8N5S9.
TopDownProteomicsiQ8N5S9-2. [Q8N5S9-2]

PTM databases

iPTMnetiQ8N5S9.
PhosphoSiteiQ8N5S9.

Miscellaneous databases

PMAP-CutDBQ8N5S9.

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

Protein-protein interaction databases

BioGridi123981. 24 interactions.
IntActiQ8N5S9. 16 interactions.
MINTiMINT-3040241.

Chemistry

BindingDBiQ8N5S9.

Structurei

3D structure databases

ProteinModelPortaliQ8N5S9.
SMRiQ8N5S9. Positions 123-435, 438-463.
ModBaseiSearch...
MobiDBiSearch...

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 domainAdd
BLAST
Regioni435 – 4406Autoinhibitory domainBy similarity
Regioni438 – 46326Calmodulin-bindingBy similarityAdd
BLAST

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
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

GeneTreeiENSGT00530000063214.
HOGENOMiHOG000007846.
HOVERGENiHBG052262.
InParanoidiQ8N5S9.
KOiK07359.
PhylomeDBiQ8N5S9.
TreeFamiTF313013.

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]

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti375 – 3751E → G.2 Publications
Corresponds to variant rs7214723 [ dbSNP | Ensembl ].
VAR_020531

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei228 – 2281L → LALQNQAQNIQLDSTNIAKP HSLLPSEQQDSGSTWAARS in isoform 2. 3 PublicationsVSP_012140
Alternative sequencei483 – 50523Missing in isoform 2. 3 PublicationsVSP_012141Add
BLAST

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_757343.1. NM_172206.1. [Q8N5S9-1]
NP_757344.2. NM_172207.2. [Q8N5S9-2]
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

Cross-referencesi

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_757343.1. NM_172206.1. [Q8N5S9-1]
NP_757344.2. NM_172207.2. [Q8N5S9-2]
UniGeneiHs.8417.

3D structure databases

ProteinModelPortaliQ8N5S9.
SMRiQ8N5S9. Positions 123-435, 438-463.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123981. 24 interactions.
IntActiQ8N5S9. 16 interactions.
MINTiMINT-3040241.

Chemistry

BindingDBiQ8N5S9.
ChEMBLiCHEMBL5256.
GuidetoPHARMACOLOGYi1956.

PTM databases

iPTMnetiQ8N5S9.
PhosphoSiteiQ8N5S9.

Polymorphism and mutation databases

BioMutaiCAMKK1.
DMDMi56404620.

Proteomic databases

EPDiQ8N5S9.
MaxQBiQ8N5S9.
PeptideAtlasiQ8N5S9.
PRIDEiQ8N5S9.
TopDownProteomicsiQ8N5S9-2. [Q8N5S9-2]

Protocols and materials databases

DNASUi84254.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi84254.
GeneCardsiCAMKK1.
H-InvDBHIX0135620.
HGNCiHGNC:1469. CAMKK1.
HPAiCAB009111.
HPA028062.
MIMi611411. gene.
neXtProtiNX_Q8N5S9.
PharmGKBiPA26051.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00530000063214.
HOGENOMiHOG000007846.
HOVERGENiHBG052262.
InParanoidiQ8N5S9.
KOiK07359.
PhylomeDBiQ8N5S9.
TreeFamiTF313013.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiCAMKK1. human.
GeneWikiiCAMKK1.
GenomeRNAii84254.
PMAP-CutDBQ8N5S9.
PROiQ8N5S9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000004660.
CleanExiHS_CAMKK1.
ExpressionAtlasiQ8N5S9. baseline and differential.
GenevisibleiQ8N5S9. HS.

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...

Entry informationi

Entry nameiKKCC1_HUMAN
AccessioniPrimary (citable) accession number: Q8N5S9
Secondary accession number(s): Q9BQH3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 7, 2004
Last modified: September 7, 2016
This is version 136 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.