CALM2 calmodulin 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CALM2provided by HGNC
Official Full Name: calmodulin 2provided by HGNC
Primary source: HGNC:HGNC:1445
See related: Ensembl:ENSG00000143933 MIM:114182; AllianceGenome:HGNC:1445
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; CAM3; CAMC; PHKD; CAMII; LQT15; PHKD2; CALML2; CAMIII
Summary: This gene is a member of the calmodulin gene family. There are three distinct calmodulin genes dispersed throughout the genome that encode the identical protein, but differ at the nucleotide level. Calmodulin is a calcium binding protein that plays a role in signaling pathways, cell cycle progression and proliferation. Several infants with severe forms of long-QT syndrome (LQTS) who displayed life-threatening ventricular arrhythmias together with delayed neurodevelopment and epilepsy were found to have mutations in either this gene or another member of the calmodulin gene family (PMID:23388215). Mutations in this gene have also been identified in patients with less severe forms of LQTS (PMID:24917665), while mutations in another calmodulin gene family member have been associated with catecholaminergic polymorphic ventricular tachycardia (CPVT)(PMID:23040497), a rare disorder thought to be the cause of a significant fraction of sudden cardiac deaths in young individuals. Pseudogenes of this gene are found on chromosomes 10, 13, and 17. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]
Expression: Ubiquitous expression in brain (RPKM 152.2), testis (RPKM 98.3) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p21

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (47160082..47176936, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (47165201..47182048, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (47387221..47404075, complement)

Chromosome 2 - NC_000002.12 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?

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.
microRNA-651-5p affects the proliferation, migration, and invasion of lung cancer cells by regulating Calmodulin 2 expression.
Title: microRNA-651-5p affects the proliferation, migration, and invasion of lung cancer cells by regulating Calmodulin 2 expression.
Circular RNA circ_0010729 Knockdown Attenuates Oxygen-Glucose Deprivation-Induced Human Cardiac Myocytes Injury by miR-338-3p/CALM2 Axis.
Title: Circular RNA circ_0010729 Knockdown Attenuates Oxygen-Glucose Deprivation-Induced Human Cardiac Myocytes Injury by miR-338-3p/CALM2 Axis.
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.
Targeting CALM2 Inhibits Hepatocellular Carcinoma Growth and Metastasis by Suppressing E2F5-mediated Cell Cycle Progression.
Title: Targeting CALM2 Inhibits Hepatocellular Carcinoma Growth and Metastasis by Suppressing E2F5-mediated Cell Cycle Progression.
Liver fibrosis caused by hepatitis C virus results in down-regulation of hepatic CALM2 expression.
Title: Identification of TAF1, HNF4A, and CALM2 as potential therapeutic target genes for liver fibrosis.
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.
Novel Association of a De Novo CALM2 Mutation With Long QT Syndrome and Hypertrophic Cardiomyopathy.
Title: Novel Association of a De Novo CALM2 Mutation With Long QT Syndrome and Hypertrophic Cardiomyopathy.
Impaired Ca(2+)-dependent inactivation in human cardiomyocytes as the plausible mechanism for Long QT Syndrome associated with 2 novel CaM mutations.
Title: Novel calmodulin mutations associated with congenital long QT syndrome affect calcium current in human cardiomyocytes.
Authors successfully recapitulated the disease phenotypes of LQT15 and revealed that inactivation of LTCC currents was impaired in CALM2-N98S hiPSC model.
Title: Allele-specific ablation rescues electrophysiological abnormalities in a human iPS cell model of long-QT syndrome with a CALM2 mutation.

