CALM3 calmodulin 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CALM3provided by HGNC
Official Full Name: calmodulin 3provided by HGNC
Primary source: HGNC:HGNC:1449
See related: Ensembl:ENSG00000160014 MIM:114183
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CaM; CALM; CAM1; CAM2; CAMB; PHKD; CPVT6; LQT16; PHKD3; CaMIII; HEL-S-72
Summary: This gene encodes a member of a family of proteins that binds calcium and functions as a enzymatic co-factor. Activity of this protein is important in the regulation of the cell cycle and cytokinesis. Multiple alternatively spliced transcript variants have been observed at this gene. [provided by RefSeq, Aug 2016]
Expression: Ubiquitous expression in brain (RPKM 470.4), testis (RPKM 108.1) and 23 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 19q13.32

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	19	NC_000019.10 (46601074..46610782)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (47104512..47114039)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Novel CALM3-E141K and CALM1-E141V are associated with congenital arrhythmia susceptibility.
Title: Genetic Mosaicism in Calmodulinopathy.
Protein molecular diagnosis of autosomal dominant calmodulin mutations causing irregular heart rhythms has been presented.
Title: Protein phenotype diagnosis of autosomal dominant calmodulin mutations causing irregular heart rhythms.
Study identified the structure and function of Ca2+-dependent interaction of CaM with the inactivation gate (IG) of NaV1.5 channels. Models of full-length NaV1.5 suggest that CaM binding to the IG directly modulates its function by destabilizing the inactivated state, which would promote resetting of the IG after channels close.
Title: A Mechanism of Calmodulin Modulation of the Human Cardiac Sodium Channel.
results suggest that ACE2, TNNI3K and CALM3 polymorphisms are associated with increased risk of hypertrophic cardiomyopathies and dilated cardiomyopathies and may act as disease modifiers of these diseases.
Title: ACE2, CALM3 and TNNI3K polymorphisms as potential disease modifiers in hypertrophic and dilated cardiomyopathies.
We discovered a novel CPVT mutation in the CALM3 gene that shares functional characteristics with established CPVT-associated mutations in CALM1. A small proportion of A103V-CaM is sufficient to evoke arrhythmogenic Ca disturbances via ryanodine receptor 2 dysregulation, which explains the autosomal dominant inheritance.
Title: Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V) Activates Arrhythmogenic Ca Waves and Sparks.
the spectrum and prevalence of pathogenic CaM variants in a cohort of genetically elusive long QT syndrome, were determined.
Title: Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome and Functional Characterization of a Novel Long QT Syndrome-Associated Calmodulin Missense Variant, E141G.
CALM3 had the highest ranking in the 1629-gene LQTS nodal network of the 7 genes identified through our filtering process.
Title: CALM3 mutation associated with long QT syndrome.
the association of EGFR, CALM3 and SMARCD1 gene polymorphisms with bone mineral density in white women, as conducted.
Title: Comprehensive analysis of the association of EGFR, CALM3 and SMARCD1 gene polymorphisms with BMD in Caucasian women.
Differentiation paralleled the activation of Wnt5/Calmodulin signalling by autocrine/paracrine intense secretion of Wnt5a and Wnt5b
Title: Mesodermal progenitor cells (MPCs) differentiate into mesenchymal stromal cells (MSCs) by activation of Wnt5/calmodulin signalling pathway.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Using genetic and clinical factors to predict tacrolimus dose in renal transplant recipients.

Submit: New GeneRIF Correction See all GeneRIFs (15)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. GeneReviews: Not available
LONG QT SYNDROME 16 MedGen: CN263287 OMIM: 618782 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	The calmodulin-binding domains in HIV-1 gp160 are involved in Fas-mediated apoptosis	PubMed
	env	The carboxyl-terminal domains (residues 768-788 and 826-854) of HIV-1 gp160 bind to calmodulin (CaM)	PubMed
Envelope transmembrane glycoprotein gp41	env	The carboxyl terminus (amino acid residues 768-788 and 828-855) of HIV-1 gp41 binds efficiently to purified calmodulin (CaM) and inhibits in vitro CaM-mediated stimulation of phosphodiesterase activity	PubMed
	env	The fusion between CD4+ human cells and cells stably expressing HIV-1 gp41 and gp120 is inhibited by calmodulin	PubMed
Nef	nef	HIV-1 Nef induces interleukin 10 expression through an interaction with the calcium/calmodulin-dependent phosphodiesterase signal transduction pathway	PubMed
	nef	HIV-1 Nef-induced CCL-2/MCP-1 upregulation in astrocytes depends on the myristoylation moiety (residues 2-3) of Nef and requires functional calmodulin	PubMed
	nef	Fluorescence spectroscopy analyses indicate the myristoylated N-terminal eight amino acids of HIV-1 Nef directly interact with calcium bound calmodulin	PubMed
matrix	gag	An HIV-1 MA peptide (residues 8-43) binds to CaM with a very high affinity with dissociation constant 25 nm	PubMed
	gag	Calmodulin (CaM) binding to HIV-1 MA induces the extrusion of the myristate group, suggesting that hydrophobic contacts between CaM and MA are critical for binding	PubMed
	gag	Calmodulin binds to both HIV-1 Gag and Matrix proteins through an extended calmodulin-binding domain in Matrix (amino acids 11-46)	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH11519 (e-PCR)
- UniSTS:68920

