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Protein

Calcium/calmodulin-dependent protein kinase type 1

Gene

CAMK1

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 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-694', 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. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. 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.By similarity8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei49ATP1
Active sitei141Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi26 – 34ATP9

GO - Molecular functioni

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • negative regulation of protein binding Source: UniProtKB
  • nucleocytoplasmic transport Source: Ensembl
  • positive regulation of dendritic spine development Source: UniProtKB
  • positive regulation of muscle cell differentiation Source: BHF-UCL
  • positive regulation of neuron projection development Source: UniProtKB
  • positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
  • positive regulation of protein acetylation Source: UniProtKB
  • positive regulation of protein export from nucleus Source: UniProtKB
  • positive regulation of protein serine/threonine kinase activity Source: UniProtKB
  • positive regulation of synapse structural plasticity Source: UniProtKB
  • positive regulation of syncytium formation by plasma membrane fusion Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of muscle cell differentiation Source: UniProtKB
  • regulation of protein binding Source: UniProtKB
  • regulation of protein localization Source: UniProtKB
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Differentiation, Neurogenesis

Keywords - Ligandi

ATP-binding, Calmodulin-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS05815-MONOMER.
BRENDAi2.7.11.17. 2681.
SignaLinkiQ14012.
SIGNORiQ14012.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:CAMK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:1459. CAMK1.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Predominantly cytoplasmic.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi49K → A: Catalytically inactive form; prevents CDK4 activation. 2 Publications1
Mutagenesisi177T → A: Loss of activation by CaMKK1. 1 Publication1
Mutagenesisi177T → D: Partial activation in absence of CaMKK1. 1 Publication1

Organism-specific databases

DisGeNETi8536.
OpenTargetsiENSG00000134072.
PharmGKBiPA26048.

Chemistry databases

ChEMBLiCHEMBL2493.
GuidetoPHARMACOLOGYi1952.

Polymorphism and mutation databases

BioMutaiCAMK1.
DMDMi3122301.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860761 – 370Calcium/calmodulin-dependent protein kinase type 1Add BLAST370

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki59Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei177Phosphothreonine; by CaMKK1 and CaMKK21 Publication1
Modified residuei363PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by CaMKK1 and CaMKK2 on Thr-177.3 Publications
Polybiquitinated by the E3 ubiquitin-protein ligase complex SCF(FBXL12), leading to proteasomal degradation.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ14012.
MaxQBiQ14012.
PaxDbiQ14012.
PeptideAtlasiQ14012.
PRIDEiQ14012.

PTM databases

iPTMnetiQ14012.
PhosphoSitePlusiQ14012.

Expressioni

Tissue specificityi

Widely expressed. Expressed in cells of the zona glomerulosa of the adrenal cortex.2 Publications

Gene expression databases

BgeeiENSG00000134072.
CleanExiHS_CAMK1.
ExpressionAtlasiQ14012. baseline and differential.
GenevisibleiQ14012. HS.

Organism-specific databases

HPAiCAB031904.
HPA051409.

Interactioni

Subunit structurei

Monomer. Interacts with XPO1 (By similarity). Interacts with MARK2, ARHGEF7/BETAPIX and GIT1.By similarity2 Publications

Protein-protein interaction databases

BioGridi114106. 29 interactors.
DIPiDIP-41906N.
IntActiQ14012. 5 interactors.
MINTiMINT-201810.
STRINGi9606.ENSP00000256460.

Chemistry databases

BindingDBiQ14012.

Structurei

Secondary structure

1370
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi16 – 18Combined sources3
Beta strandi20 – 29Combined sources10
Beta strandi32 – 39Combined sources8
Turni40 – 42Combined sources3
Beta strandi45 – 52Combined sources8
Helixi66 – 70Combined sources5
Beta strandi81 – 86Combined sources6
Beta strandi88 – 95Combined sources8
Beta strandi100 – 102Combined sources3
Helixi103 – 109Combined sources7
Helixi115 – 134Combined sources20
Helixi144 – 146Combined sources3
Beta strandi147 – 152Combined sources6
Beta strandi158 – 160Combined sources3
Helixi166 – 168Combined sources3
Helixi173 – 178Combined sources6
Turni182 – 184Combined sources3
Helixi187 – 190Combined sources4
Helixi198 – 213Combined sources16
Helixi223 – 232Combined sources10
Turni239 – 244Combined sources6
Helixi247 – 256Combined sources10
Turni261 – 263Combined sources3
Helixi267 – 272Combined sources6
Helixi274 – 277Combined sources4
Helixi287 – 297Combined sources11
Helixi301 – 311Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4FG7X-ray2.70A1-293[»]
4FG8X-ray2.20A/B1-315[»]
4FG9X-ray2.40A/B1-320[»]
4FGBX-ray2.60A1-320[»]
ProteinModelPortaliQ14012.
SMRiQ14012.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 276Protein kinasePROSITE-ProRule annotationAdd BLAST257

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni276 – 316Autoinhibitory domainAdd BLAST41
Regioni296 – 317Calmodulin-bindingBy similarityAdd BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi315 – 321Nuclear export signalBy similarity7

Domaini

The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate.1 Publication

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0032. Eukaryota.
ENOG410XRMJ. LUCA.
GeneTreeiENSGT00760000118944.
HOGENOMiHOG000233016.
HOVERGENiHBG108055.
InParanoidiQ14012.
KOiK08794.
OMAiVTVEKRY.
OrthoDBiEOG091G0HK9.
PhylomeDBiQ14012.
TreeFamiTF314166.

