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Protein

Calcium/calmodulin-dependent protein kinase type 1

Gene

CAMK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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-x2-[ST]-x3-[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.

Activity 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

Keywordsi

Molecular functionAllosteric enzyme, Calmodulin-binding, Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Differentiation, Neurogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000134072.10
HGNCiHGNC:1459 CAMK1
MIMi604998 gene
neXtProtiNX_Q14012

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

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

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
ProteomicsDBi59795
TopDownProteomicsiQ14012

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 Expressed in 172 organ(s), highest expression level in left adrenal gland
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114106, 36 interactors
DIPiDIP-41906N
IntActiQ14012, 8 interactors
STRINGi9606.ENSP00000256460

Chemistry databases

BindingDBiQ14012

Structurei

Secondary structure

1370
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Phylogenomic databases

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

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, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JES6C9JES6_HUMAN
Calcium/calmodulin-dependent protei...
CAMK1
122Annotation score:
H7C071H7C071_HUMAN
Calcium/calmodulin-dependent protei...
CAMK1
260Annotation score:
F8W6S9F8W6S9_HUMAN
Calcium/calmodulin-dependent protei...
CAMK1
39Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040596217P → S in a metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs907102077Ensembl.1
Natural variantiVAR_040597361E → K1 PublicationCorresponds to variant dbSNP:rs56033923Ensembl.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

Similar proteinsi

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, 36 interactors
DIPiDIP-41906N
IntActiQ14012, 8 interactors
STRINGi9606.ENSP00000256460

Chemistry databases

BindingDBiQ14012
ChEMBLiCHEMBL2493

PTM databases

iPTMnetiQ14012
PhosphoSitePlusiQ14012

Polymorphism and mutation databases

BioMutaiCAMK1
DMDMi3122301

Proteomic databases

EPDiQ14012
MaxQBiQ14012
PaxDbiQ14012
PeptideAtlasiQ14012
PRIDEiQ14012
ProteomicsDBi59795
TopDownProteomicsiQ14012

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
EuPathDBiHostDB:ENSG00000134072.10
GeneCardsiCAMK1
HGNCiHGNC:1459 CAMK1
HPAiCAB031904
HPA051409
MIMi604998 gene
neXtProtiNX_Q14012
OpenTargetsiENSG00000134072
PharmGKBiPA26048
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BRENDAi2.7.11.17 2681
SignaLinkiQ14012
SIGNORiQ14012

Miscellaneous databases

GeneWikiiCAMK1
GenomeRNAii8536
PROiPR:Q14012
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134072 Expressed in 172 organ(s), highest expression level in left adrenal gland
CleanExiHS_CAMK1
ExpressionAtlasiQ14012 baseline and differential
GenevisibleiQ14012 HS

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, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKCC1A_HUMAN
AccessioniPrimary (citable) accession number: Q14012
Secondary accession number(s): Q3KPF6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: October 10, 2018
This is version 188 of the entry and version 1 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, Direct protein sequencing, Reference proteome

Documents

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