NIB1538 (e-PCR)
- UniSTS:24147

MARC_7076-7077:992008234:1 (e-PCR)
- UniSTS:231299

Homology

Homologs of the CALM3 gene: The CALM3 gene is conserved in chimpanzee, Rhesus monkey, cow, chicken, S.pombe, M.oryzae, N.crassa, A.thaliana, and rice.
Orthologs from Annotation Pipeline: 242 organisms have orthologs with human gene CALM3
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
N-terminal myristoylation domain binding	IPI Inferred from Physical Interaction more info	PubMed
adenylate cyclase activator activity	IDA Inferred from Direct Assay more info	PubMed
adenylate cyclase binding	IPI Inferred from Physical Interaction more info	PubMed
calcium ion binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
calcium-dependent protein binding	IEA Inferred from Electronic Annotation more info
disordered domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enzyme regulator activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
ion channel binding	IPI Inferred from Physical Interaction more info	PubMed
nitric-oxide synthase binding	IEA Inferred from Electronic Annotation more info
nitric-oxide synthase regulator activity	IEA Inferred from Electronic Annotation more info
phosphatidylinositol 3-kinase binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
protein phosphatase activator activity	IDA Inferred from Direct Assay more info	PubMed
protein serine/threonine kinase activator activity	TAS Traceable Author Statement more info	PubMed
titin binding	IPI Inferred from Physical Interaction more info	PubMed
type 3 metabotropic glutamate receptor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
G2/M transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
activation of adenylate cyclase activity	IEA Inferred from Electronic Annotation more info
calcium-mediated signaling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
detection of calcium ion	IMP Inferred from Mutant Phenotype more info	PubMed
establishment of protein localization to mitochondrial membrane	IEA Inferred from Electronic Annotation more info
microtubule cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of high voltage-gated calcium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of peptidyl-threonine phosphorylation	TAS Traceable Author Statement more info	PubMed
negative regulation of ryanodine-sensitive calcium-release channel activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of DNA binding	IEA Inferred from Electronic Annotation more info
positive regulation of cyclic-nucleotide phosphodiesterase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of nitric-oxide synthase activity	IEA Inferred from Electronic Annotation more info
positive regulation of peptidyl-threonine phosphorylation	TAS Traceable Author Statement more info	PubMed
positive regulation of phosphoprotein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of protein autophosphorylation	TAS Traceable Author Statement more info	PubMed
positive regulation of protein dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of protein serine/threonine kinase activity	TAS Traceable Author Statement more info	PubMed
positive regulation of ryanodine-sensitive calcium-release channel activity	IDA Inferred from Direct Assay more info	PubMed
regulation of cardiac muscle cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of cardiac muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	IC Inferred by Curator more info
regulation of cell communication by electrical coupling involved in cardiac conduction	IC Inferred by Curator more info
regulation of cytokinesis	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of heart rate	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
regulation of synaptic vesicle endocytosis	IEA Inferred from Electronic Annotation more info
regulation of synaptic vesicle exocytosis	IEA Inferred from Electronic Annotation more info
response to amphetamine	IEA Inferred from Electronic Annotation more info
response to calcium ion	IDA Inferred from Direct Assay more info	PubMed
response to corticosterone	IEA Inferred from Electronic Annotation more info
substantia nigra development	HEP more info	PubMed

Component	Evidence Code	Pubs
calcium channel complex	IDA Inferred from Direct Assay more info	PubMed
catalytic complex	IDA Inferred from Direct Assay more info	PubMed
centrosome	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	TAS Traceable Author Statement more info	PubMed
growth cone	IEA Inferred from Electronic Annotation more info
mitochondrial membrane	IEA Inferred from Electronic Annotation more info
myelin sheath	IEA Inferred from Electronic Annotation more info
nucleus	HDA more info	PubMed
plasma membrane	TAS Traceable Author Statement more info	PubMed
protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
sarcomere	IDA Inferred from Direct Assay more info	PubMed
spindle microtubule	IDA Inferred from Direct Assay more info	PubMed
spindle pole	IDA Inferred from Direct Assay more info	PubMed
synaptic vesicle membrane	IEA Inferred from Electronic Annotation more info
vesicle	HDA more info	PubMed
voltage-gated potassium channel complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: calmodulin-3