Submit: New GeneRIF Correction See all GeneRIFs (24)

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 15 MedGen: C4015695 OMIM: 616249 GeneReviews: Long QT Syndrome Overview	Compare labs

EBI GWAS Catalog

Description
Genome-wide association scan for survival on dialysis in African-Americans with type 2 diabetes. 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
Tat	tat	Calmodulin and calmodulin-dependent protein kinase-II (CaMK-II)-activated p38 MAPK play a role in extracellular Tat-induced IL-10 expression in primary human monocytes	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

GDB:193857 (e-PCR)
- UniSTS:155765

RH125634 (e-PCR)
- UniSTS:163232

WI-9106 (e-PCR)
- UniSTS:52170

SHGC-30221 (e-PCR)
- UniSTS:28148

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 channel inhibitor activity	IDA Inferred from Direct Assay 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	ISS Inferred from Sequence or Structural Similarity 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	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of calcium ion transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
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	IDA Inferred from Direct Assay more info	PubMed
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 phosphoprotein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein autophosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of protein dephosphorylation	IDA Inferred from Direct Assay 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	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of ryanodine-sensitive calcium-release channel activity	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of calcium-mediated signaling	ISS Inferred from Sequence or Structural Similarity more info
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
part_of catalytic complex	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in membrane	ISS Inferred from Sequence or Structural Similarity 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
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
located_in vesicle	ISS Inferred from Sequence or Structural Similarity more info
part_of voltage-gated potassium channel complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: calmodulin-2

Names: Calmodulin-1; Calmodulin-3; LP7057 protein; calmodulin 2 (phosphorylase kinase, delta); phosphorylase kinase delta; phosphorylase kinase subunit delta; phosphorylase kinase subunit delta 2; prepro-calmodulin 2

NP_001292553.1

EC 2.7.11.19

NP_001292554.1

EC 2.7.11.19

NP_001292555.1

EC 2.7.11.19

NP_001734.1

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_042065.1 RefSeqGene

Range

5426..21853

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001305624.1 → NP_001292553.1 calmodulin-2 isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AI873701, BC017385, BG563041, HY022313

UniProtKB/Swiss-Prot

P0DP24

Conserved Domains (1) summary

PTZ00184
Location:50 → 197

PTZ00184; calmodulin; Provisional
NM_001305625.2 → NP_001292554.1 calmodulin-2 isoform 3

See identical proteins and their annotated locations for NP_001292554.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate exon in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus than isoform 1. Both variants 3 and 4 encode the same protein.

Source sequence(s)

AI873701, BC017385, HY108355

Consensus CDS

CCDS92749.1

UniProtKB/TrEMBL

A0A9K3Y7M0, D6W5B3, E7ETZ0, H0Y7A7, Q96HY3

Related

ENSP00000499266.1, ENST00000655450.1

Conserved Domains (1) summary

PTZ00184
Location:1 → 113

PTZ00184; calmodulin; Provisional
NM_001305626.1 → NP_001292555.1 calmodulin-2 isoform 3

See identical proteins and their annotated locations for NP_001292555.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in its 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus than isoform 1. Both variants 3 and 4 encode the same protein.

Source sequence(s)

AC073283, AI873701, BC017385, BC047553

Consensus CDS

CCDS92749.1

UniProtKB/TrEMBL

A0A9K3Y7M0, D6W5B3, E7ETZ0, H0Y7A7, Q96HY3

Related

ENST00000460218.5

Conserved Domains (1) summary

PTZ00184
Location:1 → 113

PTZ00184; calmodulin; Provisional
NM_001743.6 → NP_001734.1 calmodulin-2 isoform 2

See identical proteins and their annotated locations for NP_001734.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the 5' coding region, and uses an alternate start codon compared to variant 1. The encoded isoform (2) has a shorter N-terminus compared to isoform 1, and is the same protein encoded by other calmodulin gene family members.

Source sequence(s)

AI873701, BC017385

Consensus CDS

CCDS1832.1

UniProtKB/Swiss-Prot

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

UniProtKB/TrEMBL

B2RDW0, B4DJ51

Related

ENSP00000272298.7, ENST00000272298.12

Conserved Domains (1) summary

PTZ00184
Location:1 → 149

PTZ00184; calmodulin; Provisional