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; AllianceGenome:HGNC:1449
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
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Genomic context

Location:: 19q13.32

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (46601074..46610782)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (49426688..49436397)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (47104331..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 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?

Calmodulinopathy in Japanese Children - Their Cardiac Phenotypes Are Severe and Show Early Onset in Fetal Life and Infancy.
Title: Calmodulinopathy in Japanese Children　- Their Cardiac Phenotypes Are Severe and Show Early Onset in Fetal Life and Infancy.
CALM3 affects the prognosis of leukemia and hemorrhoids.
Title: CALM3 affects the prognosis of leukemia and hemorrhoids.
Novel CALM3 Variant Causing Calmodulinopathy With Variable Expressivity in a 4-Generation Family.
Title: Novel CALM3 Variant Causing Calmodulinopathy With Variable Expressivity in a 4-Generation Family.
Prevalence and Phenotypic Correlations of Calmodulinopathy-Causative CALM1-3 Variants Detected in a Multicenter Molecular Autopsy Cohort of Sudden Unexplained Death Victims.
Title: Prevalence and Phenotypic Correlations of Calmodulinopathy-Causative CALM1-3 Variants Detected in a Multicenter Molecular Autopsy Cohort of Sudden Unexplained Death Victims.
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.

Submit: New GeneRIF Correction See all GeneRIFs (19)

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
Long QT syndrome 16 MedGen: C5394068 OMIM: 618782 GeneReviews: Long QT Syndrome Overview	Compare labs

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2024-07-09) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2024-07-09) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

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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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables adenylate cyclase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables adenylate cyclase binding	IPI Inferred from Physical Interaction more info	PubMed
enables calcium ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables calcium-dependent protein binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activator activity	TAS Traceable Author Statement more info	PubMed
enables titin binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmembrane transporter binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in G2/M transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in detection of calcium ion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of calcium ion export across plasma membrane	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of high voltage-gated calcium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of peptidyl-threonine phosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of ryanodine-sensitive calcium-release channel activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cyclic-nucleotide phosphodiesterase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of peptidyl-threonine phosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of protein autophosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of protein serine/threonine kinase activity	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of ryanodine-sensitive calcium-release channel activity	IDA Inferred from Direct Assay more info	PubMed
involved_in presynaptic endocytosis	IEA Inferred from Electronic Annotation more info
involved_in regulation of calcium-mediated signaling	IEA Inferred from Electronic Annotation more info
involved_in regulation of cardiac muscle cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cardiac muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	IC Inferred by Curator more info
involved_in regulation of cell communication by electrical coupling involved in cardiac conduction	IC Inferred by Curator more info
involved_in regulation of cytokinesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of heart rate	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
involved_in response to calcium ion	IDA Inferred from Direct Assay more info	PubMed
involved_in substantia nigra development	HEP more info	PubMed

Component	Evidence Code	Pubs
part_of calcium channel complex	IDA Inferred from Direct Assay more info	PubMed
located_in calyx of Held	IEA Inferred from Electronic Annotation more info
part_of catalytic complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in centrosome	IBA Inferred from Biological aspect of Ancestor more info
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
is_active_in myelin sheath	IBA Inferred from Biological aspect of Ancestor more info
located_in myelin sheath	IEA Inferred from Electronic Annotation more info
located_in nucleus	HDA more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed
located_in presynaptic cytosol	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
located_in sarcomere	IDA Inferred from Direct Assay more info	PubMed
located_in sperm midpiece	IEA Inferred from Electronic Annotation more info
located_in spindle microtubule	IDA Inferred from Direct Assay more info	PubMed
located_in spindle pole	IDA Inferred from Direct Assay more info	PubMed
located_in vesicle	HDA more info	PubMed
part_of 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; phosphorylase kinase subunit delta 3; 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), LRG_1082

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

A0A9K3Y7M0, D6W5B3, E7ETZ0, H0Y7A7, 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

P02593, P0DP23, P0DP24, P0DP25, P62158, P70667, P99014, Q13942, Q53S29, Q61379, Q61380, Q96HK3

UniProtKB/TrEMBL

B2RDW0, 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/TrEMBL

A0A9K3Y7M0, D6W5B3, E7ETZ0, H0Y7A7, 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/TrEMBL

A0A9K3Y7M0, D6W5B3, E7ETZ0, H0Y7A7, Q96HY3

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/TrEMBL

A0A9K3Y7M0, D6W5B3, E7ETZ0, H0Y7A7, Q96HY3

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/TrEMBL

A0A9K3Y7M0, D6W5B3, E7ETZ0, H0Y7A7, Q96HY3

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

P02593, P0DP23, P0DP24, P0DP25, P62158, P70667, P99014, Q13942, Q53S29, Q61379, Q61380, Q96HK3

UniProtKB/TrEMBL

B2RDW0, B4DJ51

Related

ENSP00000291295.8, ENST00000291295.14

Conserved Domains (1) summary

PTZ00184
Location:1 → 149

PTZ00184; calmodulin; Provisional