Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
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Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

CAMK1 (Q14012) - Overview - Molecular Target Synopsis

Protein


CAMK1, Calcium/calmodulin-dependent protein kinase type 1
Enzyme Classification 2.7.11.17
UniProt Q14012

Also Known as KCC1A_HUMAN, CAMK1

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 Ca(2+) 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. Monomer. Interacts with XPO1 (By similarity). Interacts with MARK2, ARHGEF7/BETAPIX and GIT1.

4FG7
CRYSTAL STRUCTURE OF HUMAN CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE I 1-293 IN COMPLEX WITH ATP
RCSB/PDB
Inspect Structure
See all 3D Structures for CAMK1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: CAMK1 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: CAMK1 is active in the following subcellular-locations: cytoplasm, glutamatergic synapse, nucleus, postsynaptic density.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project CAMK1 has gain in 4 cell-lines, loss in 2 cell-lines and no signal in 999 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HL_60, SN12C, NCI_H522

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HEL, WSU-DLCL2, OCI-AML2

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, IMR-90, NHLF

(see details)

RNA Interference


CAMK1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SUM44, CAOV3. (see details)

3D Structures


For CAMK1 there are:
4 structures (6 chains) solved
3 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


CAMK1 has been screened with 425 compounds (707 bioactivities), 4 compounds have bioactivities that show binding affinity of <= 500nM (7 bioactivities). (see details)