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. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q14012-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLGAVEGPRW KQAEDIRDIY DFRDVLGTGA FSEVILAEDK RTQKLVAIKC
60 70 80 90 100
IAKEALEGKE GSMENEIAVL HKIKHPNIVA LDDIYESGGH LYLIMQLVSG
110 120 130 140 150
GELFDRIVEK GFYTERDASR LIFQVLDAVK YLHDLGIVHR DLKPENLLYY
160 170 180 190 200
SLDEDSKIMI SDFGLSKMED PGSVLSTACG TPGYVAPEVL AQKPYSKAVD
210 220 230 240 250
CWSIGVIAYI LLCGYPPFYD ENDAKLFEQI LKAEYEFDSP YWDDISDSAK
260 270 280 290 300
DFIRHLMEKD PEKRFTCEQA LQHPWIAGDT ALDKNIHQSV SEQIKKNFAK
310 320 330 340 350
SKWKQAFNAT AVVRHMRKLQ LGTSQEGQGQ TASHGELLTP VAGGPAAGCC
360 370
CRDCCVEPGT ELSPTLPHQL
Length:370
Mass (Da):41,337
Last modified:November 1, 1996 - v1
Checksum:i57FA20ECE00FA76C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040596217P → S in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040597361E → K.1 PublicationCorresponds to variant rs56033923dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L41816 mRNA. Translation: AAA99458.1.
BC106754 mRNA. Translation: AAI06755.1.
BC106755 mRNA. Translation: AAI06756.1.
CCDSiCCDS2582.1.
PIRiS57347.
RefSeqiNP_003647.1. NM_003656.4.
UniGeneiHs.434875.

Genome annotation databases

EnsembliENST00000256460; ENSP00000256460; ENSG00000134072.
GeneIDi8536.
KEGGihsa:8536.
UCSCiuc003bst.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L41816 mRNA. Translation: AAA99458.1.
BC106754 mRNA. Translation: AAI06755.1.
BC106755 mRNA. Translation: AAI06756.1.
CCDSiCCDS2582.1.
PIRiS57347.
RefSeqiNP_003647.1. NM_003656.4.
UniGeneiHs.434875.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4FG7X-ray2.70A1-293[»]
4FG8X-ray2.20A/B1-315[»]
4FG9X-ray2.40A/B1-320[»]
4FGBX-ray2.60A1-320[»]
ProteinModelPortaliQ14012.
SMRiQ14012.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114106. 29 interactors.
DIPiDIP-41906N.
IntActiQ14012. 5 interactors.
MINTiMINT-201810.
STRINGi9606.ENSP00000256460.

Chemistry databases

BindingDBiQ14012.
ChEMBLiCHEMBL2493.
GuidetoPHARMACOLOGYi1952.

PTM databases

iPTMnetiQ14012.
PhosphoSitePlusiQ14012.

Polymorphism and mutation databases

BioMutaiCAMK1.
DMDMi3122301.

Proteomic databases

EPDiQ14012.
MaxQBiQ14012.
PaxDbiQ14012.
PeptideAtlasiQ14012.
PRIDEiQ14012.

Protocols and materials databases

DNASUi8536.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000256460; ENSP00000256460; ENSG00000134072.
GeneIDi8536.
KEGGihsa:8536.
UCSCiuc003bst.4. human.

Organism-specific databases

CTDi8536.
DisGeNETi8536.
GeneCardsiCAMK1.
HGNCiHGNC:1459. CAMK1.
HPAiCAB031904.
HPA051409.
MIMi604998. gene.
neXtProtiNX_Q14012.
OpenTargetsiENSG00000134072.
PharmGKBiPA26048.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0032. Eukaryota.
ENOG410XRMJ. LUCA.
GeneTreeiENSGT00760000118944.
HOGENOMiHOG000233016.
HOVERGENiHBG108055.
InParanoidiQ14012.
KOiK08794.
OMAiVTVEKRY.
OrthoDBiEOG091G0HK9.
PhylomeDBiQ14012.
TreeFamiTF314166.

Enzyme and pathway databases

BioCyciZFISH:HS05815-MONOMER.
BRENDAi2.7.11.17. 2681.
SignaLinkiQ14012.
SIGNORiQ14012.

Miscellaneous databases

GeneWikiiCAMK1.
GenomeRNAii8536.
PROiQ14012.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134072.
CleanExiHS_CAMK1.
ExpressionAtlasiQ14012. baseline and differential.
GenevisibleiQ14012. 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. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKCC1A_HUMAN
AccessioniPrimary (citable) accession number: Q14012
Secondary accession number(s): Q3KPF6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 173 of the entry and version 1 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

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

Documents

  1. Human chromosome 3
    Human chromosome 3: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.