Names: Calmodulin-1; Calmodulin-2; epididymis secretory protein Li 72; phosphorylase kinase subunit delta; prepro-calmodulin 3

NP_001316850.1

EC 2.7.11.19

NP_001316851.1

EC 2.7.11.19

NP_001316852.1

EC 2.7.11.19

NP_001316853.1

EC 2.7.11.19

NP_001316854.1

EC 2.7.11.19

NP_001316855.1

EC 2.7.11.19

NP_005175.2

EC 2.7.11.19

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_051331.1 RefSeqGene

Range

5257..14709

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001329921.1 → NP_001316850.1 calmodulin-3 isoform 2

Status: REVIEWED

Source sequence(s)

AC093503

Consensus CDS

CCDS86783.1

UniProtKB/TrEMBL

Q96HY3

Related

ENSP00000375785.2, ENST00000391918.6

Conserved Domains (1) summary

PTZ00184
Location:1 → 113

PTZ00184; calmodulin; Provisional
NM_001329922.1 → NP_001316851.1 calmodulin-3 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and initiates translation from an alternate start codon compared to variant 1. Both variants 1 and 3 encode the same protein (isoform 1).

Source sequence(s)

AC093503, AK295927, AL050207, BC005137, DC316124

Consensus CDS

CCDS86782.1

UniProtKB/Swiss-Prot

P0DP23, P0DP24, P0DP25

UniProtKB/TrEMBL

B4DJ51

Related

ENSP00000472141.1, ENST00000596362.1

Conserved Domains (1) summary

PTZ00184
Location:1 → 149

PTZ00184; calmodulin; Provisional
NM_001329923.1 → NP_001316852.1 calmodulin-3 isoform 2

Status: REVIEWED

Source sequence(s)

AC093503, AK310762, AL050207, BC005137

Consensus CDS

CCDS86783.1

UniProtKB/Swiss-Prot

P0DP25

UniProtKB/TrEMBL

Q96HY3

Related

ENSP00000471225.1, ENST00000599839.5

Conserved Domains (1) summary

PTZ00184
Location:1 → 113

PTZ00184; calmodulin; Provisional
NM_001329924.2 → NP_001316853.1 calmodulin-3 isoform 2

Status: REVIEWED

Source sequence(s)

AC093503, AL050207, BC005137, BQ428612

Consensus CDS

CCDS86783.1

UniProtKB/Swiss-Prot

P0DP25

UniProtKB/TrEMBL

Q96HY3, Q9BRL5

Conserved Domains (1) summary

PTZ00184
Location:1 → 113

PTZ00184; calmodulin; Provisional
NM_001329925.2 → NP_001316854.1 calmodulin-3 isoform 2

Status: REVIEWED

Source sequence(s)

AC093503, AL050207, BC005137, DC405050

Consensus CDS

CCDS86783.1

UniProtKB/Swiss-Prot

P0DP25

UniProtKB/TrEMBL

Q96HY3, Q9BRL5

Related

ENSP00000470502.1, ENST00000598871.5

Conserved Domains (1) summary

PTZ00184
Location:1 → 113

PTZ00184; calmodulin; Provisional
NM_001329926.2 → NP_001316855.1 calmodulin-3 isoform 2

Status: REVIEWED

Source sequence(s)

AC093503, AL050207, BC005137, BC006182, DA138677

Consensus CDS

CCDS86783.1

UniProtKB/Swiss-Prot

P0DP25

UniProtKB/TrEMBL

Q96HY3, Q9BRL5

Related

ENSP00000468877.1, ENST00000594523.5

Conserved Domains (1) summary

PTZ00184
Location:1 → 113

PTZ00184; calmodulin; Provisional
NM_005184.4 → NP_005175.2 calmodulin-3 isoform 1

See identical proteins and their annotated locations for NP_005175.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Variants 1 and 3 encode the same protein (isoform 1).

Source sequence(s)

AW883334, BC005137, BC006182

Consensus CDS

CCDS33061.1

UniProtKB/Swiss-Prot

P0DP23, P0DP24, P0DP25

UniProtKB/TrEMBL

B4DJ51, Q9BRL5

Related

ENSP00000291295.8, ENST00000291295.14

Conserved Domains (1) summary

PTZ00184
Location:1 → 149

PTZ00184; calmodulin; Provisional